Split (3)

train · 3.75k rows

review_id stringlengths 8 8	pmid list	title list	abstract list	target stringlengths 56 2.23k
CD008131	[ "17700083", "10784079", "11144634", "14560166" ]	[ "A randomized, controlled trial of a home-based intervention program for children with autism and developmental delay.", "Multi-method psycho-educational intervention for preschool children with disruptive behavior: preliminary results at post-treatment.", "A preschool program for safety and injury prevention delivered by home visitors.", "Brief psychoeducational parenting program: an evaluation and 1-year follow-up." ]	[ "This study aimed to (1) investigate whether provision of a home-based program in addition to a center-based program improves development in young children with disabilities and coping abilities of their families and (2) describe the characteristics of children and families who benefit most from the intervention.\n Fifty-nine children, aged 3-5 years, with no cerebral palsy, participated in the study. Half of the group was randomized to receive an additional program in their homes. A special education teacher provided 40 visits over 12 months working with the families to help generalize skills to the home environment and assist with their concerns. All children were assessed before and after the intervention, and families completed questionnaires assessing family stress, support, and empowerment on both occasions. Differences in change over time and between the intervention and control group were analyzed by repeated measures and the association between characteristics of children and families with improved outcome by multivariate analysis of variance.\n Change in cognitive development and behavior (in the centers) over time favored the children who received the extra intervention (p = .007 and p = .007, respectively). The groups did not differ on any of the family measures of change. Multivariate analysis of variance revealed more improvement for children in the intervention group from higher than lower stressed families.\n Results suggest the need for daily reinforcement of skills learned at the center-based program and the importance of involving families, especially those with few resources and relatively high stress.", "Annual screenings of preschool children at kindergarten registration identified 158 children having high levels of aggressive, hyperactive, impulsive, and inattentive behavior. These \"disruptive\" children were randomly assigned to four treatment conditions lasting the kindergarten school year: no treatment, parent training only, full-day treatment classroom only, and the combination of parent training with the classroom treatment. Results showed that parent training produced no significant treatment effects, probably owing largely to poor attendance. The classroom treatment produced improvement in multiple domains: parent ratings of adaptive behavior, teacher ratings of attention, aggression, self-control, and social skills, as well as direct observations of externalizing behavior in the classroom. Neither treatment improved academic achievement skills or parent ratings of home behavior problems, nor were effects evident on any lab measures of attention, impulse control, or mother-child interactions. It is concluded that when parent training is offered at school registration to parents of disruptive children identified through a brief school registration screening, it may not be a useful approach to treating the home and community behavioral problems of such children. The kindergarten classroom intervention was far more effective in reducing the perceived behavioral problems and impaired social skills of these children. Even so, most treatment effects were specific to the school environment and did not affect achievement skills. These findings must be viewed as tentative until follow-up evaluations can be done to determine the long-term outcomes of these interventions.", "To evaluate the feasibility, acceptability, and effectiveness of an injury prevention program delivered by school based home visitors to the families of low income children attending preschool enrichment programs in Washington State.\n The families of children attending preschool Head Start programs in two regions were eligible. A total of 213 families (77.8% of those eligible) from intervention sites, and 149 families (71.9% of those eligible) from concurrent comparison sites, agreed to participate and completed the trial.\n Trained school personnel conducted home safety inspections as part of a planned home visit. Intervention families were offered educational materials as well as smoke detectors, batteries, ipecac, and age appropriate car safety restraints based on results of the home inspection.\n At a repeat home visit three months later, the proportion of families with a positive change in injury prevention knowledge or behavior among those in the intervention group was compared with the proportion in the comparison group. Smoke detector presence and function were observed.\n Among families without a working smoke detector at baseline, the intervention was associated with an increased probability of having a working detector at follow up (relative risk (RR) 3.3, 95% confidence interval (CI) 1.3 to 8.6). Intervention families were also more likely to report the presence of ipecac in the home (RR 4.7, 95% CI 3.0 to 7.3) at follow up and to have obtained an age appropriate booster seat (RR 4.1, 95% CI 1.9 to 8.8). The program was acceptable to client families and to the home visitors who conducted the intervention.\n Among the families of low income children enrolled in preschool enrichment programs, home safety inspections and the distribution of safety supplies by school based home visitors appears to improve knowledge and behavior related to poisoning, smoke detector installation, and car safety seat use over three months of follow up.", "Despite recognition of the need for parenting interventions to prevent childhood behavioral problems, few community programs have been evaluated. This report describes the randomized controlled evaluation of a four-session psychoeducational group for parents of preschoolers with behavior problems, delivered in community agencies.\n In 1998, 222 primary caregivers, recruited through community ads, filled out questionnaires on parenting practices and child behavior. Parents were randomly assigned to immediate intervention or a wait-list control. The intervention comprised three weekly group sessions and a 1-month booster, the focus being to support effective discipline (using the video 1-2-3 Magic) and to reduce parent-child conflict.\n Using an intent-to-treat analysis, repeated-measures analyses of variance indicated that the parents who received the intervention reported significantly greater improvement in parenting practices and a significantly greater reduction in child problem behavior than the control group. The gains in positive parenting behaviors were maintained at 1-year follow-up in a subset of the experimental group.\n This brief intervention program may be a useful first intervention for parents of young children with behavior problems, as it seems both acceptable and reasonably effective." ]	This review does not provide evidence of the effectiveness of home-based interventions that are specifically targeted at improving developmental outcomes for preschool children from socially disadvantaged families. Future studies should endeavour to better document and report their methodological processes.
CD006633	[ "17194269", "16585434", "11481167", "9989566", "18562423", "9131723", "8610833", "11041534", "16449469", "7509495", "12893670", "11823268", "16818861", "9221965", "863344", "12766921" ]	[ "A double-blind study of combination of clozapine with risperidone in patients with schizophrenia: effects on cognition.", "Effectiveness of clozapine versus olanzapine, quetiapine, and risperidone in patients with chronic schizophrenia who did not respond to prior atypical antipsychotic treatment.", "A double-blind comparative study of clozapine and risperidone in the management of severe chronic schizophrenia.", "Clozapine and risperidone in chronic schizophrenia: effects on symptoms, parkinsonian side effects, and neuroendocrine response.", "Efficacy and tolerability of ziprasidone versus risperidone as augmentation in patients partially responsive to clozapine: a randomised controlled clinical trial.", "Improvement of cognitive function in schizophrenic patients receiving clozapine or zotepine: results from a double-blind study.", "Different side effect profiles of risperidone and clozapine in 20 outpatients with schizophrenia or schizoaffective disorder: a pilot study.", "Risperidone versus clozapine in treatment-resistant schizophrenia: a randomized pilot study.", "Why olanzapine beats risperidone, risperidone beats quetiapine, and quetiapine beats olanzapine: an exploratory analysis of head-to-head comparison studies of second-generation antipsychotics.", "Risperidone versus clozapine in the treatment of schizophrenic patients with acute symptoms: a double blind, randomized trial.", "Clozapine v. conventional antipsychotic drugs for treatment-resistant schizophrenia: a re-examination.", "Clozapine, olanzapine, risperidone, and haloperidol in the treatment of patients with chronic schizophrenia and schizoaffective disorder.", "Childhood-onset schizophrenia: A double-blind, randomized clozapine-olanzapine comparison.", "Clozapine versus placebo in Huntington's disease: a double blind randomised comparative study.", "Some methodological considerations for the clinical evaluation of neuroleptics--comparative effects of clozapine and haloperidol on schizophrenics.", "The impact upon extra-pyramidal side effects, clinical symptoms and quality of life of a switch from conventional to atypical antipsychotics (risperidone or olanzapine) in elderly patients with schizophrenia." ]	[ "Atypical antipsychotic drugs produce improvement in some domains of cognition as well as psychopathology in patients with schizophrenia. However, the effect of combinations of atypical antipsychotic drugs on cognitive function is unknown. The aim of this study was to compare the effect of risperidone or placebo on cognitive function in patients with schizophrenia who were previously treated with clozapine monotherapy.\n This prospective, randomized, double-blind, placebo-controlled, 6-week study included 30 patients with DSM-IV schizophrenia. Patients whose psychopathology was no more than partially responsive to clozapine treatment were randomly assigned to receive adjunctive treatment with risperidone (N = 16) up to 6 mg/day or placebo (N = 14). Cognitive test scores for verbal learning and memory, verbal fluency, attention, executive function, verbal working memory, and motor function were the primary outcome measures. Secondary outcome measures included assessment of psychopathology, extrapyramidal side effects, and global functioning. Data were collected between November 2001 and July 2003.\n Significant improvement was found in both treatment groups in a variety of cognitive measures, but there was significantly greater improvement in the placebo-augmented group on measures of initial learning acquisition and attention. The improvement in cognition was not correlated with improvement in psychopathology. There were significant correlations between improvement in verbal working memory, verbal learning and memory, and attention and quality of life and global functioning in the placebo-augmented but not the risperidone-augmented group.\n Adjunctive treatment with risperidone for 6 weeks in patients with schizophrenia who had received chronic treatment with clozapine does not significantly improve cognitive function.", "When a schizophrenia patient has an inadequate response to treatment with an antipsychotic drug, it is unclear what other antipsychotic to switch to and when to use clozapine. In this study, the authors compared switching to clozapine with switching to another atypical antipsychotic in patients who had discontinued treatment with a newer atypical antipsychotic in the context of the Clinical Antipsychotic Trials for Interventions Effectiveness (CATIE) investigation.\n Ninety-nine patients who discontinued treatment with olanzapine, quetiapine, risperidone, or ziprasidone in phase 1 or 1B of the trials, primarily because of inadequate efficacy, were randomly assigned to open-label treatment with clozapine (N=49) or blinded treatment with another newer atypical antipsychotic not previously received in the trial (olanzapine [N=19], quetiapine [N=15], or risperidone [N=16]).\n Time until treatment discontinuation for any reason was significantly longer for clozapine (median=10.5 months) than for quetiapine (median=3.3), or risperidone (median=2.8), but not for olanzapine (median=2.7). Time to discontinuation because of inadequate therapeutic effect was significantly longer for clozapine than for olanzapine, quetiapine, or risperidone. At 3-month assessments, Positive and Negative Syndrome Scale total scores had decreased more in patients treated with clozapine than in patients treated with quetiapine or risperidone but not olanzapine. One patient treated with clozapine developed agranulocytosis, and another developed eosinophilia; both required treatment discontinuation.\n For these patients with schizophrenia who prospectively failed to improve with an atypical antipsychotic, clozapine was more effective than switching to another newer atypical antipsychotic. Safety monitoring is necessary to detect and manage clozapine's serious side effects.", "This prospective, double-blind, multicenter, parallel-group study compared the efficacy and safety of therapeutic doses of clozapine and risperidone in patients with severe chronic schizophrenia and poor previous treatment response.\n Male or female patients aged 18-65 years who met DSM-IV criteria for schizophrenia and study requirements for poor previous treatment response (N=273) were randomly assigned to double-blind treatment with either clozapine or risperidone administered over 12 weeks in increasing increments. The primary efficacy measures were the magnitude of improvement in Brief Psychiatric Rating Scale (BPRS) and Clinical Global Impression (CGI) scores. Adverse events were recorded throughout the study.\n The magnitude of improvement in mean BPRS and CGI scores from baseline to end of the study was significantly greater in the clozapine group than in the risperidone group. Statistically significant differences in favor of clozapine were also seen for most of the secondary efficacy measures (Positive and Negative Syndrome Scale, Calgary Depression Scale, Psychotic Depression Scale, and Psychotic Anxiety Scale). The adverse event profile was similar for both treatment groups, with a lower risk of extrapyramidal symptoms in the clozapine group.\n Clozapine showed superior efficacy over risperidone in this patient population. Both treatments were equally well tolerated as demonstrated through their adverse event profiles, although as expected clozapine was associated with a lower risk of extrapyramidal symptoms than risperidone.", "Clozapine and risperidone were the first two \"second-generation\" antipsychotic drugs approved for schizophrenia. There is currently little information about their comparative efficacy from head-to-head clinical trials. The purpose of this study was to examine the comparative efficacy of clozapine and risperidone for positive and negative symptoms, depression, parkinsonian side effects, and indexes of neuroendocrine function in schizophrenic patients who met a priori criteria for partial response to traditional neuroleptic agents.\n After a baseline fluphenazine treatment period, 29 patients participated in a 6-week, double-blind, parallel-group comparison of the effects of these agents.\n Clozapine was superior to risperidone for positive symptoms and parkinsonian side effects, but there were no significant differences between the drugs on two measures of negative symptoms, Brief Psychiatric Rating Scale total scores, and depression scores. The clozapine patients, but not the risperidone patients, demonstrated significant reductions from the fluphenazine baseline in positive symptoms, total symptoms, and depression. In addition, clozapine produced fewer effects on plasma prolactin than risperidone or fluphenazine. The mean daily doses during week 6 of the trial were 403.6 mg of clozapine and 5.9 mg of risperidone.\n The findings from this study indicate that these drugs have both important differences and similarities in their comparative efficacy in chronically ill, partially responsive patients with schizophrenia. Further research on second-generation antipsychotic drugs in this patient population that addresses key methodological issues, such as optimal dose and treatment duration, are needed.", "Patients suffering from schizophrenic psychoses sometimes insufficiently respond to antipsychotic monotherapy and then combination approaches are preferred. We aimed in validating the add-on of ziprasidone and risperidone to clozapine, and we performed a randomised head-to-head trial. Patients with partial response to clozapine were randomly attributed to augmentation with ziprasidone (n = 12) or risperidone (n = 12). Efficacy assessments included the Positive and Negative Syndrome Scale (PANSS), the Scale for the Assessment of Negative Symptoms (SANS), the Hamilton Depression Scale (HAMD), the Clinical Global Impression (CGI) and the Global Assessment of Functioning (GAF). Furthermore, several safety and tolerability measures were obtained. After six weeks, both groups showed significant reductions of positive and negative symptoms. In addition, affective state, psychosocial functioning and clozapine side effects improved without significant differences between the groups. Both approaches were well tolerated. However, the ziprasidone group experienced a small elongation of the QTc interval and a reduction of extrapyramidal symptoms. Patients under clozapine-risperidone therapy developed a rise of serum prolactin levels. The clozapine augmentation with ziprasidone or risperidone resulted in significant psychopathological improvements. The side effects differed between the treatment groups. Further head-to-head comparisons of atypical antipsychotics as add-on to clozapine are necessary.", "Clinical interest in the so-called atypical antipsychotics currently focuses on the possibility of improving the negative symptoms of schizophrenia and the cognitive dysfunction associated with the disease. While clozapine has been shown to be effective in this respect, no data are available on zotepine. We report on a double-blind randomized study designed to evaluate the impact of zotepine and clozapine on cognitive dysfunction in schizophrenia. Cognitive function was operationalized by a maze test in which patients traversed computer-displayed mazes of increasing complexity. Passage time, route, and motor errors were evaluated. 25 schizophrenic (DSM-IIIR) patients were included in each group. After washout, they were randomized on zotepine or clozapine and given up to 450 mg of substance each. Patients were followed for six weeks and evaluated weekly. We report on a subsample of 26 patients matched for baseline BPRS, SANS, and age. 13 matched healthy persons were recruited as controls. ANOVA with group and course over time as factors was used for analysis. Both clozapine and zotepine achieved a highly significant decrease in overall symptoms (BPRS) and negative symptoms (SANS). Zotepine and clozapine were equally effective. In the maze tests, motor errors in simple mazes were stable over time and differentiated schizophrenics from controls as a \"trait\" marker. In passage time and maze route, schizophrenics performed worse than controls. An improvement by medication was evident in both medication groups, but was more pronounced in the zotepine-treated group. The study confirms previous results on the efficacy of clozapine and zotepine in treating negative symptoms of schizophrenia. The data presented show for the first time that zotepine is efficacious in improving cognitive dysfunction, confirming this substance's value as an atypical antipsychotic.", "The purpose of this study was to compare the side effect +profiles of clozapine and risperidone.\n The subjects were 20 outpatients with schizophrenia or schizoaffective disorder who were clinically stable on a regimen of clozapine at the time of screening. They underwent a randomized-order crossover comparison of 6 weeks of risperidone treatment and 6 weeks of clozapine treatment. Clinical and neurocognitive variables were assessed by raters blind to medication status, and severity of side effects was determined from patients' self-reports.\n Side effect measures, but not clinical ratings, were significantly different after 6 weeks of treatment with the two drugs. Patients required more benztropine for motor effects and complained of more insomnia with risperidone and more sedation with clozapine. Body weight was higher at the end of clozapine treatment than at the end of risperidone treatment.\n In this exploratory study, the side effect profiles of clozapine and risperidone were consistent with the different pharmacodynamic profiles of the two drugs.", "1. The atypical antipsychotic risperidone may constitute an alternative to clozapine, the current treatment of choice for refractory schizophrenia. The objectives of this study were to evaluate the effectiveness of risperidone in comparison to clozapine in everyday practice and to assess the feasibility of a pragmatic trial procedure. 2. Patients were randomly assigned to open-label clozapine or risperidone treatment for 10 weeks and treatment outcomes were assessed blindly. Twenty-one patients were recruited and nineteen entered the randomized phase. 3. Five of 10 participants allocated to clozapine and one of nine risperidone participants dropped out before study completion. Five clozapine patients and six risperidone patients achieved clinical improvement, defined as a 20% decrease in the Positive and Negative Symptom Scale (PANSS) total score. No significant differences between the groups were detected in baseline or endpoint positive or negative symptoms, disease severity, or global or social functioning scores. Patients' opinion on the drugs did not differ between groups. 4. The findings of the intention-to-treat analysis of this study corroborates previous findings that risperidone may be equally effective as clozapine, and supports the feasibility and need of a multicenter randomized pragmatic trial with sufficient power to detect differences between treatments.", "In many parts of the world, second-generation antipsychotics have largely replaced typical antipsychotics as the treatment of choice for schizophrenia. Consequently, trials comparing two drugs of this class--so-called head-to-head studies--are gaining in relevance. The authors reviewed results of head-to-head studies of second-generation antipsychotics funded by pharmaceutical companies to determine if a relationship existed between the sponsor of the trial and the drug favored in the study's overall outcome.\n The authors identified head-to-head comparison studies of second-generation antipsychotics through a MEDLINE search for the period from 1966 to September 2003 and identified additional head-to-head studies from selected conference proceedings for the period from 1999 to February 2004. The abstracts of all studies fully or partly funded by pharmaceutical companies were modified to mask the names and doses of the drugs used in the trial, and two physicians blinded to the study sponsor reviewed the abstracts and independently rated which drug was favored by the overall outcome measures. Two authors who were not blinded to the study sponsor reviewed the entire report of each study for sources of bias that could have affected the results in favor of the sponsor's drug.\n Of the 42 reports identified by the authors, 33 were sponsored by a pharmaceutical company. In 90.0% of the studies, the reported overall outcome was in favor of the sponsor's drug. This pattern resulted in contradictory conclusions across studies when the findings of studies of the same drugs but with different sponsors were compared. Potential sources of bias occurred in the areas of doses and dose escalation, study entry criteria and study populations, statistics and methods, and reporting of results and wording of findings.\n Some sources of bias may limit the validity of head-to-head comparison studies of second-generation antipsychotics. Because most of the sources of bias identified in this review were subtle rather than compelling, the clinical usefulness of future trials may benefit from minor modifications to help avoid bias. The authors make a number of concrete suggestions for ways in which potential sources of bias can be addressed by study initiators, peer reviewers of studies under consideration for publication, and readers of published studies.", "1. In order to verify the hypothesis that risperidone is a useful therapeutic alternative to clozapine the authors carried out a randomized double blind trial in 59 patients with paranoid hallucinatory psychoses. 2. In a treatment lasting 28 days three groups of patients received either 4 mg risperidone (N = 20), 8 mg risperidone (N = 19), or 400 mg clozapine (N = 20) daily. 3. The tolerance of 4 mg risperidone was globally assessed as being better than that of 400 mg clozapine. Drop-outs under clozapine were mostly caused by side effects, whereas under risperidone they tended to occur for therapeutic inefficacy. 4. The antipsychotic effect was highly significant and clinically relevant under both risperidone and clozapine.", "Although there is a consensus that clozapine is more effective than conventional antipsychotic drugs for treatment-resistant schizophrenia, there is great heterogeneity among results of relevant trials.\n To re-evaluate the evidence comparing clozapine with conventional antipsychotics and to investigate sources of heterogeneity.\n Individual studies were inspected with assessment of clinical relevance of results. Meta-regression analysis was performed to investigate sources of heterogeneity.\n Ten trials were examined. Recent large-scale studies have not found a substantial advantage for clozapine, especially in terms of a clinically relevant effect. Meta-regression showed that shorter study duration, financial support from a drug company and higher baseline symptom score consistently predicted greater advantage of clozapine.\n It may be inappropriate to combine studies in meta-analysis, given the degree of heterogeneity between their findings. The benefits of clozapine compared with conventional treatment may not be substantial.", "The authors compared the efficacy and safety of three atypical antipsychotics (clozapine, olanzapine, and risperidone) with one another and with haloperidol in the treatment of patients with chronic schizophrenia or schizoaffective disorder.\n In a double-blind trial, 157 inpatients with a history of suboptimal treatment response were randomly assigned to treatment with clozapine, olanzapine, risperidone, or haloperidol for 14 weeks (an 8-week escalation and fixed-dose period followed by a 6-week variable-dose period).\n Clozapine, risperidone, and olanzapine (but not haloperidol) resulted in statistically significant improvements in total score on the Positive and Negative Syndrome Scale. Improvements seen in total and negative symptom scores with clozapine and olanzapine were superior to haloperidol. The atypical drugs, particularly olanzapine and clozapine, were associated with weight gain.\n The effects of atypical antipsychotics in this population were statistically significant but clinically modest. The overall pattern of results suggests that clozapine and olanzapine have similar general antipsychotic efficacy and that risperidone may be somewhat less effective. Clozapine was the most effective treatment for negative symptoms. However, the differences among treatments were small.", "Childhood-onset schizophrenia is a rare but severe form of the disorder that is frequently treatment resistant. The psychiatrist has a limited evidence base to guide treatment, particularly as there are no trials in children comparing atypical antipsychotics, the mainstay of current treatment.\n To compare the efficacy and safety of olanzapine and clozapine, hypothesizing that clozapine would be more efficacious.\n Double-blind randomized 8-week controlled trial, with a 2-year open-label follow-up.\n National Institute of Mental Health study, January 1998 to June 2005. Patients underwent reassessment 2 years after discharge.\n Children and adolescents recruited nationally, aged 7 to 16 years, meeting unmodified DSM-IV criteria for schizophrenia, and resistant to treatment with at least 2 antipsychotics.\n After drug washout and a 1- to 3-week antipsychotic-free period, patients were randomized to treatment with clozapine (n = 12) or olanzapine (n = 13).\n The Clinical Global Impression Severity of Symptoms Scale and Schedule for the Assessment of Negative/Positive Symptoms.\n Clozapine was associated with a significant reduction in all outcome measures, whereas olanzapine showed a less consistent profile of clinical improvement. While there were moderate to large differential treatment effects in favor of clozapine, these reached significance only in the alleviation of negative symptoms from an antipsychotic-free baseline (P = .04; effect size, 0.89). Clozapine was associated with more overall adverse events. At 2-year follow-up, 15 patients were receiving clozapine with evidence of sustained clinical improvement, but additional adverse events emerged, including lipid anomalies (n = 6) and seizures (n = 1).\n While not demonstrating definitively the superiority of clozapine compared with olanzapine in treatment-refractory childhood-onset schizophrenia, the study suggests that clozapine has a more favorable profile of clinical response, which is balanced against more associated adverse events.", "To establish the effect of the atypical neuroleptic clozapine on chorea, voluntary motor performance, and functional disability in patients with Huntington's disease.\n Thirty three patients with Huntington's disease participated in a double blind randomised trial. A maximum of 150 mg/day clozapine or placebo equivalent was given for a period of 31 days. Assessments were performed in the week before and at the last day of the trial. Chorea was scored using the abnormal involuntary movement scale (AIMS), the chorea score of the unified Huntington's disease rating scale (UHDRS), and judgement of video recordings. Voluntary motor performance was assessed using the UHDRS motor scale. Patients and their partners completed a questionnaire regarding functional disability. Twelve patients already used other neuroleptic medication, which was kept unchanged during the trial period. Results of neuroleptic naive and neuroleptic treated patients were analysed separately.\n Clozapine tended to reduce chorea in neuroleptic naive patients only (AIMS); improvement seemed more pronounced in patients receiving higher doses of clozapine. Other measures of chorea (UHDRS chorea score, video ratings) showed no improvement. Clozapine had no beneficial effect on chorea in patients already receiving neuroleptic medication. Voluntary motor performance did not improve with clozapine. Neuroleptic naive patients reported aggravation of functional disability, possibly reflecting the frequent occurrence of side effects. Adverse reactions forced trial termination in six patients and dose reduction in another eight, and consisted mainly of drowsiness, fatigue, anticholinergic symptoms, and walking difficulties.\n Clozapine has little beneficial effect in patients with Huntington's disease, although individual patients may tolerate doses high enough to reduce chorea. Because adverse reactions are often encountered, clozapine should be used with restraint in this patient group.", "For the purpose of evaluating objectively the characteristics of clinical effects of clozapine and haloperidol, a double-blind comparative trial was conducted on 91 schizophrenic in-patients. The changes of symptoms were assessed by means of several psychiatric and behavioral rating scales. The results were analyzed by means of nonparametric statistical methods. Furthermore, application of multivariate analysis was considered. After 12 weeks of treatment, though no significant difference in general improvement rate was noted between the two groups, a marked different spectrum of clinical effects was observed according to the rating scales. Clozapine is superior in anti-delusional, contact-promoting and sedative anxiolytic effect, while haloperidol is superior in anti-autistic effect. Among the side-effects, extrapyramidal symptoms appeared significatly more severe in the haloperidol group. The frequency of appearance of fever, was significantly greater in the clozapine group than the other. The four dropout cases of the clozapine group were all caused by fever. Through this clinical trial, clinical availability and validity of various statistical analytical methods were reconsidered.", "Atypical antipsychotics are commonly used in the management of schizophrenia in late life with evidence suggesting they induce lower rates of motor disturbance, but have similar efficacy to conventional antipsychotics. Trials in the elderly have been either retrospective, small, of short duration or of a single-arm design.\n To demonstrate the effects upon motor side-effects, efficacy, safety and quality of life (QOL) of switching elderly patients with schizophrenia from conventional antipsychotics to olanzapine or risperidone.\n Elderly patients with schizophrenia were randomly allocated to olanzapine or risperidone and followed through an open-label crossover period. Between and within group intention to treat analyses were conducted.\n 66 patients were randomised (mean age 69.6 [SD +/- 6.2]). Four (11.8%) patients on olanzapine and 8 (26.7%) patients on risperidone failed to complete the crossover because of treatment failure [Odds Ratio (OR) = 2.73[0.73-10.2] p = 0.14]. The mean doses upon completion of switching in each arm were 9.9 mg (SD = 4.2) and 1.7 mg (SD = 1.2) for olanzapine and risperidone respectively. In both arms there was improvement in Parkinsonism, though only olanzapine was associated with a reduction in dyskinetic symptoms. The Brief Psychiatric Rating Scale, Scale for the assessment of Negative Symptoms and Montgomery and Asberg Depression Rating Scale scores all improved through the crossover period in both arms with no between group differences. Treatment with olanzapine was associated with a better response over risperidone on the psychological domain of the World Health Organisation-Quality Of Life [Brief] (WHO-QOL-BREF) scale ( p = 0.02). Patients in the olanzapine arm also demonstrated improvement from baseline in the WHO-QOL-BREF physical, psychological and health satisfaction domains, but risperidone had no effect on any Quality of Life (QOL) measure.\n After switching from a conventional antipsychotic, olanzapine and risperidone were associated with improvement in core symptoms of schizophrenia and motor side effects. Subjects switched to olanzapine were more likely to complete the switching process and show an improvement in psychological QOL.\n Copyright 2003 John Wiley & Sons, Ltd." ]	Clozapine may be a little more efficacious than zotepine and risperidone but further trials are required to confirm this finding. Clozapine differs more clearly in adverse effects from other second generation antipsychotics and the side-effect profile could be key in the selection of treatment depending on the clinical situation and a patient’s preferences. Data on other important outcomes such as cognitive functioning, quality of life, death or service use are currently largely missing, making further large and well-designed trials necessary. It is also important to take into account that the large number of people leaving the studies early limits the validity and interpretation of our findings.
CD003163	[ "380773", "12911781", "16176400" ]	[ "Flunisolide nasal spray for perennial rhinitis in children.", "Usefulness of specific immunotherapy in patients with severe perennial allergic rhinitis induced by house dust mite: a double-blind, randomized, placebo-controlled trial.", "Three-year follow-up of clinical and inflammation parameters in children monosensitized to mites undergoing sub-lingual immunotherapy." ]	[ "Twenty-seven children with perennial rhinitis entered a double-blind cross-over study comparing nasal sprays of flunisolide---a new topical corticosteroid---and placebo. Symptoms were assessed over two consecutive monthly periods with each treatment. Weekly diary cards, monthly clinical assessments, and end-of-trial preferences all favoured the active drug. At the end of the trial 20 patients preferred the treatment month with flunisolide, four preferred the placebo month, and two rated the periods equally. Side effects were mild, the commonest being transient nasal stinging. Seventeen children who derived benefit from flunisolide continued with the treatment for a six-month open-study period. Many reduced the dosage from three times to twice or once daily without losing benefit. The effect of flunisolide on the pituitary-adrenal axis was assessed in seven children by measuring the 0900 blood cortisol concentrations at two-month intervals over the six months. No effect was observed. The results show that flunisolide is effective and safe for the treatment and prophylaxis of perennial rhinitis in children.", "To evaluate the effectiveness of specific immunotherapy (SIT) in patients with severe house dust mite (HDM)-induced perennial allergic rhinitis using diary cards and objective endpoints.\n Thirty-six adult patients were selected with moderate to severe allergic rhinitis due to HDM allergy uncontrolled by regular anti-allergic drugs. Twenty-eight patients completed the study, 22 of these patients also had mild asthma. Subjects were stratified for HDM sensitivity on the basis of their 4-week diary card score and the size of their immediate and late-phase skin reaction to HDM. The groups were well matched for all relevant parameters. Patients were randomized to receive active preparation (Alutard(R)-SQ, ALK, Dermatophagoides pteronyssinus extract) or an identical placebo preparation. Increasing doses were administered until the maintenance dose was reached. This dose was then given once a month for 12 months.\n Clinical efficacy was evaluated by symptom medication diary cards recorded for 4 weeks after 12 months of continuous treatment and compared with pre-treatment scores. Skin test reactivity was re-measured after 12 months of treatment to HDM, cat dander and codeine phosphate. After 1 year of treatment, the actively treated group showed a 58% reduction in diary card symptom scores (P<0.002) and a 20% reduction in the use of rescue medication. The placebo group had a 32% reduction in symptom scores (P=NS), but no reduction in rescue medication requirements. The active group showed 36% reduction in skin prick test sensitivity to D. pteronyssinus (P=0.006), while the placebo group values were unchanged. Skin reactivity to codeine was unchanged in both groups. No significant adverse reactions to SIT were encountered.\n One year of SIT for D. pteronyssinus in patients with poorly controlled rhinitis (+/-mild asthma) produced clinically useful improvement as shown by symptom-medication diary cards and reductions in immediate skin reactions compared with placebo treatment.", "Parallel follow-up of clinical and inflammatory markers during sub-lingual immunotherapy (SLIT) is highly beneficial. Twenty-four children (age 4-16) monosensitized to house dust mite were randomized to receive either active or placebo SLIT for 1 yr in a double-blind placebo controlled design (Marcucci et al., Allergy 2003: 58: 657-62). Thereafter, for 2 yr they all received active treatment. Symptom scores for rhinitis, asthma, and drug usage were daily recorded. Eosinophil cationic protein (ECP) and tryptase in sputum and nasal secretions, serum and nasal mite-specific immunoglobulin E (IgE) were recorded before treatment and at 10-12 months intervals. Nasal ECP and nasal tryptase after specific nasal provocation tests were significantly reduced as compared to baseline values (p = 0.0043 and 0.0195, respectively) in the third year of active treatment. None of the other inflammatory parameters was increased. In placebo treated patients all these parameters tended to decrease only after switching to active treatment. Clinical scores did not improve in treated vs. placebo patients in the double-blind placebo-controlled phase of the study. In both cohorts a clinical benefit was observed as intra-group score reduction as compared to baseline. A significant difference was reached in patients treated for 2 yr for rhinitis and asthma (p = 0.0009 and 0.0019, respectively) but not for drug usage and in patients treated for 3 yr for rhinitis, asthma, and drug usage (p = 0.0105, 0.0048, and 0.02, respectively). SLIT in children monosensitized to mites reverted the spontaneous increase in nasal IgE and in local parameters of allergic inflammation. These outcomes were followed by a consolidated clinical improvement in the second and third year of treatment." ]	The three included trials provided some weak and unreliable evidence for the effectiveness of Beconase® and flunisolide used topically intranasally for the treatment of intermittent and persistent allergic rhinitis in children. The reduction of severity in symptoms as assessed by the trialists could not be confirmed with the data provided and decisions on the use of these medications should, until such time as more robust evidence is available, be guided by the physician's clinical experience and patients' individual circumstances and preferences.
CD000216	[ "2407200", "3897499", "9105740" ]	[ "Randomised trial of early tapping in neonatal posthaemorrhagic ventricular dilatation. Ventriculomegaly Trial Group.", "Serial lumbar punctures in prevention of post-hemorrhagic hydrocephalus in preterm infants.", "Failure of fibrinolytic endoventricular treatment to prevent neonatal post-haemorrhagic hydrocephalus. A case-control trial." ]	[ "Treatment of posthaemorrhagic ventricular dilatation by early repeated cerebrospinal fluid taps was compared with conservative management in a randomised controlled trial of 157 infants in 15 centres. Thirty infants died and six moved abroad before follow up. During the first 14 days after randomisation, the early treatment group had five times more taps, and 12 times more cerebrospinal fluid removed. Infection of the cerebrospinal fluid occurred in seven of the early treated and four of the conservatively managed infants. Of survivors, 62% in both groups ultimately had ventricular shunts. Neurodevelopmental assessment of survivors at 12 months was carried out by a single experienced examiner. Of survivors, 103 (85%) had abnormal neuromotor signs and 88 (73%) had disabilities. There was no detectable benefit of early treatment for children who did not have parenchymal lesions at the time they entered the trial. Nearly all those with parenchymal lesions had neuromotor impairment, but early treatment was associated with a significant reduction in other impairments.", "We studied 47 infants with either grade 3 or grade 4 intraventricular hemorrhage, to assess the efficacy of intermittent lumbar punctures in the prevention of post-hemorrhagic hydrocephalus in a prospective controlled trial. The control group received supportive care only, whereas the treatment group additionally underwent intermittent spinal taps. The spinal taps were started at postnatal age 11 +/- 5 days and continued for 20 +/- 16 days, with the removal of 67 +/- 101 ml cerebrospinal fluid using 16 +/- 12 taps. The two groups were comparable with regard to birth weight, gestational age, race, sex, Apgar score, and severity of hemorrhage. Three infants in the control group died, compared with two infants in the study group. Nine infants in the control group and 10 infants in the study group developed hydrocephalus requiring a ventriculoperitoneal shunt or a ventricular catheter reservoir. These differences in the outcome in the two groups are not statistically significant. We conclude that serial lumbar punctures were unsuccessful in prevention of hydrocephalus in this group of preterm infants with intraventricular hemorrhage.", "Post-haemorrhagic hydrocephalus is assumed to result from obstruction of the cerebrospinal fluid (CSF) pathways by blood clots and subsequent chronic infiltration with collagen. The aim of this work was to evaluate the possibility of preventing permanent shunt dependence by enhancing the endoventricular fibrinolysis by means of an endoventricular streptokinase infusion in babies affected by posthaemorrhagic ventricular dilation. A case-control trial was carried out in 12 neonates affected by intraventricular haemorrhage and subsequent progressive ventriculomegaly. Six of them were treated with 20,000 U/day of streptokinase infused over 96 h through a percutaneous ventricular catheter. Our results show that the percentage of shunted babies was identical in treated and control patients despite the enhancement of endoventricular fibrinolysis obtained in all treated patients. On the basis of our results we do not recommend intraventricular streptokinase infusion for routine use in post-haemorrhagic ventricular dilatation." ]	Early repeated CSF tapping cannot be recommended for neonates at risk of, or actually developing, post-hemorrhagic hydrocephalus.
CD001015	[ "3479525", "3897460", "6802657", "7119136", "7198209", "6889709", "2642499", "2182613", "9581210" ]	[ "Failure of long term high-dose lecithin to retard progression of early-onset Alzheimer's disease.", "A double-blind, placebo controlled trial of high-dose lecithin in Alzheimer's disease.", "Lecithin treatment of cognitively impaired Parkinson's patients.", "A dose-ranging study of lecithin in the treatment of primary degenerative dementia (Alzheimer disease).", "Alzheimer disease: lack of effect of lecithin treatment for 3 months.", "Lecithin administration in Alzheimer dementia.", "Chronic oral physostigmine without lecithin improves memory in Alzheimer's disease.", "A crossover study of lecithin treatment of tardive dyskinesia.", "Short-term administration of selegiline for mild-to-moderate dementia of the Alzheimer's type." ]	[ "We conducted a six-month, randomized, double-blind trial of lecithin therapy in early-onset Alzheimer's disease. We hypothesized that such therapy would retard the progression of the clinical and neuropsychological manifestations of this illness. Of the 73 referred patients, 37 met strict requirements for diagnosis and compliance. The 21 placebo and 16 lecithin-treated patients (mean age 63 years) had a comparable degree of severity of dementia (mean Clinical Dementia Rating 1.6). Lecithin therapy produced an increase in mean plasma choline levels from a baseline of 15.9 to 28.8 nmol/ml. Patients were evaluated by the physician using clinical assessments (CDR, Lawton ADL and other rating scales) and by the neuropsychologist who determined the outcome of therapy on a battery of tests (Mini Mental State Examination, Wepman Aphasia Screen, Verbal Fluency Test, Verbal Selective Reminding Test and Spatial Memory Test). Only 6 (37.5%) of the 16 lecithin-treated patients were considered by the neurologist to be clinically stable or improved as compared to 12 (57.1%) of the 21 patients given placebo (difference -19.6%, 95% confidence limits of -51% to 12%). The neuropsychologic scores showed no differences in the stability of the dementing process over time between the lecithin-treated (50.0%) and placebo (47.6%) groups. On the basis of these clinical and neuropsychological findings, it appears that lecithin alone has no important therapeutic effect in early-onset Alzheimer's disease.", "The first long-term double-blind placebo controlled trial of high dose lecithin in senile dementia of the Alzheimer type is reported. Fifty one subjects were given 20-25 g/day of purified soya lecithin (containing 90% phosphatidyl plus lysophosphatidyl choline) for six months and followed up for at least a further six months. Plasma choline levels were monitored throughout the treatment period. There were no differences between the placebo group and the lecithin group but there was an improvement in a subgroup of relatively poor compliers. These were older and had intermediate levels of plasma choline. It is suggested that the effects of lecithin are complex but that there may be a \"therapeutic window\" for the effects of lecithin in the condition and that this may be more evident in older patients.", "To test the effects of lecithin on cognitive deficits associated with Parkinson's disease, sixteen elderly and mentally-impaired outpatients with Parkinson's disease participated in a 9-week double-blind placebo-controlled study. Each patient took a daily dose of approximately 32 g of a commercial lecithin preparation containing 25% phosphatidylcholine, or an equivalent amount of powdered skim milk placebo. Marked clinical improvement was not observed, but some indications of a positive treatment effect were obtained on memory, cognition, and motility tests.", "nan", "Eleven outpatients with Alzheimer disease of moderate severity completed a double-blind placebo-controlled crossover trial of lecithin. Each patient received 10 gm three times daily of a placebo for 3 months. Plasma choline levels rose threefold and remained at that level throughout the lecithin administration period. A significant difference between mean baseline scores and treatment scores was found on tests of new learning ability, indicating a practice effect in these tests. However, there were no differences between mean placebo and lecithin scores on any of the psychological test measures.", "nan", "Sixteen patients with early Alzheimer's disease (AD) completed a 3-month outpatient double-blind parallel trial of oral physostigmine versus placebo. Ten subjects received drug; six received placebo. After a dose-titration phase, each patient was placed on his or her best dose of drug or placebo. Subjects were evaluated with both memory and nonmemory tasks. Seven of the ten drug-treated patients, but none of the six placebo-treated patients, demonstrated improvement on a selective reminding task, a test of verbal memory. Family members reported improvement in six of ten drug-treated patients and none of six placebo-treated individuals. There was a trend toward greater improvement with increasing drug dose. There was no improvement on the nonmemory tests administered. The data indicate that oral physostigmine improves memory but not other areas of cognition.", "The authors enrolled 21 patients in a random-order, crossover, double-blind trial of phosphatidylcholine (lecithin) 20 g/day and placebo. Fourteen patients completed at least 6 weeks of the second 8-week trial and were used for efficacy analyses. Side effects were minimal. The lecithin treatment effect--about one half of an Abnormal Involuntary Movement Scale point--was seen as a statistical effect of treatment order, based on differences between patients who took the active compound before or after they took the placebo. Clinically, however, the lecithin effect was negligible.", "As a follow-up to an earlier study showing short-term benefit in inpatients with more severe dementia, the authors studied the short-term cognitive, functional, and behavioral effects of selegiline in outpatients with mild-to-moderate dementia of the Alzheimer type (DAT) by means of a double-blind, randomized, crossover study of placebo vs. selegiline. Fifty outpatients with mild-to-moderate DAT and no behavioral disturbances were given selegiline in two 8-week treatment periods separated by a 4-week washout. Outcome was assessed with standardized measures of dementia severity, daily functioning, behavior, and cognition. There was no drug-placebo difference in any outcome measure. Selegiline did not show short-term benefit in this study, contrary to the earlier study, perhaps because the patients were studied less intensively and/or lacked behavioral problems that could show response, although the medication was well tolerated." ]	Evidence from randomized trials does not support the use of lecithin in the treatment of patients with dementia. A moderate effect cannot be ruled out, but results from the small trials to date do not indicate priority for a large randomized trial.
MR000013	[ "15485728", "16157604", "16877628", "20840874", "18718924", "16904951", "9243440", "20484492", "12959796", "12196367", "17204318", "18166837", "15617949", "16279272", "19152024", "7428142", "18457756", "2343859", "15006907", "19230168", "10519499", "6717508", "17060222", "17848908", "21667366", "17149995", "2189772", "10221739", "20367586", "18386101", "10628024", "10213724", "10715289", "8399698", "16906625", "12950483", "9774295", "16954124", "12757433", "16782489", "18725823", "10025379", "11737404" ]	[ "Telephone reminders are effective in recruiting nonresponding patients to randomized controlled trials.", "Recruiting patients to medical research: double blind randomised trial of \"opt-in\" versus \"opt-out\" strategies.", "Impact of privacy legislation on the number and characteristics of people who are recruited for research: a randomised controlled trial.", "Do messages of scarcity increase trial recruitment?", "Optimising recruitment into a study of physical activity in older people: a randomised controlled trial of different approaches.", "A randomised trial of the effects of an additional communication strategy on recruitment into a large-scale, multi-centre trial.", "A randomized trial of the impact of telephone and recorded delivery reminders on the response rate to research questionnaires.", "Three controlled trials of interventions to increase recruitment to a randomized controlled trial of mobile phone based smoking cessation support.", "Successful recruitment of minorities into clinical trials: The Kick It at Swope project.", "Informing breast cancer patients about clinical trials: a randomized clinical trial of an educational booklet.", "Recruiting pregnant smokers into a clinical trial: using a network-model managed care organization versus community-based practices.", "An educational video to increase clinical trials enrollment among lung cancer patients.", "Blinding decreased recruitment in a prevention trial of postmenopausal hormone therapy.", "A randomized trial of recruitment methods for older African American men in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial.", "An educational video to increase clinical trials enrollment among breast cancer patients.", "Recruitment of patients to cooperative group clinical trials.", "Participant recruitment to a randomized trial of a community-based behavioral intervention for pre- and interconceptional women findings from the Central Pennsylvania Women's Health Study.", "Effectiveness of various mailing strategies among nonrespondents in a prospective cohort study.", "A large population-based randomized controlled trial to increase attendance at screening for cervical cancer.", "Experiences of randomization: interviews with patients and clinicians in the SPCG-IV trial.", "Randomized trial of informed consent and recruitment for clinical trials in the immediate preoperative period.", "Physicians' reasons for not entering eligible patients in a randomized clinical trial of surgery for breast cancer.", "Impact of on-site initiation visits on patient recruitment and data quality in a randomized trial of adjuvant chemotherapy for breast cancer.", "A randomised controlled study of an audiovisual patient information intervention on informed consent and recruitment to cancer clinical trials.", "A novel recruitment message to increase enrollment into a smoking cessation treatment program: preliminary results from a randomized trial.", "Use and impact of an automated telephone outreach system for asthma in a managed care setting.", "Recruitment in a primary care trial on smoking cessation.", "Cost effectiveness of screening for clinical trials by research assistants versus senior investigators.", "Improving communication when seeking informed consent: a randomised controlled study of a computer-based method for providing information to prospective clinical trial participants.", "Effects of disclosing financial interests on attitudes toward clinical research.", "Virtual outreach: a telemedicine pilot study using a cluster-randomized controlled design.", "Is recruitment more difficult with a placebo arm in randomised controlled trials? A quasirandomised, interview based study.", "Factors that predict the referral of breast cancer patients onto clinical trials by their surgeons and medical oncologists.", "Response to mail surveys: effect of a request to explain refusal to participate. The ARIC Study Investigators.", "Standardized audiotape versus recorded consultation to enhance informed consent to a clinical trial in breast oncology.", "Effect of a triage-based E-mail system on clinic resource use and patient and physician satisfaction in primary care: a randomized controlled trial.", "Safety and effectiveness of nurse telephone consultation in out of hours primary care: randomised controlled trial. The South Wiltshire Out of Hours Project (SWOOP) Group.", "Interest in an online smoking cessation program and effective recruitment strategies: results from Project Quit.", "Educational workshop improved information-seeking skills, knowledge, attitudes and the search outcome of hospital clinicians: a randomised controlled trial.", "Effect of enhanced feedback and brief educational reminder messages on laboratory test requesting in primary care: a cluster randomised trial.", "Implementing an intervention to promote colon cancer screening through e-mail over the Internet: lessons learned from a pilot study.", "Accrual to breast cancer clinical trials at a university-affiliated hospital in metropolitan Detroit.", "Does an HIV clinical trial information booklet improve patient knowledge and understanding of HIV clinical trials?" ]	[ "Studies investigating means of recruiting participants to randomized controlled trials (RCTs) are sparse. We investigated the effects of telephone reminders as a recruitment strategy.\n Sick-listed employees received a written invitation to participate in a study comparing standard treatments with a solution-focused follow-up and were randomly allocated to an intervention or control group (n=703). Those who did not respond within 2 weeks received either 'no reminder' (n=242) or 'attempted telephone reminder' (n=256). Outcome was enrollment to the RCT.\n An intention to recruit analysis revealed no significant differences between the groups (P=.229). An intention to phone analysis among nonresponders revealed significant differences between 'no reminder' (recruited 4.5%) and 'attempted telephone reminder' (recruited 12.1%) (P=.003, odds ratio 2.89, 95% confidence interval [CI] 1.42-5.90). An analysis of numbers needed to phone showed that to recruit one more person in this group of nonresponders, we needed to phone 13 persons (95% CI=8-33).\n Systematic use of telephone calls can increase the recruitment rate among nonresponders in RCTs.", "To evaluate the effect of opt-in compared with opt-out recruitment strategies on response rate and selection bias.\n Double blind randomised controlled trial.\n Two general practices in England.\n 510 patients with angina.\n Patients were randomly allocated to an opt-in (asked to actively signal willingness to participate in research) or opt-out (contacted repeatedly unless they signalled unwillingness to participate) approach for recruitment to an observational prognostic study of patients with angina.\n Recruitment rate and clinical characteristics of patients.\n The recruitment rate, defined by clinic attendance, was 38% (96/252) in the opt-in arm and 50% (128/258) in the opt-out arm (P = 0.014). Once an appointment had been made, non-attendance at the clinic was similar (20% opt-in arm v 17% opt-out arm; P = 0.86). Patients in the opt-in arm had fewer risk factors (44% v 60%; P = 0.053), less treatment for angina (69% v 82%; P = 0.010), and less functional impairment (9% v 20%; P = 0.023) than patients in the opt-out arm.\n The opt-in approach to participant recruitment, increasingly required by ethics committees, resulted in lower response rates and a biased sample. We propose that the opt-out approach should be the default recruitment strategy for studies with low risk to participants.", "Privacy laws have recently created restrictions on how researchers can approach study participants. Method: In a randomised trial of 152 patients, 50-74 years old, in a family practice, 60 were randomly selected to opt-out and 92 to opt-in methods. Patients were sent an introductory letter by their doctor in two phases, opt-out before and opt-in after introduction of the new Privacy Legislation in December 2001. Opt-out patients were contacted by researchers. Opt-in patients were contacted if patients responded by email, free telephone number or a reply-paid card.\n Opt-in recruited fewer patients (47%; 43/92) after invitation compared with opt-out (67%; 40/60); (-20%; [-4% to -36%]). No proportional difference in recruitment was found between opt-in and opt-out groups varied by age, sex or socioeconomic status. The opt-in group had significantly more people in active decision-making roles (+30%; [10% to 50%]; p = 0.003). Non-significant trends were observed towards opt-in being less likely to include people with lower education (-11.8%; [-30% to 6.4%]; p = 0.13) and people who were not screened (-19.1%; [-40.1% to 1.9%]; p = 0.08). Opt-in was more likely to recruit people with a family history of colorectal cancer (+12.7%; [-2.8%, 28.2%]; p = 0.12).\n The number of participants required to be approached was markedly increased in opt-in recruitment. Existing participants (eg, screening attendees) with a vested interest such as increased risk, and those preferring an active role in health decision making and with less education were likely to be recruited in opt-in. Research costs and generalisability are affected by implementing privacy legislation.", "Psychological theory suggests that participants may be more likely to volunteer to join a clinical trial if they perceive places in the trial are a scarce commodity.\n We conducted a single blind, randomized controlled trial to test recruitment strategies within the larger txt2stop smoking cessation trial. 1862 people who were eligible for the txt2stop trial but had not yet consented to join were randomized to receive either A) a reminder about the txt2stop trial plus a message that there were only 300 places left, or B) a reminder about the trial only. The outcome was the participant's consent to join the txt2stop trial 3days after messages were sent.\n Of 895 participants randomized to the intervention group, 90 (10.1%) had consented to join the txt2stop trial. Of the 967 participants randomized to the control group, 67 (6.9%) had consented to join the txt2stop trial (OR=1.50, 95% CI 1.07-2.12).\n Scarcity messages were an effective way to increase recruitment into the txt2stop trial and could be relevant to other trials.\n Communicating scarcity is an effective way to increase trial recruitment.\n Copyright © 2010 Elsevier Inc. All rights reserved.", "physical activity studies in older people often have poor recruitment. Including a questionnaire with the invitation would provide information about non-participants and selection bias, but could reduce recruitment. Telephone contact might encourage participation.\n to test the effects of different strategies for recruitment into a study of physical activity in older people.\n factorial randomised controlled trial. Randomisation by household into four groups: telephone contact plus questionnaire, telephone contact only, questionnaire only, neither.\n primary care, Oxfordshire, United Kingdom.\n 560 patients > or = 65 years randomly selected after exclusions.\n questionnaire to assess health, functional ability and physical activity. Telephone contact by the research nurse a week after sending study information.\n recruitment into physical activity study.\n telephone contact increased recruitment: contact 47.9% (134/280), no contact 37.9% (106/280), difference (adjusted for the clustering effect of household) 10.0% (95% CI 0.2-19.8). Questionnaire inclusion did not significantly reduce recruitment: no questionnaire 44.3% (124/280) questionnaire 41.4% (116/280) difference -2.9% (95% CI -12.7-7.0).\n telephone contact significantly increased recruitment and should be considered in studies where recruitment may be low. While inclusion of a questionnaire provided valuable information on non-participants and did not significantly reduce recruitment, an adverse recruitment effect could not be excluded.", "Timely participant recruitment remains a significant challenge for most clinical trials. We evaluated the effects on participant recruitment of communication between the central trial coordinators and the clinical sites in the setting of a large international multi-centre clinical trial. The effects of communication were determined in a single-blind randomised controlled trial involving 167 clinical sites in 19 countries. Clinical sites were randomised to either additional or usual communication strategies - the additional communication group received a communication package based on additional, individually-tailored feedback about recruitment, in addition to the usual correspondence from the central trial coordinators that was provided to the control group. The two study outcomes were the median time to half randomisation target and the median total number of participants randomised per clinical site. Eighty-five clinical centres were randomised to receive additional communication and 82 to receive usual communication. At the conclusion of recruitment, there was no significant difference in the median number of participants randomised per centre between the additional and usual groups (37.5 vs. 37.0, p=0.68). The median time to half randomisation target was lower in the additional communication group compared to the usual group, however this difference did not achieve conventional levels of statistical significance (4.4 months vs. 5.8 months, p=0.08). The findings suggest that the additional communication strategy may be of some incremental benefit in helping sites achieve recruitment targets sooner.", "A range of factors have been shown to affect the response rate to mailed questionnaires, but particular strategies to improve patients' response in trials conducted in general practice require further study.\n Non-responders in a larger trial were randomized to receive a telephone or recorded delivery reminder on the third contact. The cost of administration of each method was estimated.\n Significantly more patients returned completed questionnaires when sent questionnaires by recorded delivery, although the cost per patient contacted was nearly three times more than for contact by telephone.\n Our study indicates that sending reminders by recorded delivery, although more expensive, is more effective than telephone reminders for recruiting patients to a study in general practice using research questionnaires.", "Recruitment is a major challenge for trials but there is little evidence regarding interventions to increase trial recruitment. We report three controlled trials of interventions to increase recruitment to the Txt2stop trial.\n To evaluate: Trial 1. The impact on registrations of a text message regarding an online registration facility; Trial 2. The impact on randomizations of sending pound5 with a covering letter to those eligible to join the trial; Trial 3. The impact on randomizations of text messages containing quotes from existing participants.\n Single blind controlled trials with allocation concealment. Interventions: Trial 1: A text message regarding our new online registration facility; Trial 2: A letter with pound5 enclosed; Trial 3: A series of four text messages containing quotes from participants. The control group in each trial received standard Txt2stop procedures.\n Trial 1: 3.6% (17/470) of the intervention group and 1.1% (5/467) of the control group registered for the trial, risk difference 2.5% (95% CI 0.6-4.5). 0% (0/ 470) of the intervention group and 0.2% (1/467) of the control group registered successfully online, risk difference -0.2 (95% CI -0.6-0.2); Trial 2: 4.5% (11/246) of the intervention group and 0.4% (1/245) of the control group were randomized into the Txt2stop trial, risk difference 4.0% (95% CI 1.4-6.7); Trial 3: 3.5% (14/405) of the intervention group and 0% (0/406) of the control group were randomized into the Txt2stop trial, risk difference 3.5 (95% CI 1.7-5.2).\n There were no baseline data available for trial 1. Allocation of participant IDs in trials 2 and 3 were systematic.\n Sending a text message about an online registration facility increased registrations to Txt2stop, but did not increase online registrations. Sending a pound5 reimbursement for participants' time and sending text messages containing quotes from existing participants increased randomizations into the Txt2stop trial. Clinical Trials 2010; 7: 265-273. http://ctj.sagepub.com.", "Ethnic minorities are often underrepresented in clinical trials, and their recruitment can challenge researchers. Developing and communicating effective and efficient recruitment strategies may help researchers enroll more minorities into research studies. Kick It at Swope was a double-blind, randomized trial that evaluated bupropion for smoking cessation among 600 adult African Americans who smoked 10 or more cigarettes a day. Proactive recruitment strategies (in-person appeals by study staff and health care providers) and reactive recruitment strategies (disseminating information that asked people to call a study hotline) were implemented sequentially in an additive fashion over 16 months. Resulting patterns of recruitment are described and the two phases are compared based on their relative effectiveness, efficiency, and cost. More enrollees were recruited in the reactive phase (n=534) than in the proactive phase (n=66). Those recruited in the reactive phase were more likely to be eligible (OR=4.8) and more likely to be enrolled (OR=4.2) than those recruited in the proactive phase. Participants recruited in the reactive phase reported significantly higher levels of education and income, better health, and significantly lower indicators of depression and life hassles, compared with those recruited in the proactive phase. The reactive recruitment phase was less expensive than the proactive recruitment phase (22 US Dollars/enrollee vs. 159 US Dollars/enrollee). Reactive recruitment strategies added to multiple proactive clinic-based recruitment strategies were more effective, more efficient, and less costly than proactive recruitment alone. Close monitoring combined with the use of multiple recruitment methods and flexible recruitment plans can lead to successful, efficient, and low-cost recruitment of minorities into clinical trials.", "To evaluate the impact of an educational booklet on women's knowledge of and willingness to participate in a randomized clinical trial of treatment for breast cancer.\n Women undergoing surgery for newly diagnosed early stage breast cancer were randomized to receive, or not, an information booklet explaining the need for and manner in which randomized trials are conducted.\n Eighty-three women with newly diagnosed early stage breast cancer completed a questionnaire assessing attitudes to random clinical trials (RCTs) and were randomized to receive usual information treatment options provided from their oncologist, or the educational booklet in addition to usual information from their oncologist (42 usual information, 41 booklet). Fewer women who received the clinical trials booklet (40% versus 47%) would consider participating in the hypothetical clinical trial (P = 0.6). Mean knowledge scores increased for both groups; moreover, women who did not receive the booklet showed similar improvements to women who received the booklet [mean difference 0.09, 95% confidence interval (CI) -0.66 to 0.83]. In a multivariate analysis women who would consider participating in the clinical trial were more anxious [odds ratio (OR) 5.9, P = 0.02] had involved lymph nodes (OR 5.8, P = 0.02) and were less influenced by negative aspects of clinical trials (OR 7.7, P = 0.0001). After adjustment for these variables women who received the educational booklet were significantly less likely to consider trial participation (OR 0.22, P = 0.05).\n Educating women about clinical trials in this manner appears ineffective in improving recruitment to RCTs. Women appear to be more influenced by their perception of risk than understanding. This finding has ethical implications for communication of information about RCTs.", "Recruiting pregnant smokers into smoking cessation intervention trials is challenging. Changes in health care systems offer new opportunities to overcome many of the obstacles encountered by researchers attempting to address the significant harm from maternal smoking. Investigators could facilitate smoking cessation study recruitment by collaborating with health care systems that systematically collect patient smoking status and record it in a centralized, retrievable fashion. This paper reports the results of utilizing this novel approach and compares it with a typical decentralized practice-based recruitment strategy.\n The study was conducted at Massachusetts General Hospital, in Boston, Massachusetts, from 2000 to 2005. Four hundred forty-two pregnant smokers were recruited for a randomized controlled trial of telephone-delivered smoking counseling from two sources: a network-model managed care health plan and community-based practices (CBP). At the health plan, study recruitment was built on an existing system that permitted pregnant smokers to be identified centrally. At the CBPs, identification and referral systems had to be developed at each practice specifically for the study. The two strategies were compared on the efficiency of recruitment, characteristics of enrollees, and study outcome and process measures.\n The health plan strategy generated referrals nearly twice as fast as the CBP strategy (30.4 vs. 17.0 per month), but because referrals were not timely, a large proportion of women from the plan were too advanced in pregnancy to be eligible to enroll in the study. As a result, the two strategies yielded a comparable enrollment rate. Participants from the health plan were older, better educated, less racially diverse, more likely to be living with the baby's father, and less likely to have smokers in their environment. These differences were largely explained by the socioeconomic diversity of women recruited from the CBPs. Smoking cessation outcomes did not differ by recruitment source.\n A recruitment strategy using a health plan's centralized system was more efficient than a practice-based recruitment strategy at identifying potential study participants, but less efficient at generating study participants from the referrals received. Importantly, participants recruited by the two strategies differed by socioeconomic, but not cessation-related, characteristics. To date, recruiting pregnant smokers into intervention studies remains resource intensive and time consuming. Participant identification and recruitment will be greatly enhanced by health system innovations such as implementation of electronic medical records.", "Only 3 to 5% of new adult cancer patients participate in clinical trials nationwide. The lack of knowledge and awareness about clinical trials is a significant barrier to clinical trials participation. A randomized trial was conducted to test the effect of an educational video on positively changing patients' knowledge and attitudes regarding clinical trials and thereby increasing enrollment rates.\n Lung cancer patients were randomized to viewing either an 18-minute video about clinical trials before first clinic appointment or to standard care. Participants completed a baseline and 2-week postintervention survey to assess their knowledge and attitudes toward trials participation. Fisher's exact test tests, t tests, and regression were used to compare patient characteristics and outcomes between arms.\n Of 145 subjects randomized, 126 (63/arm) satisfied all inclusion criteria and were included in the analysis. A linear regression showed that the video intervention was significantly associated with patients' self-assessed likelihood to enroll score measured at 2-week follow-up (p = 0.019). Although statistically insignificant, enrollment rates were found to be higher in the intervention arm for therapeutic trials alone (17.5% versus 11.1%) and for therapeutic and nontherapeutic trials combined (25.4% versus 15.9%).\n The brief educational video seems to be effective in positively changing lung cancer patients' attitudes about participation in clinical trials. Higher enrollment rates were also observed in the intervention group but the differences did not reach statistical significance. These findings suggest a potential impact of the educational video on clinical trial enrollment; however, larger studies are needed to confirm these findings.", "To compare the effect of blind design (active drug and placebo) and nonblind design (active drug and no treatment) on recruitment.\n A primary prevention trial with postmenopausal hormone therapy in Estonia.\n Women who were eligible and willing to participate on the basis of the questionnaire survey were randomized into blind and nonblind groups. Recruitment rates are based on record keeping, and reasons for participating were requested in the first-year follow-up.\n The recruitment was 30% higher in the nonblind group: of the 4,295 women invited, 37% (95% confidence interval CI=35-39%) in the blind group and 48% (95% CI=46-49%) in the nonblind group were recruited. In both groups, once randomized, most of the losses were women who did not attend the first clinical examination: 49% (blind; 95% CI=47-51%) and 40% (nonblind; 95% CI=38-42%). The rest were found ineligible or lost their interest during clinical examinations. The reasons for joining the trial were relatively similar in the two groups.\n Blinding decreased women's interest in joining a long-term preventive trial. Women's reasons for joining the trial were not influenced by blinding.", "Incidence rates for many types of cancer are higher among African American men than in the general population, yet African American men are less likely to participate in cancer screening trials. This paper describes the outcomes of a randomized trial (the AAMEN Project) designed to recruit African American men aged 55-74 years to a prostate, lung and colorectal cancer screening trial.\n The recruitment interventions address four types of barriers to clinical trial participation: sociocultural barriers, economic barriers, individual barriers and barriers inherent in study design. Subjects were randomized to a control group or one of three increasingly intensive intervention arms, which used different combinations of mail, phone and in person church-based recruitment.\n Of the 39,432 African American men residing in the geographically defined study population (southeastern Michigan and northern Ohio), 17,770 men (45%) could be contacted, and 12,400 (31% of 39,432) were found to be eligible to participate. No statistically significant differences in age, education or income level were found among participants in the four study arms. A significantly greater enrollment yield (3.9%) was seen in the most intensive, church-based intervention arm, compared to the enrollment yields in the other two intervention arms (2.5 and 2.8%) or the control group (2.9%) (P < 0.01).\n The intervention that involved the highest rate of face-to-face contact with the study participants produced the highest enrollment yield, but several strategies that were thought could improve yield had no effect. These findings, which are consistent with current literature on population-based recruitment, should facilitate the development of future recruitment efforts involving older African American men.", "Only 3% of women with breast cancer participate in cancer clinical trials nationwide. The lack of awareness about clinical trials is a significant barrier towards clinical trials participation. A study was conducted at a large urban Comprehensive Cancer Center to test (1) the effectiveness of an 18-min educational video on improving attitudes toward clinical trials and trials enrollment among new breast cancer patients seen at the Karmanos Cancer Institute, and (2) to assess racial differences in attitudes regarding clinical trials. Participants were randomized to either the educational intervention prior to their first oncology clinic appointment or to standard care. A baseline and 2-week post-intervention survey to assess attitudes toward clinical trials participation was completed by participants. Of 218 subjects recruited, 196 (55% white vs. 45% African American (AA)) eligible patients were included in the analysis. A small increase in therapeutic clinical trial enrollment was observed in the intervention arm but was not statistically significant (10.4% vs. 6.1%; P = 0.277). The intervention also did not result in a clear improvement in patients' attitudes toward clinical trials at posttest. However, a lower enrollment rate for the AA women was noted after adjusting for stage (OR = 0.282, P = 0.049). Significantly more negative scores were noted in 3 out of the 5 baseline attitudinal scales for AA women. The educational video did not significantly increase enrollment in breast cancer clinical trials. The findings that AA women had significantly more negative attitudes toward clinical trials than white women may partially explain the racial disparity in enrollment. An educational video remains a simple and cost-effective way to educate patients. Future studies should focus on designing a new educational video to specifically target cultural and attitudinal barriers in the AA population to more effectively change attitudes and increase trial enrollment.", "One of the prerequisites for a successful clinical trial is the accrual of a sufficient number of patients for study. Because the sample-size requirements for a randomized clinical trial can rarely be met by a single institution in a short period of time, cooperative groups have taken in a major role in conducting clinical trials. In this paper, the recruitment of patients at our institution to a lung cancer clinical trial is evaluated. A total of 653 lung cancer cases were reviewed. Of the 77 cases which were eligible for the trial, 41 were accessioned. The reasons why eligible patients were not accessioned to the trial are discussed.", "Community-based health studies rely on the ability of researchers to successfully recruit and retain participants from target populations, rather than from clinical settings. Many prior women's health studies have recruited in urban and suburban areas, but rural populations pose specific challenges. We describe the recruitment strategies employed in the Central Pennsylvania Women's Health Study to recruit 692 women in 15 low-income rural communities to a randomized trial of a behavioral intervention for pre- and interconceptional women.\n The organization of the project is described. Qualitative (e.g., focus groups of local project facilitators) and quantitative methods (e.g., surveys of participants) were used to assess the effectiveness of various recruitment techniques and the characteristics of the final enrolled sample.\n A triangular recruitment approach was used in 15 communities, which included partnering with local community organizations and use of both active and passive recruitment techniques. The most effective recruitment methods were (1) actively recruiting women in social service and childcare settings, (2) use of a toll-free project telephone number printed on all passive recruitment material, and (3) the combination of passive and active recruitment in educational settings. Together, these methods successfully achieved the recruitment goals: enrolling participants who were more likely to be rural, poor or near poor, non-white, and to have less access to health care than their counterparts residing in the target communities.\n Successful recruitment of typically hard-to-reach women, such as low-income rural women, is possible through implementation of a triangular recruitment approach in local communities.", "Measures of association in prospective studies can be distorted by incomplete follow-up. Various mailing strategies were used to contact 12,233 cohort members of the Health Professionals Follow-up Study who had not responded to three successive bulk-rate mailings. Response rates were highest, 79.5% overall, from participants who were sent a certified mailing in phase 1 (63.2%), followed by a repeat certified mailing to nonrespondents (44.3%). Although altering the physical appearance of the envelope and using other postal rates were tested, certified mail was the most effective approach for reaching study members who were nonrespondents to a mailed questionnaire.", "Although cervical cancer is one of the potentially most preventable malignancies, it is still fairly common. In settings with established screening programs, increased compliance is important for future reduction in cervical cancer incidence, but it is presently unclear how this can be effectively achieved.\n We conducted a randomized controlled trial including all 12,240 women invited to organized screening in Sweden. To increase compliance, three successive interventions were tested: (a) modified invitation versus the standard invitation letter, (b) reminder letter to nonattenders after the first intervention versus no reminder letter, and (c) phone reminder to nonattenders after the reminder letter versus no phone reminder. We analyzed the proportion of women attending screening after each intervention and the cumulative proportion after the interventions as well as the cumulative proportions of cytologic abnormalities.\n The modified invitation did not increase attendance compared with the standard invitation letter [difference 1.3% 95% confidence interval (CI) -0.3 to 2.9]. In contrast, a reminder letter increased the proportion of women attending with 9.2% (95% CI 7.9-10.5) compared with women who did not receive a reminder letter, and a phone reminder increased the proportion of women attending with 31.4% (95% CI 26.9-35.9). Combinations of modified invitation, written reminder, and phone reminder almost doubled attendance within 12 months, and the number of detected cytologic abnormalities was more than tripled.\n Simple reminders by mail and phone can drastically increase women's participation in Papanicolaou smear screening and increase the number of detected precursor lesions and thereby save lives.", "Recruitment of both patients and clinicians to randomized trials is difficult. Low participation carries the risk of terminating studies early and making them invalid owing to insufficient statistical power. This study investigated patients' and clinicians' experiences of randomization with the aim of facilitating trial participation in the future.\n This was a qualitative study using content analysis. Patients offered to participate in a randomized trial and randomizing clinicians were interviewed. Five participants, four non-participants and five randomizing clinicians were interviewed, 2-8 years from randomization.\n Clinicians used strategies in interaction with the patients to facilitate decision making. Patients' attitudes differed and experiences of relatives or friends were often stated as reasons for treatment preferences. Patients described that letting chance decide treatment was a difficult barrier to overcome for randomization. The clinicians used a number of different strategies perceived to make randomization more acceptable to their patients. The clinicians' own motivation for randomizing patients for trials depended on the medical relevance of the study question and the clinicians' major obstacle was to maintain equipoise over time. Regular meetings with the study group helped to maintain equipoise and motivation.\n To establish a good platform for randomization the clinician needs to know about the patient's treatment preferences and the patient's attitude concerning the role of the clinician to facilitate decision making. The strategies used by the clinicians were perceived as helpful and could be tested in an intervention study.", "The standard process of obtaining informed consent sometimes prevents physicians or patients from participating in clinical trials, partly because they are concerned about eventual treatment allocation or the physician is concerned the patient might harbor some uncertainty about the best treatment. Alternative randomization methods have been advocated that may address these and other concerns.\n After institutional ethics committee gave its approval, the authors interviewed 770 patients before operation and asked them to consider enrolling in a mock anesthesia trial. Patients were allocated randomly to one of five methods of randomization and consent: one-sided informed consent (the most common approach), prerandomized consent to experimental treatment, prerandomized consent to standard treatment, one-sided physician-modified informed consent, or one-sided patient-modified informed consent. Recruitment rates were compared and sociodemographic and perioperative predictors of recruitment were identified.\n The randomization method did not result in any significant difference in recruitment rates: one-sided informed consent, 55.6%; prerandomized consent to experimental treatment, 53.3%; prerandomized consent to standard treatment, 53%; one-sided physician-modified informed consent, 60.7%; and one-sided patient-modified informed consent, 56.7% (P = 0.66). Multivariate predictors of recruitment were patient age >45 yr (odds ratio, 1.44; 95% confidence interval [CI], 1.08 to 1.93), English-speaking at home (1.49; 1.0 to 2.21), and male researcher-male patient interaction (1.37; 1.20 to 1.57).\n No evidence emerged that alternative randomization and consent designs resulted in increased recruitment rates compared with simple one-sided informed consent for a sham anesthesia trial in patients awaiting elective surgery. Older, male patients were more likely to provide consent.", "We studied the reasons surgical principal investigators chose not to enter patients in a large, multicenter trial sponsored by a cooperative group. In 1976 the National Surgical Adjuvant Project for Breast and Bowel Cancers (NSABP) initiated a clinical trial to compare segmental mastectomy and postoperative radiation, or segmental mastectomy alone, with total mastectomy. Because the low rates of accrual were threatening to close the trial prematurely, we mailed a questionnaire to the 94 NSABP principal investigators, asking why they were not entering eligible patients in the trial. A response rate of 97 per cent was achieved. Physicians who did not enter all eligible patients offered the following explanations: (1) concern that the doctor-patient relationship would be affected by a randomized clinical trial (73 per cent), (2) difficulty with informed consent (38 per cent), (3) dislike of open discussions involving uncertainty (22 per cent), (4) perceived conflict between the roles of scientist and clinician (18 per cent), (5) practical difficulties in following procedures (9 per cent), and (6) feelings of personal responsibility if the treatments were found to be unequal (8 per cent). Further investigation into the behavioral aspects of the investigator-patient relationship is particularly pressing, since fear of change in this relationship was the most common reason given for not entering eligible patients in the trial.", "To provide empirical evidence on the impact of on-site initiation visits on the following outcomes: patient recruitment, quantity and quality of data submitted to the trial coordinating office, and patients' follow-up time.\n This methodological study was performed as part of a randomized trial comparing two combination chemotherapies for adjuvant treatment of breast cancer. Centers participating to the trial were randomized to either receive systematic on-site visits (Visited group), or not (Non-visited group).\n The study was terminated after two years, while the main randomized trial continued. Of the 135 centers that had expressed an interest in the trial, only 69 randomized at least one patient (35/68 in the Visited group, 34/67 in the Non-visited group). Almost two-thirds of the patients were entered by 17 centers (10 in the Visited group, seven in the Non-visited group) that accrued more than 10 patients each. None of the prespecified outcomes favored the group of centers submitted to on-site initiation visits (ie, mean number of queries par patient: 6.1 +/- 9.7 versus 5.4 +/- 6.4, respectively for the Visited and Non-visited groups). Spontaneous transmittal of case report forms, although required by protocol, was low in both randomized groups (mean number of pages per patient: 1.5 +/- 2.0 versus 2.1 +/- 2.3, respectively), with investigators submitting about one-third of the expected forms on time (29% and 39%, respectively).\n This study could not evaluate the impact of repeated on-site visits on clinical outcomes.\n Systematic on-site initiation visits did not contribute significantly to this clinical trial.", "Recruitment to cancer clinical trials needs to be improved, as does patient knowledge and understanding about clinical trials, in order for patients to make an informed choice about whether or not to take part. Audiovisual patient information (AVPI) has been shown to improve knowledge and understanding in various areas of practice, but there is limited information about its effect in the cancer clinical trial setting, particularly in relation to consent rates. In this study, 173 patients were randomised to receive either the AVPI, in addition to the standard trial-specific written information, or the written information alone. There was no difference in clinical trial recruitment rates between the two groups with similar study entry rates: 72.1% in the AVPI group and 75.9% in the standard information group. The estimated odds ratio for refusal (intervention/no intervention) was 1.19 (95% CI 0.55-2.58, P=0.661). Knowledge scores increased more in the AVPI group compared to the standard group (P=0.0072). The change in anxiety score between the arms was also statistically significant (P=0.011) with anxiety improving in the intervention arm more than in the no intervention arm. Audiovisual patient information was shown to be a useful tool in improving patient knowledge and anxiety, but further work is necessary in relation to its effect on clinical trial recruitment rates.", "Most smokers do not utilize approved interventions for nicotine dependence, reducing the probability of cessation. Smoking cessation programs typically use recruitment messages emphasizing the health threats of smoking. Augmenting this threat message by describing the genetic aspects of nicotine addiction may enhance enrollment into a cessation program. During telephone recruitment, 125 treatment-seeking smokers were randomized to receive by phone either a standard threat message or a threat plus genetic prime message and were offered open-label varenicline and counseling. There was a greater rate of enrollment into the cessation program for the threat plus genetic prime participants (51.7%) versus the threat-only participants (37.7%; p = .03). Smokers who self-identified from racial/ethnic minority groups were less likely to enroll in the cessation program (p = .01) versus smokers who self-identified as Caucasian. These preliminary data suggest that a simple, affordable, and transportable communication approach enhances enrollment of smokers into a smoking cessation program. A larger clinical trial to evaluate a genetic prime message for improving recruitment into smoking cessation programs is warranted.", "To test the ability of an automated telephone outreach intervention to reduce acute healthcare utilization and improve quality of life among adult asthma patients in a large managed care organization.\n Randomized clinical trial.\n Patients with persistent asthma were randomly assigned to telephone outreach (automated = 3389, live caller = 192) or usual care (n = 3367). Intervention participants received 3 outreach calls over a 10-month period. The intervention provided brief, supportive information and flagged individuals with poor asthma control for follow-up by a provider. A survey was mailed to 792 intervention participants and 236 providers after the intervention. Additional feedback was obtained as part of the final intervention contact.\n The intent-to-treat analysis found no significant differences between the intervention and usual-care groups for medication use, healthcare utilization, asthma control, or quality of life. Post hoc analyses found that, compared with the control group, individuals who actually participated in the intervention were significantly more likely to use inhaled steroids and to have had a routine medical visit for asthma during the follow-up period and less likely to use short-acting beta-agonists. They also reported higher satisfaction with their asthma care and better asthma-specific quality of life. Of surveyed providers, 59% stated the program helped them to clinically manage their asthma patients and 70% thought the program should be continued.\n This study did not find improved health outcomes in the primary analyses. The intervention was well accepted by providers, however, and the individuals who participated in the calls appeared to have benefited from them. These findings suggest that further studies of automated telephone outreach interventions seem warranted.", "The purpose of this study was to describe and compare the rates of recruitment during a randomized clinical trial on smoking cessation in two primary care practices. One site was a five-physician private family practice setting with about 15,000 patients. During 34 days, 576 patients were screened, of whom 22% were smokers. Among the smokers screened, 54% consented, 33% refused consent, and 13% were called in too early to consent. The other site was a six-physician academic medical practice with about 16,000 patients. During 53 days, 1,692 subjects were screened, of whom 16.2% were smokers. Among the smokers, 19% consented, 81% refused consent, and none were called in early. The enrollment of smokers was 3.3 times greater in the private practice than the academic practice. At the first site, study personnel screened 26.6 subjects per day, whereas the practice receptionist screened only 13.4 subjects per day (P less than .01). A randomized trial of having subjects read the informed consent versus having study personnel read it to them showed no differences in recruitment. The data suggest that private practices may have greater potential for subject recruitment than academic sites, that using study personnel improves recruitment, and that having study personnel actively involved in informed consent does not improve recruitment.", "This study evaluates the relationship between interviewer level of experience and the positive predictive value and cost of telephone screening of subjects for randomized clinical trials. This is a previously uninvestigated area. Respondents to advertisements for chronic depression treatment research received brief, semi-structured telephone interviews (N = 347) either by research assistants (RAs) or by a senior investigator (SI). Those who met criteria based on the phone interview were then interviewed in person using the SCID-P. The RAs did not significantly differ from the SI in the proportion of phone screen positives who were also SCID positive or the proportion of phone screen positives who were randomized. While the SI performed phone interviews significantly faster than the RAs, the SI's higher salary generated a phone screening cost per randomized subject 56% more than that of RAs. The results suggest that trained research assistants are more cost effective than senior investigators for initial screening of depressed patients for research protocols. Further studies are needed to determine whether the findings reported would generalize to other research settings or patient populations.", "To assess the efficacy, with respect to participant understanding of information, of a computer-based approach to communication about complex, technical issues that commonly arise when seeking informed consent for clinical research trials.\n An open, randomised controlled study of 60 patients with diabetes mellitus, aged 27-70 years, recruited between August 2006 and October 2007 from the Department of Diabetes and Endocrinology at the Alfred Hospital and Baker IDI Heart and Diabetes Institute, Melbourne.\n Participants were asked to read information about a mock study via a computer-based presentation (n = 30) or a conventional paper-based information statement (n = 30). The computer-based presentation contained visual aids, including diagrams, video, hyperlinks and quiz pages.\n Understanding of information as assessed by quantitative and qualitative means.\n Assessment scores used to measure level of understanding were significantly higher in the group that completed the computer-based task than the group that completed the paper-based task (82% v 73%; P = 0.005). More participants in the group that completed the computer-based task expressed interest in taking part in the mock study (23 v 17 participants; P = 0.01). Most participants from both groups preferred the idea of a computer-based presentation to the paper-based statement (21 in the computer-based task group, 18 in the paper-based task group).\n A computer-based method of providing information may help overcome existing deficiencies in communication about clinical research, and may reduce costs and improve efficiency in recruiting participants for clinical trials.", "The effects of disclosing financial interests to potential research participants are not well understood.\n To examine the effects of financial interest disclosures on potential research participants' attitudes toward clinical research.\n Computerized experiment conducted with 3,623 adults in the United States with either diabetes mellitus or asthma, grouped by lesser and greater severity. Respondents read a description of a hypothetical clinical trial relevant to their diagnosis that included a financial disclosure statement. Respondents received 1 of 5 disclosure statements.\n Willingness to participate in the hypothetical clinical trial, relative importance of information about the financial interest, change in trust after reading the disclosure statement, surprise regarding the financial interest, and perceived effect of the financial interest on the quality of the clinical trial.\n Willingness to participate in the hypothetical clinical trial did not differ substantially among the types of financial disclosures. Respondents viewed the disclosed information as less important than other factors in deciding to participate. Disclosures were associated with some respondents trusting the researchers less, although trust among some respondents increased. Most respondents were not surprised to learn of financial interests. Researchers owning equity were viewed as more troubling than researchers who were compensated for the costs of research through per capita payments.\n Aside from a researcher holding an equity interest, the disclosure to potential research participants of financial interests in research, as recommended in recent policies, is unlikely to affect willingness to participate in research.", "A pilot study was carried out in preparation for a full-scale randomized controlled trial of teleconsultations versus routine outpatient consultation. The method of study recruited sufficient numbers of patients and avoided selection bias. Over five months, 439 referrals were received, but 297 patients were not eligible to enter the trial because they did not fall within the specialties/consultants included in it. Of the 132 referrals entering the trial, 62 were randomized to the intervention group and 70 to the control group. Consent to participate in the experimental arm of the trial was obtained for all but 13 patients. The results also suggested that patient satisfaction with teleconsultation may exceed that with conventional outpatient consultation, with a strong indication of overall time savings for patients.", "To investigate whether including a placebo arm in a clinical trial of hormone replacement therapy influenced women's stated willingness to participate.\n Quasirandomised, interview based study. Setting: 10 group practices in the Medical Research Council's General Practice Research Framework.\n 436 postmenopausal women aged 45-64 who had not had a hysterectomy.\n Stated willingness to enter a trial and reasons for the decisions made.\n Of 218 women told about the trial without a placebo arm, 85 (39%) indicated their willingness to enter compared with 65 (30%) of the 218 women told about the trial with the placebo arm (P=0.06). Part of this difference was due to explicit reluctance to take a placebo. Altruism and personal benefit were the reasons most frequently given for wanting to take part in a trial. The reasons most frequently cited for not wanting to take part were reluctance to restart periods, not wanting to take unknown or unnecessary tablets, or not wanting to interfere with present good health.\n For preventive trials the inclusion of a placebo arm may reduce patients' willingness to participate.", "To improve understanding of physicians' reluctance to refer patients to clinical trials.\n This study was conducted in a large metropolitan region from 1993 to 1995 using a two-staged population-based sampling strategy. A total of 147 physicians discussed 245 patient cases and their own knowledge, attitudes, and practices toward clinical trials.\n Ninety-three patients (38. 0%) were offered a trial, and 49 (52.7%) of them agreed to participate. Forty-five patients (18.4%) actually received their adjuvant therapy on trial. Older patients and those with a poorer prognosis were less likely to be referred. Patients who delayed their decision were more than three times as likely to participate in a trial and more than eight times as likely to participate when they were reported to be actively involved in making the decision. Generally, physicians in university settings and who had formal support from a cooperative group were more likely to refer patients to trials. More specifically, surgeons referred more patients to trials when they felt comfortable explaining trials or believed that treatment should not stray from protocol. Oncologists were less likely to make referrals if they perceived the paperwork to be onerous or entry requirements to be too stringent. Surgeons' participation in recommending adjuvant therapy to patients resulted in more trial referrals unless they treated their patients with tamoxifen.\n (1) Physicians still need to overcome attitudinal and practical barriers to trial participation, (2) more support for physicians is needed, (3) surgeons may play a pivotal role in the recruitment of patients to adjuvant therapy trials, and (4) garnering patient enthusiasm for trial participation and involving them in the choice of adjuvant therapy may be key components to increasing trial enrollment.", "As part of a mailed health survey, we investigated the effect on the response rate of a request to explain refusal to participate. Subjects (N = 1,240) were randomized either to receive or not to receive, with the first mailing, a letter requesting an explanation of their decision not to fill out the questionnaire, if they chose that option. There was a slightly higher cumulative response during most of the study from subjects who had been sent the request, but little difference between the two study groups in the ultimate response rate [80% from the intervention group vs 83% from the control group; response rate difference = -3%; 95% confidence limits (CL) = -7%, 1%]. Of 209 individuals who were sent the request and did not return the questionnaire, only 15 (7%) sent back an explanation. A request to explain a refusal to participate in a mail survey neither jeopardized the response rate nor enhanced it.", "The purpose of this study was to systematically compare two audiotape formats for the delivery of information relevant to informed consent to participate in a clinical trial in breast oncology, and to establish the feasibility of adding a consultation recording protocol to a clinical treatment trial.\n Participants were 69 women with newly diagnosed breast cancer and 21 oncologists from 5 Canadian cancer centers. Patients were block randomized to one of three groups: 1. standardized audiotape; 2. consultation audiotape; or 3. both audiotapes. Patients received their tapes immediately following the clinical trial consultation. Patient outcomes included perception of being informed about clinical trials, knowledge of information relevant to providing informed consent to a clinical trial, and satisfaction with communication during the consultation.\n The consultation audiotapes contained less trial-related information than the standardized audiotape but there were no differences in clinical trial knowledge or perception of being informed across the intervention groups. Patients expressed a marginally significant preference for consultation audiotapes over standardized audiotapes.\n Patients tended to prefer receiving an audiotape of their own consultation over a standardized audiotape. The majority of oncologists considered the audiotape intervention feasible but were less enthusiastic about being involved in a larger study given the accrual challenges that arose when trying to \"piggy-back\" one randomized controlled trial on an existing clinical trial.\n Copyright (c) 2006 John Wiley & Sons, Ltd.", "E-mail communication between patients and their providers has diffused slowly in clinical practice. To address concerns about the use of this technology, we performed a randomized controlled trial of a triage-based e-mail system in primary care. DESIGN AND PATIENTS/PARTICIPANTS: Physicians in 2 university-affiliated primary care centers were randomized to a triage-based e-mail system promoted to their patients. E-mails from patients of intervention physicians were routed to a central account and parsed to the appropriate staff for response. Control group physicians and their patients did not have access to the system. We collected information on patient e-mail use, phone calls, and visit distribution by physician over the 10 months and performed physician and patient surveys to examine attitudes about communication.\n E-mail volume was greater for intervention versus control physicians (46 weekly e-mails per 100 scheduled visits vs 9 in the control group at the study midpoint; P <.01) but there were no between-group differences in phone volume (67 weekly phone calls per 100 scheduled visits vs 55 in the control group; P =.45) or rates of patient no-shows (5% in both groups; P =.77). Intervention physicians reported more favorable attitudes toward electronic communication than did control physicians but there were no differences in attitudes toward patient or staff communication in general. There were few between-group differences in patient attitudes toward electronic communication or communication in general.\n E-mail generated through a triage-based system did not appear to substitute for phone communication or to reduce visit no-shows in a primary care setting. Physicians' attitudes toward electronic communication were improved, but physicians' and patients' attitudes toward general communication did not change. Growth of e-mail communication in primary care settings may not improve the efficiency of clinical care.", "To determine the safety and effectiveness of nurse telephone consultation in out of hours primary care by investigating adverse events and the management of calls.\n Block randomised controlled trial over a year of 156 matched pairs of days and weekends in 26 blocks. One of each matched pair was randomised to receive the intervention.\n One 55 member general practice cooperative serving 97 000 registered patients in Wiltshire.\n All patients contacting the out of hours service or about whom contact was made during specified times over the trial year.\n A nurse telephone consultation service integrated within a general practice cooperative. The out of hours period was 615 pm to 1115 pm from Monday to Friday, 1100 am to 1115 pm on Saturday, and 800 am to 1115 pm on Sunday. Experienced and specially trained nurses received, assessed, and managed calls from patients or their carers. Management options included telephone advice; referral to the general practitioner on duty (for telephone advice, an appointment at a primary care centre, or a home visit); referral to the emergency service or advice to attend accident and emergency. Calls were managed with the help of decision support software.\n Deaths within seven days of a contact with the out of hours service; emergency hospital admissions within 24 hours and within three days of contact; attendance at accident and emergency within three days of a contact; number and management of calls in each arm of the trial.\n 14 492 calls were received during the specified times in the trial year (7308 in the control arm and 7184 in the intervention arm) concerning 10 134 patients (10.4% of the registered population). There were no substantial differences in the age and sex of patients in the intervention and control groups, though male patients were underrepresented overall. Reasons for calling the service were consistent with previous studies. Nurses managed 49.8% of calls during intervention periods without referral to a general practitioner. A 69% reduction in telephone advice from a general practitioner, together with a 38% reduction in patient attendance at primary care centres and a 23% reduction in home visits was observed during intervention periods. Statistical equivalence was observed in the number of deaths within seven days, in the number of emergency hospital admissions, and in the number of attendances at accident and emergency departments. Conclusions Nurse telephone consultation produced substantial changes in call management, reducing overall workload of general practitioners by 50% while allowing callers faster access to health information and advice. It was not associated with an increase in the number of adverse events. This model of out of hours primary care is safe and effective.", "The Internet is a promising venue for delivering smoking cessation treatment, either as a stand-alone program or as an adjunct to pharmacotherapy. However, there is little data to indicate what percent of smokers are interested in receiving online smoking cessation services or how best to recruit smokers to Internet-based programs.\n Using a defined recruitment sample, this study aimed to identify the percentage of smokers who expressed interest in or enrolled in Project Quit, a tailored, online, cognitive-behavioral support program offered with adjunctive nicotine replacement therapy patches. In addition, we examined the effectiveness of several individual-level versus population-level recruitment strategies.\n Members from two large health care organizations in the United States were invited to participate in Project Quit. Recruitment efforts included proactive invitation letters mailed to 34533 likely smokers and reactive population-level study advertisements targeted to all health plan members (> 560000 adults, including an estimated 98000 smokers across both health care organizations).\n An estimated 1.6% and 2.5% of adult smokers from each health care organization enrolled in Project Quit. Among likely smokers who received proactive study invitations, 7% visited the Project Quit website (n = 2260) and 4% (n = 1273) were eligible and enrolled. Response rates were similar across sites, despite using different sources to assemble the invitation mailing list. Proactive individual-level recruitment was more effective than other forms of recruitment, accounting for 69% of website visitors and 68% of enrollees.\n Smokers were interested in receiving online smoking cessation support, even though they had access to other forms of treatment through their health insurance. Uptake rates for this program were comparable to those seen when smokers are advised to quit and are referred to other forms of smoking cessation treatment. In this sample, proactive mailings were the best method for recruiting smokers to Project Quit.", "A double-blind randomised controlled trial was conducted on a group of Hong Kong hospital clinicians. The objective was to test if a three-hour educational workshop (with supervised hands-on practice) is more effective (than no training) to improve clinical question formulation, information-seeking skills, knowledge, attitudes, and search outcomes. The design was a post-test-only control group; recruitment by stratified randomization (by profession), blocked at 800. End-user training was more effective than no training in improving clinical question formulation, in raising awareness, knowledge, confidence and use of databases, but had made no impact on preference for secondary databases. It changed the attitude of clinicians to become more positive towards the use of electronic information services (EIS). Participants had higher search performance and outcomes (satisfaction with information obtained (NNT = 3), EIS satisfaction (NNT = 3) and success in problem solving (NNT = 4)). The workshop improved knowledge and skills in evidence-based searching, but this effect gradually eroded with time. Search logs confirmed that follow-up is required if effects are to be sustained. Longer effects on search behaviours appear to be positive. A randomised controlled trial is valuable in identifying cause-and-effect relations and to quantify the magnitude of the effects for management decision-making.", "Laboratory services play an important part in screening, diagnosis, and management of patients within primary care. However, unnecessary use of laboratory tests is increasing. Our aim was to assess the effect of two interventions on the number of laboratory tests requested by primary-care physicians.\n We did a cluster randomised controlled trial using a 2x2 factorial design, involving 85 primary-care practices (370 family practitioners) that request all laboratory tests from one regional centre. The interventions were quarterly feedback of practice requesting rates for nine laboratory tests, enhanced with educational messages, and brief educational reminder messages added to the test result reports for nine laboratory tests. The primary outcome was the number of targeted tests requested by primary-care practices during the 12 months of the intervention. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN06490422.\n Practices that received either or both the enhanced feedback and the reminder messages were significantly less likely than the control group to request the targeted tests in total (enhanced feedback odds ratio 0.87, 95% CI 0.81-0.94; reminder messages 0.89, 0.83-0.93). The effect of the interventions varied across the targeted tests individually, although the number of tests requested for both interventions was generally reduced. Neither intervention was consistently better than the other.\n Enhanced feedback of requesting rates and brief educational reminder messages, alone and in combination, are effective strategies for reducing test requesting in primary care. Both strategies are feasible within most laboratory settings.", "Colon cancer screening (CRCS) tests are underused. Multiple CRCS options may confuse patients and lead to inaction. E-mail between patients and physicians may raise awareness about CRCS and allow physicians to answer questions about test options.\n To develop and implement an electronic intervention, the InterNet LETter (NetLET), to increase interest in and use of CRCS among patients with and without e-mail access at home or work.\n During 2004-2005, 97 patients over 49 years old were recruited during a clinic visit. Patients with e-mail at home or work were assigned to the private access arm; patients without e-mail but willing to use the public library system were assigned to the public access arm. Within each arm, patients were randomized to the NetLET or control group. The NetLET consisted of a personalized e-mail from the physician reminding the patient to undergo CRCS and providing a link to a webpage with information about CRCS. Control groups were mailed a reminder letter from their physician. All were mailed a fecal occult blood test (FOBT) kit.\n In the public access intervention group, only 1 of 11 patients viewed the NetLET. In the private access intervention group, 10 of 42 viewed it. Eleven of 42 (26%) private access intervention group participants, and 8 of 35 (23%) private access control group participants returned an FOBT. No public access intervention group patients, but 3 of 9 control group patients, returned an FOBT.\n We concluded that it was not feasible to implement the NetLET, but reasons for lack of success differed for the private and public access arms.", "Despite the large number of available studies, most women with breast cancer do not participate in clinical trials, and this is especially true among lower income and minority women. In this study the authors surveyed the practice patterns of four medical oncologists who comprised the clinical breast service at a large urban university hospital to develop a better understanding of the clinical trials enrollment process for women with breast cancer. Of 136 new female breast cancer patients seen by the four physicians over a 7-month period, there were 47 women (34%) offered participation in a clinical trial, and 16 women (12%) were eventually enrolled. Women who were offered participation were more likely to be younger (p = 0.068) and to have earlier stage disease then were women not offered participation (p = 0.008). Women enrolled into a trial were also more likely to be younger, although this difference was not statistically significant (p = 0.114). Patient race was not associated with the accrual or enrollment process. Over half of the women were not offered participation in clinical trials because of the lack of available studies. Further work evaluating the process of patient enrollment and physician and patient barriers is necessary to develop effective strategies for recruitment into breast cancer clinical trials.", "To evaluate the impact of an information booklet on HIV clinical trials, Clinical Trials in HIV and AIDS: Information For People Who Are Thinking About Joining a Trial, in addition to the standard trial information (SI) on patients' knowledge; understanding and attitudes about clinical trials; and to investigate patients' motivations and reasons for enrolling or not enrolling in a clinical trial.\n Fifty HIV-1 positive patients who attended the HIV clinic at a west London hospital were randomized to receive either SI alone (n = 27) or SI and a 16 page information booklet explaining the principles and procedures of HIV clinical trials (n = 23). A self-administered questionnaire was used at baseline to assess past experience and attitudes to clinical trials (10 questions), knowledge and understanding of HIV treatments (8 questions) and clinical trials (11 questions). At 2-6 months after randomization, a second interviewer-administered questionnaire addressed the patient's assessment of the usefulness and comprehensiveness of the information provided by the SI and information booklet, whether or not the patient had enrolled in a clinical trial and reasons for enrolling/not enrolling, knowledge of specific aspects of the trial protocol the patient was eligible to join (13 questions) and general knowledge of clinical trial procedures (repeat of 11 baseline questions). Changes in the attitudes and scores on knowledge and understanding of clinical trials were compared for the two groups.\n In both groups, patient knowledge of clinical trial procedures improved significantly over the study period. The median score increased from 30 at baseline to 35/44 at follow-up (SI only) vs. 24-31/44 (SI plus booklet), but this did not differ significantly between the two groups. However, knowledge of the specific trial protocol was poor [median score 13/25, interquartile range (IQR) 8-14], and there was no difference in the scores for the two groups. The prime motivations for joining a clinical trial were to benefit personal health and to gain access to new treatments. Potential side-effects were the main concern of prospective trial participants.\n This small trial shows that, while the patients' general knowledge and understanding of clinical trials improved over time, this was not improved by the information booklet and recollection of the details of the relevant trial protocol remained poor." ]	There are promising strategies for increasing recruitment to trials: telephone reminders; requiring potential participants to opt-out of being contacted by the trial team regarding taking part in a trial, rather than them having to opt-in, and open designs. Some strategies (e.g. open trial designs) need to be considered carefully before use because they also have disadvantages. For example, opt-out procedures are controversial and open designs are by definition unblinded.
CD001968	[ "10023787", "9447532" ]	[ "Prevention of chronic lung disease in preterm infants by early postnatal dexamethasone therapy.", "Comparative efficacy of exosurf and survanta surfactants on early clinical course of respiratory distress syndrome and complications of prematurity." ]	[ "Recent studies suggest that early dexamethasone therapy may lessen the pulmonary inflammation in preterm infants with respiratory distress syndrome (RDS). To investigate whether early (<12 hr) postnatal dexamethasone therapy would reduce the incidence of chronic lung disease (CLD), a randomized, double-blind, controlled trial was conducted in 40 infants (birth weights from 500 to 1,999 gm) who had severe RDS and required mechanical ventilation within 6 hr of birth. All infants received one dose of Survanta before they were randomly assigned to control (saline placebo) or dexamethasone-treated groups (0.5 mg/kg/d for 1 week, then tapered over 3 weeks). Sequential analysis was performed with the end point of assessment being the presence or absence of CLD on postnatal Day 28. Statistical significance favoring dexamethasone was reached when 12 consecutive pairs in which one infant had CLD and the other did not have CLD showed that ten pairs favored dexamethasone and two pairs favored control treatment. Among the survivors, 12/15 were extubated in the dexamethasone group and 9/16 in the control group at the end of study. Infants in the treated group had transient hyperglycemia and hypertension. There was no difference between the groups in mortality and in incidence of sepsis or intraventricular hemorrhage. We conclude that early postnatal dexamethasone therapy is potentially effective in the lessening of CLD in preterm infants. To substantiate our result, large randomized controlled trials are needed and warranted.", "To determine the comparative efficacy of Exosurf Neonatal and Survanta surfactants on the early course of respiratory distress syndrome (RDS), arterial blood gases, ventilatory support, outcome morbidity rate, and complications of prematurity and RDS.\n Medical records from 203 premature newborn infants undergoing mechanical ventilation for respiratory distress syndrome, and who received up to four rescue doses of either Exosurf or Survanta, were retrospectively reviewed.\n All groups were comparable for birth weight and gestational age. Although the two randomized groups were similar in severity of RDS based on fraction of inspired oxygen (FIO2) and ventilatory support, a significantly greater improvement in respiratory function as evidenced by FIO2, mean airway pressure, alveolar-arterial partial pressure of oxygen difference, and oxygen index, was observed in the Survanta group from 12 hours (p < 0.05) through 48 hours (p < 0.01). Comparison of outcome morbidity rate by gestational age showed a higher occurrence of retinopathy of prematurity (p < 0.02) among the older infants (28 to 32 weeks) who were treated with Exosurf.\n Survanta exerted a significantly faster response in the early clinical course of RDS compared with Exosurf. However, no difference in the impact on eventual respiratory outcome was observed. We therefore conclude that both surfactants are effective for the treatment of RDS." ]	Based on currently available published trials, there is insufficient evidence to draw firm conclusions about the efficacy of superoxide dismutase in preventing chronic lung disease of prematurity. Data from a small number of treated infants suggest that it is well tolerated and has no serious adverse effects.
CD003793	[ "10767227", "8162979", "18399862", "12683707", "8620707", "10714421", "19075206", "19272084", "8162723", "16778272", "21474911", "16140230", "10856310", "1456568", "11399694", "7025334", "8980974", "10974183", "12947128", "20435864", "10599897", "16327534", "9032501", "9493664", "1588521", "9271771" ]	[ "Long-term effects of outpatient rehabilitation of COPD: A randomized trial.", "Quality of life in patients with chronic obstructive pulmonary disease improves after rehabilitation at home.", "Effects of pulmonary rehabilitation in patients with idiopathic pulmonary fibrosis.", "Pulmonary rehabilitation in patients with chronic obstructive pulmonary disease.", "A comparison between an outpatient hospital-based pulmonary rehabilitation program and a home-care pulmonary rehabilitation program in patients with COPD. A follow-up of 18 months.", "Rehabilitation of patients with chronic obstructive pulmonary disease. Exercise twice a week is not sufficient!", "Effects of home-based pulmonary rehabilitation in patients with chronic obstructive pulmonary disease: a randomized trial.", "Does early pulmonary rehabilitation reduce acute health-care utilization in COPD patients admitted with an exacerbation? A randomized controlled study.", "The effect of comprehensive outpatient pulmonary rehabilitation on dyspnea.", "Improvement in quadriceps strength and dyspnea in daily tasks after 1 month of electrical stimulation in severely deconditioned and malnourished COPD.", "The effects of controlled breathing during pulmonary rehabilitation in patients with COPD.", "Extending a home from hospital care programme for COPD exacerbations to include pulmonary rehabilitation.", "Supplemental oxygen during pulmonary rehabilitation in patients with COPD with exercise hypoxaemia.", "Physiologic effects of oral supplemental feeding in malnourished patients with chronic obstructive pulmonary disease. A randomized control study.", "The effectiveness of outpatient pulmonary rehabilitation in chronic lung disease: a randomized controlled trial.", "Randomised controlled trial of rehabilitation in chronic respiratory disability.", "Low intensity peripheral muscle conditioning improves exercise tolerance and breathlessness in COPD.", "Short- and long-term effects of outpatient rehabilitation in patients with chronic obstructive pulmonary disease: a randomized trial.", "Nutritional enhancement of exercise performance in chronic obstructive pulmonary disease: a randomised controlled trial.", "Outpatient pulmonary rehabilitation following acute exacerbations of COPD.", "Long-term effects of a pulmonary rehabilitation programme in outpatients with chronic obstructive pulmonary disease: a randomized controlled study.", "Managing chronic obstructive pulmonary disease in the community. A randomized controlled trial of home-based pulmonary rehabilitation for elderly housebound patients.", "The effects of a community-based pulmonary rehabilitation programme on exercise tolerance and quality of life: a randomized controlled trial.", "Out-patient rehabilitation improves activities of daily living, quality of life and exercise tolerance in chronic obstructive pulmonary disease.", "Benefits and weaknesses of a cardiac rehabilitation programme.", "Acupressure as an adjunct to a pulmonary rehabilitation program." ]	[ "To examine the short- and long-term effects of an outpatient pulmonary rehabilitation program for COPD patients on dyspnea, exercise, health-related quality of life, and hospitalization rate.\n Secondary-care respiratory clinic in Barcelona.\n We conducted a randomized controlled trial with blinding of outcome assessment and follow-up at 3, 6, 9, 12, 18, and 24 months. Sixty patients with moderate to severe COPD (age 65 +/- 7 years; FEV(1) 35 +/- 14%) were recruited. Thirty patients randomized to rehabilitation received 3 months of outpatient breathing retraining and chest physiotherapy, 3 months of daily supervised exercise, and 6 months of weekly supervised breathing exercises. Thirty patients randomized to the control group received standard care.\n We found significant differences between groups in perception of dyspnea (p < 0.0001), in 6-min walking test distance (p < 0.0001), and in day-to-day dyspnea, fatigue, and emotional function measured by the Chronic Respiratory Questionnaire (p < 0. 01). The improvements were evident at the third month and continued with somewhat diminished magnitude in the second year of follow-up. The PR group experienced a significant (p < 0.0001) reduction in exacerbations, but not the number of hospitalizations. The number of patients needed to treat to achieve significant benefit in health-related quality of life for a 2-year period was approximately three.\n Outpatient rehabilitation programs can achieve worthwhile benefits that persist for a period of 2 years.", "We have developed a rehabilitation programme at home and have investigated its effects on quality of life (QOL), lung function, and exercise tolerance in patients with chronic obstructive pulmonary disease (COPD). We studied 43 patients with severe airflow obstruction: forced expiratory volume in one second (FEV1) 1.3 +/- 0.4 l (mean +/- SD), FEV1/inspiratory vital capacity (IVC) 37 +/- 7.9%. After stratification, 28 patients were randomly allocated in a home rehabilitation programme for 12 weeks. Fifteen patients in a control group received no rehabilitation. The rehabilitation group received physiotherapy by the local physiotherapist, and supervision by a nurse and a general practitioner. Quality of life was assessed by the four dimensions of the Chronic Respiratory Questionnaire (CRQ). We found a highly significant improvement in the rehabilitation group compared to the control group for the dimensions dyspnoea, emotion, and mastery. Lung function showed no changes in the rehabilitation group. The exercise tolerance improved significantly in the rehabilitation group compared to the control group. The improvement in quality of life was not correlated with the improvement in exercise tolerance. Rehabilitation of COPD patients at home may improve quality of life; this improvement is not correlated with an improvement in lung function and exercise tolerance.", "Although pulmonary rehabilitation is effective for patients with COPD, its efficacy in patients with IPF is unknown. The purpose of this study was to evaluate the effects of pulmonary rehabilitation in IPF.\n Thirty patients diagnosed with IPF, according to the consensus statement, were randomly assigned to the rehabilitation group or the control group. The pulmonary rehabilitation mainly consisted of a 10-week programme of exercise training. Pulmonary function, blood gas analysis, 6MWD, dyspnoea rating with the baseline dyspnoea index and health-related quality of life score on the St George's Respiratory Questionnaire were evaluated at baseline and after the programme.\n Assessment of efficacy was carried out on 13 patients who completed the programme and 15 patients in the control group. There were no significant effects of the programme on measures of pulmonary function, values of arterial blood gas analysis or dyspnoea rating. Although there were some differences in the baseline 6MWD and total health-related quality of life score which were not statistically significant, marked improvements were observed in the 6MWD (mean difference 46.3 m (95% CI: 8.3-84.4), P < 0.05) and the total health-related quality of life score (-6.1 (95% CI: -11.7 to -0.5), P < 0.05).\n Pulmonary rehabilitation improves both exercise capacity and health-related quality of life in patients with IPF.", "Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality in India. Drug treatment alone does not optimize therapy. Pulmonary rehabilitation has been found to improve the physical efficiency of COPD patients. Therefore, we evaluated the effect of domiciliary pulmonary rehabilitation programme in patients of COPD.\n Forty patients of stable COPD having severe airflow obstruction were included in the study. They were divided into control and experimental groups randomly. Rehabilitation included walking, breathing exercises, postural drainage, controlled coughing and changes in life style activities. Exercises of 30 minutes duration were performed at home twice daily for four weeks supervision. Six-minute walking distance, forced expiratory volume in one seocond (FEV1) and various indices of chronic respiratory disease questionnaire (CRDQ) were measured in both experimental and control groups before and after completion of the study.\n In the experimental group, after four weeks, the mean (+/- SD) difference in six-minute walking distance, dyspnoea, mastery, fatigue and emotion scores were 54.2 (26.7) meters, 0.96 (0.26), 0.89 (0.44), 0.90 (0.40) and 0.91 (0.32) respectively. Changes in all these parameters were statistically significant (p < 0.001) as compared to the control group. There was no significant change in FEV1.\n It was concluded that domiciliary pulmonary rehabilitation for four weeks results in significant improvement in the quality of life and exercise tolerance, even without improvement in FEV1.", "In this study, the effects of a 12-week hospital-based outpatient pulmonary rehabilitation program (HRP) are compared with those of a 12-week home-care rehabilitation program (HCRP) in COPD patients. A control group received no rehabilitation therapy.\n After randomization and stratification, effects on lung function, exercise performance (4-min walking test and cycle ergometer test), dyspnea, and leg effort during exercise, and well-being were assessed in 45 COPD patients with moderate to severe airflow limitation (mean [SD] FEV1 percent predicted, 42.8 [8.4]).\n After HRP and HCRP, at 3 to 6 months after the start of the study, equal improvements were detected in exercise capacity and in Borg dyspnea and leg effort scores at similar work levels during the cycle test. However, whereas after HRP at longer term values tended to return to baseline outcome, after HCRP a further ongoing significant improvement in exercise capacity was observed, while Borg dyspnea scores remained significantly improved over 18 months. Improvements in cycle workload and dyspnea score were significantly better maintained after HCRP as compared with HRP. Lung function, arterial oxygen saturation, and heart frequency during exercise did not change. A significant improvement in well-being was maintained over 18 months in both rehabilitation groups.\n Beneficial effects are achieved both after a HRP and a HCRP in COPD patients with moderate to severe airflow limitation. Yet we recommend to initiate HCRPs as improvements are maintained longer and are even further strengthened in this setting.", "Several studies of chronic obstructive pulmonary disease (COPD) have shown that pulmonary rehabilitation, consisting of at least three training sessions a week, improves exercise performance and health status. This study investigates feasibility, effect and economic aspects of a rehabilitation programme consisting of two sessions a week for 8 weeks. Twenty-four patients with moderate COPD were randomized to rehabilitation and 21 to placebo. Patients were assigned to an 8-week programme of exercise plus education (Exercise group) or conventional community care (Placebo group). The rehabilitation program was carried out in a hospital outpatient setting and consisted of 16 h exercise and 13.5 h of education. The exercise group received physiotherapy and education twice a week. Seven patients did not complete the programme. The characteristics of the 38 COPD-patients at baseline were the following: (mean +/- SD) forced expiratory volume in 1 sec (FEV1) 1.1+/-0.4 1 (47% of predicted), 6-min walking distance (6MWD) 413+/-75 m, score of St. George's Respiratory Questionnaire (SGRQ) 44+/-21. Health-status, assessed by SGRQ and The Psychological General Well-being (PGWB) Index, did not improve. Rehabilitation resulted in an insignificant improvement in the 6MWD [29 m (95% confidence interval: -8 -66 m)]. We conclude that a rehabilitation program consisting of exercise and education twice a week for 8 weeks had no effect on exercise performance and well being in patients with moderate COPD.", "Home-based rehabilitation is a promising approach to improve access to pulmonary rehabilitation.\n To assess whether self-monitored, home-based rehabilitation is as effective as outpatient, hospital-based rehabilitation in patients with chronic obstructive pulmonary disease (COPD).\n Randomized, multicenter, noninferiority trial.\n 10 academic and community medical centers in Canada.\n 252 patients with moderate to severe COPD.\n After a 4-week education program, patients took part in home-based rehabilitation or outpatient, hospital-based rehabilitation for 8 weeks. They were followed for 40 weeks to complete the 1-year study.\n The primary outcome was the change in Chronic Respiratory Questionnaire dyspnea subscale score at 1 year. The primary analysis took a modified intention-to-treat approach by using all patients who provided data at the specified follow-up time, regardless of their level of adherence. The analysis used regression modeling that adjusted for the effects of center, sex, and baseline level. All differences were computed as home intervention minus outpatient intervention.\n Both interventions produced similar improvements in the Chronic Respiratory Questionnaire dyspnea subscale at 1 year: improvement in dyspnea of 0.62 (95% CI, 0.43 to 0.80) units in the home intervention (n = 107) and 0.46 (CI, 0.28 to 0.64) units in the outpatient intervention (n = 109). The difference between the 2 treatments at 1 year was small and clinically unimportant. The 95% CI of the difference did not exceed the prespecified noninferiority margin of 0.5: difference in dyspnea score of 0.16 (CI, -0.08 to 0.40). Most adverse events were related to COPD exacerbations. No serious adverse event was considered to be related to the study intervention.\n The contribution of the educational program to the improvement in health status and exercise tolerance cannot be ascertained.\n Home rehabilitation is a useful, equivalent alternative to outpatient rehabilitation in patients with COPD.", "In COPD, hospital admissions and readmissions account for the majority of health-care costs. The aim of this prospective randomized controlled study was to determine if early pulmonary rehabilitation, commenced as an inpatient and continued after discharge, reduced acute health-care utilization.\n Consecutive COPD patients (n = 397), admitted with an exacerbation, were screened: 228 satisfied the eligibility criteria, of whom 97 consented to randomization to rehabilitation or usual care. Both intention-to-treat and per-protocol analyses are reported with adherence being defined a priori as participation in at least 75% of rehabilitation sessions.\n The participants were elderly with severe impairment of pulmonary function, poor health-related quality of life and high COPD-related morbidity. The rehabilitation group demonstrated a 23% (95% CI: 11-36%) risk of readmission at 3 months, with attendees having a 16% (95% CI: 0-32%) risk compared with 32% (95% CI: 19-45%) for usual care. These differences were not significant. There were a total of 79 COPD-related readmission days (1.7 per patient, 95% CI: 0.6-2.7, P = 0.19) in the rehabilitation group, compared with 25 (1.3 per patient, 95% CI: 0-3.1, P = 0.17) for the attendees and 209 (4.2 per patient, 95% CI: 1.7-6.7) for usual care. The BMI, airflow obstruction, dyspnoea and exercise capacity index showed a non-significant trend to greater improvement among attendees compared with those receiving usual care (5.5 (2.3) and 5.6 (2.7) at baseline, improving to 3.7 (1.9) and 4.5 (2.5), respectively, at 3 months). No adverse effects were identified.\n Early inpatient-outpatient rehabilitation for COPD patients admitted with an exacerbation was feasible and safe, and was associated with a non-significant trend towards reduced acute health-care utilization.", "To evaluate the effect of outpatient pulmonary rehabilitation (OPR) on dyspnea, we measured this symptom using a visual analogue scale during graded treadmill exercise testing and with baseline and transitional dyspnea indices (TDI). The latter measure overall dyspnea in three spheres: functional impairment, magnitude of task, and magnitude of effort. Twenty patients with COPD referred for OPR were randomly assigned to either a treatment group (T, n = 10), with dyspnea evaluated at baseline then shortly following a 6-week OPR program, or a control group (C, n = 10), with dyspnea evaluated at baseline then following a 6-week waiting period. No significant change in maximal exercise performance from baseline to repeated testing was observed in either group. Dyspnea at maximum treadmill workload (Dmax), which did not significantly change in C, decreased from 74.4 +/- 18.9 percent at baseline to 50.5 +/- 23.2 percent post-OPR in T (p = 0.006). The Dmax related to minute ventilation (Dmax/VEmax) and oxygen consumption (Dmax/VO2max) also significantly decreased following OPR. The reduction in exertional dyspnea was apparent by the second minute of exercise. Additionally, TDI focal scores were significantly higher in T than C (2.3 +/- 1.06 vs 0.2 +/- 1.75 units, p = 0.006), indicating decreased overall dyspnea following OPR. These results point to significant improvements in both exertional and clinically assessed dyspnea following OPR.", "Low body weight in COPD patients is associated with worsening dyspnea, reduced leg strength, and poor prognosis. Classical rehabilitation strategies are then limited by reduced exercise tolerance. Thus, we proposed to evaluate whether electrostimulation (ES) was a beneficial technique in the rehabilitation programs for severely deconditioned COPD patients after an acute exacerbation.\n Randomized, controlled study.\n Pulmonary rehabilitation center.\n Seventeen patients with severe COPD (mean [ +/- SD] FEV(1), 30 +/- 3% predicted) and low body mass index (BMI) [18 +/- 2.5 kg/m(2)].\n Patients were randomly assigned either to usual rehabilitation (UR) alone or to a UR-plus-ES program for 4 weeks. Quadriceps muscle strength, total muscle mass (MM), exercise capacity, and health-related quality of life were measured before and after rehabilitation.\n The training with ES plus UR induced a significant twofold improvement in the mean number of maximal voluntary contraction (MVC) compared to UR alone (97 +/- 71 vs 36 +/- 34 contractions, respectively; p = 0.03) and resulted in a more significant improvement in dyspnea when performing daily tasks (decrease in the dyspnea domain score of the 28-item Maugeri Foundation Respiratory Failure questionnaire, -1.7 +/- 1.0 vs -0.2 +/- 1.2 points, respectively; p = 0.05). There was also a significant increase in walking distance (63 +/- 40 m; p = 0.01) and BMI (0.6 +/- 0.5 kg/m(2); p = 0.02) after training in the ES + UR group. A significant relationship was found between changes in MVC and changes in MM after training in the ES + UR group (r = 0.94; p = 0.03).\n The combination of ES and UR was associated with greater improvement in quadriceps strength and dyspnea during the performance of daily tasks than UR alone in severely disabled COPD patients with low BMI. In this population, ES has been revealed as a useful procedure, complementing the usual pulmonary rehabilitation.", "Conventional pulmonary rehabilitation programs improve exercise tolerance but have no effect on pulmonary function in patients with chronic obstructive pulmonary disease (COPD). The role of controlled breathing using respiratory biofeedback during rehabilitation of patients with COPD remains unclear.\n To compare the effects of a conventional 4-week pulmonary rehabilitation program with those of rehabilitation plus controlled breathing interventions.\n A randomized controlled trial was performed. Pulmonary function (FEV1), exercise capacity (6-min walking distance, 6 MWD), health-related quality of life (chronic respiratory questionnaire, CRQ) and cardiac autonomic function (rMSSD) were evaluated.\n Forty COPD patients (mean±SD age 66.1±6.4, FEV1 45.9±17.4% predicted) were randomized to rehabilitation (n=20) or rehabilitation plus controlled breathing (n=20). There were no statistically significant differences between the two groups regarding the change in FEV1 (mean difference -0.8% predicted, 95% CI -4.4 to 2.9% predicted, p=0.33), 6 MWD (mean difference 12.2 m, 95% CI -37.4 to 12.2 m, p=0.16), CRQ (mean difference in total score 0.2, 95% CI -0.1 to 0.4, p=0.11) and rMSSD (mean difference 2.2 ms, 95% CI -20.8 to 25.1 ms, p=0.51).\n In patients with COPD undergoing a pulmonary rehabilitation program, controlled breathing using respiratory biofeedback has no effect on exercise capacity, pulmonary function, quality of life or cardiac autonomic function.\n Copyright © 2011 S. Karger AG, Basel.", "The principals of rehabilitation medicine are to prevent muscle atrophy and improve mobility. Exacerbations of chronic obstructive pulmonary disease (COPD) are associated with muscle atrophy and yet many patients do not undergo pulmonary rehabilitation until they have been in stable health for some time. We investigated the outcome of a supervised home exercise programme initiated immediately after hospitalisation for an exacerbation of COPD. Thirty-one patients were randomised into an exercise group (n=16, FEV(1) 0.94+/-0.34 L) and a control group (n=15, FEV(1) 1.08+/-0.33 L). The exercise group received a twice-weekly supervised exercise programme, in their homes, for 6 weeks. Spirometry, exercise capacity, isometric muscle strength, dyspnea level, quality of life at baseline and 6 weeks as well as subsequent exacerbations were quantified. At 6 weeks, the exercise group, improved the shuttle walk test (198 m+/-95-304+/-136 m) and increased 3 min step test capacity (119+/-40-163+/-26s) (both P<0.001). Knee extensor muscle strength and quality of life scores also increased. Neither exercise capacity nor muscle strength altered in the control group. Follow-up at 3 months showed that three of the control group and none of the exercise group had experienced subsequent exacerbations (P=0.06). Early rehabilitation via a home from hospital programme improved exercise tolerance, muscle strength, dyspnea scores, quality of life in COPD patients and reduced the number of subsequent exacerbations.", "Supplemental oxygen in patients with chronic obstructive pulmonary disease (COPD) and exercise hypoxaemia improves exercise capacity and dyspnoea. However, the benefit of oxygen during pulmonary rehabilitation in these patients is still unknown.\n Twenty five patients with stable COPD (mean (SD) forced expiratory volume in one second (FEV(1)) 0.76 (0.29) l and 30.0 (9.89)% predicted, arterial oxygen tension (PaO(2)) 8.46 (1.22) kPa, arterial carbon dioxide tension (PaCO(2)) 6.32 (1.01) kPa) and significant arterial desaturation on exercise (82.0 (10.4)%) were entered onto a pulmonary rehabilitation programme. Patients were randomised to train whilst breathing oxygen (OT) (n = 13) or air (AT) (n = 12), both at 4 l/min. Assessments included exercise tolerance and associated dyspnoea using the shuttle walk test (SWT) and Borg dyspnoea score, health status, mood state, and performance during daily activities.\n The OT group showed a significant reduction in dyspnoea after rehabilitation compared with the AT group (Borg mean difference -1.46 (95% CI -2.72 to -0.19)) but there were no differences in other outcome measures: SWT difference -23.6 m (95% CI -70.7 to 23.5), Chronic Respiratory Disease Questionnaire 3.67 (95% CI -7.70 to 15.1), Hospital Anxiety and Depression Scale 1. 73 (95% CI -2.32 to 5.78), and London Chest Activity of Daily Living Scale -2.18 (95% CI -7.15 to 2.79). At baseline oxygen significantly improved SWT (mean difference 27.3 m (95% CI 14.7 to 39.8) and dyspnoea (-0.68 (95% CI -1.05 to -0.31)) compared with placebo air.\n This study suggests that supplemental oxygen during training does little to enhance exercise tolerance although there is a small benefit in terms of dyspnoea. Patients with severe disabling dyspnoea may find symptomatic relief with supplemental oxygen.", "The association between severe nutritional depletion and chronic obstructive pulmonary disease (COPD) has long been recognized. A potential therapeutic benefit to nutritional support was previously suggested by us in a pilot investigation. Subsequent studies have reported conflicting results regarding the role of nutritional therapy in this clinical population. We report a randomized controlled study of nutritional therapy in underweight patients with COPD that combines an initial inpatient investigation (controlled nutritional support) with a prolonged outpatient follow-up interval. Provision of adequate calorie and protein support, adjusted to metabolic requirements, resulted in weight gain (intervention = +2.4 kg versus control -0.5 kg), improved handgrip strength (intervention = +5.5 kg-force versus control -6.0 kg-force), expiratory muscle strength (intervention = +14.9 cm H2O versus control -9.2 cm H2O), and walking distance (intervention = +429 feet versus control -1.0 foot). Inspiratory muscle strength was also improved (intervention = +11.4 cm H2O versus control +4.8 cm H2O) although this did not quite reach statistical significance. We conclude that provision of adequate nutrient supply under controlled conditions results in significant clinical improvements in the COPD patient population. However, the intervention is costly, time-intensive, and of limited therapeutic magnitude. More detailed work of alternative outpatient strategies combined with additional rehabilitative measures is indicated to delineate the full therapeutic potential of nutritional support for this clinical population.", "Patients with chronic pulmonary disease have been shown to benefit from pulmonary rehabilitation programs. Published work has often been from specialized teaching centers and has involved inpatient stay. We assessed an entirely outpatient-based program of pulmonary rehabilitation in patients with chronic lung disease, using the St. George's Respiratory Questionnaire (SGRQ) (which measures health-related quality of life) as the primary outcome measure.\n We undertook a randomized, prospective, parallel-group controlled study of an outpatient rehabilitation program in 65 patients with COPD (44 men and 21 women; mean age, 69.5 years [SD, 9.2 years]; FEV(1), 41% predicted [SD, 18.5%]). The active group (n = 36) took part in a 6-week program of education (2 h weekly) and exercise (1 h weekly). The control group (n = 29) were reviewed routinely as medical outpatients. The SGRQ was administered under supervision by a blinded observer at study entry, 12 weeks, and 24 weeks.\n The SGRQ in the active group was 59.9 (SE, 2.0) at study entry (n = 36), 47.4 (SE, 2.3) at 12 weeks (n = 32), and 50.6 (SE, 2.5) at 24 weeks (n = 24). The SGRQ in the control group was 59.3 (SE, 2.5) at study entry and did not change significantly over 24 weeks. There was a difference of 10.4 points (confidence interval [CI], 3.6 to 17.3) between the two groups at 12 weeks (p < 0.001) and of 8.1 points (CI, 1.4 to 14.9) at 24 weeks (p = 0.02) in favor of the active group.\n A 6-week outpatient-based program significantly improved quality of life in patients with moderate-to-severe COPD. Benefit was still evident after 24 weeks.", "A randomised controlled study of the effects of exercise training in 39 patients with chronic respiratory disability was performed. Exercise training began with six weeks in a rehabilitation centre and was continued at home. The original control group attended the rehabilitation centre after the controlled part of the study. The treated group experienced subjective benefit from rehabilitation. The 12-minute walking distance increased on average from 523 m to 643 m in the treatment group and from 564 m to 607 m in the control group. The treatment effect of 77 m (SE 33 m) was significant at the 5% level. Treadmill exercise performance changed little and resting lung function was unaltered after rehabilitation. The treatment group maintained most of their improvement seven months later and the original control subjects improved after their rehabilitation. The study confirms the beneficial effects of exercise training in the chronically breathless and it suggests that the 12-minute walking distance is a useful index of changes in everyday exercise tolerance.", "This randomized, controlled study investigated the physiological effects of a specially designed 12 week programme of isolated conditioning of peripheral skeletal muscle groups. The programme required minimal infrastructure in order to allow continued rehabilitation at home after familiarization within hospital. Forty eight patients, aged 40-72 yrs with chronic obstructive pulmonary disease (COPD) (mean (SD) forced expiratory volume in one second (FEV1) 61 (27)% of predicted normal) were randomly allocated into training (n = 32) and control (n = 16) groups. Physiological assessments were performed before and after the 12 week study period, and included peripheral muscle endurance and strength, whole body endurance, maximal exercise capacity (maximum oxygen consumption (V'O2,max)) and lung function. The training group showed significant improvement in a variety of measures of upper and lower peripheral muscle performance, with no additional breathlessness. Whole body endurance measured by free arm treadmill walking increased by 6,372 (3,932-8,812) 3 (p < 0.001). Symptom-limited maximal V'O2 was unchanged. However, the training group showed a reduction in ventilatory equivalents for oxygen and carbon dioxide, both at peak exercise and at equivalent work rate (Wmax). In summary, low intensity isolated peripheral muscle conditioning is well-tolerated, simple and easy to perform at home. The various physiological benefits should enable patients across the range of severity of chronic obstructive pulmonary disease to improve daily functioning.", "Pulmonary rehabilitation programs are effective in patients with severe chronic obstructive pulmonary disease (COPD) in the short term, but their long-term effects are not known. We investigated the short- and long-term effects of a 6-month outpatient rehabilitation program in patients with severe COPD.\n One hundred patients were randomly assigned to receive either an exercise training program that included cycling, walking, and strength training (n = 50) or usual medical care (n = 50). Thirty-four patients in the training group were evaluated after 6 months (end of training), and 26 were evaluated after 18 months of follow-up. In the control group, 28 patients were evaluated at 6 months and 23 after 18 months. We measured pulmonary function, 6-minute walking distance, maximal exercise capacity, peripheral and respiratory muscle strength, and quality of life (on a 20 to 140-point scale), and estimated the cost-effectiveness of the program.\n At 6 months, the training group showed improvement in 6-minute walking distance [mean difference (training - control) of 52 m; 95% confidence interval (CI), 15 to 89 m], maximal work load (12 W; 95% CI, 6 to 19 W), maximal oxygen uptake (0.26 liters/min; 95% CI, 0.07 to 0.45 liters/min), quadriceps force (18 Nm; 95% CI, 7 to 29 Nm), inspiratory muscle force (11 cm H(2)O; 95% CI, 3 to 20 cm H(2)O), and quality of life (14 points; 95% CI, 6 to 21 points; all P <0.05). At 18 months all these differences persisted (P <0.05), except for inspiratory muscle strength. For 6-minute walking distance and quality of life, the differences between the training group and controls at 18 months exceeded the minimal clinically-important difference.\n Among patients who completed the 6-month program, outpatient training resulted in significant and clinically relevant changes in 6-minute walking distance, maximal exercise performance, peripheral and respiratory muscle strength, and quality of life. Most of these effects persisted 18 months after starting the program.", "Pulmonary rehabilitation is effective in improving exercise performance and health status in chronic obstructive pulmonary disease (COPD). However, the role of nutritional support in the enhancement of the benefits of exercise training has not been explored. A double blind, randomised, controlled trial of carbohydrate supplementation was undertaken in patients attending outpatient pulmonary rehabilitation.\n 85 patients with COPD were randomised to receive a 570 kcal carbohydrate rich supplement or a non-nutritive placebo daily for the duration of a 7 week outpatient pulmonary rehabilitation programme. Primary outcome measures were peak and submaximal exercise performance using the shuttle walk tests. Changes in health status, body composition, muscle strength, and dietary macronutrient intake were also measured.\n Patients in both the supplement and placebo groups increased shuttle walking performance and health status significantly. There was no statistically significant difference between treatment groups in these outcomes. Patients receiving placebo lost weight whereas supplemented patients gained weight. In well nourished patients (BMI >19 kg/m(2)) improvement in incremental shuttle performance was significantly greater in the supplemented group (mean difference between groups: 27 (95% CI 1 to 53) m, p<0.05). Increases in incremental shuttle performance correlated with increases in total carbohydrate intake.\n When universally prescribed, carbohydrate supplementation does not enhance the rehabilitation of patients with COPD. This study suggests that exercise training results in negative energy balance that can be overcome by supplementation and that, in selected patients, this may improve the outcome of training. The finding of benefit in well nourished patients may suggest a role for nutritional supplementation beyond the treatment of weight loss in COPD.", "BACKGROUND Exacerbations of chronic obstructive pulmonary disease (COPD) are characterised by increased dyspnoea, reduced quality of life and muscle weakness. Re-exacerbation and hospital admission are common. Pulmonary rehabilitation (PR) administered after hospital admission for an exacerbation can improve quality of life and exercise capacity. OBJECTIVE To determine whether outpatient post-exacerbation PR (PEPR) could reduce subsequent hospital admission episodes. METHODS Patients admitted to hospital for an exacerbation of COPD were randomised to receive either usual follow-up care (UC) or PEPR after discharge. Hospital admission and emergency department attendances for COPD exacerbations were recorded over a 3-month period and analysed on an intention-to-treat basis. Secondary outcomes included exercise capacity and quadriceps strength. RESULTS 60 patients underwent concealed randomisation at the time of their hospital discharge (UC: n=30, mean (SD) age 65 (10) years, forced expiratory volume in 1 s (FEV(1)) 52 (22)% predicted; PEPR: n=30, 67(10) years, 52 (20)% predicted). The proportion of patients re-admitted to hospital with an exacerbation was 33% in the UC group compared with 7% in those receiving PEPR (OR 0.15, 95% CI 0.03 to 0.72, p=0.02). The proportion of patients that experienced an exacerbation resulting in an unplanned hospital attendance (either admission or review and discharge from the emergency department) was 57% in the UC group and 27% in those receiving PEPR (OR 0.28, 95% CI 0.10 to 0.82, p=0.02). CONCLUSIONS Post-exacerbation rehabilitation in COPD can reduce re-exacerbation events that require admission or hospital attendance over a 3-month period. Clinical Trials Registration Number NCT00557115.", "Fifty patients with severe chronic obstructive pulmonary disease (FEV1 < 50% pred.) were randomized to a rehabilitation group and a control group. The rehabilitation group took part in an individualized multidisciplinary, outpatient 12-month rehabilitation programme. Exercise training was intensive during the first 6 weeks and was then gradually replaced by an individual home-training programme and booster sessions. Controls received the usual outpatient care. Positive effects were found in terms of maximum symptom-limited exercise tolerance and walking distance (13.5 and 12.1% increase, respectively) in the rehabilitation group compared with the controls. Quality of life measurements showed minor beneficial effects on the Sickness Impact Profile, indicating a higher level of activity. No effect was seen on the St George's Respiratory Questionnaire or the Mood Adjective Check List. Patients expressed their enthusiasm for the rehabilitation programme in a study-specific questionnaire.", "Pulmonary rehabilitation is essential for managing chronic obstructive pulmonary disease (COPD). Housebound COPD patients are frequently excluded from this treatment because they are unable to access outpatient pulmonary rehabilitation programs because of the severity of their disease. This randomized controlled trial assesses the effects of a 12-week home-based pulmonary rehabilitation program for 60 housebound COPD patients older than 60 years.\n Intervention patients received an individually tailored supervised walking and arm exercise program as well as individual multidisciplinary education sessions on COPD and its management. Outcomes were assessed using the 6-minute walk test, St George's respiratory questionnaire, and Borg score of perceived breathlessness. Healthcare utilization was assessed using hospital admission rates with exacerbation of COPD and average length of stay at readmission.\n Complete data for 23 patients in each group were available for analysis. There was no significant difference between groups on baseline measures. Compared with the control group, intervention patients demonstrated a significant improvement in 6-minute walk test (P = .023), Borg score of perceived breathlessness (P = .024), St George's respiratory questionnaire total score (P = .020), and impact subscore (P = .024). At 6 months, the intervention group had a significantly shorter average length of stay at readmission to hospital with exacerbation (P = .035).\n A 12-week home-based pulmonary rehabilitation is effective in improving exercise tolerance, perception of breathlessness, and quality of life for housebound COPD patients. To manage COPD in the community more effectively, health services should focus on expanding home-based pulmonary rehabilitation.", "The present multicentre study evaluates the differences in efficacy between a 3 month rehabilitation programme including drug treatment, and a 3 month control period of drug treatment only, for asthmatic patients and patients with chronic obstructive pulmonary disease (COPD). The programme was run by physiotherapists in eight local practices, and included exercise training, patient education, breathing retraining, evacuation of mucus, relaxation techniques, and recreational activities. In a randomized controlled trial with a cross-over design, the effects of rehabilitation were evaluated 3 and 6 months after baseline measurements in terms of exercise tolerance and quality of life (QOL). Exercise tolerance was assessed using submaximal cycle ergometer tests and 6 min walking tests. QOL was evaluated by means of the Chronic Respiratory Disease Questionnaire (CRDQ). After 3 months, the patients who started with rehabilitation showed significant improvements in endurance time (421 s) and cardiac frequency (6 beats.min-1) during cycling, walking distance (39 m), and total CRDQ score (17 points) compared to the control group. These improvements were still significant after 6 months. Additional analysis indicated that the asthmatic patients and the patients with COPD responded to rehabilitation in a similar way, with the exception that there was a greater improvement in walking distance for asthmatics. Improvements in exercise tolerance were not significantly correlated with improvements in QOL. Rehabilitation of patients with asthma or chronic obstructive pulmonary disease in local physiotherapy practices improves exercise tolerance and quality of life.", "The purpose of this study was to investigate the effects on activities of daily living, quality of life, and exercise tolerance of a comprehensive out-patient rehabilitation programme for patients with moderate-to-severe chronic obstructive pulmonary disease. In this randomized and controlled trial, the main outcome measures were Activities of Daily Living (ADL) score, York Quality of Life Questionnaire (YQLQ) score, Chronic Respiratory Disease Questionnaire (CRDQ) score, 6 min walking distance (6MWD), forced expiratory volume in one second (FEV1), and forced vital capacity (FVC). The rehabilitation programme included physical training, occupational therapy, education, and smoking cessation therapy, and lasted for 12 weeks. The patients were evaluated at entry, halfway through, and at the end of the programme. Follow-up was at 24 weeks. Forty seven patients were recruited, and 16 in each group completed the trial. There were significant differences in the improvements in ADL and CRDQ between the control and the treatment groups at 12 and 24 weeks, and at 24 weeks, respectively. At 6, 12 and 24 weeks, improvements in the 6MWD were 21.6 versus 79.8, 36.1 versus 113.1 and 21.4 versus 96.2 for control and treatment groups, respectively (p<0.004). A correlation matrix showed only ADL and 6MWD to be significantly correlated; the matrix was also used to validate the translated questionnaires. The programme required 124 staff-hours in total. An inexpensive, comprehensive out-patient rehabilitation programme can produce long-term improvement in activities of daily living, quality of life, and exercise tolerance in patients with moderate-to-severe chronic obstructive pulmonary disease.", "The British Heart Foundation and the Chest, Heart and Stroke Association have allocated funds to develop cardiac rehabilitation programmes. We have recently completed and now evaluate an exercise-based rehabilitation course reinforced with advice about return to normal activity for 110 patients who had suffered acute myocardial infarction. Patients admitted to the Plymouth cardiac care unit were randomised into groups: a control group to receive standard hospital care, and a rehabilitation group who, in addition, received an exercise programme reinforced with advice. Patients were assessed at entry to the study and at intervals thereafter. Assessment was by questionnaire and objective tests consisting of a 12-minute walking test and weekly outpatient pedometry. In the rehabilitation group patients were able to walk further and faster, return to work earlier, undertake more housework, and resume normal sexual activity; they were less short of breath and did not experience more angina. However, the rehabilitation course brought little benefit to the patients' perception of well-being and their anxiety about health or their outlook on life. Exercise and advice are important components of a rehabilitation programme, but more attention needs to be given to the psychological aspects of recovery from a heart attack.", "Acupressure is a therapy in which gentle pressure is applied with fingers at specific acupoints on the body. It is reported to relieve pain and have other beneficial effects. This study was designed to ascertain the value of self-administered acupressure as an adjunct to a pulmonary rehabilitation program (PRP) for relief of dyspnea and other symptoms in patients with chronic obstructive pulmonary disease (COPD).\n A single-blind pretest-posttest, cross-over design was used. Thirty-one new patients beginning a 12-week PRP at two private hospitals were randomly assigned to one of two groups. Patients in group 1 were taught acupressure and practiced it daily at home for 6 weeks, then sham acupressure for the following 6 weeks. In group 2, the order of acupressure and sham acupressure was reversed. During weeks 1, 6, and 12, patient dyspnea, other symptoms associated with COPD, activity tolerance, lung function, and functional exercise capacity were assessed.\n Real acupressure was more effective than sham acupressure for reducing dyspnea as measured by a visual analog scale (P = .009, one-tailed), and was minimally effective for relieving decathexis (P = .044, one-tailed). Sham acupressure seemed to be more effective than real acupressure for reducing peripheral sensory symptoms (P = .002, two-tailed), but the presence of these symptoms may also be an indication that the acupressure is affecting the body.\n Acupressure seems to be useful to patients with COPD as an adjunct to a PRP in reducing dyspnea. Some persons who are not initially familiar with traditional Chinese medicine can learn and will accept self-administered acupressure as part of their self-care." ]	Rehabilitation relieves dyspnea and fatigue, improves emotional function and enhances patients' sense of control over their condition. These improvements are moderately large and clinically significant. Rehabilitation forms an important component of the management of COPD.
MR000008	[ "2343859", "2705601", "9829873", "9243440", "2081243", "15972931", "18174120", "10330737", "16085200", "9245178", "9629829", "892969", "2223198", "11665338", "16765279", "10623399", "15531624", "2213259", "8237986", "9440402", "16250910", "7490595", "15509406", "11812810", "12218773", "7122824", "18177791", "9503730", "2348155", "12026752", "10943176", "2705425", "8399698", "11449019", "7777738", "9175409", "15533256", "9141738", "15485729", "10408998", "15537429", "10522120", "15598859", "14973100", "8228774", "10183331", "12589865", "11131931", "12950483", "9400085", "9658516", "9101691", "12177036", "11011481", "11233582", "20157016", "11176557", "1897510", "15485728", "14664782", "8862992", "11782286", "18507819", "11255905", "16109160", "9431335", "17938061", "1342326", "15026104", "8238685", "12392866", "15937989", "7406007", "10691065", "18677882", "10901785", "17149995", "1573368", "15515991", "11302275", "19775439", "15222889", "3823668", "7861879", "16286502", "9457003", "11297894", "10302610", "10513763", "10983211", "14588132", "15894697", "16944192", "8046692", "8413069", "16091137", "17027429", "9578863", "15762903", "11009863" ]	[ "Effectiveness of various mailing strategies among nonrespondents in a prospective cohort study.", "Increasing response rates in physicians' mail surveys: an experimental study.", "Controlled trial of the effect of length, incentives, and follow-up techniques on response to a mailed questionnaire.", "A randomized trial of the impact of telephone and recorded delivery reminders on the response rate to research questionnaires.", "Effects of mailing strategies on response rate, response time, and cost in a questionnaire study among nurses.", "Increasing response to mailed questionnaires by including a pencil/pen.", "No increase in response rate by adding a web response option to a postal population survey: a randomized trial.", "Primer postcard improves postal survey response rates.", "Initial nonresponders had an increased response rate after repeated questionnaire mailings.", "[Mail questionnaires. A useful strategy for the follow-up of patients with a cerebrovascular stroke?].", "Labour-saving strategies to maintain survey response rates: a randomised trial.", "A study of mail survey method.", "Possible factors affecting response to postal questionnaires: findings from a study of general practitioner services.", "Increasing the response rate to a mailed questionnaire by including more stamps on the return envelope: a cotwin control study.", "Enclosing a pen with a postal questionnaire can significantly increase the response rate.", "Physician participation in research surveys. A randomized study of inducements to return mailed research questionnaires.", "Short report: encouraging GPs to complete postal questionnaires--one big prize or many small prizes? A randomized controlled trial.", "Survey response rates to a professional association mail questionnaire.", "Randomized trial of use of a monetary incentive and a reminder card to increase the response rate to a mailed health survey.", "Response rate to mailed epidemiologic questionnaires: a population-based randomized trial of variations in design and mailing routines.", "A randomised controlled trial to assess the effectiveness of offering study results as an incentive to increase response rates to postal questionnaires [ISRCTN26118436].", "Timing payments to subjects of mail surveys: cost-effectiveness and bias.", "Increasing response rates to postal questionnaires: a randomised trial of variations in design.", "Telephone reminders are a cost effective way to improve responses in postal health surveys.", "Randomized trial of 5 dollars versus 10 dollars monetary incentives, envelope size, and candy to increase physician response rates to mailed questionnaires.", "Effects of characteristics of the survey instrument on response rates to a mail survey of community hospitals.", "Questionnaire order significantly increased response to a postal survey sent to primary care physicians.", "Maximising response rates in a survey of general practitioners. Lessons from a Victorian survey on sexually transmissible diseases.", "Does anonymity increase response rate in postal questionnaire surveys about sensitive subjects? A randomised trial.", "Questionnaire color and response rates to mailed surveys. A randomized trial and a meta-analysis.", "Mailed survey follow-ups--are postcard reminders more cost-effective than second questionnaires?", "A comparison of response rate, data quality, and cost in the collection of data on sexual history and personal behaviors. Mail survey approaches and in-person interview.", "Response to mail surveys: effect of a request to explain refusal to participate. The ARIC Study Investigators.", "Provision of pen along with questionnaire does not increase the response rate to a postal survey: a randomised controlled trial.", "Day-of-the-week effect on doctors' response to a postal questionnaire.", "[Response rates and non-response bias in a health-related mailed survey].", "A randomised controlled trial to determine the effect on response of including a lottery incentive in health surveys [ISRCTN32203485].", "Differential effectiveness of telephone prompts by medical and nonmedical staff in increasing survey response rates: a randomised trial.", "Prepayment was superior to postpayment cash incentives in a randomized postal survey among physicians.", "Effect of mailed reminders on the response rate in surveys among patients in general practice.", "Increasing response to a postal survey of sedentary patients - a randomised controlled trial [ISRCTN45665423].", "Evaluation of general practice computer templates. Lessons from a pilot randomised controlled trial.", "Does a deadline improve men's participation in self-administered health surveys? A randomized controlled trial in general practice.", "No difference in response rate to a mailed survey among prostate cancer survivors using conditional versus unconditional incentives.", "Impact of a postcard versus a questionnaire as a first reminder in a postal lifestyle survey.", "A randomized trial of the impact of certified mail on response rate to a physician survey, and a cost-effectiveness analysis.", "Does questionnaire structure influence response in postal surveys?", "The impact of different response alternatives on responders' reporting of health-related behaviour in a postal survey.", "Effect of a triage-based E-mail system on clinic resource use and patient and physician satisfaction in primary care: a randomized controlled trial.", "An informational versus monetary incentive in increasing physicians' response rates.", "Response rate according to title and length of questionnaire.", "The effect of cash and other financial inducements on the response rate of general practitioners in a national postal study.", "Do postage-stamps increase response rates to postal surveys? A randomized controlled trial.", "A randomised trial of telephone versus postcard prompts to enhance response rate in a phased population-based study about community preferences.", "The effects of variations in mode of delivery and monetary incentive on physicians' responses to a mailed survey assessing STD practice patterns.", "Effects of a mail and telephone intervention on breast health behaviors.", "Effects of different monetary incentives on the return rate of a national mail survey of physicians.", "The effect of two mailing strategies on the response to a survey of physicians.", "Telephone reminders are effective in recruiting nonresponding patients to randomized controlled trials.", "Factors impacting questionnaire response in a Dutch retrospective cohort study.", "Use of a coded postcard to maintain anonymity in a highly sensitive mail survey: cost, response rates, and bias.", "Effect of paper quality on the response rate to a postal survey: a randomised controlled trial. ISRCTN 32032031.", "Do postage stamps versus pre-paid envelopes increase responses to patient mail surveys? A randomised controlled trial.", "Do income questions and seeking consent to link medical records reduce survey response rates? A randomised controlled trial among older people.", "The effect of a monetary incentive on return of a postal health and development questionnaire: a randomised trial [ISRCTN53994660].", "Conducting physician mail surveys on a limited budget. A randomized trial comparing $2 bill versus $5 bill incentives.", "Selected questionnaire size and color combinations were significantly related to mailed survey response rates.", "The effect on response rates of offering a small incentive with a mailed questionnaire.", "Physician response rates to a mail survey by specialty and timing of incentive.", "Improving response rates through incentive and follow-up: the effect on a survey of physicians' knowledge of genetics.", "The end-of-study patient survey: methods influencing response rate in the AVID Trial.", "Response rates and representativeness: a lottery incentive improves physician survey return rates.", "Screening optometric patients by questionnaire: methods of improving response.", "Effects on subject response of information brochures and small cash incentives in a mail-based case-control study.", "The effectiveness of tailored feedback and action plans in an intervention addressing multiple health behaviors.", "[Evaluation of inpatient satisfaction. Comparison of different survey methods].", "Use and impact of an automated telephone outreach system for asthma in a managed care setting.", "What can you ask about? The effect on response to a postal screen of asking about two potentially sensitive questions.", "Crossing the digital divide: evaluating online communication between patients and their providers.", "Effectiveness of personalized written feedback through a mail intervention for smoking cessation: a randomized-controlled trial in Spanish smokers.", "A randomized controlled trial evaluating the impact of knowledge translation and exchange strategies.", "Effect of prize draw incentive on the response rate to a postal survey of obstetricians and gynaecologists: a randomised controlled trial. [ISRCTN32823119].", "Some experiments with factors that might affect the response of mothers to a postal questionnaire.", "Randomised controlled trial of routine individual feedback to improve rationality and reduce numbers of test requests.", "A monetary incentive increases postal survey response rates for pharmacists.", "Collecting saliva samples by mail.", "A mail survey of United States hematologists and oncologists: a comparison of business reply versus stamped return envelopes.", "Encouraging patient question-asking: a clinical trial.", "Comparison of open and closed questionnaire formats in obtaining demographic information from Canadian general internists.", "Maintaining mammography adherence through telephone counseling in a church-based trial.", "A randomized trial of incentives to improve response rates to a mailed women's health questionnaire.", "Response rates to a mailed survey targeting childhood cancer survivors: a comparison of conditional versus unconditional incentives.", "Effectiveness and efficiency of a literature search strategy to answer questions on the etiology of occupational diseases: a controlled trial.", "Dentists' response to financial incentives in a mail survey of malpractice liability experience.", "Preparing and updating systematic reviews of randomized controlled trials of health care.", "Effect on survey response rate of hand written versus printed signature on a covering letter: randomised controlled trial [ISRCTN67566265].", "Longer response scales improved the acceptability and performance of the Nottingham Health Profile.", "Does requesting sensitive information on postal questionnaires have an impact on response rates? A randomised controlled trial in the south west of England.", "Can computer-generated evidence-based care suggestions enhance evidence-based management of asthma and chronic obstructive pulmonary disease? A randomized, controlled trial.", "Effects of incentive size and timing on response rates to a follow-up wave of a longitudinal mailed survey." ]	[ "Measures of association in prospective studies can be distorted by incomplete follow-up. Various mailing strategies were used to contact 12,233 cohort members of the Health Professionals Follow-up Study who had not responded to three successive bulk-rate mailings. Response rates were highest, 79.5% overall, from participants who were sent a certified mailing in phase 1 (63.2%), followed by a repeat certified mailing to nonrespondents (44.3%). Although altering the physical appearance of the envelope and using other postal rates were tested, certified mail was the most effective approach for reaching study members who were nonrespondents to a mailed questionnaire.", "It is becoming increasingly difficult to obtain high response rates in physicians' mail surveys. In 1983-84, we tested the effectiveness of two techniques among 604 Quebec physicians who had not responded to an initial letter. A handwritten thank you note at the bottom of the letter accompanying the questionnaire and a more personalized mailout package increased response rates by 40.7 per cent and 53.1 per cent, respectively, compared to control groups.", "Mailed questionnaires are an economical method of data collection for epidemiologic studies, but response tends to be lower than for telephone or personal interviews. As part of a follow-up study of volunteers who provided a brief health history and blood sample for a blood specimen bank in 1989, the authors conducted a controlled trial of the effect of length, incentives, and follow-up techniques on response to a mailed questionnaire. Interventions tested included variations on length of the questionnaire, effect of a monetary incentive, and effect of a postcard reminder versus a letter accompanied by a second questionnaire. Response was similar for the short (16-item, 4-page) and long (76-item, 16-page) questionnaire groups. The non-monetary [corrected] incentive did not improve the frequency of response. The second mailing of a questionnaire was significantly better than a postcard reminder in improving responses (23% vs. 10%). It is important to systematically test marketing principles to determine which techniques are effective in increasing response to mailed questionnaires for epidemiologic studies.", "A range of factors have been shown to affect the response rate to mailed questionnaires, but particular strategies to improve patients' response in trials conducted in general practice require further study.\n Non-responders in a larger trial were randomized to receive a telephone or recorded delivery reminder on the third contact. The cost of administration of each method was estimated.\n Significantly more patients returned completed questionnaires when sent questionnaires by recorded delivery, although the cost per patient contacted was nearly three times more than for contact by telephone.\n Our study indicates that sending reminders by recorded delivery, although more expensive, is more effective than telephone reminders for recruiting patients to a study in general practice using research questionnaires.", "We conducted a pilot study to determine the most efficient mailing strategy for a postal questionnaire study among nurses in Ontario, Canada. Five mailing strategies involving types of stamps on the return envelopes were considered: no stamp, business-reply stamp, metered stamp, small regular stamp, and large commemorative stamp. We found that paper stamps, especially large commemorative stamps, on return envelopes increased the response rate and reduced the response time, as compared with other mailing strategies. Business-reply stamps had the lowest cost per response received and a low total cost.", "Nonmonetary incentives lead to small increases in response rates to mailed questionnaires. However, inclusion of a pen or pencil, which may be a facilitating factor as well as a reward, has not been shown to improve response to health surveys in prior trials. In 2001 and 2002, the authors conducted two US trials in which a study-logo pen or pencil was randomly included in a second questionnaire mailed to nonresponders to a first mailing. In the first study, of 10,686 nonresponders to a cohort recruitment mailing, response to the second mailing was 55% with inclusion of a pen versus 40% without one (p < 0.001). In the second study, of 141 nonresponders to a pilot follow-up survey conducted 2 years after entry into a cohort, response was 43% with inclusion of a pencil versus 24% without one (p = 0.02). This 15-19 percentage point increase for mailing 2 translated to a 5-6 percentage point increase after the two mailings combined. In a simulated study of three mailings based on these studies, the overall response rate increased by 4 percentage points at no added cost through inclusion of a pencil in the second mailing. The additional cost of the pencil was compensated for by the reduced number of nonrespondents sent packets at the third mailing. This study supports including a study-logo pen or pencil in a second questionnaire mailing to nonrespondents as a cost-effective method of increasing response rates.", "There is substantial interest in use of the Internet for surveys, but there have been few health-oriented, large, randomized trials of general population surveys on the Internet. It is unclear whether providing the option to respond via Internet increases the response rate, and to what degree the results will differ.\n The aim of the study was to evaluate changes in response rate and outcomes in a postal respiratory health survey by adding an optional Web response alternative.\n This was a randomized trial of a random sample of 4213 permanent residents of Norway, aged 20-40 years. Participants were randomized into a traditional survey arm, where they were asked to return the survey by mail, and an arm where they were also offered the option to respond via a Web form.\n A total of 1928/4213 subjects responded, a response rate of 45.8% across both arms. The total response rate was 44.8% (944/2105) in the postal plus optional Internet response arm and 46.7% (984/2108) in the usual postal survey arm, with no statistically significant difference between the randomized groups (P = .24). In the optional Internet arm, 8.3% (175/2105) of the sample responded using the Internet and 36.5% (769/2105) responded by post. Thus, Internet response was chosen by 18.5% (175/944) of those who replied in the optional Internet arm. In the multivariate analysis, Internet response was associated with being male, frequency and type of Internet access (home users more likely to respond by Internet than work users), and smoking habit, with current smokers being more likely to be Internet responders. 57% preferred postal response (1102/1928), 38% preferred Internet response (733/1928), and 3% preferred telephone interview (54/1928), with no difference between randomization arms (P = .56). But among those who indicated that they preferred the Internet response and who were randomized to the optional Internet arm, only 47% actually chose the Internet response. Asthma prevalence was higher among participants choosing the Internet response mode (16.7% vs 12.4%).\n We failed to increase survey response rates by adding an optional Internet response. Asthma diagnosis was higher in the Internet response group, suggesting nonresponse bias. Method comparison studies should be carried out before Internet studies are accepted in new populations or new subject matters.", "This study measures the effect of an intervention to improve mailed survey response rates.\n A randomised controlled trial of a 'primer' postcard was performed as part of a large survey in Victoria in 1997. Prior to the survey mailout, half the sample of 800 general practitioners supplied by the Health Insurance Commission was sent, at random, a primer card to request prompt return of the survey.\n The intervention resulted in a more rapid return of the survey and improved overall response rates from 60% to 66%. The increased cost per returned survey (40 cents) was largely offset by fewer non-responders requiring follow-up.\n A primer postcard is a time and cost-efficient method to increase response rates in general practitioner surveys.\n Public health researchers should consider implementing this intervention to improve response rates to postal surveys. Reports of other response maximising strategies should report the cost per returned survey to allow better comparison.", "There is a growing evidence base on methods to improve response rates in surveys among patients. This study aimed to determine the additional effect of two intensive follow-up procedures compared to a simple follow-up procedure.\n Randomized controlled trial that compared repeated mailing of the questionnaire and a request to explain nonparticipation with a simple reminder card. The study population comprised 955 elderly adults registered with 26 general practitioners in The Netherlands.\n A total of 530 adults (56%) returned the questionnaire within 3 weeks and a total of 640 (67%) after follow-up. Repeated mailing of the questionnaire had additional effect compared to the simple reminder card in the group of initial nonresponders (relative risk=1.60, 95% confidence interval: 1.11-2.31), but not regarding the overall response rate. A request to explain nonparticipation did not have additional effect.\n Repeated mailing of the questionnaire increased the effectiveness of follow-up among initial nonresponders.", "Although not frequently used in Portugal, postal questionnaires allow the collection of information on patient's follow-up. In this study we assessed the rate of response and the usefulness of a postal questionnaire in a sample of patients with acute stroke. A prospective study was designed and analysed as a case-control: postal questionnaires were sent to 138 patients together with a randomly assigned stamped or post-free return envelope. The percentage of responders was 60% (n=78) and we found no significant differences in response rates according to the mailing strategy (58% for stamped and 62% for post-free return envelopes, p = 0.786). The time gap between hospital discharge and sending of the questionnaire had no significant influence in the response rate. Elder patients and women tend to respond more frequently, but these characteristics also do not change the response rate. Analysing socio-demographic variables reported at the acute phase, we only found differences in response rate for the smoking status: smoking was associated with a lower participation. In conclusion, the present study showed that a postal questionnaire is a useful method for the follow-up of stroke cases and that we must pay special attention to smokers for whom alternative strategies of contact or information should be used to increase compliance with postal questionnaire follow-up.", "To evaluate response-aiding strategies feasible in large surveys, we randomly allocated general practitioners (GPs) to one of four intervention groups: Group 1 received 'exhaustive' telephone prompts by a medical peer in advance of a questionnaire; Group 2, inclusion of an embossed pen with the questionnaire; Group 3, an advance letter prompt; and Group 4, a 'single attempt' advance telephone prompt by a non-medical research assistant. Follow-up procedures were identical. Response rates by group were not significantly different overall (chi 2 = 4.59, df = 3, p = 0.20) although advance prompts by a medical peer were significantly more effective than other strategies for male GPs. The difference in overall response rates between males (63%) and females (74%) was significant (chi 2 = 15.40, df = 1, p < 0.01). No other response bias was evident. Our demonstration of a significant interaction between respondent sex and response-aiding strategy invites further research.", "A major disadvantage of the mail survey in medical research is non-response, which may introduce bias. This study measured the effect of two simple factors on the response rate to a questionnaire concerning headache and migraine in a survey of 2,508 electors. The two factors were the class of postage and the colour of envelopes used; neither was found to have a significant effect. It was concluded that cheaper mailing methods are not likely to jeopardise response.", "Poor response rates affect the validity of results from postal questionnaires. The effect of three controllable factors upon response rates was examined in a recent study of patients' experiences and views of general practitioner services. The factors studied were the institution from which questionnaires were dispatched, the length of the questionnaire and the inclusion of a potentially sensitive question about ethnic origin. Questionnaires sent out by local Family Practitioner Committees were more likely to be returned than those sent out by a London-based independent research unit, but there were no differences in the nature of replies obtained. Neither the length of the questionnaire nor the inclusion of the potentially sensitive question affected response rates. The results of the study indicate that Family Practitioner Committees wishing to carry out postal surveys of users of general practitioner services can obtain satisfactory response rates.", "Twins taking part in two unrelated studies were sent a questionnaire together with a self-addressed envelope that either carried one or multiple (up to 5) stamps to the same value. The unprompted proportion of questionnaires returned (before commencement of telephone reminder calls) was increased from 62% to 71% in one study, and from 43% to 52% in the other study (test for common odds ratio in studies, p = 0.04).", "It is important to maximize response rates to postal questionnaires. We compared the impact of three low-cost interventions on response rates.\n A 2 x 2 x 2 factorial trial was conducted, nested within TOMBOLA (Trial Of Management of Borderline and Other Low-grade Abnormal smears). Three interventions were evaluated: (1) enclosing a TOMBOLA-branded pen with the questionnaire (as opposed to no pen); (2) sending the questionnaires by first class post (as opposed to second class); and (3) enclosing a preaddressed return envelope on which there was a second class postage stamp (rather than a freepost business-reply envelope). Nine hundred thirty women, aged 20-59 years, due to receive a TOMBOLA psychosocial questionnaire by post during June-August 2003 were randomized.\n Enclosing a pen resulted in a statistically significant 7.0% increase in the cumulative proportion of questionnaires returned (from 61.5 to 68.5%; P = .002). The adjusted odds of response was significantly raised (odds ratio [OR] = 1.38, 95% confidence interval [CI] 1.04-1.82). Neither first class post nor providing a stamped envelope had a significant impact on response. There were no interactions between the interventions.\n Enclosing a pen with a questionnaire can significantly increase response. This low-cost strategy was effective against a background of \"good practice\" with regard to the administration of postal questionnaires.", "The authors randomly selected 400 physicians from a population of 1,545 practicing physicians providing follow-up care to patients who received bone marrow or blood stem cell transplants at the Fred Hutchinson Cancer Research Center to determine interest in receiving Internet-based transplant information. In a two-factor completely randomized factorial design, the 400 physicians were assigned to receive mailed surveys with either no compensation or a $5 check and either no follow-up call or a follow-up call 3 weeks after mailing. Overall, 51.5% of the physicians returned the mailed surveys. Comparison of logit models showed that inclusion of a $5 check in the mailer significantly (p = .016) increased the probability of returning the surveys (57.5% vs. 45.5%). In contrast, the telephone follow-up had no overall effect. The authors concluded a modest financial reward can significantly improve physician response rates to research surveys but a telephone follow-up may be inefficient and even ineffective.", "Low response rates to surveys are a problem in general practice. There is evidence that offering GPs incentives improves response rates to postal questionnaires. However, there is less evidence about the most effective form of incentive.\n Our trial aimed to maximize response to a postal questionnaire and to test the most effective form of incentive.\n The study involved a randomized controlled trial of a postal survey\n The incentive of a lottery for six bottles of champagne generated a response rate of 79%. Furthermore, one chance of six bottles generated 9% more responses than six chances of one bottle.\n This study has established that, among incentives for postal questionnaires, one big prize improves the yield more than many small prizes despite the lower odds of winning. It has also confirmed that offering a modest incentive to GPs generates good response rates for postal questionnaires.", "The purpose of this research was to study the effect of various direct mail techniques on professional nurses' response rates to questionnaires. A random sample of 700 registered professional nurses consisting of five groups who were members of New York State Nurses Association (NYSNA) were mailed a questionnaire with 22 items. The study demonstrated that the response rates were directly attributable to techniques used. Providing information about the association was related to significantly decreased response rates and monetary incentives with significantly increased response rates. A combined direct mailing for questionnaire completion and membership solicitation was not effective for either purpose.", "Insufficient response rates are a frequent problem in mailed epidemiologic health surveys. As part of a health survey of 1,235 young adults conducted from November 1992 through January 1993 in Geneva, Switzerland, a randomized factorial trial was carried out to assess the contributions of two tactics to increase response rates. The first incentive was the promise of sending 10 Swiss francs (7 US dollars) to respondents; the second was a red postcard, mailed 2 days after the questionnaire, which reminded potential participants to complete the questionnaire. The most effective strategy according to interim analysis was to be selected for follow-up mailings. Two weeks after the first mailing, response rates were 65% for those who had received both incentives, 57% for those who had been offered the money reward only, 54% for recipients of the reminder card, and 48% for those who had received neither incentive (p based on chi 2 (3 df) test < 0.001). The relative hazards of responding were 1.34 (95% confidence interval 1.15-1.55) for the money reward and 1.22 (95% confidence interval 1.05-1.41) for the reminder card. Follow-up mailings to all nonrespondents included both incentives. At the end of data collection, 1,007 persons (82%) had returned the questionnaire. The final response rates were 83, 84, 82, and 78% in the four groups, respectively (p = 0.29). Both the promise of a monetary reward and a reminder postcard considerably improved early response rates. The use of both incentives in follow-up mailings brought final response rates above 80%, except for those who had received no initial incentive. Testing various combinations of incentives in the early stages of a mailed health survey may be a generally useful strategy.", "Although self-administered questionnaires are major sources of information in epidemiology, comparatively little has been done to study practical aspects of design and mailing. The objective of this study was to evaluate various measures taken to increase the response rate. A questionnaire was mailed in July 1995 to a random sample (n = 2,000) of the Swedish population aged 20-79 years. Using a randomized factorial study design, the questionnaire and mailing procedures were changed in three ways: preliminary notification, length of the questionnaire, and mention of telephone contact. The overall questionnaire retrieval rate was 49%. Preliminary notification (adjusted odds ratio of receiving a completed questionnaire = 1.30, 95% confidence interval (CI) 1.08-1.56 relative to the absence of preliminary notification) and short length of the questionnaire (odds ratio = 1.24, 95% CI 1.04-1.48 relative to a long questionnaire) were both independently associated with a higher retrieval rate. Of eight possible combinations, the one comprising preliminary notification, a short questionnaire, and no mention of telephone contact gave the highest retrieval rate, 56%. The lowest retrieval rate, 40%, was observed for the combination of no preliminary notification, a long questionnaire, and mention of telephone contact. Young age, male sex, and urban residence significantly lowered the retrieval rate. Although there was a positive association between the questionnaire retrieval rate and partial nonresponse (missing answers in retrieved questionnaires), the marginal losses due to the latter did not cancel the gains by optimized mailing routines. Old age was the strongest determinant of partial nonresponse. The data provide evidence that design and mailing strategies, as well as demographic characteristics, may greatly influence the response rate of mailed epidemiologic questionnaires.", "Postal questionnaires are widely used to collect outcome data on participants. However, a poor response to questionnaires will reduce the statistical power of the study and may introduce bias. A meta analysis of ten trials offering study results, largely in the fields of education and marketing, was shown to be ineffective, with the odds ratio for response with offering research findings is 0.92 (95% CI 0.75 to 1.11). However uncertainty still exists as it is uncertain whether results from such trials can be extrapolated to that of a health care setting. The aim of this study was to assess whether offering participants study results increases the response rates to postal questionnaires.\n 1038 women aged over 70 years were remotely randomised by computer in a 3:1 ratio. 250 participants did not receive the offer of knowing the results of the trial and 788 participants were offered the results of the trial in a postal questionnaire. The main outcome measure was response rate. Chi square test was used to evaluate the overall differences in response rate between the two groups. An adjusted analysis, adjusting for whether the participant was taking calcium and age was also undertaken.\n The response rates were not significantly different Odds Ratio 0.88 (95% confidence intervals 0.48 to 1.63) p = 0.69.\n Offering study results to women living in the community aged over 70 does not increase response rates to postal questionnaires. Although researchers have an ethical obligation to offer participants study results, since 10% of women did not wish to receive the results, investigators should give participants the option to opt out of receiving the study's results.", "Although mailed surveys are an important component of epidemiological research, results from mailed surveys are often suspect because of poor response rates and the potential for nonresponse bias. Previous work has demonstrated that paying subjects to complete questionnaires increases response rates, but this work has not well addressed the impact of the timing of incentives on total cost, cost effectiveness, and response bias. We surveyed 400 university employees about health benefits. By random allocation, half received a check for $5 along with the mailed survey, and the other half received the promise of $5 on return of a completed survey. The response rates for both groups were about the same (64 and 59%, respectively), but prepayment was less expensive in aggregate and less expensive per response. In addition, we found that subjects with lower salaries were more likely to respond when paid in advance. We conclude that prepayment may actually be less expensive and more cost effective than payment on completion, but that the timing of payment may influence the profile of respondents.", "Low response rates to postal questionnaires can threaten the validity of studies by reducing the effective sample size and introducing bias. The identification of methods with which to optimise response rates could, therefore, improve the quality of studies. In an attempt to identify such methods, we undertook a randomised trial of two simple variations in questionnaire design.\n Using a 2 x 2 factorial design, we conducted a randomised trial to test two variations in questionnaire design; the questionnaires were printed on either single-sided or double-sided paper and had either a single- or multiple-booklet layout. Using equal random allocation, 3836 women were randomised to receive one of these questionnaires as part of a study investigating risk factors for osteoporotic fractures.\n One thousand eight hundred and seventy questionnaires were returned, giving an overall response rate of 48.7%. There were no significant differences in the overall response to each of the four questionnaire designs. When the number of responders who completed at least 50% of each of the three sections was identified, it was found that single-booklet questionnaires had a better response than the multiple-booklet questionnaires and that single-sided questionnaires had a better response than double-sided questionnaires. However, these results were not significant at the 5% level. There were no significant differences in the response to questions on the odd (left-hand side) pages for the single- compared with the double-sided questionnaires.\n As the most cost-effective use of resources, we would advocate the use of double- rather than single-sided questionnaires, and use of a single- rather than multiple-booklet design.", "To assess the effectiveness of a telephone reminder in increasing responses to postal surveys and to calculate the differential costs per completed questionnaire.\n Randomised controlled trial.\n Australian university and rehabilitation medicine practice.\n The trial was conducted in 1999 among the 143 non-respondents to a questionnaire about work related neck and upper body disorders. The questionnaire was sent to two Australian female samples: 200 office workers (Sample A) and 92 former rehabilitation medicine patients (Sample B). A reminder letter, another copy of the questionnaire and a final letter were sent at two week intervals. Half of the non-respondents within each sample were randomly selected to receive a telephone reminder just after the second mailout of the questionnaire. All direct costs were calculated.\n Responses were significantly higher among those who received the telephone reminder intervention (relative risk 2.54, 95% confidence intervals 1.43 to 4.52). Analysed by intention to phone, 47% of non-respondents in Sample A and 38% in Sample B returned a complete questionnaire after the intervention, compared with 21% and 10%, respectively, in the control groups. For the 112 women (combined samples) who returned completed questionnaires before randomisation, the average cost per respondent was AUD14. There was a higher total cost for the intervention groups (AUD851 versus AUD386 for controls), but the significantly higher number of additional completed responses (31 versus 12) resulted in a 15% lower marginal cost per completed questionnaire in those groups.\n Telephone reminders are cost effective in improving responses to postal surveys.", "The validity of the results of mailed surveys is often threatened by nonresponse bias, which is made more likely when response rates are low. However, the effectiveness and cost-effectiveness of several strategies to increase response rates are uncertain.\n To assess three strategies to increase response rates to mailed physician surveys: including a 10 dollars versus a 5 dollars cash incentive in the initial mailing, including a mint candy or not, and using a large versus small outgoing envelope.\n Using a 2 x 2 x 2 factorial design, a randomized trial of these strategies was conducted in a survey of 1200 physicians randomly selected from the American Medical Association's Master File.\n Including a 10 dollars incentive yielded a significantly higher response rate (60.5% vs. 52.8%) (P = 0.009). The mailing and incentive costs per completed response were 12.24 dollars (95% CI, 11.75 dollars, 13.64 dollars) in the 5 dollars group and 18.48 dollars (95% CI, 17.77 dollars, 20.69 dollars) in the 10 dollars group. Each additional response obtained in the 10 dollars group came at an incremental cost of 61.26 dollars (95% CI, 36.98 dollars, 200.80 dollars). Neither inclusion of a mint nor use of a large envelope influenced the response rate.\n Investigators may increase response rates by including more money in the initial questionnaire packet, but there may be diminishing returns to serial increments in incentives greater than 5 dollars. Including smaller incentives in more questionnaires may maximize total responses.", "A 4-factor, 16-cell experimental design was used to investigate the relationship between response rates of community hospitals to a survey conducted by the American Hospital Association (AHA) and 4 characteristics of the survey instrument, each varied dichotomously: the perceived length of the questionnaire, the order of questions, the orientation of the appeal made in the cover letter, and the presence or absence of a promise to share the results of the study with respondents. Response rate variations between the various cells were examined and multiple logistic regression was used to analyze the significance of the association between response rates and each of the four survey instrument variables while controlling for the effect of the others. At the same time, control was also maintained for the effects of five institutional characteristics of hospitals which a previous study had shown to have a significant relationship to response: bed size, location within or outside a standard metropolitan statistical area, AHA membership status, type of ownership, and form of control. The perceived length of the questionnaire and the order of questions were found to have a significant effect on response rates, but the orientation of the cover letter and a promise to share the results of the study with the respondents were found to be insignificant.", "Primary care physicians are increasingly being asked to participate in postal surveys. Difficulties in achieving adequate response rates among physicians have been reported. We investigated the effect of two low-cost interventions on response to a primary care physician postal questionnaire.\n A 2x2 factorial trial was developed within the context of a national survey assessing views and practices of physicians regarding prostate-specific antigen testing. We evaluated questionnaire order (version 1: demographics first, version 2: topic-specific questions first) and written precontact. A national database of primary care physicians was compiled. One thousand five hundred ninety-nine physicians were randomly selected, stratified by health board, and randomized.\n 47.9% of eligible physicians completed a questionnaire. There was a statistically significant 5.1% higher response rate among physicians receiving version 1 of the questionnaire than those receiving version 2 (50.6% vs. 45.4%, P=0.05); the adjusted odds of response were significantly raised (odds ratio=1.24; 95% confidence interval=1.01-1.54). Precontact resulted in a nonsignificant 3.6% increase in response (49.8% vs. 46.2%; P=0.16). The interventions did not interact.\n Ordering questionnaires with general questions first can significantly increase response rates, whereas precontact can achieve a modest increase. These strategies may enhance response while adding little to the cost of a physician survey.", "To describe factors that influence participation by general practitioners (GPs) in survey research, and in particular to examine the effectiveness of telephone prompts made by a GP researcher compared with non-medical researchers in a survey of GPs on sexually transmissible diseases (STDs).\n A questionnaire survey of knowledge, attitudes, behaviour and practice (KABP) in relation to STDs was distributed to 520 Victorian GPs randomly selected from the Australian Medical Publishing Company's (AMPCo) database of Australian medical practitioners.\n Number of GPs able to be contacted by telephone and cumulative and overall response rates to the questionnaire.\n The overall response rate was 85%. Although the GP researcher was able to make contact by telephone in a higher proportion of cases (80%) than the non-GP researchers combined (69%, p < 0.01) response rates were not significantly different (83% versus 87%).\n Telephone prompts to encourage GP response in survey research need not be made by a medical practitioner. Other important factors in relation to response rate that should be considered by researchers are GP involvement in the developing and piloting of the survey instrument, incentives and provision of detailed feedback of the results of the survey.", "The aim of the study was to determine whether complete anonymity improves the response rates to a postal questionnaire.\n The study derived from a series of postal surveys on AIDS knowledge conducted on six different dates in 1986 and 1987. The sample was randomly divided into two, each group being sent the same questionnaire. One group was informed that the replies were anonymous, the other that they were not. The latter were sent reminders.\n Recipients of the questionnaires were drawn from the Southampton electoral rolls.\n 300 people in each survey (total 1800) were sent questionnaires, representing on each occasion a different 1:500 systematic sample.\n Response rate was 49% for the anonymous questionnaires and 51% for the numbered questionnaires. Reminders boosted the response in the numbered group to 72%.\n There is no evidence that anonymity improves response to postal questionnaires, but the use of reminders may do so.", "The authors conducted a randomized trial in Geneva, Switzerland, to assess whether response rates to a mailed survey could be increased by printing the questionnaire on green paper. The authors also conducted a meta-analysis of 10 experimental studies that tested the effect of colored questionnaires on response rates. The randomized trial showed no effect (relative risk of responding [RR] = 1.00). The meta-analysis showed that mailing questionnaires on pink paper increased response rates by 12% (RR = 1.12, 95% confidence interval = 1.01 to 1.25, p = 0.04). Other colors had no statistically significant effect (blue: RR = 1.03, p = 0.49; green: RR = 1.02, p = 0.23; yellow: RR = 0.96, p = 0.30). Overall, using colored instead of white paper had no effect (RR = 1.02, p = 0.17). Thus, printing questionnaires on colored paper does not substantially increase response rates in surveys, except for pink paper.", "Finding cost-effective ways to increase response to mailed surveys is a concern for many nurse researchers. This study compared two follow-up methods: sending a second questionnaire packet versus sending a reminder postcard to those who did not respond to an initial mailing. Although the second questionnaire yielded a higher response than did the postcard, the cost per additional response was approximately 2 1/2 times higher for the questionnaire than for the postcard when the differential cost of the two mailings is considered.", "The authors examined differences in rate of response, data quality, and cost between mail approaches and in-person interview in the collection of data on sexual history and personal behaviors. A sample of women from a midwestern United States university (n = 342) was identified from health service medical records as having been seen for a sexually transmitted disease (cases) or a contraceptive visit (controls) during the latter half of 1985. The women were randomly assigned to one of three data collection strategies. A total of 268 subjects (78%) participated. Results indicated no differences in validity by method of data collection or by case-control status but there were significant differences in completeness, cost, and response rates. In-person interviews resulted in more complete data than mail approaches, although all instruments had low proportions of missing data (0.001-0.006). Response rate differences were not found when data collection methodologies were compared (75-82%) but were found in case-control analyses. Cases were consistently less likely to participate and significantly less likely to respond by mail (p less than 0.05). The cost of the in-person interview was approximately four times that of the mail survey for the data collection. Implications of the case-control response rate difference suggest that mail methodologies, although low in cost, may introduce sampling bias in studies of sexually transmitted diseases.", "As part of a mailed health survey, we investigated the effect on the response rate of a request to explain refusal to participate. Subjects (N = 1,240) were randomized either to receive or not to receive, with the first mailing, a letter requesting an explanation of their decision not to fill out the questionnaire, if they chose that option. There was a slightly higher cumulative response during most of the study from subjects who had been sent the request, but little difference between the two study groups in the ultimate response rate [80% from the intervention group vs 83% from the control group; response rate difference = -3%; 95% confidence limits (CL) = -7%, 1%]. Of 209 individuals who were sent the request and did not return the questionnaire, only 15 (7%) sent back an explanation. A request to explain a refusal to participate in a mail survey neither jeopardized the response rate nor enhanced it.", "nan", "To test a possible day-of-the-week effect on doctors' response rate to a postal questionnaire.\n Dispatch of postal questionnaire randomized to Thursday or Saturday.\n A nationwide survey on doctors' attitudes.\n 200 general practitioners and 260 practising specialists/consultants.\n Response rate and Kaplan-Meier survival curve for no-response.\n The probability of response was not influenced by receiving the questionnaire just before or just after a week-end.\n Response rates in postal surveys sent to doctors cannot be improved by their receiving the questionnaire just before a week-end.", "A health-related mailed survey was conducted to investigate the effect of follow-up mailings to response rates. In addition, the answer distributions among early and late respondents were compared to check non-response bias. Approximately 3,000 persons aged 40-64 were randomized into two groups; a questionnaire with four pages (twenty-two questions) was assigned to the first group, and a questionnaire with eight pages (thirty-five questions) to the second group. Both questionnaires contained questions of current health status, health-related practice, smoking status, etc. Follow-up mailings were sent twice to non-respondents. Response rates were increased from 38% to 62% by the first follow-up mail, and to 71% by the second follow-up mail. Although the length of the questionnaire did not affect response rates, response rates among the older subjects was higher than the younger subjects. Positive response to current smoking status was 10% lower among early respondents than late respondents, collected after the second follow-up mailing, and response to regular participation in physical/medical checkup was 15% higher among early respondents, whereas there were few differences for answers to other questions. Odds ratios between current health status and several health-related questions may not be biased by late response. However, increased response rates are needed to prevent non-response bias, because there were some differences in responses from follow-up mailings.", "Postal questionnaires are an economical and simple method of data collection for research purposes but are subject to non-response bias. Several studies have explored the effect of monetary and non-monetary incentives on response. Recent meta-analyses conclude that financial incentives are an effective way of increasing response rates. However, large surveys rarely have the resources to reward individual participants. Three previous papers report on the effectiveness of lottery incentives with contradictory results. This study aimed to determine the effect of including a lottery-style incentive on response rates to a postal health survey.\n Randomised controlled trial. Setting: North and West Birmingham. 8,645 patients aged 18 or over randomly selected from registers of eight general practices (family physician practices). Intervention: Inclusion of a flyer and letter with a health questionnaire informing patients that returned questionnaires would be entered into a lottery-style draw for pound 100 of gift vouchers. Control: Health questionnaire accompanied only by standard letter of explanation. Main outcome measures: Response rate and completion rate to questionnaire.\n 5,209 individuals responded with identical rates in both groups (62.1%). Practice, patient age, sex and Townsend score (a postcode based deprivation measure) were identified as predictive of response, with higher response related to older age, being female and living in an area with a lower Townsend score (less deprived).\n This RCT, using a large community based sample, found that the offer of entry into a lottery style draw for pound 100 of High Street vouchers has no effect on response rates to a postal health questionnaire.", "We conducted a randomised trial to determine the differential effectiveness of a telephone prompt by a medical researcher compared with a nonmedical research assistant in improving response rates of general practitioners to a survey and to compare personnel costs. A national random sample of Australian general practitioners was allocated randomly to two intervention groups. In advance of a self-administered questionnaire, Group A (n = 184) received a telephone prompt by a medical researcher and Group B (n = 189) a prompt by an experienced nonmedical research assistant. Other aspects of survey administration were identical for both groups. The five-month cumulative response rate obtained by the medical researcher (81 per cent) was not significantly different from that of 72 percent obtained by the research assistant (chi 2 = 3.3, 1 df, P = 0.07). For Group A, 279 telephone calls, consuming 23 hours 15 minutes, were made. Group B required more calls (384) and more time (32 hours). Using the relevant award pay scales, the estimated personnel costs for each group were $631 and $601 respectively. We conclude that an experienced nonmedical research assistant is as effective as a medical practitioner in administering telephone prompts to enhance survey response rates, although savings are not necessarily made.", "Improving response rates, particularly among physicians, is important to minimize nonresponder bias and increase the effective sample size in epidemiologic research. We conducted a randomized trial to examine the impact of prepayment vs. postpayment incentives on response rates.\n Self-completion postal questionnaires were mailed to 949 physicians who were respondents to an earlier survey and representative of the general physician population in Hong Kong. These physicians were randomly allocated to receive a HK dollar 20 cash prepayment incentive that accompanied the survey (n=474) or a postpayment reward of the same amount on receipt of the completed questionnaire (n=475).\n The final prepayment response rate was 82.9%, compared with 72.5% in the postpayment arm (P < .001). Of the eight alternative incentive and follow-up strategies evaluated, three lie on the efficiency frontier (i.e., not dominated), including postpayment with three mailings at HK dollar 42.7, prepayment with three mailings at HK dollar 66.5 and prepayment with three mailings and telephone follow-up at HK dollar 112.1 per responder recruited (US dollar 1=HK dollar 7.8).\n The findings demonstrate that prepayment cash incentives are superior to postpayment of the equivalent amount in improving response rates among a representative sample of Hong Kong physicians. Further research should concentrate on confirming the generalizability of these findings in other health care occupation groups and settings.", "Randomized trials were performed in Denmark and The Netherlands to determine the effect of mailed reminders on the response rate in surveys among patients in general practice. In both countries, general practitioners handed out questionnaires to 200 adult patients who came to visit them. An intervention group of 100 patients received reminders at 3 weeks after the visit, whereas a control group of the remaining 100 patients did not receive reminders. The response rate was significantly higher in the intervention groups than in the control group in The Netherlands (86% versus 55%, respectively) but not in Denmark (87% versus 81%, respectively). Mailed reminders can improve the response rate in surveys related to a general practice, but they are not effective in all situations.", "A systematic review identified a range of methods, which can influence response rates. However, analysis specific to a healthcare setting, and in particular, involving people expected to be poor responders, was missing, We examined the effect of pre-warning letters on response rates to a postal survey of sedentary patients whom we expected a low rate of response.\n Participants were randomised to receive a pre-warning letter or no pre-warning letter, seven days before sending the main questionnaire. The main questionnaire included a covering letter and pre-paid return envelope. After seven days, non-responders were sent a reminder letter and seven days later, another reminder letter with a further copy of the questionnaire and return envelope.\n 627 adults, with a mean age of 48 years (SD 13, range 18 to 78) of whom 69.2% (434/627) were women, were randomised. 49.0% (307/627) of patients were allocated to receive a pre-warning letter and 51.0% (320/627) no pre-warning letter, seven days in advance of posting the main questionnaire. The final response rate to the main questionnaire was 30.0% (92/307) amongst those sent a pre-warning letter and 20.9% (67/320) not sent a pre-warning letter, with an adjusted odds ratio of 1.60 (95% CI 1.1, 2.30).\n The relatively low cost method of sending a pre-warning letter had a modest impact on increasing response rates to a postal questionnaire sent to a group of patients for whom a low response rate was anticipated. Investigators should consider incorporating this simple intervention when conducting postal surveys, to reduce the potential for nonresponse bias and to increase the study power. Methods other than postal surveys may be needed however when a low response rate to postal surveys is likely.", "We conducted a pilot randomised trial of computerised templates for the management of asthma and diabetes in general practice in six general practices in North London. Uptake of the guidelines by general practitioners and practice nurses was assessed using qualitative (semi-structured interviews designed to assess the users' views) and quantitative (change in use of the template during the study period) outcome measures. The practice nurses used the templates frequently but general practitioners rarely used them. Several reasons were offered for non-use of the templates, such as the length of the template and non-involvement in the care of asthma or diabetes. Despite this, however, health professionals were favourably disposed to the use of templates for general clinical care. Pilot investigations of computerised templates are best achieved by observational or quasi-experimental methods rather than a randomised controlled trial. The use of both qualitative and quantitative methods in this study allowed exploration of the barriers to use of computers.", "Self-administered questionnaires are commonly used in experimental studies to elicit quality of life or other outcomes. Hence, achieving an acceptable level of follow-up from patients is critical to minimizing bias. Many methods for maximizing follow-up remain untested. It is also unclear what level of follow-up is required to prevent bias being introduced.\n We recruited 246 men from general practice surgeries in Sydney, Australia. These 246 men were randomized to receive a covering letter with their follow-up questionnaire either advising of a deadline to reply (Deadline, n = 126) or a standard letter without a deadline (No Deadline, n = 120). Four standardized reminder prompts subsequently were administered. We calculated interim response rates and the final proportion of follow-up questionnaires received according to group. We also compared scores on two main outcomes, namely, knowledge and decisional conflict at each time when reminder prompts were administered.\n One hundred and twelve (88.9%) men in the Deadline group returned their follow-up questionnaires compared with 102 (85.0%) men in the No Deadline group. This difference was not statistically significant [odds ratio = 1.41, 95% confidence interval (CI) = 0.67-2.99; p = 0.36]. Time to response also was not significantly affected by cover letter received (hazard ratio = 0.96; 95% CI = 0.73-1.25; p = 0.76). Results of the original RCT were similar in terms of direction and effect size at all times irrespective of when reminder prompts were administered.\n The addition of a deadline adds no further impact in improving response rates from male patients compared with an unspecified letter. Despite the accepted wisdom that higher response protects against bias, differences in outcomes were consistent throughout the post-test data collection period.", "Mailed surveys are widely used to collect epidemiological and health service data on cancer populations. Nonresponse can threaten the validity of surveys and various strategies, including the enclosure of modest incentives, are often used to increase response rates. A study was undertaken to determine whether response rate to a mailed survey differed with provision of immediate versus delayed incentives. A six-page mailed survey to ascertain dietary supplement use was sent to 1402 men who had been diagnosed with prostate cancer. Subjects were block randomized into two groups based on age (< or =65 years versus >65 years), race (white versus nonwhite), and disease status (locoregional versus distant). One group received a 30-min prepaid phone card concurrently with their blank survey (unconditional incentive), whereas the other group received the incentive only on receipt of their completed survey (conditional incentive). A 60% overall response rate was achieved, and no differences in response rates were noted between conditional and unconditional incentive groups (overall, as well as within defined age, race, and disease-defined strata). Nonwhites, however, were significantly less likely to respond than whites (P < 0.0001). In conclusion, acceptable response rates to a mailed survey can be achieved in a general population of cancer survivors using modest incentives. Given no differences in response rates using conditional versus unconditional incentives, the decision to provide immediate versus delayed incentives is one that should be considered on a study-specific basis, and a decision based primarily on cost. Other means, however, appear necessary to achieve acceptable response rates among minority group cancer survivors.", "The study aimed to consider the impact of two different types of reminder on response rates and costs in a postal survey.\n The study was a cross sectional survey. A self-completion lifestyle questionnaire was used. Those who did not respond after the initial mailing were randomly allocated to receive either a postcard or questionnaire as a first reminder. All outstanding non-responders received a questionnaire as a second reminder.\n A representative sample of 698 adults aged 16-70 was used, drawn from a family health services authority register.\n Postcard reminders were as effective as questionnaire reminders in increasing response whether one or two reminders are sent. The costs per response were calculated. Two questionnaires as reminders were found to be 1.7 times more expensive than a postcard plus questionnaire. Including the initial mailing, the cost per response using all questionnaires was 1.3 times the cost when a postcard was used for the first reminder.\n To increase the response to a postal survey effectively and economically, two reminders should be sent--first a postcard and then a questionnaire.", "This study's goals were to (a) determine whether sending a survey by certified mail results in a higher response rate from physicians compared to sending by first-class mail and (b) evaluate the cost-effectiveness of this method. The study sample was 409 physicians who were nonrespondents to two previous mailings of a medical specialty society survey. Eligible physicians were designated at random to receive a final mailing either by U.S. Postal Service certified mail including a return-receipt postcard or by first-class mail. There was a higher response rate from the certified mail group compared with the first-class mail group (41.3% versus 24.8%; relative risk = 1.66, 95% Confidence interval 1.25, 2.21). A cost-effectiveness analysis showed that the cost per respondent was higher using certified mail versus first-class mail in the third mailing ($2.77 versus $2.34). Thus, use of certified mail is effective in increasing survey response but more costly.", "This study tested the effect of questionnaire structure on response, speed of return, and content of answers in a postal survey. All 259 patients aged 30-59 years who consulted with back pain at four UK general practices from March to June 2001 were randomly allocated to receive either a traditionally or chronologically structured self-completion questionnaire. The response was higher and the returns quicker (P =.05) for the chronologic questionnaire. There were no statistically significant differences in completion rates or scores on the SF-36, Chronic Pain Grade, Hospital Anxiety and Depression Scale, or Roland-Morris Disability Questionnaire between the two types of questionnaire, and test-retest reliability was high for all scales. Changing questionnaire structure to make questions chronologic does not substantially affect the answers given, but may make a questionnaire more acceptable and easier to complete and speed up returns.", "Previous experimental research in other topic areas has shown that the choice of response alternatives can influence respondents' reporting of the frequency of vaguely defined events and that the set of response alternatives is treated as information in the interpretation of the question. The aim of this study was to examine whether such affects would occur in the context of respondents reporting of health-related events using high and medium frequency closed format response categories, which might be used interchangeably by researchers. The study consisted of a postal survey of n = 518 patients aged > or = 18 years randomly selected from the patient list of a diabetes centre and who were equally and randomly allocated to one of three conditions (Condition A: high frequency response alternatives/horizontal orientation; condition B: medium frequency response alternatives/horizontal orientations; condition C: high frequency response alternatives/vertical orientation). Testing for the effect of response alternatives for the combined responses of five vaguely defined questions between conditions A and B was chi 2 = 5.5, p = 0.019, for the difference in proportions, indicating that overall, those respondents presented with response alternatives discriminating at medium frequency, reported significantly fewer target events than those presented with high frequency response alternatives. Testing for the effect of orientation of the combined question responses between conditions A and C, differences in proportions between conditions, did not reach statistical significance (p > 0.05). Findings from this and previous studies indicate that response alternatives provide information on the interpretation of vaguely defined questionnaire items and that their choice should not be left to intuition alone when designing questionnaire items.", "E-mail communication between patients and their providers has diffused slowly in clinical practice. To address concerns about the use of this technology, we performed a randomized controlled trial of a triage-based e-mail system in primary care. DESIGN AND PATIENTS/PARTICIPANTS: Physicians in 2 university-affiliated primary care centers were randomized to a triage-based e-mail system promoted to their patients. E-mails from patients of intervention physicians were routed to a central account and parsed to the appropriate staff for response. Control group physicians and their patients did not have access to the system. We collected information on patient e-mail use, phone calls, and visit distribution by physician over the 10 months and performed physician and patient surveys to examine attitudes about communication.\n E-mail volume was greater for intervention versus control physicians (46 weekly e-mails per 100 scheduled visits vs 9 in the control group at the study midpoint; P <.01) but there were no between-group differences in phone volume (67 weekly phone calls per 100 scheduled visits vs 55 in the control group; P =.45) or rates of patient no-shows (5% in both groups; P =.77). Intervention physicians reported more favorable attitudes toward electronic communication than did control physicians but there were no differences in attitudes toward patient or staff communication in general. There were few between-group differences in patient attitudes toward electronic communication or communication in general.\n E-mail generated through a triage-based system did not appear to substitute for phone communication or to reduce visit no-shows in a primary care setting. Physicians' attitudes toward electronic communication were improved, but physicians' and patients' attitudes toward general communication did not change. Growth of e-mail communication in primary care settings may not improve the efficiency of clinical care.", "This study examined return rates for a cancer prevention survey by pediatricians in relation to an informational booklet versus a monetary incentive in the first of a three-wave mailing. Of the 300 surveys sent which included an informational booklet incentive, 189 (64%) were returned. Of the 300 surveys sent which included a $1.00 incentive 227 (79%) were returned, indicating the $1.00 incentive was more effective than the informational incentive in increasing return rates in this sample of physicians.", "The purpose of this study was to investigate how response rates to a postal questionnaire are affected by title and length of the survey instrument. Five questionnaires, which differed according to title and length, were designed. Each questionnaire was mailed to a random sample of one thousand Norwegian women aged, 35-49 years. A total of 3,106 questionnaires were returned (62.1%). The highest response rate (70.2%) was achieved by a two-page questionnaire entitled \"Women and Cancer\". An otherwise identical questionnaire entitled \"Oral Contraceptives and Cancer\" had a response rate of 60.7%. Questionnaires entitled \"Women and Cancer\" with a length of four and six pages had a response rate of 62.8% and 63.3%, respectively. The four page questionnaire entitled \"Women, Lifestyle and Health\" had the lowest response rate of 57.1%. This study shows that in a general population of Norwegian women the title of a postal questionnaire influences the response rate. The results indicate that although the shortest questionnaire had the highest response rate, the most extensive survey instrument did not have the lowest response rate. The distribution of risk factors for breast cancer did not vary according to response rate or design of questionnaire. The overall findings of this study suggest that the benefits from the increased information obtained from extensive postal questionnaires out-weighs a potential non-response bias due to a somewhat lower response rate.", "Low response rates are acknowledged as a potential source of bias in survey results. Response rates are a particular problem in surveys of GPs. Thus, the methods used to encourage response to mailed surveys and the influence of inducements in maximizing response rates are fundamental issues to be examined when addressing the problem of response bias.\n To increase the overall response rate to a national study of GPs and to explore the effects of financial and non-financial inducements on response rates.\n Two mailing waves of a postal questionnaire to a 20% random sample of all GPs in England and Wales had achieved a 33% response rate. For the third mailing wave, the non-responding GPs were then divided into a control group, a group who were offered a donation to charity to complete the questionnaire and a group who were offered cash. The charity and cash groups were further subdivided into 5 pounds and 10 pounds groups to assess the effect of the size of the inducement offered. For the control group, a fourth wave was sent the offer of a 5 pounds or 10 pounds incentive.\n Response was positively affected by the offer of an inducement. Cash, however, had a more substantial effect than the offer of a donation to charity. Older GPs were less likely to participate overall, whereas male GPs were more likely to respond to a cash inducement. Doctors who had seen more patients were less likely to reply earlier and were more likely to respond to the offer of cash.\n Primary care is going through many changes, some of which have increased the workload of the GP. It may now be that, to achieve the response rates needed to validate policy-related research, the offer of inducements will become a necessary part of the research process.", "nan", "nan", "High response rates from physicians are key to obtaining valid and generalizable data regarding their sexually transmitted disease (STD) diagnosis, treatment, and control practices. A factorial (3 x 2) study was designed using varying cash incentives ($0, $15, $25) and delivery modes (Federal Express, U.S. mail). Surveys, with three follow-up mailings, were sent to a national probability sample of 311 physicians in OB-GYN, family practice, internal and emergency medicine, and pediatrics specialties. Overall, 156 physicians returned completed surveys (56% overall response rate). Significant effects for incentive level (F = 28.2, df = 2, p < .01) and delivery mode (F = 4.1, df = 1, p < .05) existed. Highest response was among physicians in the $25-FedEx condition (81%). High response rates from busy practicing physicians can be achieved if surveys are relevant to clinical practice, sponsored by a reputable organization (the Centers for Disease Control and Prevention), include a monetary incentive, and are delivered by courier.", "This study evaluated a mail and telephone intervention to improve breast health behaviors while maintaining quality of life. Women recruited from the general public were randomized to a stepped-intensity intervention consisting of mailings, telephone calls, and counseling (if requested or appropriate given a woman's genetic risk for breast cancer) or to a delayed treatment control group. Outcomes (mammography screening and quality of life) were measured at baseline in a telephone survey and again at a 12-month follow-up period. Women in the intervention group significantly increased screening mammography uptake by 12% and quality of life by 5.3 scale points compared to control participants. Changes in knowledge of breast cancer, genetic testing, and cancer worry all significantly predicted intervention changes. This successful intervention can help women make better breast health choices without causing increased worry.", "Mail surveys of physicians have been characterized by lower response rates than general population surveys, raising concerns about nonresponse bias. Although monetary incentives have routinely been used to improve survey response among physicians, questions remain regarding how much of an incentive is most cost-effective. The present study seeks to further examine the effects of incentive size on response rates to a national mail survey of physicians.\n This study used a random sample of 873 physicians practicing in the United States; the response rate was 65% (n = 563). Respondents were randomly assigned to receive a $5, $10, or $20 cash incentive in the initial mailing. Except for the magnitude of the incentive, the procedures for each condition were identical, with each respondent receiving up to 3 follow-up mailings and 2 telephone calls.\n Overall response rates ranged from 60.3% for the $5 incentive category to 68.0% for the $10 incentive category. Differences in overall response rates across the incentive categories, however, were not significant. Higher levels of incentives also did not significantly reduce the number of mail and/or telephone interventions required to reach the target response rate of 60.0%. As expected, aggregate costs (excluding labor) were lowest for the $5 incentive group.\n Our findings suggest that changes in the magnitude of incentive do not automatically result in increases in survey response among physicians. Possible reasons for this lack of effect as well as alternatives to monetary incentives are addressed.", "In 1989, the authors tested the effectiveness of two response-enhancing techniques, a postage stamped or franked return envelope and a prenotification letter, in a survey of pregnancy among 10,047 resident physicians in the United States. The techniques were randomly assigned using a factorial design. No significant interactions were observed between the techniques. After two mailings, those who received a stamped return envelope had a response of 71.2%, compared with 68.2% for those who received a franked return envelope (95% confidence interval 1.3-4.9%). Men who received the stamped envelope had a 5.9% greater response than those who received the franked envelope (p less than 0.001), but the type of postage did not influence response among women (p = 0.84); this interaction was statistically significant (p = 0.006). Physicians who received a prenotification letter had a response of 69.0%, compared with 70.5% for those who did not receive the letter (95% confidence interval -3.3 to 0.2%). The authors conclude that seemingly minor changes in survey design could have saved from 12% to 19% of the total cost of the study.", "Studies investigating means of recruiting participants to randomized controlled trials (RCTs) are sparse. We investigated the effects of telephone reminders as a recruitment strategy.\n Sick-listed employees received a written invitation to participate in a study comparing standard treatments with a solution-focused follow-up and were randomly allocated to an intervention or control group (n=703). Those who did not respond within 2 weeks received either 'no reminder' (n=242) or 'attempted telephone reminder' (n=256). Outcome was enrollment to the RCT.\n An intention to recruit analysis revealed no significant differences between the groups (P=.229). An intention to phone analysis among nonresponders revealed significant differences between 'no reminder' (recruited 4.5%) and 'attempted telephone reminder' (recruited 12.1%) (P=.003, odds ratio 2.89, 95% confidence interval [CI] 1.42-5.90). An analysis of numbers needed to phone showed that to recruit one more person in this group of nonresponders, we needed to phone 13 persons (95% CI=8-33).\n Systematic use of telephone calls can increase the recruitment rate among nonresponders in RCTs.", "To study questionnaire length, type of consent, approach to recruitment, and subject characteristics on participation in epidemiologic studies.\n As part of a health survey among Dutch subjects treated for ear, nose, and throat disorders in childhood, we conducted a pilot study of 200 individuals who were randomly assigned to one of four categories, defined by length of questionnaire (long vs. short) and type of consent form (basic vs. multi-option). In addition, among 8402 subjects eligible to be in the main study (average age 41 years in 1997), we examined the effect of approach to recruitment and subject characteristics on participation rates.\n The pilot study showed a non-significant 10% increase in participation rate using the shorter questionnaire, but no differences by type of consent form. In the full survey, the participation rate was 49% after the first mailing. Response increased by 15% after a written reminder and by 10% after a telephone survey. The total participation rate was 74%. Attained age, sex, exposure status, age at exposure, and response to an earlier survey were determinants of participation rates. Among male non-participants, outright refusal was less frequent than non-response. The refusal rate, unlike the non-response rate, was positively associated with older age at time of survey.\n Health survey participation is influenced by questionnaire length, frequency of contact, and subject characteristics.", "In a survey about euthanasia, 1,600 critical care nurses were randomly assigned to receive either three complete, anonymous mailings of the questionnaire or, with each mailing, a coded postcard to be returned separately from the questionnaire to reduce subsequent mailings to previous responders. The response rate in these two groups was 76.5% [95% confidence interval (CI) = 73.6-79.4%] and 69% (95% CI = 65.7-72.4%), respectively. The two strategies yielded similar responses, and costs were much lower for the postcard group. Using coded postcards to be returned separately from completed instruments appears to lower the response rate to anonymous mail surveys, but it also lowers cost and may not introduce additional bias.", "Response rates to surveys are declining and this threatens the validity and generalisability of their findings. We wanted to determine whether paper quality influences the response rate to postal surveys\n A postal questionnaire was sent to all members of the British Society of Gynaecological Endoscopy (BSGE). Recipients were randomised to receiving the questionnaire printed on standard quality paper or high quality paper.\n The response rate for the recipients of high quality paper was 43/195 (22%) and 57/194 (29%) for standard quality paper (relative rate of response 0.75, 95% CI 0.33-1.05, p = 0.1\n The use of high quality paper did not increase response rates to a questionnaire survey of gynaecologists affiliated to an endoscopic society.", "Studies largely from the market research field suggest that the inclusion of a stamped addressed envelope, rather than a pre-paid business reply, increases the response rate to mail surveys. The evidence that this is also the case regarding patient mail surveys is limited.\n The aim of this study is to investigate whether stamped addressed envelopes increase response rates to patient mail surveys compared to pre-paid business reply envelopes and compare the relative costs. A sample of 477 initial non-responders to a mail survey of patients attending breast clinics in Greater Manchester between 1/10/2002 - 31/7/2003 were entered into the trial: 239 were randomly allocated to receive a stamped envelope and 238 to receive a pre-paid envelope in with their reminder surveys. Overall cost and per item returned were calculated.\n The response to the stamped envelope group was 31.8% (95% CI: 25.9% - 37.7%) compared to 26.9% (21.3% - 32.5%) for the pre-paid group. The difference (4.9% 95% CI: -3.3% - 13.1%) is not significant at alpha = 0.05 (chi2 = 1.39; 2 tailed test, d.f. = 1; P = 0.239). The stamped envelopes were cheaper in terms of cost per returned item (1.20 pounds) than the pre-paid envelopes (1.67 pounds). However if the set up cost for the licence to use the pre-paid service is excluded, the cost of the stamped envelopes is more expensive than pre-paid returns (1.20 pounds versus 0.73 pounds).\n Compared with pre-paid business replies, stamped envelopes did not produce a statistically significant increase in response rate to this patient survey. However, the response gain of the stamped strategy (4.9%) is similar to that demonstrated in a Cochrane review (5.3%) of strategies to increase response to general mail surveys. Further studies and meta analyses of patient responses to mail surveys via stamped versus pre-paid envelopes are needed with sufficient power to detect response gains of this magnitude in a patient population.", "Traditional measures of socioeconomic status may not be reliable for older people and income may be a useful measure for research into inequalities in health. At the same time, researchers increasingly wish to link survey findings to individual data taken from medical records. For this, consent must be sought. To examine whether questions on household income and seeking consent for medical record linkage affected response rates, a postal health survey of patients aged 65 to 74 was undertaken in an inner London practice. The overall response rate was 62.8%. In this study, the inclusion of an income question or seeking consent to access medical records did not reduce response rates to a health survey among older people.", "Postal questionnaires are widely used to collect data in healthcare research but a poor response rate may reduce the validity and reliability of results. There was a lack of evidence available relating to use of a monetary incentive to improve the response rate in the healthcare setting.\n The MRC ORACLE Children Study is assessing the health and development of nearly 9000 seven year old children whose mothers' joined the MRC ORACLE Trial. We carried out a randomised controlled trial of inclusion of monetary incentive (five pound voucher redeemable at many high street stores) with the reminder questionnaire to parents. This trial took place between April 2002 and November 2003. When the parents were sent the reminder questionnaire about their child's health and development they were randomly assigned by concealed computer-generated allocation stratified by week of birthday to receive a five pound voucher or no incentive. The population were 722 non-responders to the initial mailing of a 12-page questionnaire. Main outcome measures: Difference in response rate between the two groups.\n Inclusion of the voucher with the reminder questionnaire resulted in a 11.7%(95% CI 4.7% to 18.6%) improvement in the response rate between the two groups.\n This improvement in response rate and hence the validity and reliability of results obtained appears to be justified ethically and financially.", "The effects of incentive size on physicians' response rates to a mail survey were determined.\n One thousand US primary care physicians were assigned randomly to receive a survey with either a $5 bill or a $2 bill as an incentive. For each of the two incentive groups, the overall response rate for three mailing waves, the total cost, and the total cost per usable response were measured.\n The response rate among those receiving the $5 bill (61%) was 32% higher than the response rate among those receiving the $2 bill (46%); overall costs were slightly higher in the $5 group, but the cost per response for each group was similar ($15.46 versus $14.93). For the same cost, a higher response rate could have been achieved in the $2 group if costs saved from foregoing the third mailing were instead used to increase the incentive for a portion of the subjects.\n A $5 bill incentive yielded a higher response rate among the physicians in this study than did a $2 bill incentive. Moreover, the powerful effect of the incentive size, combined with the consequent decline in the costs of subsequent mailing waves, suggests that resources in a fixed survey budget are allocated more efficiently to increasing the initial incentive rather than to providing a third wave to nonresponders.", "To determine the degree to which mailed survey response rates, response times, and nonresponse bias are affected by questionnaire size and color.\n Questionnaires were mailed to a random sample of 2,000 Mayo Clinic patients in one of four size/color \"test\" groups. One thousand three hundred nine surveys were completed, approximately two-thirds in each group.\n A small (6 (1/8) x 8 (1/4) in) questionnaire booklet on white paper had a higher response rate (68.4%) than a similarly sized questionnaire on blue paper (62.3%). A large (8 (1/4) x 11 in) questionnaire on white paper had a 62.7% rate, whereas a large, blue questionnaire had a response rate of 68.6%. Median response times did not differ by questionnaire size/color. No evidence of differential nonresponse bias was observed across the four test groups.\n This study supports the use of a small/white questionnaire format advocated by the Total Design Method advanced by Don Dillman at Washington State University. We observed a favorable response rate for a large questionnaire printed on blue paper; however, if time and resources are limited, use of a small/white questionnaire appears preferable.", "To determine whether response rates to a mailed questionnaire sent to population control subjects could be increased through offer of a small incentive, half of the control subjects (n = 477) in a case-control study of renal cell carcinoma were randomly selected to receive a contact letter offering a lottery ticket if a completed questionnaire was returned; the remaining subjects (n = 477) received the same letter but with no mention of a lottery ticket. Overall response rates did not differ between the two groups (72.6% versus 74.4%), although a higher percentage of those offered a lottery ticket responded without follow-up (24.4% versus 18.5%). Binomial regression modeling of the effect of the lottery ticket offer, sex, age, and percent of urban dwellers on response indicated a significant effect only for percent of urban dwellers, the rate of response increasing with a decreasing percentage of urban dwellers. The effect of sex was of borderline significance (P = 0.05), with females having the higher rate of response.", "Historically, achieving a high response rate on physician surveys has been a challenging task. Given such concerns, understanding research strategies that facilitate adequate response rates is important. Primary care physician responses to a mail survey on smoking cessation are summarized by physician specialty and timing of incentive.\n A stratified random-sample design, stratified by patient populations-adults, adolescents, and pregnant women-was used. The sampling frame included New Jersey internists, general practitioners, family physicians, pediatricians, and obstetrician-gynecologists. A total of 2100 physicians, 700 physicians from each patient strata, were sampled and mailed a smoking-cessation survey in summer 2002. The sample was randomized by incentive timing: Half received the incentive (i.e., 25 dollars gift card) with the first survey mailing, and half received the incentive on receipt of their completed survey.\n The promised-incentive group achieved a significantly lower response rate (56%) compared with the up-front-incentive group (71.5%). Response rates by medical specialty varied overall and within incentive groups. The difference between the incentive groups was greatest among obstetrician-gynecologists (i.e., 20.2 percentage points) and was least among pediatricians (i.e., 5.8 percentage points).\n Physician response rates to mail surveys are greatly improved, especially among certain medical specialties, by using up-front incentives.", "This study assessed efforts to increase response rates to a mailed physician survey and examined whether, as a result, nonresponse bias was reduced.\n Randomly selected physicians and geneticists were mailed a questionnaire concerning genetics knowledge and attitudes. In the final but not the pilot survey, a $25 incentive and intensive follow-up were used to increase the response rate.\n The response rate from physicians in the final survey was 64.8% (n = 1140), compared with 19.6% in the pilot test (n = 69). Sample representatives in sociodemographic and practice characteristics was improved by follow-up. Respondents recruited with more difficulty did not differ on the principal outcome variable, genetics knowledge, except on one subscore. Pilot study and final survey respondents did not differ in knowledge.\n Although the effect of increased response rates on the principal outcome variable in this study was minimal, this may not be the case for other studies. Every effort should be made to attain as high a response rate as is practical and to establish that respondents are representative of the population being sampled.", "Patient surveys are commonly distributed at the end of a multicenter clinical trial. This Antiarrhythmics Versus Implantable Defibrillators (AVID) substudy prospectively explored the relationship between methods used in distributing a survey and the quantity of responses received. AVID was a multicenter, randomized trial comparing survival in arrhythmia patients treated with antiarrhythmic drugs versus implantable defibrillators. At study termination, a patient satisfaction survey was mailed to the 664 surviving participants. Questions included reasons for study participation, study benefits and problems and quality of care. Survey mailings were stratified by four factors in a 2x2x2x2 factorial design: delivery mode (overnight vs. regular mail), certificate of appreciation, timing of administration (\"early\" vs. \"late\") and cover letter signed by a physician versus coordinator. Patients were randomly assigned to received one of 16 combinations of these four factors. Clinical characteristics and response rates were evaluated. Patients were more likely to return surveys delivered by overnight mail (75% vs. 68%, p=0.04), with no certificate of appreciation enclosed (75% vs. 68%, p=0.05) and administered close to the time of study closeout (79% vs. 72%, p=0.085). Compared to the 184 nonrespondents, the 456 (71%) respondents were older, Caucasian, lived with others, were high school graduates and less likely to have Medicare/Medicaid or HMO insurance (p<0.03). Physician recommendation was the most common reason cited for trial participation. Main benefits included increased knowledge of their medical condition and improved health. Reported problems included parking, transportation and excess clinic wait time. This randomized study demonstrated that methods of patient survey distribution affect the survey return rate. Additional studies should explore mechanisms for maximizing return rates.\n Copyright 2002 Elsevier Science Inc.", "To test the effect of a AU dollars 2 scratch lottery ticket on response rates to a national mailed questionnaire of Australian general practitioners (GPs) and medical specialists.\n A randomized controlled trial was conducted and the incentive sent to half of the participants with the first mailing. A single follow-up mailing without incentive was sent to all non-respondents. Survey respondents were then informed of the research question regarding incentives and allowed to withdraw their study data. Differences in response rates between doctors receiving and not receiving the incentive, and between respondents and non-respondents, were examined.\n The overall response rate was 47% (443 respondents). Twenty-two respondents (5%) withdrew their data after being informed of the research question. Of the remaining 421 respondents, 233 had received the incentive (response rate 49.7%) and 188 had not (40.1%, p=0.0032). The absolute increase in response rate with the incentive (9.6%, 95%CI 3.2, 15.9) was quantitatively similar in effect to the reminder mailing (11.8%). The incentive had a larger effect among the GP sample compared with specialists (13.4 vs. 5.9%), although the difference was not statistically significant (p=0.20). There were no systematic differences in demographic characteristics between respondents and non-respondents.\n Increased response rates associated with a small incentive may reduce the need for a second mailed reminder, but strong views about the use of incentives may negatively influence the participation of some practitioners. While the overall response rate was low, there was no evidence of bias in our sample.\n Copyright (c) 2005 John Wiley & Sons, Ltd.", "Mailed questionnaires are a quick and cheap means of obtaining data, but they have two disadvantages. They often produce low response rates irrespective of the nature of the group sampled, and they may seem inappropriate for clinical samples with visual problems. High response rates are needed for reliable results and valid conclusions. This paper presents a set of techniques enabling high response rates to be obtained. It also reports research showing that such techniques are appropriate even for the partially sighted.", "To investigate the impact on subject response of an information brochure and cash incentives included with mailed questionnaires in case-control studies.\n A randomized trial was carried out within a case-control study investigating cancer in the Province of Ontario. Brochures were included with half of the mailed questionnaires sent to 7487 cases and 2561 controls. Controls were also sent cash incentives of $2, $5, or no money.\n With the brochure, response changed from 75.0% to 75.8% in cases, and from 70.3% to 71.1% in controls. Adjusting for differences in age, residence, sex, and cancer site/status, the change was 0.2% [95% confidence interval (CI) = -1.7-2.1] in cases, and 0.6% (95% CI = -3.1-4.3) in controls. The $2 and $5 incentives increased overall response in controls from 61.9% to 72.8% and 77.2%, respectively, i.e., by 10.9% (95% CI = 6.1-15.6) and 15.1% (95% CI = 10.4-19.7), after adjustment. This effect was largely confined to urban areas (for $2 and $5, respectively: 5.5% and 14.2% in Toronto, 15.3% and 20.4% in other urban areas vs. 2.7% and 1.0% in rural areas; p = 0.02). Response time showed little or no improvement when the brochure was included, but was markedly reduced for both the $2 and $5 incentives.\n Cash incentives can improve subject response in epidemiologic studies, whereas information brochures do not appear to have an effect.", "Examine the effects of three iterative tailored feedback letters addressing smoking; physical activity; and fruit, vegetable, and fat intake, and test the additional effects of providing feedback on action plans.\n A tailored, print-based intervention was developed and tested in a randomized control trial with a posttest after 9 months.\n A total of 2827 respondents agreed to participate. They were recruited from a random sample of 35,000 addresses obtained through the Dutch national telephone company.\n The mean age was 49 years, and 55% were female. Intervention. The experimental group received three printed tailored letters, and the control group received three printed generic letters. Respondents from the experimental group randomly received either a third letter with tailored information or tailored information and action-planning feedback. MEASURES; The questionnaire assessed physical activity; smoking; consumption of fruit, vegetables and fat; motivational determinants; action plans; and demographics.\n Tailored information resulted in more improvement over time than generic information for the intake of fruit, vegetables, and fat and for physical activity. No differences between the conditions were found for smoking because of high cessation rates in all conditions. Action-planning feedback did not increase the effects.\n Tailored lifestyle information can be effective for adults in changing nutrition behavior and physical activity.", "To assess the impact of patient satisfaction survey method on response rate, data quality and satisfaction.\n Four modes of data collection were assessed during a randomized trial that included 400 inpatients discharged from a teaching hospital.\n The response rate was 58% within the mail survey group (72% with follow-up letter) versus 73% and 81% within the home and telephone interview group (p < 0.01). 69% of the mailed questionnaires contained no missing values versus 94% and 96% for home and telephone interview modes (p < 0.01). The global satisfaction scale score was greater within the mail survey groups (8.1/10 without follow-up letter and 7.9 with follow-up letter) than within the telephone interview group (7.8) and the face to face interview group (7.3), (p < 0.05).\n Mail survey with follow-up letter constitutes an operational method despite lower data quality and overestimation of patients' satisfaction scores.", "To test the ability of an automated telephone outreach intervention to reduce acute healthcare utilization and improve quality of life among adult asthma patients in a large managed care organization.\n Randomized clinical trial.\n Patients with persistent asthma were randomly assigned to telephone outreach (automated = 3389, live caller = 192) or usual care (n = 3367). Intervention participants received 3 outreach calls over a 10-month period. The intervention provided brief, supportive information and flagged individuals with poor asthma control for follow-up by a provider. A survey was mailed to 792 intervention participants and 236 providers after the intervention. Additional feedback was obtained as part of the final intervention contact.\n The intent-to-treat analysis found no significant differences between the intervention and usual-care groups for medication use, healthcare utilization, asthma control, or quality of life. Post hoc analyses found that, compared with the control group, individuals who actually participated in the intervention were significantly more likely to use inhaled steroids and to have had a routine medical visit for asthma during the follow-up period and less likely to use short-acting beta-agonists. They also reported higher satisfaction with their asthma care and better asthma-specific quality of life. Of surveyed providers, 59% stated the program helped them to clinically manage their asthma patients and 70% thought the program should be continued.\n This study did not find improved health outcomes in the primary analyses. The intervention was well accepted by providers, however, and the individuals who participated in the calls appeared to have benefited from them. These findings suggest that further studies of automated telephone outreach interventions seem warranted.", "The purpose was to determine whether asking about ethnic origin and housing tenure in a postal survey affects the response rate.\n The study derived from a postal survey designed to determine eligibility for a study of outpatients. A two way factorial design was used to look at the two experimental factors, questionnaires being randomly divided into four groups with or without questions about ethnic origin and housing tenure.\n 10,000 people (1000 from each of 10 areas) were systematically sampled from electoral registers, the areas being chosen to give a nationally representative sample.\n The response rate was 66% irrespective of whether ethnic origin was asked about, but was 65% and 67% respectively to questionnaires with and without questions about housing tenure.\n Asking about ethnic origin did not affect the overall response to this survey although it is possible that the response from some ethnic minority groups was lower. Asking about housing tenure slightly, but significantly, decreased response.", "To address provider, payer, and patient concerns about the use of online communication in healthcare settings by performing a randomized controlled trial of a Web-based patient-provider communication tool in primary care.\n Forty-one staff physicians and 91 residents in 4 primary care centers were randomized to a Web-based online communication system. Patients of intervention physicians were encouraged to communicate via the system about health issues, scheduling, prescription renewals, referrals, and billing. Data collected included patient Web use, e-mail use, telephone calls, visit distribution, and physician and patient attitudes toward and satisfaction with communication.\n One thousand thirty-eight patients sent 2238 messages during the 40-week study. Half of the messages were directly related to a patient's health; half were administrative. Patient Web use peaked at 8.5 weekly messages per 100 scheduled visits. Patient e-mail and telephone volume remained similar across groups. Intervention physicians reported more positive attitudes toward Web-based communication than control physicians (mean Web benefits scale score, 4.0 vs 1.1; P = .008), but there were no between-group differences in attitudes toward communication in general. Patients and physicians reported differential preferences for the use of online communication based on problem complexity and sensitivity.\n Web-based messaging was lower than expected because of patient-related factors and limitations of the technology. Patients, physicians, and staff had positive attitudes toward online communication. There was no detectable difference in communication volume between study groups, but more sensitive measures of work burden need to be developed and evaluated.", "This study evaluated the effects of written feedback adapted to a self-help mail intervention. The efficacy of the standard mail intervention treatment was 37% at the end of treatment, 22% at the 3-month follow-up, 19% at the 6-month follow-up, and 13% at the 12-month follow-up. In contrast, the standard mail program combined with personalized written feedback resulted in an efficacy of 51% at the end of treatment, 37% at the 3-month follow-up, 32% at the 6-month follow-up, and 27% at the 12-month follow-up. Both groups were significantly different from the control group at the end of treatment (0%), at the 3-month follow-up (1%), and at the 6-month follow-up (1%). There was a significant reduction in the number of cigarettes smoked daily among continuing smokers under both experimental conditions. The authors conclude that written feedback substantially increases abstinence rates when it is applied following similar guidelines to those used in clinical settings.", "Significant resources and time are invested in the production of research knowledge. The primary objective of this randomized controlled trial was to evaluate the effectiveness of three knowledge translation and exchange strategies in the incorporation of research evidence into public health policies and programs.\n This trial was conducted with a national sample of public health departments in Canada from 2004 to 2006. The three interventions, implemented over one year in 2005, included access to an online registry of research evidence; tailored messaging; and a knowledge broker. The primary outcome assessed the extent to which research evidence was used in a recent program decision, and the secondary outcome measured the change in the sum of evidence-informed healthy body weight promotion policies or programs being delivered at health departments. Mixed-effects models were used to test the hypotheses.\n One hundred and eight of 141 (77%) health departments participated in this study. No significant effect of the intervention was observed for primary outcome (p < 0.45). However, for public health policies and programs (HPPs), a significant effect of the intervention was observed only for tailored, targeted messages (p < 0.01). The treatment effect was moderated by organizational research culture (e.g., value placed on research evidence in decision making).\n The results of this study suggest that under certain conditions tailored, targeted messages are more effective than knowledge brokering and access to an online registry of research evidence. Greater emphasis on the identification of organizational factors is needed in order to implement strategies that best meet the needs of individual organizations.\n The trial registration number and title are as follows: ISRCTN35240937 -- Is a knowledge broker more effective than other strategies in promoting evidence-based physical activity and healthy body weight programming?", "Response rates to postal questionnaires are falling and this threatens the external validity of survey findings. We wanted to establish whether the incentive of being entered into a prize draw to win a personal digital assistant (PDA) would increase the response rate for a national survey of consultant obstetricians and gynaecologists.\n A randomised controlled trial was conducted. This involved sending a postal questionnaire to all Consultant Obstetricians and Gynaecologists in the United Kingdom. Recipients were randomised to receiving a questionnaire offering a prize draw incentive (on response) or no such incentive.\n The response rate for recipients offered the prize incentive was 64% (461/716) and 62% (429/694) in the no incentive group (relative rate of response 1.04, 95% CI 0.96 - 1.13)\n The offer of a prize draw incentive to win a PDA did not significantly increase response rates to a national questionnaire survey of consultant obstetricians and gynaecologists.", "The effects of a number of controllable factors on the response rate of mothers to a postal questionnaire were assessed by a series of experiments. In one a factorial design was used to look at seven factors with a random sample of 1600 mothers. The main findings were that the responses to questionnaires of 8, 16 or 24 pages were similar, but that rather more mothers replied when the questionnaires contained only factual questions than when they covered both facts and attitudes. Another experiment, based on a similar sample, compared the response rates when the questionnaires were sent out by a government organization or by the Institute for Social Studies in Medical Care, and found no difference. The final experiment looked at the effect of precoding the answers or asking respondents to tick boxes beside their replies and again found no difference in response rates. The overall response rate was 79 per cent, but this varied between 66 and 87 per cent in the ten randomly selected study areas--a much greater variation than that found with any of the experimental factors.", "Feedback can be described as a way to provide information on doctors' performance to enable changes in future behaviour. Feedback is used with the aim of changing test-ordering behaviour. It can lead to reductions in test usage and cost savings. It is not sufficiently clear, however, whether feedback leads to more appropriate test use. Since 1985, the Diagnostic Coordinating Center Maastricht has been giving feedback on diagnostic tests as a routine health care activity to all family doctors in its region. Both quantity and quality of requests are discussed. In a randomised, controlled trial over 2.5 years, discussion of tests not included previously was added to the existing routine feedback. One group of family doctors (n = 39) received feedback on test-group A (electrocardiography, endoscopy, cervical smears, and allergy tests), the other (n = 40) on test-group B (radiographic and ultrasonographic tests). Thus, each group of doctors acted as a control group for the other. Changes in volume and rationality of requests were analysed. The number of requests decreased during the trial (p = 0.036). Request numbers decreased particularly for test-group A (p = 0.04). The proportion of requests that were non-rational decreased more in the intervention than in the control groups (p = 0.009). Rationality improved predominantly for test-group B (p = 0.043). Thus, routine feedback can change the quantity and quality of requests.", "Achieving acceptable response rates from health care providers via postal questionnaires is an ongoing challenge. The use of monetary incentives is one of the most effective strategies for increasing response rates. However, the effect and cost of such an incentive on retail pharmacists' response rates has not been well studied.\n A sample of 700 pharmacies was selected at random from the electronic Yellow Pages in NSW Australia and mailed a brief survey regarding pharmacotherapies and advice for smoking cessation. Half of the sample was randomly allocated to receive an offer of an 14 US dollars gift voucher.\n The response rates were 65.9% for the voucher group and 53.5% for the no-voucher group. The odds of response from the voucher group was 1.68 (95%CI = 1.23, 2.30) times greater than for the no-voucher group. The cost per additional respondent was 67.95 US dollars. The incentive also reduced follow up costs by 10%.\n A moderately sized monetary incentive is able to achieve a significant increase in response rates for retail pharmacists, thereby reducing potential bias in the sample.", "Collecting saliva samples by mail can serve numerous purposes in epidemiologic research. The objectives of this study were to assess what proportion of participants in a mail survey would provide a saliva sample and whether incentives could improve participation. In 1995, 2,994 students, faculty, and staff members of Geneva University, Geneva, Switzerland, were randomized to receive, together with a mailed questionnaire about smoking, a saliva vial, a ballpoint pen, the offer of a lottery, or any combination of these. After one mailing and a reminder letter, response rates were 52% among those who had been requested to provide saliva and 63% among controls (p < 0.001). In the former group, most respondents (98%) provided a saliva sample. Incentives improved participation only among those who were asked to provide saliva (lottery: +11% response, p = 0.003; pen: +6% response, p = 0.1). The final participation, after up to three reminders, was 76% overall. The authors conclude that while the collection of saliva samples by mail is feasible it tends to decrease response rates.", "Mailed surveys are a popular means of obtaining data on large populations. In July 1999 a mail survey was conducted among 3000 randomly selected members of the American Society of Hematology to assess their approach to diagnosis and treatment of polycythemia vera. Because the researchers and the study population are members of the same professional organization with a vested interest in the results, we anticipated that the advantages of return stamped postage seen in previous studies would be less significant. The response rate for stamped return envelopes was 38% versus 32% for business reply envelopes. This statistically significant difference (P =.0005) of six percentage points is comparable to previous research. Excluding labor, the total cost per returned survey was $2.62 for business reply envelopes versus $1.82 for stamped return envelopes. We conclude that stamped return envelopes are a more effective and cost-efficient means of procuring data from physician specialists.", "Increases in patient participation in medical interactions have been achieved to date using structured waiting-room interviews. In this pilot study, a printed intervention was tested as an inexpensive alternative with potential for wider dissemination. Sixty-seven family medicine patients were assigned randomly to one to two educational conditions just prior to their medical visit: a treatment booklet stressing the importance of recognizing information needs and encouraging patients to ask questions; or a placebo education booklet similar in format but not in content. The patient-physician interactions were audiotaped to determine the number of questions patients asked, and a questionnaire was administered after each encounter to assess patient satisfaction with care. The mean numbers of questions asked in the experimental and control groups were 7.46 and 5.63, respectively; the mean difference of 1.83 questions was statistically non-significant (P greater than 0.05). Question-asking did not correlate with reported satisfaction. Suggestions for modification to this research approach are presented.", "The objective of this study was to compare the impact of closed- versus open-ended question formats on the completeness and accuracy of demographic data collected in a mailed survey questionnaire. We surveyed general internists in five Canadian provinces to determine their career satisfaction. We randomized respondents to receive versions of the questionnaire in which 16 demographic questions were presented in a closed-ended or open-ended format. Two questions required respondents to make a relatively simple computation (ensuring that three or four categories of response added to 100%). The response rate was 1007/1192 physicians (80.0%). The proportion of respondents with no missing data for all 16 questions was 44.7% for open-ended and 67.0% for closed-ended formats (P < 0.001). The odds of having missing items remained higher for open-ended response options after adjusting for a number of respondent characteristics (2.67, 95% confidence interval 2.01 to 3.55). For the two questions requiring computations focused on professional activity and income, there were more missing data (P = 0.02, 0.02, respectively) but fewer inaccurate responses (P = 0.009, 0.20, respectively) for the open-ended compared to the closed-ended format. Investigators can achieve higher response rates for demographic items using closed format response options, but at the risk of increasing inaccuracy in response to questions requiring computation.", "This study assessed the effectiveness of telephone counseling in a church-based mammography promotion intervention trial.\n Thirty churches were randomized to telephone counseling and control conditions; telephone interview data were used in assessing intervention effects on mammography adherence. Separate analyses were conducted for baseline-adherent participants (maintaining adherence) and baseline-nonadherent participants (conversion to adherence).\n Year 1 follow-up data indicated that the telephone counseling intervention maintained mammography adherence among baseline-adherent participants and reduced the nonadherence rate from 23% to 16%.\n Partnerships between the public health and faith communities are potentially effective conduits to promote maintenance of widely endorsed health behaviors such as regular cancer screening.", "Mailed questionnaires can be a convenient method for collecting data on women's health, although poor response rates are a concern.\n As part of a survey of women's health conducted in Maryland in 2001, a randomized trial was performed to assess the effects of two incentives (US dollars 1.00 or a lottery ticket) as well as precontact with an introductory postcard on response rates. Questionnaires were mailed to 3000 women aged 40-60 who were randomized to one of six incentive/precontact groups: lottery/postcard, money/postcard, postcard only, lottery only, money only, or no incentive/no postcard.\n The overall response rate was 37.6%. Each incentive/precontact group yielded a higher response rate than the no incentive/no postcard group, although only the response rates for the lottery/postcard group (41.3%) and the money only group (40.0%) were significantly higher than that of the no incentive/no postcard group (33.1%). Money was the only factor that had a significant independent effect on likelihood of response (hazards ratio [HR] compared to no incentive = 1.22, 95% confidence interval [CI] = 1.03, 1.43). Response rates were lower in minority ZIP codes, although the effects of the incentives were generally greater than in the nonminority ZIP codes.\n These results indicate that response rates to mailed women's health questionnaires may be improved with modest incentives, particularly cash incentives.", "Mailed surveys are widely used to collect epidemiologic and health service data. Given that nonresponse can threaten the validity of surveys, modest incentives are often used to increase response rates. A study was undertaken among childhood cancer survivors and their parents to determine if response rate to a mailed survey differed with provision of immediate versus delayed incentives.\n A self-administered survey designed to ascertain health behaviors was mailed to 397 childhood cancer survivors (and their parents if the survivor was <18 years of age). Subjects were randomized into two groups based on gender, age, race, and cancer type. One group received a 10 US dollars incentive with their blank survey (unconditional incentive), whereas the other group received the incentive upon receipt of their completed survey (conditional incentive). If children were minors, both the parent and the child received incentives.\n No significant differences in response rates were observed with respect to gender, age, race, or cancer type. However, significant differences in response rates were observed between incentive groups, with unconditional incentives yielding significantly higher response rates than conditional incentives for child survivors who were > or =18 years (64.4% versus 49.0%), as well as younger child survivors (62.5% versus 43.6%) and their parents (64.8% versus 41.5%; all P < 0.05).\n The provision of an immediate incentive generated significantly higher response rates to this mailed health survey among childhood cancer survivors and their parents. Given that survey studies are commonly conducted across various pediatric populations, these findings may help inform the design of future pediatric survey research.", "To evaluate the effectiveness and efficiency of a search strategy to find evidence-based answers to questions related to the possible occupational etiology of diseases.\n A controlled trial of 70 occupational health physicians and 55 insurance physicians who were asked to answer one out of four 'occupational disease case-vignettes' following the steps of evidence-based medicine (EBM). The intervention group were given the search strategy as a tool.\n The intervention group scored significantly better than the control group in answering the main question of the case-vignette correctly (57% versus 37%) using more adequate search terms. The intervention group scored significantly better regarding satisfaction with the applied search strategy (28% very satisfied versus 8%). We found no differences in time spent in solving the case or in the intention of future practice of EBM.\n The introduction and application of specific search strategies can have a positive effect on the effectiveness of searching literature. Future initiatives for developing and testing specific search strategies in the field of occupational health should be encouraged.", "This two-part methodologic research was designed to evaluate the effects of a financial incentive on questionnaire response rate and response bias for general dentists surveyed by mail. Subjects were 517 clinicians randomly selected from a two-state population of practitioners insured by a single malpractice liability carrier. Subjects received a check for either $5 or $10 in the original mailing. In Study 1, a single mailing and postcard follow-up resulted in a 57.8 percent (111/192) response rate. In Study 2, employing Dillman's Total Design Method, a 69.6 percent (208/299) response was obtained after a third mailing. Analysis of response rate by incentive level in each study revealed no significant differences. In contrast, early responders (first mailing and follow-up postcard) differed from late responders (second and third mailings) on age (41.4 vs 37.0 years; T = 2.17; P = .032), non-Caucasians (27.7% vs 63.9%; chi 2 = 17.3; df = 4; P < .002), females (13.9% vs 27.8%; chi 2 = 3.9; df = 1; P < .05), foreign-trained (7.0% vs 19.4%; chi 2 = 16.5; df = 2; P < .001), and dissatisfaction with practice (31% vs 51%; chi 2 = 7.8; df = 4; P = .10). Thus, the magnitude of the financial incentive in this experiment had no differential effect on response rate. But differences in responses from late responders (proxies for nonresponders) on demographic characteristics and key study variables suggest the persistence of response bias despite an acceptable response rate. Future dental health survey research should employ tests for response bias on both sets of variables.", "People providing health care tend to turn to review articles rather than reports of primary research when seeking information to guide their practices. For this reason, the process of reviewing the results of primary research must respect scientific principles. Reviews must be kept up to date and disseminated in appropriate ways to the people who make decisions about health care, including policy makers, practitioners, and users of the health services. This article describes the methods developed and used in an attempt to address these challenges for care during pregnancy and childbirth.", "It is important that response rates to postal surveys are as high as possible to ensure that the results are representative and to maximise statistical power. Previous research has suggested that any personalisation of approach helps to improve the response rate. This experiment tested whether personalising questionnaires by hand signing the covering letter improved the response rate compared with a non-personalised group where the investigator's signature on the covering letter was scanned into the document and printed.\n Randomised controlled trial. Questionnaires about surgical techniques of caesarean section were mailed to 3,799 Members and Fellows of the Royal College of Obstetricians and Gynaecologists resident in the UK. Individuals were randomly allocated to receive a covering letter with either a computer printed signature or a hand written signature. Two reminders were sent to non-respondents. The outcome measures were the proportion of questionnaires returned and their time to return.\n The response rate was 79.1% (1506/1905) in the hand-signed group and 78.4% (1484/1894) in the scanned and printed signature group. There was no detectable difference between the groups in response rate or time taken to respond.\n No advantage was detected to hand signing the covering letter accompanying a postal questionnaire to health professionals.", "To test alternative response formats for the Nottingham Health Profile (NHP), in terms of acceptability, score distributions, and measurement properties.\n Randomized trial of four response formats for the NHP: original \"yes/no\" format, a 3-point similarity format (\"applies completely/in part/not at all\"), a 5-point intensity format (\"completely true\" to \"completely false\"), and a 5-point frequency format (\"all the time\" to \"never\"). Respondents were patients discharged from a hospital. We compared scores distributions, reliability coefficients, correlations with dimension-specific numerical scales, and patient ratings of the instrument.\n Response rates were similar for the four versions. The original response format had the fewest fully completed questionnaires, and the largest ceiling effects. Internal consistency and test-retest coefficients were acceptable for all versions, but were higher for the two 5-point formats. Correlations reflecting convergent and discriminant validity were higher for the longer response formats than for the original version. The frequency format received the highest ratings from patients, particularly from the sicker and older subgroups.\n The psychometric performance and patient acceptability of the NHP can be improved by using a 5-point frequency response format instead of the original dichotomous response format.", "nan", "Translation of evidence-based guidelines into clinical practice has been inconsistent. We performed a randomized, controlled trial of guideline-based care suggestions delivered to physicians when writing orders on computer workstations.\n Inner-city academic general internal medicine practice.\n Randomized, controlled trial of 246 physicians (25 percent faculty general internists, 75 percent internal medicine residents) and 20 outpatient pharmacists. We enrolled 706 of their primary care patients with asthma or chronic obstructive pulmonary disease. Care suggestions concerning drugs and monitoring were delivered to a random half of the physicians and pharmacists when writing orders or filling prescriptions using computer workstations. A 2 x 2 factorial randomization of practice sessions and pharmacists resulted in four groups of patients: physician intervention, pharmacist intervention, both interventions, and controls. DATA EXTRACTION/COLLECTION METHODS: Adherence to the guidelines and clinical activity was assessed using patients' electronic medical records. Health-related quality of life, medication adherence, and satisfaction with care were assessed using telephone questionnaires.\n During their year in the study, patients made an average of five scheduled primary care visits. There were no differences between groups in adherence to the care suggestions, generic or condition-specific quality of life, satisfaction with physicians or pharmacists, medication compliance, emergency department visits, or hospitalizations. Physicians receiving the intervention had significantly higher total health care costs. Physician attitudes toward guidelines were mixed.\n Care suggestions shown to physicians and pharmacists on computer workstations had no effect on the delivery or outcomes of care for patients with reactive airways disease.", "Young adults who had previously participated in a longitudinal survey of youth were sent a questionnaire. They were randomly assigned to receive a $20 prepayment, a $20 postpayment, or a $25 postpayment for participation in the latest survey. Those in the large incentive condition were 7 percentage points more likely to return a survey than those in the smaller, postpayment group. Prepayment had a smaller, less reliable effect. Effects of incentive magnitude and timing were consistent at each month of the study period; only better high school grades distinguished early responders from late responders. Nonresponders had characteristics suggestive of low social conformity and were more likely than responders to be African American and male and have low SES. The discussion centers on motivations for participating in research and differences in the incentives likely to promote continued response versus initial study enrollment." ]	Health researchers using postal and electronic questionnaires can increase response using the strategies shown to be effective in this systematic review.
CD005051	[ "11978259", "11978262", "1846723", "2841662", "15531671", "8112194", "20851308", "9093546" ]	[ "Do whole-grain oat cereals reduce the need for antihypertensive medications and improve blood pressure control?", "Oat ingestion reduces systolic and diastolic blood pressure in patients with mild or borderline hypertension: a pilot trial.", "Effects on serum lipids of adding instant oats to usual American diets.", "Serum lipid response to a fat-modified, oatmeal-enhanced diet.", "Changes in whole-grain, bran, and cereal fiber consumption in relation to 8-y weight gain among men.", "Long-term comparison of three dietary prescriptions in the treatment of NIDDM.", "Randomized, controlled trial promotes physical activity and reduces consumption of sweets and sodium among overweight and obese adults.", "A long-term study on the effect of spontaneous consumption of reduced fat products as part of a normal diet on indicators of health." ]	[ "Our study compared 2 whole grain oat-based cereals with 2 refined grain wheat-based cereals to determine their effects on the need for antihypertensive medications in people with high blood pressure (BP).\n This 12-week, randomized controlled parallel-group trial with = 6 weeks of voluntary follow-up was designed to investigate the antihypertensive effects of oats. After 4 weeks of baseline feeding, medication dose was maintained or reduced by half or completely throughout the middle 4 weeks of the study. In the final 4 weeks, participants continued cereal consumption; medication was adjusted according to the protocol.\n Men and women (n = 88) being treated for hypertension with a mean baseline BP below 160/100.\n Primary study outcomes included change in SBP and DBP as well as antihypertensive medication reduction. Secondary measures included blood lipid, fasting glucose, and insulin levels and side effects related to elevated BP and increased dietary fiber intake.\n Seventy-three percent of participants in the oats group versus 42% in the control group were able to stop or reduce their medication by half. Treatment group participants whose medication was not reduced had substantial decreases in BP. The oats group experienced a 24.2-mg/dL reduction in total cholesterol levels, a 16.2-mg/dL decrease in low-density lipoprotein cholesterol levels, and a 15.03-mg/dL drop in plasma glucose levels vs controls.\n Results suggest that a diet containing soluble fiber-rich whole oats can significantly reduce the need for antihypertensive medication and improve BP control. Considering the lipid and glucose improvements as well, increased consumption of whole oats may significantly reduce cardiovascular disease risk.", "We assessed the short-term antihypertensive effects of soluble fiber-rich whole oat cereals when added to a standard American diet. In addition, multiple assessments of insulin sensitivity were conducted.\n This was a randomized, controlled, parallel-group pilot study designed to compare an oat cereal group (standardized to 5.52 g/day beta-glucan) to a low-fiber cereal control group (less than 1.0 g/day total fiber) over 6 weeks.\n A total of 18 hypertensive and hyperinsulinemic (= 10 U/mL or more) men and women completed the trial.\n Primary study outcomes were changes in systolic blood pressure (SBP) and diastolic blood pressure (DBP). Secondary outcomes included blood lipid, fasting glucose, and insulin levels and side effects related to elevated blood pressure and increased dietary fiber intake.\n The oat cereal group experienced a 7.5 mm Hg reduction in SBP (P &lt.01) and a 5.5 mm Hg reduction in DBP (P &lt.02), while there was virtually no change in either SBP or DBP in the control group. In the oat cereal group, a trend was observed for a lower total insulin response to a glucose load, suggesting improved insulin sensitivity. However, this could not be confirmed using estimates from the Bergman Minimal Model, perhaps because of our small sample size. The oats group experienced a significant reduction in both total cholesterol (9%) and low-density lipoprotein cholesterol (14%).\n The addition of oat cereals to the normal diet of patients with hypertension significantly reduces both SBP and DBP. Soluble fiber-rich whole oats may be an effective dietary therapy in the prevention and adjunct treatment of hypertension.", "This study was designed as a test of the serum lipid response and dietary adaptation to recommended daily inclusion of instant oats in an otherwise regular diet. Hypercholesterolemic adults were randomly assigned to a control or intervention group. Participants in the intervention group were given packages of instant oats and requested to eat two servings per day (approximately two ounces dry weight), substituting the oats for other carbohydrate foods in order to maintain baseline calorie intake and keep weight stable. Serum lipids were measured in blood collected by venipuncture at baseline, four weeks, and eight weeks. Baseline mean total cholesterol (TC) levels were 6.56 mmol/L and 6.39 mmol/L for intervention and control groups, respectively. After eight weeks, mean serum total cholesterol of the intervention group was lower by -0.40 mmol/L, and mean net difference in TC between the two groups was 0.32 mmol/L (95% CI: 0.09, 0.54). Low-density lipoprotein-cholesterol was similarly reduced with mean net difference of 0.25 mmol/L (95% CI: 0.02, 0.48) between the two groups. Mean soluble fiber intake increased along with slight self-imposed reductions in mean total fat, saturated fat, and dietary cholesterol intake in the intervention group. Neither group changed mean body weight. Daily inclusion of two ounces of oats appeared to facilitate reduction of serum total cholesterol and LDL-C in these hyperlipidemic individuals.", "The purpose of this study was to confirm and extend previous findings that serum cholesterol response to a fat-modified diet is enhanced by oat fiber. Participants (n = 236) were recruited from the Continental Illinois National Bank in Chicago. Data including weight, serum lipid level, lipoproteins, and 3-day food records were collected at baseline and every 4 weeks for 12 weeks. All participants were instructed to follow the fat-modified (Phase II) diet recommended by the American Heart Association (AHA). After 4 weeks, participants were randomly assigned to one of two groups. While both groups continued to follow the AHA diet, Group 1 was instructed to include 2 oz (56 g, dry wt) of oatmeal, isocalorically substituted for other carbohydrate foods. Group 2 served as the control and consumed no oat products throughout the study. Serum cholesterol values at baseline and after 4 weeks of the AHA diet were similar for both groups (203.9 and 193.0 mg/dl for Group 1 and 205.3 and 194.5 mg/dl for Group 2). After 4 weeks of oatmeal intervention, mean group differences were -6.8 and -2.1 mg/dl (P = 0.008 one-tailed t test) for Groups 1 and 2, respectively. Following an additional 4 weeks of oatmeal intervention, the Group 1 mean cholesterol increased slightly (0.9 mg/dl), while the Group 2 level decreased slightly (-0.7 mg/dl). Overall serum cholesterol responses for the two groups from Visit 2 to Visit 4 were -6.0 and -2.8 mg/dl for Groups 1 and 2, respectively (P = 0.074, one tail). Changes in weight were small and nonsignificant. Subgroup analyses revealed greater reductions in serum cholesterol among participants with the highest baseline serum cholesterol (-8.0 mg/dl vs -1.7 mg/dl for Subgroups 1 and 2, respectively). These data support previous findings that inclusion of oatmeal in a fat-modified diet is helpful in lowering serum cholesterol, particularly for individuals with elevated serum cholesterol levels.", "Epidemiologic studies that directly examine changes in whole-grain consumption in relation to weight gain are sparse, and characterization of this association has been obscured by methodologic inconsistencies in the assessment of whole grains.\n We aimed to ascertain the associations between changes in new quantitative estimates of whole-grain intake and 8-y weight gain among US men.\n The study was conducted in a prospective cohort of 27 082 men aged 40-75 y at baseline in 1986. Data on lifestyle factors were obtained periodically by using self-reported questionnaires, and participants measured and reported their body weight in 1986 and 1994.\n In multivariate analyses, an increase in whole-grain intake was inversely associated with long-term weight gain (P for trend < 0.0001). A dose-response relation was observed, and for every 40-g/d increment in whole-grain intake from all foods, weight gain was reduced by 0.49 kg. Bran that was added to the diet or obtained from fortified-grain foods further reduced the risk of weight gain (P for trend = 0.01), and, for every 20 g/d increase in intake, weight gain was reduced by 0.36 kg. Changes in cereal and fruit fiber were inversely related to weight gain. No associations were observed between changes in refined-grain or added germ consumption and body weight.\n The increased consumption of whole grains was inversely related to weight gain, and the associations persisted after changes in added bran or fiber intakes were accounted for. This suggests that additional components in whole grains may contribute to favorable metabolic alterations that may reduce long-term weight gain.", "To compare three sets of dietary guidelines for the treatment of non-insulin-dependent diabetes (NIDDM) in free-living individuals and to observe the effects on metabolic control over an 18-month period.\n Seventy volunteer subjects with NIDDM were randomly assigned to one of three diets, a weight-management diet, a high-carbohydrate/fiber diet, or a modified-lipid diet and followed for 18 months. Nutrient intakes, weight, blood lipids, and glycemic control were measured.\n In all diet groups, glycated hemoglobin (HbA1) fell significantly before diet intervention began, remaining lower throughout the study and at follow-up 9 months later. Low-density lipoprotein (LDL) cholesterol showed a sustained fall in all groups after diet intervention. Apart from transient changes in high-density lipoprotein (HDL) cholesterol and triglyceride (TG) in the diet groups with the higher carbohydrate intake, no lasting differences were found between the three diet groups.\n In the long term, there were few differences in the outcome of the three dietary prescriptions. Even with intensive instruction, participants found it difficult to meet recommended nutrient intakes; however, specific dietary advice did result in an improvement in LDL cholesterol. Adverse changes in HDL cholesterol and TG because of diet intervention were transient. The significant improvement in glycemic control during the recruitment phase may have been the result of participants' previous dietary knowledge and the increased attention that they received during the intervention.", "The present study sought to assess the impact of an intervention to reduce weight and control risk factors of noncommunicable chronic diseases in overweight or obese adults who are users of primary and secondary healthcare units of the public health system of Pelotas, Brazil. We hypothesized that individuals who received an educational intervention regarding how to lose weight and prevent other noncommunicable chronic disease risk factors through nutrition would lose weight and acquire active habits during leisure time more frequently than individuals under regular care. Two hundred forty-one participants from the Nutrition Outpatient Clinic of the Medical Teaching Hospital of the Federal University of Pelotas, Brazil, aged 20 years or older and classified as overweight or obese were randomly allocated to either the intervention group (IG; n = 120) or control group (CG; n = 121). The IG received individualized nutritional care for 6 months, and the CG received individualized usual care of the health services. Intention-to-treat analyses showed that at 6 months, mean fasting glycemia and daily consumption of sweet foods and sodium were reduced, and the time spent on physical leisure activity was increased in IG. Analysis of adherence to the protocol of the study revealed that individuals from IG had lost more in body weight, waist circumference, and fasting glucose compared to the CG. Leisure time physical activity increased in IG. Individuals adhered equally to the dietetic recommendations, irrespective of the nutrition approach that was used.\n Copyright © 2010 Elsevier Inc. All rights reserved.", "The growing public concern with the adverse effects on health of a high fat intake has led to a proliferation on the market of reduced fat products. However, no consensus exists on the effectivity of reduced fat products to decrease energy intake. The studies that have investigated this topic have included small numbers of subjects, studied under laboratory conditions and over a relatively short period of time. Therefore, we have executed a long-term study in which volunteers had free access to both reduced fat, commercially available products in the laboratory as well as to products obtained from regular shops. We here report the feasibility of such a type of study and the effects of consumption of reduced fat products on blood levels of cholesterol, haemostasis variables, antioxidants and parameters of the immune system. The study was a multicentre parallel comparison trial of six months (so-called MSFAT-study). 241 volunteers received either reduced fat products or full-fat products and the products were clearly labelled as such. Two months before the start of the study, a 1 month adaptation period was executed to optimize the experimental procedures. Food intake was recorded before the start of the adaptation period and 2-4 weeks, 3 months and 6 months after the start of the study. Blood samples were taken before, after 2, 4 and 6 months of the study. In addition, a selection of the reduced fat and full-fat products was sensorically evaluated three times during the study by a subgroup of the volunteers. 220 volunteers completed the study. The reduced fat group consumed on average 46% less fat from the so-called MSFAT-products obtained from the shop at the laboratory than the control group and consumption of these MSFAT-products did not decrease in either of the groups during the time course of the study. The palatability of the reduced fat and full-fat products was similar and as expected, the perceived fattiness of the full-fat products was higher than that of the reduced fat products. No effects were found on blood levels of cholesterol, haemostasis variables, parameters of antioxidant status and immune system characteristics. In conclusion, the experimental manipulation of the fat content of the diet that was achieved and that remained stable throughout the 6 months of the study indicates that this type of set-up is feasible to assess the effects of long-term nutritional intervention in large groups of volunteers under semi-controlled conditions. The regular use of reduced fat products did not positively but also not adversely affect blood cholesterol levels, antioxidant status, haemostasis factors and the body's immune system." ]	Despite the consistency of effects seen in trials of wholegrain oats, the positive findings should be interpreted cautiously. Many of the trials identified were short term, of poor quality and had insufficient power. Most of the trials were funded by companies with commercial interests in wholegrains. There is a need for well-designed, adequately powered, longer term randomised controlled studies in this area. In particular there is a need for randomised controlled trials on wholegrain foods and diets other than oats.
CD002792	[ "2179650", "16330624", "19755362", "17976288", "9217619", "7496238", "10675118", "10320115", "11593835", "10420862", "18025916" ]	[ "Improving physicians' recognition and treatment of depression in general medical care. Results from a randomized clinical trial.", "Systematic detection and multidisciplinary care of depression in older medical inpatients: a randomized trial.", "Case management for depression by health care assistants in small primary care practices: a cluster randomized trial.", "Graduate mental health worker case management of depression in UK primary care: a pilot study.", "A randomized trial of office-based screening for common problems in older persons.", "Twelve month outcome of depression in general practice: does detection or disclosure make a difference?", "Effects of a clinical-practice guideline and practice-based education on detection and outcome of depression in primary care: Hampshire Depression Project randomised controlled trial.", "Case-finding for depression in primary care: a randomized trial.", "Randomised controlled trial of tailored strategies to implement guidelines for the management of patients with depression in general practice.", "Effectiveness of an educational strategy to improve family physicians' detection and management of depression: a randomized controlled trial.", "The effects and expense of augmenting usual cancer clinic care with telephone problem-solving counseling." ]	[ "A randomized clinical trial was performed to assess whether the results of a depression screening instrument, when provided to physicians, could influence their recognition and treatment of depression in a primary care setting. The intervention consisted of randomly informing or not informing physicians of the depression status of 100 patients who screened positively for depression on both the Zung Self-rating Depression Scale (SDS) and a DSM-III screen. For 12 months patients were followed to assess depression status, and medical records were audited to assess depression recognition and treatment. Results show that feedback to physicians of SDS scores of previously unrecognized depressed patients makes a significant difference in greater recognition (56.2% vs. 34.6%) and treatment (56.2% vs. 42.3%) of depression over the 12-month study period. This was especially true for patients with high somatic (P less than 0.05) or low psychologic symptoms of depression (P less than 0.05). These results suggest that routine use of a depression screening instrument can improve physician recognition of depression, with increased initiation of treatment.", "Major depression is a frequent and serious disorder in older medical inpatients. Because the condition goes undetected and untreated in most of these patients, we conducted a randomized clinical trial to evaluate the effectiveness of a strategy of systematic detection and multidisciplinary treatment of depression in this population.\n Consecutive patients aged 65 years or more admitted to general medical services in a primary care hospital between October 1999 and November 2002 were screened for depression with the Diagnostic Interview Schedule (DIS) within 48 hours after admission. Patients found to have major depression were randomly allocated to receive the intervention or usual care. The intervention involved consultation and treatment by a psychiatrist and follow-up by a research nurse and the patient's family physician. Research assistants, blind to group allocation, collected data from the patients at enrollment and at 3 and 6 months later using the Hamilton Depression Rating Scale (HAMD), the Medical Outcomes 36-item Short Form (SF-36), the DIS, the Mini-Mental State Examination (MMSE), the Older Americans Resources and Services (OARS) questionnaire to assess basic and instrumental activities of daily living (OARS-ADL and OARS-IADL) and the Rating Scale for Side Effects. Data on the severity of illness, length of hospital stay, health services and medication use, mortality and process of care were also collected. The primary outcome measures were the HAMD and SF-36.\n Of 1500 eligible patients who were screened, 157 were found to have major depression and consented to participate (78 in the intervention group and 79 in the usual care group). At randomization, there were no clinically or statistically significant differences between the 2 groups. Sixty-four patients completed follow-up to 6 months, 57 withdrew, and 36 died. At 6 months, there were no clinically or statistically significant differences the 2 groups in HAMD or SF-36 scores or any of the secondary outcome measures.\n We were unable to demonstrate that systematic detection and multidisciplinary care of depression was more beneficial than usual care for elderly medical inpatients.", "Case management by health care assistants in small primary care practices provides unclear benefit for improving depression symptoms.\n To determine whether case management provided by health care assistants in small primary care practices is more effective than usual care in improving depression symptoms and process of care for patients with major depression.\n Cluster randomized, controlled trial. A central automated system generated the randomization scheme, which was stratified by urban and rural practices; allocation sequence was concealed until groups were assigned.\n 74 small primary care practices in Germany from April 2005 to September 2007.\n 626 patients age 18 to 80 years with major depression.\n Structured telephone interview to monitor depression symptoms and support for adherence to medication, with feedback to the family physician.\n Depression symptoms at 12 months, as measured by the Patient Health Questionnaire-9 (PHQ-9); secondary outcomes were patient assessment of chronic illness care, adherence to medication, and quality of life.\n A total of 310 patients were randomly assigned to case management and 316 to usual care. At 12 months, 249 intervention recipients and 278 control patients were assessed; 555 patients were included in a modified intention-to-treat-analysis (267 intervention recipients vs. 288 control patients). Compared with control patients, intervention recipients had lower mean PHQ-9 values in depression symptoms (-1.41 [95% CI, -2.49 to -0.33]; P = 0.014), more favorable assessments of care (3.41 vs. 3.11; P = 0.011), and increased treatment adherence (2.70 vs. 2.53; P = 0.042). Quality-of-life scores did not differ between groups.\n Patients, health care assistants, family physicians, and researchers were not blinded to group assignment, and 12-month follow-up of patients was incomplete.\n Case management provided by primary care practice-based health care assistants may reduce depression symptoms and improve process of care for patients with major depression more than usual care.\n German Ministry of Education and Research.", "Based on data from large multicentre US trials, the National Institute for Health and Clinical Excellence (NICE) is advocating a stepped-care model for the management of depression, with 'case management' or 'collaborative care' for selected patients in primary care.\n To conduct a pilot study examining the use of graduate mental health workers case managing depressed primary care NHS patients.\n A randomised controlled trial comparing usual GP care with or without case management over 16 weeks of acute antidepressant drug treatment.\n Three primary care practices in the North East of England.\n Patients with depression, aged 18-65 years, who had failed to adequately respond to antidepressant treatment, were randomised to the two treatments. Assessments were made at baseline, 12, and 24 weeks using a combination of observer and self ratings.\n Randomisation of 62 patients required screening of 1073 potential patients. There was little difference in outcome between the two treatment arms but a gradual improvement in symptoms over time was seen. Client satisfaction was assessed as high across both treatments.\n While this pilot study confirmed the integrity of the study protocol and the suitability of the outcome measures and randomisation procedure, it raises questions regarding the practicality of recruitment and feasibility of the intervention. It would be crucial to address these issues prior to the implementation of a large multi-centre randomised controlled trial.", "To test the effectiveness of a 10-minute office-staff administered screen to evaluate malnutrition/weight loss, visual impairment, hearing loss, cognitive impairment, urinary incontinence, depression, physical limitations, and reduced leg mobility among older persons seen in office practice. This screen was coupled with clinical summaries to assist the physician in further evaluating and managing the screen-included problems.\n Twenty-six community-based office practices of internists and family physicians in Los Angeles were randomized to intervention or control groups. Two hundred and sixty-one patients aged > or = 70 years and seeing these physicians for a new visit or a physical examination participated in the study. At the enrollment visit intervention group patients were administered the screening measure and their physicians were given the pertinent clinical summaries. Outcome measures were detection of, and intervention for conditions screened, and health status 6 months after the intervention.\n Hearing loss was both more commonly detected (40% intervention versus 28% control) and further evaluated (29% versus 16%) by physicians in the intervention group (P < 0.05). No other differences in the frequency of problem detection or intervention were noted between groups. Six months after the intervention no differences were noted in health status between groups.\n A brief measure to screen for common conditions in older persons was associated with more frequent detection and follow-up assessment of hearing loss. Although the measure was well accepted by physicians and their staffs, it did not appear to affect detection and intervention in regard to the other screen-included conditions, or health status at 6 months.", "To assess the extent to which the outcome of depression among primary care attenders may be affected by medical diagnosis or by feedback of questionnaire results in unrecognised cases.\n Prospective 12 month study including a randomised controlled trial of the effects of disclosure, with data on depression status and clinical management collected by questionnaire and interview.\n Two group practices in north Liverpool.\n 1099/1444 (76%) consecutive adult attenders completed the Beck depression inventory, of whom 179 with scores of at least 14 were followed up.\n Disclosure of a random 45% (52/116) of depression scores to general practitioners for subjects whose depression was undetected.\n Depression status estimated by depression score at start of study and at six and 12 months, with subsample validation against ICD-10 criteria.\n Questionnaire response rates were 76% (136/179) at six months and 68% (122/179) at 12 months and were higher for women than men. The median depression score was 19 (interquartile range 15 to 22) initially, decreasing to 16 (11 to 23) at 12 months. The median depression score decreased significantly (two sided test, P = 0.019) in subjects whose depression was unrecognised at the index consultation but increased in those whose depression had been detected by their general practitioners. Disclosure of cases of unrecognised depression to general practitioners had no effect on outcome. Intention to treat was associated with a worse prognosis, although only a minority of subjects received adequate treatment.\n Disclosure of undetected depression did not improve prognosis. A diagnosis of depression in general practice should be considered simply as a marker of its severity.", "Depression is a major individual and public-health burden throughout the world and is managed mainly in primary care. The most effective strategy to reduce this burden has been believed to be education of primary-care practitioners. We tested this assumption by assessing the effectiveness of an educational programme based on a clinical-practice guideline in improving the recognition and outcome of primary-care depression.\n We carried out a randomised controlled trial in a representative sample of 60 primary-care practices (26% of the total) in an English health district. Education was delivered to practice teams and quality tested by feedback from participants and expert raters. The primary endpoints were recognition of depression, defined by the hospital anxiety and depression (HAD) scale, and clinical improvement. Analysis was by intention to treat.\n The education was well received by participants, 80% of whom thought it would change their management of patients with depression. 21409 patients were screened, of whom 4192 were classified as depressed by the HAD scale. The sensitivity of physicians to depressive symptoms was 39% in the intervention group and 36% in the control group after education (odds ratio 1.2 [95% CI 0.88-1.61]). The outcome of depressed patients as a whole at 6 weeks or 6 months after the assessment did not significantly improve.\n Although well received, this in-practice programme, which was designed to convey the current consensus on best practice for the care of depression, did not deliver improvements in recognition of or recovery from depression.", "Depression is a highly prevalent, morbid, and costly illness that is often unrecognized and inadequately treated. Because depression questionnaires have the potential to improve recognition, we evaluated the accuracy and effects on primary care of two case-finding instruments compared to usual care.\n The study was conducted at three university-affiliated and one community-based medical clinics. Consecutive patients were randomly assigned to be asked a single question about mood, to fill out the 20-item Center for Epidemiologic Studies Depression Screen, or to usual care. Within 72 hours, patients were assessed for Diagnostic and Statistical Manual of Mental Disorders Third Revised Edition (DSM-III-R) disorders by an assessor blinded to the screening results. Process of care was assessed using chart audit and administrative databases; patient and physician satisfaction was assessed using Likert scales. At 3 months, depressed patients and a random sample of nondepressed patients were re-assessed for DSM-III-R disorders and symptom counts.\n We approached 1,083 patients, of whom 969 consented to screening and were assigned to the single question (n = 330), 20-item questionnaire (n = 323), or usual care (n = 316). The interview for DSM-III-R diagnosis was completed in 863 (89%) patients; major depression, dysthymia, or minor depression was present in 13%. Both instruments were sensitive, but the 20-item questionnaire was more specific than the single question (75% vs 66%, P = 0.03). The 20-item questionnaire was less likely to be self-administered (54% vs 90%) and took significantly more time to complete (15 vs 248 seconds). Case-finding with the 20-item questionnaire or single question modestly increased depression recognition, 30/77 (39%) compared with 11/38 (29%) in usual care (P = 0.31) but did not affect treatment (45% vs 43%, P = 0.88). Effects on DSM-III-R symptoms were mixed. Recovery from depression was more likely in the case-finding than usual care groups, 32/67 (48%) versus 8/30 (27%, P = 0.03), but the mean improvement in depression symptoms did not differ significantly (1.6 vs 1.5 symptoms, P = 0.21).\n A simple question about depression has similar performance characteristics as a longer 20-item questionnaire and is more feasible because of its brevity. Case-finding leads to a modest increase in recognition rates, but does not have consistently positive effects on patient outcomes.", "Various methods are available for implementing change in the clinical behaviour of general practitioners (GPs). Although passive dissemination of information is generally ineffective, other methods can be variably effective. Few studies have investigated the impact of tailored methods.\n To determine whether methods tailored to overcome obstacles to change using psychological theories are more effective than dissemination alone in the implementation of guidelines for depression among GPs.\n Randomised controlled trial.\n Sixty general practices in England; 30 GPs in the control group, 34 in the intervention group.\n Practitioners identified patients presenting with depression before and after the implementation of guidelines (control group n = 192 in the first data collection, n = 181 in the second; intervention group n = 210 in the first data collection and n = 197 in the second). The main outcome measures were: record of adherence to guideline recommendations in clinical records; proportion of patients with Beck Depression Inventory (BDI) score less than 11 at 16 weeks after diagnosis.\n In comparison with the control group, in the group of GPs receiving tailored implementation, there were increases in the proportions of patients assessed for suicide risk. In the intervention group, the proportion of patients with BDI scores of less than 11 at 16 weeks increased.\n Obstacles to implementation can be identified and strategies tailored to address them. The findings indicate a new approach for research to understand and develop methods of implementation.", "Depression, a common disorder often treated by family physicians, may be both underdiagnosed and undertreated. The objective of this study was to determine whether the diagnosis and treatment of depression by family physicians could be improved through an educational strategy.\n In this study, conducted between July and December 1997, 42 family physicians in Newfoundland were randomly assigned to an intervention group (3-hour case-based educational session on clinical practice guidelines [CPGs] for depression and access to a psychiatrist for consultation) or to a control group (receipt of CPGs without educational session or access to the psychiatrist). Physicians were asked to keep a log of patients with newly diagnosed depression and to record information on severity of depression, medications and referrals to mental health professionals. Patients were asked to complete the Centre for Epidemiologic Studies Depression (CES-D) scale before treatment and after 6 months of follow-up. The primary outcome measure was the \"gain\" score (difference between first and last CES-D scores).\n During the study period physicians in the intervention group diagnosed 91 new cases of depression (mean 4.1 per physician) and those in the control group diagnosed 56 (mean 2.8 per physician); the difference was not significant. Most patients (91.2% in the intervention group and 89.3% in the control group received a prescription for an antidepressant on their first visit. Similar proportions (46.2% in the intervention group and 37.5% in the control group) took their medication for the full 6 months; however, significantly more patients in the intervention group were taking an antidepressant at the 6-month follow-up (56% v. 39.3%, p = 0.02). The mean number of visits per patient was similar in the 2 groups (7.7 in the intervention group and 7.6 in the control group). Physicians in the intervention group consulted the psychiatrist 9 times. The overall rate of referrals to psychiatrists and other mental health professionals was 10.9%; however, referrals were significantly higher in the intervention group (15.4% v. 3.5%, p = 0.05). After 6 months of follow-up, a significant difference in gain scores was detected between the intervention and control groups for both the patient's self-rated CES-D scores (mean gain score 19.3 v. 15.5 respectively, p = 0.04) and the physicians' ratings of depression severity before treatment and at 6 months (mean gain 1.1 v. 0.7 respectively, p = 0.02).\n The educational strategy had a modest beneficial effect on the outcomes of patients with depression, but there are still concerns regarding the low rates of drug treatment and referral to mental health professionals by family physicians.", "This study was done to assess the effectiveness and efficiency of individualized, problem-solving counseling provided by baccalaureate nurses over the telephone to prevent the onset of depression in persons with breast, lung, or prostate cancer. Of 175 persons randomized, 149 completed the 8-month follow-up. The primary outcome measures were changes in the Jalowiec Coping Scale, the Centre for Epidemiologic Studies in Depression Scale, and the Derogotis Psychosocial Adjustment to Illness Scale. In addition, expenditures for people's use of all health and social services were computed at baseline and follow-up. Telephone counseling improved the use of more favorable coping behaviors, prevented a clinically important but not statistically significant decline into depression, and poor psychosocial adjustment in a group of people with mixed cancer. These results were associated with a greater total per person per annum expenditure for use of all other health and social services in the community compared with the control group. In a situation of limited resources and a service producing more effect for more costs, one needs either to examine what services to forgo to offer this service or to carefully target the new service to those most likely to benefit." ]	There is substantial evidence that routinely administered case finding/screening questionnaires for depression have minimal impact on the detection, management or outcome of depression by clinicians. Practice guidelines and recommendations to adopt this strategy, in isolation, in order to improve the quality of healthcare should be resisted. The longer term benefits and costs of routine screening/case finding for depression have not been evaluated. A two stage procedure for screening/case finding may be effective, but this needs to be evaluated in a large scale cluster randomised trial, with a prospective economic evaluation.
CD003712	[ "10028979", "3191758", "1896416", "18947861", "11152840", "10391261" ]	[ "Transmyocardial laser revascularisation in patients with refractory angina: a randomised controlled trial.", "Prospective trial of supranormal values of survivors as therapeutic goals in high-risk surgical patients.", "Randomized clinical trial of transabdominal versus transcervical chorionic villus sampling methods.", "Total laparoscopic hysterectomy versus abdominal hysterectomy with lymphadenectomy for early-stage endometrial cancer: a prospective randomized study.", "Impact of presentation of research results on likelihood of prescribing medications to patients with left ventricular dysfunction.", "Holmium:YAG laser transmyocardial revascularization relieves angina and improves functional status." ]	[ "Transmyocardial laser revascularisation (TMLR) is used to treat patients with refractory angina due to severe coronary artery disease, not suitable for conventional revascularisation. We aimed in a randomised controlled trial to assess the effectiveness of TMLR compared with medical management.\n 188 patients with refractory angina were randomly assigned TMLR plus normal medication or medical management alone. At 3 months, 6 months, and 12 months after surgery (TMLR) or initial assessment (medical management) we assessed exercise capacity with the treadmill test and the 12 min walk.\n Mean treadmill exercise time, adjusted for baseline values, was 40 s (95% CI -15 to 94) longer in the TMLR group than in the medical-management group at 12 months (p=0.152). Mean 12 min walk distance was 33 m (-7 to 74) further in TMLR patients than medical-management patients (p=0.108) at 12 months. The differences were not significant or clinically important. Perioperative mortality was 5%. Survival at 12 months was 89% (83-96) in the TMLR group and 96% (92-100) in the medical-management group (p=0.14). Canadian Cardiovascular Society score for angina had decreased by at least two classes in 25% of TMLR and 4% of medical-management patients at 12 months (p<0.001).\n Our findings show that the adoption of TMLR cannot be advocated. Further research may be appropriate to assess any potential benefit for sicker patients.", "Survivors of high-risk surgical operations were previously observed to have significantly higher mean CI, DO2, and VO2 than nonsurvivors. The hypothesis was proposed that increased CI and DO2 are circulatory compensations for increased postoperative metabolism. We tested this hypothesis in two series. In series 1, prospectively allocated by services, mortality and morbidity of the control group were significantly greater than those of the protocol group. In series 2, patients who fulfilled previously defined high-risk criteria were preoperatively randomized to one of three monitoring/treatment groups: CVP-control group, PA-control group and PA-protocol group. Postoperative mortalities in the CVP-control and PA-control groups were not statistically significantly different, but PA-protocol group mortality was significantly reduced compared with its control group. The PA-protocol group had reduced complications, duration of hospitalization, duration in ICU, and mechanical ventilation, and reduced costs when the PA catheter was placed preoperatively and used to augment circulatory responses.", "The relative advantages and disadvantages of transabdominal (TA) and transcervical (TC) chorionic villus sampling (CVS) in terms of fetal risks and efficacy were evaluated in a clinical trial conducted on 1194 women randomized at 7-12 weeks' gestation. The results of the study indicate that, if any, the relative risk of fetal loss following either procedure is less than double that of the alternative technique when performed by a skilled operator. Overall, the fetal loss rate (spontaneous abortions following randomization, terminations of pregnancy, and perinatal deaths) is 16.5 and 15.5 per cent, respectively, among women allocated to TA- and TC-CVS. The two procedures are equally effective, although TA-CVS is associated with a significantly lower rate of repeat device insertions; on the other hand, a higher weight of chorionic tissue is obtained, on average, with TC-CVS. Bleeding is more common following TC-CVS, while peritoneal reaction developed only after TA-CVS. No diagnostic problems specifically related to one sampling technique were identified.", "The aim of this study was to compare, in a series of 159 women the feasibility, safety and morbidity of total laparoscopic hysterectomy (LPS) and abdominal hysterectomy with lymphadenectomy (LPT) for early-stage endometrial cancer and to assess disease-free survival and recurrence rate.\n 159 patients with clinical stage I endometrial cancer were enrolled in a prospective randomized trial and treated with LPS or LPT approach. The para-aortic lymphadenectomy was performed in all cases with positive pelvic lymph nodes discovered at frozen section evaluation, in patients with poorly differentiated tumors with myometrial invasion greater than 50% (ICG3), and non-endometrioid carcinomas.\n The mean operative time was 136 min+/-31 (95% CI 118-181) in the LPS group and 123 min+/-29 (95% CI 111-198) in the LPT group (P<0.01). The mean blood loss was 50 ml+/-12 in the LPS group (95% CI 20-90) and 145 ml+/-35 in the LPT group (95% CI 60-255) (P<0.01). The mean length of hospital stay was 5.1+/-1.2 in the LPT group (95% CI 1-7) and 2.1+/-0.5 in the LPS group (95% CI 1-5) (P<0.01).\n Laparoscopy is a suitable procedure for the treatment of patients with early endometrial cancer and may offer the potential benefits of decreased discomfort with decreased convalescence time without compromising the degree of oncological radicality required; however, it does not seem to modify the disease-free survival and the overall survival, although multicenter randomized trials and long-term follow-up are required to evaluate the overall oncologic outcomes of this procedure.", "This study was conducted to evaluate willingness to prescribe medication based on identical data presented in different outcome terms to health professionals of varied discipline, geographic location, and level of training. Cross-sectional survey using a self-administered questionnaire was performed in 400 health professionals (physicians, pharmacists, physicians-in-training, and pharmacy students) in the United States and Europe. Data reflecting a clinical trial were presented in 6 outcome terms: 3 terms describing identical mortality (relative risk reduction, absolute risk reduction, and number of patients needed to be treated to prevent 1 death); and 3 distractors (increased life expectancy, decreased hospitalization rate, and decreased cost). Willingness to prescribe and rank order of medication preference assuming willingness to prescribe were measured. The results of the study showed that willingness to prescribe and first choice preference were significantly greater when study results were presented as relative risk reduction than when identical mortality data were presented as absolute risk reduction or number of patients needed to be treated to avoid 1 death (p <0.001). Increase in life expectancy was the most influential distractor. In conclusion, this study, performed in the era of \"evidence-based medicine,\" demonstrates that the method of reporting research trial results has significant influence on health professionals' willingness to prescribe. The high numerical value of relative risk reduction and the concrete and tangible quality of increased life expectancy exert greater influence on health professionals than other standard outcome terms.", "Transmyocardial revascularization (TMR) surgery uses laser channeling of diseased myocardium to treat ischemia and angina. Rigorous prospective randomized studies have been previously unavailable.\n Forty-three patients were randomized to a medication group and 43 to a group scheduled for TMR surgery and medication. All had advanced cardiac ischemia with CCSA class 3 or 4 angina, took at least 2 cardiac medications at maximum doses, and were ineligible for angioplasty or bypass.\n Forty-two of 43 TMR group patients received surgery and were discharged after hospitalizations averaging 3.2 days. Two suffered perioperative MIs, with one death. Four others died within 12 months of surgery, 3 from cardiac events and 1 from pneumonia. Five medical group patients died from cardiac events within 12 months. Three, 6, and 12 month exams showed angina class improvement in TMR patients compared to preoperative values (3.86 +/- 0.05 vs 1.71 +/- 0.2, P < 0.0001), and to controls at 12 months (3.77 +/- 0.07 vs 1.71 +/- 0.2, P < 0.0001). Exercise tolerance improved in TMR patients over preoperative values, and was better than medication group scores after 12 months (490 +/- 17 sec. vs 294 +/- 12 sec., p = 0.0002).\n Holmium:YAG laser channeling of the myocardium improves function and reduces angina in advanced cardiac patients who lack alternative therapeutic options." ]	There is insufficient evidence to conclude that the clinical benefits of TMLR outweigh the potential risks. The procedure is associated with a significant early mortality.
CD008349	[ "20508185", "22275463", "19692788", "17167194", "15890990", "21840917", "18633001", "12601321", "19118130", "18988916", "7603271", "10421300", "17332444", "15481562", "9756581", "16271575" ]	[ "Effectiveness of virtual reality using Wii gaming technology in stroke rehabilitation: a pilot randomized clinical trial and proof of principle.", "Virtual reality in the rehabilitation of the arm after hemiplegic stroke: a randomized controlled pilot study.", "Use of virtual reality to enhance balance and ambulation in chronic stroke: a double-blind, randomized controlled study.", "Virtual reality training for stroke rehabilitation.", "Virtual reality-induced cortical reorganization and associated locomotor recovery in chronic stroke: an experimenter-blind randomized study.", "Effects of robot-assisted upper limb rehabilitation on daily function and real-world arm activity in patients with chronic stroke: a randomized controlled trial.", "Satisfaction with care in post-stroke patients undergoing a telerehabilitation programme at home.", "Vestibular rehabilitation: useful but not universally so.", "Effects of constraint-induced therapy versus bilateral arm training on motor performance, daily functions, and quality of life in stroke survivors.", "Effects of training with a robot-virtual reality system compared with a robot alone on the gait of individuals after stroke.", "Effects of vestibular rehabilitation and social reinforcement on recovery following ablative vestibular surgery.", "Intensity of leg and arm training after primary middle-cerebral-artery stroke: a randomised trial.", "Mental practice in chronic stroke: results of a randomized, placebo-controlled trial.", "Preliminary study of the effect of low-intensity home-based physical therapy in chronic stroke patients.", "A randomized, controlled pilot study of a home-based exercise program for individuals with mild and moderate stroke.", "Cortical reorganization and associated functional motor recovery after virtual reality in patients with chronic stroke: an experimenter-blind preliminary study." ]	[ "Hemiparesis resulting in functional limitation of an upper extremity is common among stroke survivors. Although existing evidence suggests that increasing intensity of stroke rehabilitation therapy results in better motor recovery, limited evidence is available on the efficacy of virtual reality for stroke rehabilitation.\n In this pilot, randomized, single-blinded clinical trial with 2 parallel groups involving stroke patients within 2 months, we compared the feasibility, safety, and efficacy of virtual reality using the Nintendo Wii gaming system (VRWii) versus recreational therapy (playing cards, bingo, or \"Jenga\") among those receiving standard rehabilitation to evaluate arm motor improvement. The primary feasibility outcome was the total time receiving the intervention. The primary safety outcome was the proportion of patients experiencing intervention-related adverse events during the study period. Efficacy, a secondary outcome measure, was evaluated with the Wolf Motor Function Test, Box and Block Test, and Stroke Impact Scale at 4 weeks after intervention.\n Overall, 22 of 110 (20%) of screened patients were randomized. The mean age (range) was 61.3 (41 to 83) years. Two participants dropped out after a training session. The interventions were successfully delivered in 9 of 10 participants in the VRWii and 8 of 10 in the recreational therapy arm. The mean total session time was 388 minutes in the recreational therapy group compared with 364 minutes in the VRWii group (P=0.75). There were no serious adverse events in any group. Relative to the recreational therapy group, participants in the VRWii arm had a significant improvement in mean motor function of 7 seconds (Wolf Motor Function Test, 7.4 seconds; 95% CI, -14.5, -0.2) after adjustment for age, baseline functional status (Wolf Motor Function Test), and stroke severity.\n VRWii gaming technology represents a safe, feasible, and potentially effective alternative to facilitate rehabilitation therapy and promote motor recovery after stroke.", "To assess the feasibility of a trial to investigate the effectiveness of virtual reality-mediated therapy compared to conventional physiotherapy in the motor rehabilitation of the arm following stroke, and to provide data for a power analysis to determine numbers for a future main trial.\n Pilot randomized controlled trial.\n Clinical research facility.\n Eighteen people with a first stroke, 10 males and 8 females, 7 right and 2 left side most affected. Mean time since stroke 10.8 months.\n Participants were randomized to a virtual reality group or a conventional arm therapy group for nine sessions over three weeks.\n The upper limb Motricity Index and the Action Research Arm Test were completed at baseline, post intervention and six weeks follow-up.\n Outcome data were obtained from 95% of participants at the end of treatment and at follow-up: one participant withdrew. Compliance was high; only two people reported side-effects from virtual reality exposure. Both groups demonstrated small (7-8 points on upper limb Motricity Index and 4 points on the Action Research Arm Test), but non-significant, changes to their arm impairment and activity levels.\n A randomized controlled trial of virtual reality-mediated therapy comparable to conventional therapy would be feasible, with some suggested improvements in recruitment and outcome measures. Seventy-eight participants (39 per group) would be required for a main trial.", "To examine an additive effect of virtual reality on balance and gait function in patients with chronic hemiparetic stroke.\n Twenty-four adults with hemiparetic stroke were randomly assigned to either an experimental group (n = 12) or a control group. Both groups underwent conventional physical therapy, 40 mins a day, 4 days a week for 4 wks. The experimental group received an additional 30 mins of virtual reality therapy each session. Balance performance was determined by the Balance Performance Monitor and Berg Balance Scale tests. Gait performance was determined by the 10-m walking test and Modified Motor Assessment Scale, and spatiotemporal parameters were obtained using GAITRite. Analysis of variance and correlation statistics were performed at P < 0.05.\n In the balance test, the experimental group had improved Berg Balance Scale scores, balance and dynamic balance angles (ability to control weight shifting) compared with the controls (P < 0.05). In the gait performance test, the experimental group showed significant improvements in velocity, Modified Motor Assessment Scale scores, cadence, step time, step length, and stride length (P < 0.05). Improvement in dynamic balance angles was correlated with velocity and cadence (P < 0.01).\n This study demonstrates that virtual reality has an augmented effect on balance and associated locomotor recovery in adults with hemiparetic stroke when added to conventional therapy.", "To evaluate the effectiveness of a 2-D virtual reality (2DVR) programme in the training of people with stroke on how to access and use the station facilities of the Mass Transit Railway (MTR).\n A flat-screen 2DVR based training programme and a corresponding, typical psycho-educational programme with video modelling were developed for comparison through a research design that involved a randomised control group pre-test and post-test.\n Twenty and sixteen subjects respectively received 10 training sessions using the 2DVR strategy and a video-based psycho-educational programme. An additional 22 subjects formed the control group. They were assessed by using a behavioural checklist of MTR skills and a newly validated MTR self-efficacy scale. The subjects of both training groups showed a significant improvement in their knowledge, skills and self-efficacy in using the MTR (p<0.01), whereas, the MTR skills and self-efficacy of the control group remained stable over a four-week interval.\n Though both training programmes were effective in training the patients with stroke, they demonstrated differential improvements in MTR skills and related self-efficacy. Additional studies are recommended to identify the most effective training procedures for maintaining these skills and the best transfer ratio in the training of VR-based community living skills of people with stroke.", "Virtual reality (VR) is a new promising computer-assisted technology to promote motor recovery in stroke patients. VR-induced neuroplasticity supporting locomotor recovery is not known. We investigated the effects of VR intervention on cortical reorganization and associated locomotor recovery in stroke patients.\n Ten chronic stroke patients were assigned randomly to either the control group or the VR group. VR was designed to provide interactive real-life practice environments in which practice parameters can be individualized to optimize motor relearning. Laterality index (LI) in the regions of interests (ROIs) and locomotor recovery were measured before and after VR using functional MRI (fMRI) and standardized locomotor tests, respectively. The t test and nonparametric test were performed to compare the mean differences at P<0.05.\n There was a significant difference in the interval change in the LI score for the primary sensorimotor cortex (SMC) between the groups (P<0.05), indicating that VR practice produced a greater increase in LI for the control group. However, the interval changes in the other ROIs were not significantly different (P>0.05). Motor function was significantly improved after VR (P<0.05).\n Our novel findings suggest that VR could induce cortical reorganization from aberrant ipsilateral to contralateral SMC activation. This enhanced cortical reorganization might play an important role in recovery of locomotor function in patients with chronic stroke. This is the first fMRI study in the literature that provides evidence for neuroplasticity and associated locomotor recovery after VR.", "To compare the outcome of robot-assisted therapy with dose-matched active control therapy by using accelerometers to study functional recovery in chronic stroke patients.\n Prospective, randomized, controlled trial. Setting: Stroke units in three medical centres. Subjects: Twenty patients post stroke for a mean of 22 months. Intervention: Robot-assisted therapy (n = 10) or dose-matched active control therapy (n = 10). All patients received either of these two therapies for 90-105 minutes each day, 5 days per week, for four weeks.\n Outcome measures included arm activity ratio (the ratio of mean activity between the impaired and unimpaired arm) and scores on the Fugl-Meyer Assessment Scale, Functional Independence Measure, Motor Activity Log and ABILHAND questionnaire.\n The robot-assisted therapy group significantly increased motor function, hemiplegic arm activity and bilateral arm coordination (Fugl-Meyer Assessment Scale: 51.20 ± 8.82, P = 0.002; mean arm activity ratio: 0.76 ± 0.10, P = 0.026; ABILHAND questionnaire: 1.24 ± 0.28, P = 0.043) compared with the dose-matched active control group (Fugl-Meyer Assessment Scale: 40.90 ± 13.14; mean arm movement ratio: 0.69 ± 0.11; ABILHAND questionnaire: 0.95 ± 0.43).\n Symmetrical and bilateral robotic practice, combined with functional task training, can significantly improve motor function, arm activity, and self-perceived bilateral arm ability in patients late after stroke.", "We conducted a pilot telerehabilitation study with post-stroke patients with arm motor impairment. We compared the degree of satisfaction of patients undergoing a virtual reality (VR) therapy programme at home (Tele-VR group) to satisfaction experienced by those undergoing the same VR therapy in a hospital setting (VR-group). The rehabilitation equipment used a 3D motion tracking system to create a virtual environment in which the patient's movement was represented. In tele-therapy, the patient equipment was installed in their homes, connected to the hospital by four ISDN lines at a total bandwidth of 512 kbit/s. Rehabilitation data were transmitted via one line and videoconferencing via the other three. Ten patients with mild to intermediate arm motor impairment due to an ischaemic stroke, were randomized into VR or Tele-VR groups. A questionnaire was used at the end of treatment to measure each patient's degree of satisfaction. Tele-VR treated patients showed median values equal to or higher than the VR group patients in all 12 items investigated, except one. In motor performance, the Tele-VR group improved significantly (P < or = 0.05), while the VR group showed no significant change. Patients assigned to the Tele-VR group were able to engage in therapy at home and the videoconferencing system ensured a good relationship between the patient and the physical therapist whose physical proximity was not required.", "Although vestibular rehabilitation (VR) is gaining popularity, few data support its utility in improving locomotor stability, and no good predictors exist of whom will benefit most.\n A double-blind, placebo-controlled randomized trial of vestibular rehabilitation was conducted at a large tertiary care hospital on 124 patients (59 +/- 18 years old) with unilateral (n = 51) or bilateral (n = 73) vestibular hypofunction, of whom 86 completed a 12-week intervention. Of these 86, 27 returned for long-term (1-year) follow-up testing. The primary outcome measure was locomotor stability.\n Group A (6 weeks of VR) significantly (P < 0.01) increased their gait velocity and stability compared with group B (6 weeks of strengthening exercise), but there was a smaller difference (P = 0.05) between groups at 12 weeks, when both had had VR; there were no group differences at 1 year. Of the 86 who completed the intervention, 52 (61%) had clear locomotor gains.\n VR is helpful for most patients in providing locomotor stability, but further work is needed to determine the factors that prevent VR from being effective for all patients with vestibulopathy.", "This study investigated the relative effects of distributed constraint-induced therapy (CIT) and bilateral arm training (BAT) on motor performance, daily function, functional use of the affected arm, and quality of life in patients with hemiparetic stroke.\n A total of 60 patients were randomized to distributed CIT, BAT, or a control intervention of less specific but active therapy. Each group received intensive training for 2 hours/day, 5 days/week, for 3 weeks. Pretreatment and posttreatment measures included the Fugl-Meyer Assessment (FMA), Functional Independence Measure (FIM), Motor Activity Log (MAL), and Stroke Impact Scale (SIS). The proximal and distal scores of FMA were used to examine separate upper limb (UL) elements of movement.\n The distributed CIT and BAT groups showed better performance in the overall and the distal part score of the FMA than the control group. The BAT group exhibited greater gains in the proximal part score of the FMA than the distributed CIT and control groups. Enhanced performance was found for the distributed CIT group in the MAL, the subtest of locomotion in the FIM, and certain domains of the SIS (eg, ADL/IADL).\n BAT may uniquely improve proximal UL motor impairment. In contrast, distributed CIT may produce greater functional gains for the affected UL in subjects with mild to moderate chronic hemiparesis.", "Training of the lower extremity (LE) using a robot coupled with virtual environments has shown to transfer to improved overground locomotion. The purpose of this study was to determine whether the transfer of training of LE movements to locomotion was greater using a virtual environment coupled with a robot or with the robot alone.\n A single, blind, randomized clinical trial was conducted. Eighteen individuals poststroke participated in a 4-week training protocol. One group trained with the robot virtual reality (VR) system and the other group trained with the robot alone. Outcome measures were temporal features of gait measured in a laboratory setting and the community.\n Greater changes in velocity and distance walked were demonstrated for the group trained with the robotic device coupled with the VR than training with the robot alone. Similarly, significantly greater improvements in the distance walked and number of steps taken in the community were measured for the group that trained with robot coupled with the VR. These differences were maintained at 3 months' follow-up.\n The study is the first to demonstrate that LE training of individuals with chronic hemiparesis using a robotic device coupled with VR improved walking ability in the laboratory and the community better than robot training alone.", "This study investigated the relative effects of vestibular rehabilitation (VR) and social reinforcement (SR) on recovery following ablative vestibular surgery. Twenty-four subjects were randomly assigned to three treatment groups of either VR with SR, VR without SR, or general range of motion (ROM) exercises with SR. Outcome measures included equilibrium scores in dynamic posturography, asymmetry index in rotation testing, motion sensitivity quotient (MSQ), and dizziness handicap inventory (DHI). A multiple comparison of the overall outcome measures showed no significant differences in group performance over an 8-week period. When individual outcome measures were compared, MSQ and DHI results at the end of the 8-week treatment period revealed less motion sensitivity and dizziness handicap in groups who received VR, with or without SR, as compared with the group who received ROM exercises. These results suggest that after a vestibular injury most patients can effectively utilize central compensation mechanisms to recover from such an injury, regardless of the type of therapeutic intervention used. On the other hand, the reduction in motion sensitivity and dizziness handicap for patients who received VR could indicate a more rapid and complete recovery for these patients. This investigation is continuing as a long-term follow-up study to determine whether there are any long-term benefits in participating in a VR program.", "We investigated the effects of different intensities of arm and leg rehabilitation training on the functional recovery of activities of daily living (ADL), walking ability, and dexterity of the paretic arm, in a single-blind randomised controlled trial.\n Within 14 days after stroke onset, 101 severely disabled patients with a primary middle-cerebral-artery stroke were randomly assigned to: a rehabilitation programme with emphasis on arm training; a rehabilitation programme with emphasis on leg training; or a control programme in which the arm and leg were immobilised with an inflatable pressure splint. Each treatment regimen was applied for 30 min, 5 days a week during the first 20 weeks after stroke. In addition, all patients underwent a basic rehabilitation programme. The main outcome measures were ability in ADL (Barthel index), walking ability (functional ambulation categories), and dexterity of the paretic arm (Action Research arm test) at 6, 12, 20, and 26 weeks. Analyses were by intention to treat.\n At week 20, the leg-training group (n=31) had higher scores than the control group (n=37) for ADL ability (median 19 [IQR 16-20] vs 16 [10-19], p<0.05), walking ability (4 [3-5] vs 3 [1-4], p<0.05), and dexterity (2 [0-56] vs 0 [0-2], p<0.01). The arm-training group (n=33) differed significantly from the control group only in dexterity (9 [0-39] vs 0 [0-2], p<0.01). There were no significant differences in these endpoints at 20 weeks between the arm-training and leg-training groups.\n Greater intensity of leg rehabilitation improves functional recovery and health-related functional status, whereas greater intensity of arm rehabilitation results in small improvements in dexterity, providing further evidence that exercise therapy primarily induces treatment effects on the abilities at which training is specifically aimed.", "Mental practice (MP) of a particular motor skill has repeatedly been shown to activate the same musculature and neural areas as physical practice of the skill. Pilot study results suggest that a rehabilitation program incorporating MP of valued motor skills in chronic stroke patients provides sufficient repetitive practice to increase affected arm use and function. This Phase 2 study compared efficacy of a rehabilitation program incorporating MP of specific arm movements to a placebo condition using randomized controlled methods and an appropriate sample size. Method- Thirty-two chronic stroke patients (mean=3.6 years) with moderate motor deficits received 30-minute therapy sessions occurring 2 days/week for 6 weeks, and emphasizing activities of daily living. Subjects randomly assigned to the experimental condition also received 30-minute MP sessions provided directly after therapy requiring daily MP of the activities of daily living; subjects assigned to the control group received the same amount of therapist interaction as the experimental group, and a sham intervention directly after therapy, consisting of relaxation. Outcomes were evaluated by a blinded rater using the Action Research Arm test and the upper extremity section of the Fugl-Meyer Assessment.\n No pre-existing group differences were found on any demographic variable or movement scale. Subjects receiving MP showed significant reductions in affected arm impairment and significant increases in daily arm function (both at the P<0.0001 level). Only patients in the group receiving MP exhibited new ability to perform valued activities.\n The results support the efficacy of programs incorporating mental practice for rehabilitating affected arm motor function in patients with chronic stroke. These changes are clinically significant.", "This study was a preliminary examination of the effect of low-intensity home-based physical therapy on the performance of activities of daily living (ADL) and motor function in patients more than 1 year after stroke. Twenty patients were recruited from a community stroke register in Nan-Tou County, Taiwan, to a randomized, crossover trial comparing intervention by a physical therapist immediately after entry into the trial (Group I) or after a delay of 10 weeks (Group II). The intervention consisted of home-based physical therapy once a week for 10 weeks. The Barthel Index (BI) and Stroke Rehabilitation Assessment of Movement (STREAM) were used as standard measures for ADL and motor function. At the first follow-up assessment at 11 weeks, Group I showed greater improvement in lower limb motor function than Group II. At the second follow-up assessment at 22 weeks, Group II showed improvement while Group I had declined. At 22 weeks, the motor function of upper limbs, mobility, and ADL performance in Group II had improved slightly more than in Group I, but the between-group differences were not significant. It appears that low-intensity home-based physical therapy can improve lower limb motor function in chronic stroke survivors. Further studies will be needed to confirm these findings.", "BACKGROUND and\n Many stroke survivors have minimal to moderate neurological deficits but are physically deconditioned and have a high prevalence of cardiovascular problems; all of these are potentially modifiable with exercise. The purposes of this randomized, controlled pilot study were (1) to develop a home-based balance, strength, and endurance program; (2) to evaluate the ability to recruit and retain stroke subjects; and (3) to assess the effects of the interventions used.\n Twenty minimally and moderately impaired stroke patients who had completed inpatient rehabilitation and who were 30 to 90 days after stroke onset were randomized to a control group or to an experimental group that received a therapist-supervised, 8-week, 3-times-per-week, home-based exercise program. The control group received usual care as prescribed by the patients' physicians. Baseline and postintervention assessments included the Fugl-Meyer Motor Assessment, the Barthel Index of Activities of Daily Living (ADL), the Lawton Scale of Instrumental ADL, and the Medical Outcomes Study-36 Health Status Measurement. Functional assessments of balance and gait included a 10-m walk, 6-Minute Walk, and the Berg Balance Scale. Upper extremity function was evaluated by the Jebsen Test of Hand Function.\n Of 22 patients who met study criteria, 20 completed the study and 2 refused to participate. The experimental group tended to improve more than the control group in motor function (Fugl-Meyer Upper Extremity: mean change in score, 8. 4 versus 2.2; Fugl-Meyer Lower Extremity: 4.7 versus -0.9; gait velocity: median change, 0.25 versus .09 m/s; 6-Minute Walk: 195 versus 114 ft; Berg Balance Score: 7.8 versus 5; and Medical Outcomes Study-36 Health Status Measurement of Physical Function: 15. 5 versus 9). There were no trends in differences in change scores by the Jebsen Test of Hand Function, Barthel Index, and Lawton Instrumental ADL Scale.\n This study demonstrated that a randomized, controlled clinical trial of a poststroke exercise program is feasible. Measures of neurological impairments and lower extremity function showed the most benefit. Effects of the intervention on upper extremity dexterity and functional health status were equivocal. The lasting effects of the intervention were not assessed.", "To investigate the effects of virtual reality (VR) on cortical reorganization and motor recovery.\n Nonparametric pre- and posttest design with experimenter blinded.\n University medical center.\n Five patients with hemiparesis (age, 59.8+/-3.4y) were recruited.\n Five patients received VR for 60 minutes a day, 5 times a week for 4 weeks. VR was designed to provide a virtual rehabilitation scene where the intensity of practice and sensory feedback could be systematically manipulated to provide the most appropriate, individualized motor retraining program.\n Cortical activation and associated motor recovery were measured before and after VR using functional magnetic resonance imaging and standardized motor tests, respectively. Nonparametric tests were used at P less than .05.\n Prior to VR, the bilateral primary sensorimotor cortices (SM1s), contralesional premotor cortex, and contralesional or ipsilesional supplementary motor area were activated. After VR, the altered activations disappeared and predominantly the ipsilesional SM1 was activated (P<.05). Motor function was improved (P<.05).\n This is a novel demonstration of VR-induced neuroplastic changes and associated motor recovery in chronic stroke." ]	We found limited evidence that the use of virtual reality and interactive video gaming may be beneficial in improving arm function and ADL function when compared with the same dose of conventional therapy. There was insufficient evidence to reach conclusions about the effect of virtual reality and interactive video gaming on grip strength or gait speed. It is unclear at present which characteristics of virtual reality are most important and it is unknown whether effects are sustained in the longer term. Furthermore, there are currently very few studies evaluating the use of commercial gaming consoles (such as the Nintendo Wii).
CD007492	[ "16507032", "15966958", "18843564", "19664653", "15113492", "20008945" ]	[ "Bereaved adults with intellectual disabilities: a combined randomized controlled trial and qualitative study of two community-based interventions.", "Randomized controlled trial of assertive community treatment in intellectual disability: the TACTILD study.", "Physical health--a cluster randomized controlled lifestyle intervention among persons with a psychiatric disability and their staff.", "Five years of lifestyle intervention improved self-reported mental and physical health in a general population: the Inter99 study.", "Exploratory cluster randomised controlled trial of shared care development for long-term mental illness.", "A randomized trial of medical care management for community mental health settings: the Primary Care Access, Referral, and Evaluation (PCARE) study." ]	[ "Bereaved adults with intellectual disabilities are known to experience prolonged and atypical grief which is often unrecognized. The aim of this project was to find an effective way to improve mental health and behavioural outcomes.\n Subjects were randomized to two different therapeutic interventions: traditional counselling by volunteer bereavement counsellors, and an integrated intervention delivered by carers which offered bereavement specific support. Qualitative and quantitative methods were used to determine their effectiveness and efficacy.\n The counselling intervention resulted in measurable gains both clinically and in terms of quality of life; the second intervention proved impracticable in most settings and no improvement in mental health or behaviour resulted.\n Despite small numbers, the quantitative findings were highly significant, were supported by the qualitative data, and were of practical relevance to primary care practitioners and specialist mental health and intellectual disability staff.", "There has been a policy shift away from hospital to community in the services of all those with psychiatric disorders, including those with intellectual disability (ID), in the last 50 years. This has been accompanied recently by the growth of assertive outreach services, but these have not been evaluated in ID services.\n In a randomized controlled trial we compared assertive outreach with 'standard' community care, using global assessment of function (GAF) as the primary outcome measure, and burden and quality of life as secondary measures.\n We recruited 30 patients, considerably less than expected; no significant differences were found between the primary and secondary outcomes in the two groups. The differences were so small that a Type II error was unlikely.\n Reasons for this lack of specific efficacy of the assertive approach are discussed and it is suggested that there is a blurring of the differences between standard and assertive approaches in practice.", "The objective was to explore the impact on physical health of a lifestyle programme among persons with psychiatric disabilities, and their caregivers. Their satisfaction with the intervention was also assessed. Somatic comorbidity and an increased mortality related to the lifestyle among persons with psychiatric disabilities are well known. Few randomized controlled trials have been aimed specifically at lifestyle issues among persons with a psychiatric disability. This trial includes clients with psychiatric disabilities living in supported housing and their staff. Forty-one persons with a DSM-?V diagnosis of severe mental illness from psychiatric disability from 10 supported housing facilities and 41 of their caregivers participated in this 12-month study during 2005-2006 in Sweden. The supported housing facilities with residents and staff were randomly assigned to either a health intervention programme or a control programme with an aesthetic content. The presence of metabolic syndrome and changes in the mean of physiological parameters such as Hba1c, P-glucose, P-insulin, lipids, blood pressure, physical working capacity, body mass index, Heart Score were investigated and participants' satisfaction assessed. There was a significant reduction in the mean of metabolic syndrome criteria in the intervention group compared with the control group at the follow-up. The participants expressed satisfaction with the programme. The results indicate that health interventions on lifestyle issues when involving carers are appreciated, feasible and could be successful in reducing some health-related risk factors among persons with psychiatric disabilities.", "Self-reported health has been shown to predict mortality. We lack knowledge on whether a lifestyle intervention can improve self-reported mental and physical health in a general population.\n Inter99, Denmark (1999-2006) is a randomised population-based intervention study. We screened for ischemic heart disease and repeatedly offered advice and assistance to obtain a healthier lifestyle. Health related quality of life was measured by Short Form 12 (SF-12); completed by 9322 at baseline and 7719 at five-year follow-up. In linear mixed models we investigated the effect of the intervention on self-reported health over time.\n At baseline men had higher physical health-component scores (PCS) than women. Living with a partner, being employed, and being healthy was associated with high PCS. The mental health-component scores (MCS) showed the same socio-demographic differences, except that MCS increased with age. Significantly fewer participants in the intervention groups had decreased their PCS and MCS compared with the control group. Adjusted multilevel analyses confirmed that the intervention significantly improved physical- (p=0.008) and mental health (p<0.001) over time compared with the control group.\n Screening for ischemic heart disease and offering lifestyle intervention had a significantly beneficial effect on mental and physical self-reported health in the long term in a general population.", "Primary care clinicians have a considerable amount of contact with patients suffering from long-term mental illness. The United Kingdom's National Health Service now requires general practices to contribute more systematically to care for this group of patients.\n To determine the effects of Mental Health Link, a facilitation-based quality improvement programme designed to improve communication between the teams and systems of care within general practice. Design of study: Exploratory cluster randomised controlled trial.\n Twenty-three urban general practices and associated community mental health teams.\n Practices were randomised to service development as usual or to the Mental Health Link programme. Questionnaires and an audit of notes assessed 335 patients' satisfaction, unmet need, mental health status, processes of mental and physical care, and general practitioners' satisfaction with services and beliefs about service development. Service use and intervention costs were also measured.\n There were no significant differences in patients' perception of their unmet need, satisfaction or general health. Intervention patients had fewer psychiatric relapses than control patients (mean = 0.39 versus 0.71, respectively, P = 0.02) but there were no differences in documented processes of care. Intervention practitioners were more satisfied and services improved significantly for intervention practices. There was an additional mean direct cost of pound 63 per patient with long-term mental illness for the intervention compared with the control.\n Significant differences were seen in relapse rates and practitioner satisfaction. Improvements in service development did not translate into documented improvements in care. This could be explained by the intervention working via the improvements in informal shared care developed through better link working. This type of facilitated intervention tailored to context has the potential to improve care and interface working.", "Poor quality of healthcare contributes to impaired health and excess mortality in individuals with severe mental disorders. The authors tested a population-based medical care management intervention designed to improve primary medical care in community mental health settings.\n A total of 407 subjects with severe mental illness at an urban community mental health center were randomly assigned to either the medical care management intervention or usual care. For individuals in the intervention group, care managers provided communication and advocacy with medical providers, health education, and support in overcoming system-level fragmentation and barriers to primary medical care.\n At a 12-month follow-up evaluation, the intervention group received an average of 58.7% of recommended preventive services compared with a rate of 21.8% in the usual care group. They also received a significantly higher proportion of evidence-based services for cardiometabolic conditions (34.9% versus 27.7%) and were more likely to have a primary care provider (71.2% versus 51.9%). The intervention group showed significant improvement on the SF-36 mental component summary (8.0% [versus a 1.1% decline in the usual care group]) and a nonsignificant improvement on the SF-36 physical component summary. Among subjects with available laboratory data, scores on the Framingham Cardiovascular Risk Index were significantly better in the intervention group (6.9%) than the usual care group (9.8%).\n Medical care management was associated with significant improvements in the quality and outcomes of primary care. These findings suggest that care management is a promising approach for improving medical care for patients treated in community mental health settings." ]	There are currently no well designed studies focusing on organising the health services of persons with an intellectual disability and concurrent physical problems. There are very few studies of organisational interventions targeting mental health needs and the results of those that were found need corroboration. There is an urgent need for high quality health services research to identify optimal health services for persons with an intellectual disability and concurrent physical problem.
CD006029	[ "20346030", "1439601", "10646679", "19815264", "15879805", "2039294", "16527562" ]	[ "Extracorporeal shockwave lithotripsy vs ureteroscopy as first-line therapy for patients with single, distal ureteric stones: a prospective randomized study.", "Cost effectiveness of extracorporeal shock wave lithotripsy and percutaneous nephrolithotomy for medium-sized kidney stones. A randomised clinical trial.", "Treatment for extended-mid and distal ureteral stones: SWL or ureteroscopy? Results of a multicenter study.", "A prospective randomized study comparing shock wave lithotripsy and semirigid ureteroscopy for the management of proximal ureteral calculi.", "Prospective, randomized trial comparing shock wave lithotripsy and ureteroscopy for lower pole caliceal calculi 1 cm or less.", "Choledocholithiasis. Endoscopic sphincterotomy or common bile duct exploration.", "Prospective randomized trial comparing shock wave lithotripsy and ureteroscopic lithotripsy for management of large upper third ureteral stones." ]	[ "To compare extracorporeal shockwave lithotripsy (ESWL) and ureteroscopy (URS) as first-line treatments for patients with distal ureteric stones.\n In all, 273 patients with single, monolateral, radiopaque, distal ureteric stones of 0.5-1.5 cm were enrolled in a prospective randomized trial. Patients were randomized to undergo ESWL (137) or URS (136). The electromagnetic Modulith SLX lithotripter (Storz Medical, Switzerland) was used for ESWL and a semi-rigid ureteroscope was used for URS. Patients in both groups were compared for overall stone-free rates (SFRs), re-treatment rates, need for auxiliary procedures and complication rates. A subgroup analysis was performed in both groups according to stone size of ≤1 cm and >1 cm.\n Patients in the ESWL group achieved a 92.70% overall SFR with a 44.88% re-treatment rate and an 11.02% auxiliary procedure rate. Complications occurred in 15.32% of patients treated with ESWL. Patients in the URS group achieved a 94.85% overall SFR with a re-treatment rate of 7.75% and an auxiliary procedure rate of 18.60%. Complications occurred in 19.11% of patients treated with URS. In the ESWL group, the need for re-treatments and for auxiliary procedures as well as the incidence of complications was significantly higher in patients with stones of >1 cm. In patients with stones of ≤1 cm treated with ESWL the need for re-treatments and for auxiliary procedures as well as the incidence of complications was significantly lower than for those treated with URS.\n In centres where both techniques are available, ESWL should be the preferred treatment for patients with single distal ureteric stones of ≤1 cm and URS should be reserved for patients with stones of >1 cm.\n © 2010 THE AUTHORS. JOURNAL COMPILATION © 2010 BJU INTERNATIONAL.", "To evaluate percutaneous nephrolithotomy (PNL) and extracorporeal shock wave lithotripsy (ESWL) for their clinical effects, their cost effectiveness, their complication rates, and the patients' experiences, 55 consecutive patients were randomised to have one or other operation between October 1986 and October 1988. Six patients were excluded, 21 were treated with PNL and 28 with ESWL as primary treatment. Mean hospital stay and length of treatment were longer for PNL than for ESWL. Since 1 July 1987 all patients having ESWL have been treated without anaesthesia (n = 15), whereas epidural anaesthesia was used for all PNL. Slightly more of the ESWL patients experienced some pain during treatment. Minor complications or pain were more common after ESWL during the first 10 days after discharge from hospital. If patients with stone fragments of 4 mm or less were regarded as having a successful outcome, the success rates after one year were 94% for PNL and 77% for ESWL. The overall total cost was lower for ESWL than for PNL, the cost per successfully treated patient being 2172 pounds for PNL and 1810 pounds for ESWL. Medium sized kidney stones (6-30 mm, or 2-3 stones of 20 mm or less) can be efficiently and cheaply treated by both PNL and ESWL, though the cost of ESWL is lower. Even if effects other than cost (such as complications and patients' experience) are borne in mind, ESWL was superior to PNL for this group of patients.", "In a randomized study, we analyzed the treatment results of ureterorenoscopy (URS) and shockwave lithotripsy (SWL) for extended-mid and distal ureteral stones. We investigated also, for reasons of cost effectiveness, the factors influencing the outcome, the complications, and the need for auxiliary procedures.\n In three regional hospitals, we selected 156 patients with extended-mid and distal ureteral stones. After randomization, 87 were treated with URS, and 69 with SWL. The treatment results were studied in relation to complications, the need for auxiliary procedures and stone factors, urinary tract infection (UTI), dilatation, and kidney function.\n After retreatment of 45% of the patients, the stone-free rate after 12 weeks in the SWL group was 51%. After a retreatment rate of 9% of the patients in the URS group, the stone-free rate was 91%. Including the number of auxiliary procedures, we calculated the Efficiency Quotient (EQ) as 0.50 for SWL and 0.38 for URS. After correction and redefinition of auxiliary procedures, the EQ was 0.66. The mean treatment time for SWL was 52 minutes and for URS 39 minutes. General anesthesia was more frequently needed in URS patients. Complications occurred more often in the URS group (22 v 3 and 24 v 13, respectively). These were mostly mild, and all could be treated with a double-J stent, antibiotics, or analgetics. A lower stone-free rate was achieved in patients with larger (> or =11 mm) stones (75% v 85% for smaller stones in the URS group and 17% v 73% in the SWL group. In the URS group, the stone-free rate of patients with extended-mid ureteral stones was lower than that of patients with distal ureteral stones. Calculating the costs for URS and SWL appeared impossible because of the differences in available equipment.\n The stone-free rate after URS is much higher than after SWL, and the EQ in our series was strongly dependent on definitions. The decision about how to treat a patient with an extended-mid or distal ureteral stone therefore should not be made primarily on the basis of cost effectiveness but rather on the basis of the availability of proper equipment, the experience of the urologist, and the preference of the patient.", "To conduct a prospective randomized study comparing both techniques for the management of solitary radio-opaque upper ureteral stones < 2 cm in diameter. The ideal treatment for upper ureteral stones > 1 cm size remains to be determined with shock wave lithotripsy (SWL) and ureteroscopy (URS) being acceptable options.\n A total of 200 patients were included in the study. They were randomized into 2 equal groups. Group A underwent in situ SWL as a primary therapy. Group B underwent URS, using semirigid URS with intracorporeal lithotripsy. Efficiency quotient (EQ), cost analysis, and predictors of failure were estimated for both techniques.\n For stones of size > or = 1 cm, the initial stone-free rate for URS and SWL was 88% and 60%, respectively. The estimated EQ was 0.79 and 0.43 for both techniques respectively. For stones < 1 cm, the initial stone-free rate for URS and SWL was 100% and 80%, respectively. The estimated EQ was 0.88 and 0.70 for both techniques, respectively. The mean cumulative costs were significantly more in SWL group (P <.05). Predictors of URS failure included; male gender, failure to pass guidewire beyond the stone, and extravasation. Predictors of SWL failure included large stone size > 1 cm, calcium oxalate monohydrate stone, and higher degrees of hydronephrosis.\n URS with intracorporeal lithotripsy is an acceptable treatment modality for all proximal ureteral calculi, particularly stones > 1 cm. SWL should remain the first-line therapy for proximal ureteral calculi < or = 1 cm because of the less invasive nature and lower anesthesia (i.v. sedation).", "The optimal management of lower pole renal calculi is controversial. We compared shock wave lithotripsy (SWL) and ureteroscopy (URS) for the treatment of patients with small lower pole stones in a prospective, randomized, multicenter trial.\n A total of 78 patients with 1 cm or less isolated lower pole stones were randomized to SWL or URS. The primary outcome measure was stone-free rate on noncontrast computerized tomography at 3 months. Secondary outcome parameters were length of stay, complication rates, need for secondary procedures and patient derived quality of life measures.\n A total of 67 patients randomized to SWL (32) or URS (35) completed treatment. The 2 groups were comparable with respect to age, sex, body mass index, side treated and stone surface area. Operative time was significantly shorter for SWL than URS (66 vs 90 minutes). At 3 months of followup 26 and 32 patients who underwent SWL and URS had radiographic followup that demonstrated a stone-free rate of 35% and 50%, respectively (p not significant). Intraoperative complications occurred in 1 SWL case (unable to target stone) and in 7 URS cases (failed access in 5 and perforation in 2), while postoperative complications occurred in 7 SWL and 7 URS cases. Patient derived quality of life measures favored SWL.\n This study failed to demonstrate a statistically significant difference in stone-free rates between SWL and URS for the treatment of small lower pole renal calculi. However, SWL was associated with greater patient acceptance and shorter convalescence.", "A prospective randomized trial was conducted of preoperative endoscopic sphincterotomy and surgery (ES&S) or surgery alone (SA) in 52 patients with cholecystolithiasis and choledocholithiasis that were candidates for elective surgery. After ES&S 65% of patients were stone free. Eighty-eight per cent of patients with SA were stone free after surgery (p less than 0.05). Three patients in each group had residual stones at the completion of the operation. Five of these six had more than 20 common bile duct (CBD) stones. There was one episode of major hemorrhage in a patient in each group and no deaths. Costs were essentially equal for the individual patient with a successful ES as compared to SA. Societal costs of a program of preoperative endoscopic retrograde cholangiopancreatography and ES would be higher because of the cost of screening for patients with CBD stones. These results do not support preoperative ES as a technique for clearance of the CBD of stones on the basis of efficacy, morbidity rate, or cost.", "To conduct a prospective and randomized trial to compare the efficiency quotient and cost-effectiveness index of shock wave lithotripsy (SWL) and ureteroscopic lithotripsy (URSL) for the treatment of large upper third ureteral stones.\n A total of 35 male patients and 7 female patients with a solitary, radiopaque upper ureteral stone, 15 mm or more in diameter, who underwent SWL or URSL were enrolled in this study. The mean patient age was 53.1 +/- 14.5 years. The endpoint of the study was for the patient to be stone free or to have insignificant residual stone (3 mm or less) within the kidney.\n The mean stone length +/- SD was 17.9 +/- 3.9 cm in the SWL group and 18.5 +/- 2.9 cm in the URSL group (P > 0.05). The efficiency quotient for SWL and URSL was 0.61 and 0.63, respectively. The cost-effectiveness index, treatment time, pain score, and hospital stay were greater in the URSL group. However, the degree of hydronephrosis significantly influenced the success rate of SWL. All patients with severe hydronephrosis in the SWL group needed auxiliary surgical procedures to become stone free.\n The efficiency quotients of SWL and URSL were comparable in the treatment of large upper third ureteral stones. However, SWL should not be recommended as the first-line treatment option for the management of upper third ureteral stones larger than 1.5 cm with severe hydronephrosis. Understanding the cost-effectiveness, success rate, pain score, and patient satisfaction score for the two different approaches constitutes the indispensable requisites for choosing the optimal first-line therapeutic strategy." ]	Compared with ESWL, ureteroscopic removal of ureteral stones achieves a greater stone-free state, but with a higher complication rate and longer hospital stay.
CD006578	[ "15457381", "16481296", "12235507", "11729380" ]	[ "The AESOP robot system in laparoscopic surgery: increased risk or advantage for surgeon and patient?", "Zeus robot-assisted laparoscopic cholecystectomy in comparison with conventional laparoscopic cholecystectomy.", "Controlled trial of the introduction of a robotic camera assistant (EndoAssist) for laparoscopic cholecystectomy.", "Laparoscopic cholecystectomy versus mini-laparotomy cholecystectomy: a prospective, randomized, single-blind study." ]	[ "The aim of this study was to examine the advantages and risks of the Automated Endoscopic System for Optical Positioning (AESOP) 3000 robot system during uncomplicated laparoscopic cholecystectomies or laparoscopic hernioplasty.\n In a randomized study, we examined two groups of 120 patients each with the diagnosis cholecystolithiasis respectively the unilateral inguinal hernia. We worked with the AESOP 3000, a robotic arm system that is voice-controlled by the surgeon. The subjective and objective comfort of the surgeon as well as the course and length of the operation were measured.\n The robot-assisted operations required significantly longer preparation and operation times. With regard to the necessary commands and manual camera corrections, the assistant group was favored. The same was true for the subjective evaluation of the surgical course by the surgeon.\n Our study showed that the use of AESOP during laparoscopic cholecystectomy and hernioplasty is possible in 94% of all cases. The surgeon must accept a definite loss of comfort as well as a certain loss of time against the advantage of saving on personnel.", "The robotic surgical system overcomes many technological obstacles of conventional laparoscopic surgery, and possesses enormous clinical applied potential. The aim of this study was to compare the efficacy of Zeus robot-assisted laparoscopic cholecystectomy with conventional laparoscopic cholecystectomy.\n Forty patients undergoing elective cholecystectomy were randomly divided into two groups. Patients in group A (n=20) underwent Zeus robot-assisted laparoscopic cholecystectomy, and patients in group B (n=20) received conventional laparoscopic cholecystectomy. The parameters on operative field, operative time, the number of actions, the rate of operative errors and minimal trauma were evaluated and compared between the two groups.\n The number of clearing camera (1.1+/-1.0 times) and the time of adjusting the operative field (2.2+/-0.7 minutes) in group A were significantly less than those (4.5+/-1.5 times) and (7.5+/-1.2 minutes) in group B. The number of dissection actions (337+/-86 times) and the rate of operative errors (10%) in group A were less than those (389+/-94 times), (25%) in group B. The total operation time (104.9+/-20.5 minutes) and setup time (29.5+/-9.8 minutes) in group A were significantly longer than those (78.6+/-17.1 minutes), (12.6+/-2.5 minutes) in group B. Blood loss and postoperative hospitalization were similar. No postoperative complications occurred in both groups, and open cholecystectomy was performed in each group.\n Zeus robot-assisted cholecystectomy inherits the benefits of minimally invasive surgery. The Zeus robotic surgical system is better than conventional laparoscopic technique in controlling the operative field and can be manipulated precisely and stably though it requires more operative time.", "The role of the human camera holder during laparoscopic surgery keeps valuable personnel from other duties. EndoAssist is a robotic camera-holding device controlled by the operator's head movements. This study assesses its introduction into clinical practice.\n Ninety-three patients undergoing laparoscopic cholecystectomy were randomized to have either the robotic (40) or a human (46) assistant. Seven patients converted to open operation were excluded. Six surgeons were evaluated. Operating time and subjective assessments were recorded. Learning curves were constructed.\n The mean operating time was less using the robotic assistant (66 min) than with human assistance (74 min) (p < 0.05, two-tailed t-test). The learning curves for operating time showed that within three operations surgeons were trained in using the robot. The device was safe in use.\n The EndoAssist operating device is a significant asset in laparoscopic surgery and a suitable substitute for a human assistant. Surgeons became competent in the use of the robot within three operations. The robot offers stability and good control of the television image in laparoscopic surgery.", "To analyze outcomes after open small-incision surgery (minilaparotomy) and laparoscopic surgery for gallstone disease in general surgical practice.\n This study was a randomized, single-blind, multicenter trial comparing laparoscopic cholecystectomy (LC) to minilaparotomy cholecystectomy (MC). Both elective and acute patients were eligible for inclusion. All surgeons normally performing cholecystectomy, both trainees under supervision and consultants, operated on randomized patients. LC was a routine procedure at participating hospitals, whereas MC was introduced after a short training period. All nonrandomized cholecystectomies at participating units during the study period were also recorded to analyze the external validity of trial results. The randomization period was from March 1, 1997, to April 30, 1999.\n Of 1,705 cholecystectomies performed at participating units during the randomization period, 724 entered the trial and 362 patients were randomized to each of the procedures. The groups were well matched for age and sex, but there were fewer acute operations in the LC group than the MC group. In the LC group 264 and in the MC group 150 operations were performed by surgeons who had done more than 25 operations of that type. Median operating times were 100 and 85 minutes for LC and MC, respectively. Median hospital stay was 2 days in each group, but in a nonparametric test it was significantly shorter after LC. Median sick leave and time for return to normal recreational activities were shorter after LC than MC. Intraoperative complications were less frequent in the MC group, but there was no difference in the postoperative complication rate between the groups. There was one serious bile duct injury in each group, but no deaths.\n Operating time was longer and convalescence was smoother for LC compared with MC. Further analyses of LC versus MC are necessary regarding surgical training, surgical outcome, and health economy." ]	Robot assisted laparoscopic cholecystectomy does not seem to offer any significant advantages over human assisted laparoscopic cholecystectomy. However, all trials had a high risk of systematic errors or bias (that is, risk of overestimation of benefit and underestimation of harm). All trials were small, with few or no outcomes. Hence, the risk of random errors (that is, play of chance) is high. Further randomised trials with low risk of bias or random errors are needed.
CD003517	[ "20566605", "11242425", "16212203", "15293973", "12727395", "17398310", "7914260", "16183590", "3566318", "7660023", "1559523", "16322166", "16061595", "21402642", "15574620", "3168444" ]	[ "Prolonged and exclusive breastfeeding reduces the risk of infectious diseases in infancy.", "Promotion of Breastfeeding Intervention Trial (PROBIT): a randomized trial in the Republic of Belarus.", "Effect of exclusive breastfeeding and complementary feeding on infant growth and morbidity.", "The first six month growth and illness of exclusively and non-exclusively breast-fed infants in Nigeria.", "Effect of community-based promotion of exclusive breastfeeding on diarrhoeal illness and growth: a cluster randomised controlled trial.", "Mother-to-child transmission of HIV-1 infection during exclusive breastfeeding in the first 6 months of life: an intervention cohort study.", "Effects of age of introduction of complementary foods on infant breast milk intake, total energy intake, and growth: a randomised intervention study in Honduras.", "Breast-feeding, return of menses, sexual activity and contraceptive practices among mothers in the first six months of lactation in Onitsha, South Eastern Nigeria.", "Prolonged exclusive breast feeding and heredity as determinants in infantile atopy.", "[Promotion of breast-feeding in urban localities of southern Brazil: a randomized intervention study].", "Prolonged breast-feeding and malnutrition among rural Indian children below 3 years of age.", "Randomized, controlled trial of a prenatal and postnatal lactation consultant intervention on duration and intensity of breastfeeding up to 12 months.", "Randomized trial of donor human milk versus preterm formula as substitutes for mothers' own milk in the feeding of extremely premature infants.", "Nutrient enrichment of mother's milk and growth of very preterm infants after hospital discharge.", "Randomized, controlled trial of slow versus rapid feeding volume advancement in preterm infants.", "Breastfeeding pattern and the duration of lactational amenorrhea in urban Chilean women." ]	[ "To examine the associations of duration of exclusive breastfeeding with infections in the upper respiratory (URTI), lower respiratory (LRTI), and gastrointestinal tracts (GI) in infancy.\n This study was embedded in the Generation R Study, a population-based prospective cohort study from fetal life onward in the Netherlands. Rates of breastfeeding during the first 6 months (never; partial for <4 months, not thereafter; partial for 4-6 months; exclusive for 4 months, not thereafter; exclusive for 4 months, partial thereafter; and exclusive for 6 months) and doctor-attended infections in the URTI, LRTI, and GI until the age of 12 months were assessed by questionnaires and available for 4164 subjects.\n Compared with never-breastfed infants, those who were breastfed exclusively until the age of 4 months and partially thereafter had lower risks of infections in the URTI, LRTI, and GI until the age of 6 months (adjusted odds ratio [aOR]: 0.65 [95% confidence interval (CI): 0.51-0.83]; aOR: 0.50 [CI: 0.32-0.79]; and aOR: 0.41 [CI: 0.26-0.64], respectively) and of LRTI infections between the ages of 7 and 12 months (aOR: 0.46 [CI: 0.31-0.69]). Similar tendencies were observed for infants who were exclusively breastfed for 6 months or longer. Partial breastfeeding, even for 6 months, did not result in significantly lower risks of these infections.\n Exclusive breastfeeding until the age of 4 months and partially thereafter was associated with a significant reduction of respiratory and gastrointestinal morbidity in infants. Our findings support health-policy strategies to promote exclusive breastfeeding for at least 4 months, but preferably 6 months, in industrialized countries.", "Current evidence that breastfeeding is beneficial for infant and child health is based exclusively on observational studies. Potential sources of bias in such studies have led to doubts about the magnitude of these health benefits in industrialized countries.\n To assess the effects of breastfeeding promotion on breastfeeding duration and exclusivity and gastrointestinal and respiratory infection and atopic eczema among infants.\n The Promotion of Breastfeeding Intervention Trial (PROBIT), a cluster-randomized trial conducted June 1996-December 1997 with a 1-year follow-up.\n Thirty-one maternity hospitals and polyclinics in the Republic of Belarus.\n A total of 17 046 mother-infant pairs consisting of full-term singleton infants weighing at least 2500 g and their healthy mothers who intended to breastfeed, 16491 (96.7%) of which completed the entire 12 months of follow-up.\n Sites were randomly assigned to receive an experimental intervention (n = 16) modeled on the Baby-Friendly Hospital Initiative of the World Health Organization and United Nations Children's Fund, which emphasizes health care worker assistance with initiating and maintaining breastfeeding and lactation and postnatal breastfeeding support, or a control intervention (n = 15) of continuing usual infant feeding practices and policies.\n Duration of any breastfeeding, prevalence of predominant and exclusive breastfeeding at 3 and 6 months of life and occurrence of 1 or more episodes of gastrointestinal tract infection, 2 or more episodes of respiratory tract infection, and atopic eczema during the first 12 months of life, compared between the intervention and control groups.\n Infants from the intervention sites were significantly more likely than control infants to be breastfed to any degree at 12 months (19.7% vs 11.4%; adjusted odds ratio [OR], 0.47; 95% confidence interval [CI], 0.32-0.69), were more likely to be exclusively breastfed at 3 months (43.3% vs 6.4%; P<.001) and at 6 months (7.9% vs 0.6%; P =.01), and had a significant reduction in the risk of 1 or more gastrointestinal tract infections (9.1% vs 13.2%; adjusted OR, 0.60; 95% CI, 0.40-0.91) and of atopic eczema (3.3% vs 6.3%; adjusted OR, 0.54; 95% CI, 0.31-0.95), but no significant reduction in respiratory tract infection (intervention group, 39.2%; control group, 39.4%; adjusted OR, 0.87; 95% CI, 0.59-1.28).\n Our experimental intervention increased the duration and degree (exclusivity) of breastfeeding and decreased the risk of gastrointestinal tract infection and atopic eczema in the first year of life. These results provide a solid scientific underpinning for future interventions to promote breastfeeding.", "A cohort study was conducted in the Islamic Republic of Iran between January 1997 and February 1998 to compare the growth and morbidity of 100 infants who were exclusively breastfed for 6 months and 100 who received breast milk and complementary foods between 4-6 months. Infants' feeding pattern, weight and height were assessed and recorded. There were no significant differences in infants' weight and height gain between 4 and 6 months. The rate of diarrhoea between ages 4 and 6 months was significantly lower in exclusively breastfed infants than in complementary food-fed infants (11% versus 27%) and respiratory infections were also lower (23% versus 35%). We conclude that exclusive breastfeeding is superior at least until an infant is 6 months of age.", "To compare the growth and illness pattern of infants who were exclusively breast fed for six months with those of infants commenced on complementary feeding before the age of six months and ascertain reasons for the early introduction of complementary feeding.\n A comparative prospective study.\n Urban Comprehensive Health Centre (UCHC), Obafemi Awolowo University Teaching Hospitals Complex, Ile-Ife.\n Three hundred and fifty-two mothers and their normal birth weight babies, weighing 2.500kg or more, and aged less than 14 days were serially recruited into the study.\n Mean/median monthly weights in the first six months of life, history/outpatient presentation for illnesses.\n Of the 352 mother-infant pairs recruited into the study, 345 (98%) were successfully followed up for the first six months of life. At six months, 264 (76.5%) were exclusively breast-fed, 45 (13.1%) were started on complementary feeding, between the ages of four and six months while 36 (10.4%) commenced complementary feeding before the age of four months. Infants who were exclusively breast-fed for six months had median weights above the 50th percentiles of the WHO/NCHS reference that is currently used in the national \"road to health\" (growth monitoring) cards. Furthermore, the mean weight of these babies at age six months was above those of babies who started complementary foods before six months. They also reported fewer symptoms and had fewer illness episodes (0.1 episodes per child) compared to those who started complementary feeding before six months. Infants who commenced complementary feeding before four months reported more symptoms and had more illness episodes (1.4 episodes per child) compared to those that commenced complementary feeding between four and six months (1.2 episodes per child). Common symptoms/illnesses seen or reported during the study among the groups were fever, diarrhoea and cough. Reasons given for early introduction of complementary foods include insufficient breast milk, thirst and convenience.\n It is concluded that exclusive breast-feeding supported adequate growth during the first six months of life for most of the infants studied. Early introduction of complementary foods did not provide any advantages in terms of weight gain in our environment, it was frequently associated with illness episodes and growth faltering. Many mothers however require support, encouragement and access to health care providers to breastfeed exclusively for the first six months of life.", "Exclusive breastfeeding is recommended until age 6 months. We assessed the feasibility, effectiveness, and safety of an educational intervention to promote exclusive breastfeeding for this length of time in India.\n We developed the intervention through formative research, pair-matched eight communities on their baseline characteristics, and randomised one of each pair to receive the intervention and the other to no specific intervention. We trained health and nutrition workers in the intervention communities to counsel mothers for exclusive breastfeeding at multiple opportunities. We enrolled 1115 infants born in the 9 months after training-552 in the intervention and 473 in the control communities. Feeding at age 3 months, and anthropometry and of diarrhoea prevalence at age 3 months and 6 months were assessed. All analyses were by intention to treat.\n We assessed 483 and 412 individuals at 3 months in the intervention and control groups, respectively, and 468 and 412 at 6 months. At 3 months, exclusive breastfeeding rates were 79% (381) in the intervention and 48% (197) in the control communities (odds ratio 4.02, 95% CI 3.01-5.38, p<0.0001). The 7-day diarrhoea prevalence was lower in the intervention than in the control communities at 3 months (0.64, 0.44-0.95, p=0.028) and 6 months (0.85, 0.72-0.99, p=0.04). The mean weights and lengths, and the proportion with weight-for-height or height-for-age Z scores of 2 or less, at age 3 months and 6 months did not differ much between groups. Intervention effect on exclusive breastfeeding, diarrhoeal morbidity, and anthropometry at age 6 months in the low-birthweight subgroup was similar to that for all births.\n Promotion of exclusive breastfeeding until age 6 months in a developing country through existing primary health-care services is feasible, reduces the risk of diarrhoea, and does not lead to growth faltering.", "Exclusive breastfeeding, though better than other forms of infant feeding and associated with improved child survival, is uncommon. We assessed the HIV-1 transmission risks and survival associated with exclusive breastfeeding and other types of infant feeding.\n 2722 HIV-infected and uninfected pregnant women attending antenatal clinics in KwaZulu Natal, South Africa (seven rural, one semiurban, and one urban), were enrolled into a non-randomised intervention cohort study. Infant feeding data were obtained every week from mothers, and blood samples from infants were taken monthly at clinics to establish HIV infection status. Kaplan-Meier analyses conditional on exclusive breastfeeding were used to estimate transmission risks at 6 weeks and 22 weeks of age, and Cox's proportional hazard was used to quantify associations with maternal and infant factors.\n 1132 of 1372 (83%) infants born to HIV-infected mothers initiated exclusive breastfeeding from birth. Of 1276 infants with complete feeding data, median duration of cumulative exclusive breastfeeding was 159 days (first quartile [Q1] to third quartile [Q3], 122-174 days). 14.1% (95% CI 12.0-16.4) of exclusively breastfed infants were infected with HIV-1 by age 6 weeks and 19.5% (17.0-22.4) by 6 months; risk was significantly associated with maternal CD4-cell counts below 200 cells per muL (adjusted hazard ratio [HR] 3.79; 2.35-6.12) and birthweight less than 2500 g (1.81, 1.07-3.06). Kaplan-Meier estimated risk of acquisition of infection at 6 months of age was 4.04% (2.29-5.76). Breastfed infants who also received solids were significantly more likely to acquire infection than were exclusively breastfed children (HR 10.87, 1.51-78.00, p=0.018), as were infants who at 12 weeks received both breastmilk and formula milk (1.82, 0.98-3.36, p=0.057). Cumulative 3-month mortality in exclusively breastfed infants was 6.1% (4.74-7.92) versus 15.1% (7.63-28.73) in infants given replacement feeds (HR 2.06, 1.00-4.27, p=0.051).\n The association between mixed breastfeeding and increased HIV transmission risk, together with evidence that exclusive breastfeeding can be successfully supported in HIV-infected women, warrant revision of the present UNICEF, WHO, and UNAIDS infant feeding guidelines.", "In developing countries, the age at which breastfed infants are first given complementary foods is of public health importance because of the risk of diarrhoeal disease from contaminated weaning foods, and the potential risk of growth faltering if foods are inappropriately delayed. To evaluate whether there are any advantage of complementary feeding prior to 6 months, low-income primiparous mothers who had exclusively breastfed for 4 months were randomly assigned to one of 3 groups: continued exclusive breastfeeding to 6 months (EBF) (n = 50); introduction of complementary foods at 4 months with ad libitum nursing from 4-6 months (SF) (n = 47); and introduction of complementary foods at 4 months, with maintenance of baseline nursing frequency from 4-6 months (SF-M) (n = 44). Baby foods in jars were provided to the SF and SF-M groups from 4 to 6 months. Subjects were visited weekly and provided with lactation guidance; at 4, 5, and 6 months measurements were made of infant intake and breast milk composition. At 4 months, breast milk intake averaged 797 (139) g per day (no difference among groups). Between 4 and 6 months, breast milk intake was unchanged in EBF infants (+6) but decreased in the SF (-103), and SF-M (-62) groups (p < 0.001). Change in total energy intake (including solid foods) and infant weight and length gain did not differ significantly between groups. Weight and length gain from 4-6 months were comparable to those of breastfed infants in an affluent USA population. The results indicate that breastfed infants self-regulate their total energy intake when other foods are introduced. As a result, there is no advantage in introducing complementary foods before 6 months in this population, whereas there may be disadvantages if there is increased exposure to contaminated weaning foods.", "The objective of this study was to determine the exclusive breast-feeding practices, return of menstruation, sexual activity and contraceptive practices among breast-feeding mothers in the first six months of lactation. The study was based in Onitsha, South Eastern Nigeria. A structured questionnaire was used to obtain data from breast-feeding mothers on their age, educational attainment, breast-feeding practices, return of menstruation, sexual activity and contraceptive practices within the first six months of lactation at intervals of 6 weeks, 10 weeks 14 weeks and 6 months post delivery. Analysis of the information obtained showed that out of the 178 mothers who participated in the study 81% of the mothers were within the ages of 20 - 34 years. While all the mothers had formal education, the majority (59%) had secondary education. Seventy-three percent initiated breast-feeding within one hour of delivery. On discharge from hospital, all of them had already established breast-feeding which continued up to six weeks and dropped to 97.8% at six months. Exclusive breast-feeding which was practised by 100% on discharge dropped to 3.9% at six months. The feeding regimen was on demand as practised by 98.9% of the mothers. Menstrual flow had returned in 33.8% of the mothers by 6 weeks of lactation, and had risen to 70.2% at six months. There was more prolonged lactational amenorrheoa in exclusively breast-feeding mothers than in those who were not. By 6 weeks post delivery 31.6% of the mothers had resumed sexual activity and this rose to 93.6% at six months. With the resumption of sexual activity only 5% of the mothers resorted to contraceptive practices other than lactational amenorrhea and this increased to 54% at six months. There was no pregnancy in any of these women during the six months period. While appreciating the role of lactational amenorrhea in child spacing and considering the early return of sexual activity among the mothers the practice of introducing contraceptive practices needs to be encouraged especially in women whose menstruation has returned.", "We followed 183 infants for two years, 31 of whom were breast fed less than three and a half months (median 70 days; short breast feeding group) and a further 31 of whom were exclusively breast fed for more than nine months (long breast feeding group). We assessed heredity for atopy, number of infections, and duration of breast feeding as determinants of atopy. During the first year of life 14 infants has signs of atopy. During the second year parents reported signs of atopy in a further 31. Heredity was the only significant predictor of atopy. Atopy was seen in 33% of infants with a positive heredity and in 16% without family history for atopy. The duration of breast feeding affected the incidence of atopy only among the infants without family history for atopy: fewer in the short breast feeding group (1/18) had atopy than in the long breast feeding group (5/13). Duration of breast feeding did not associate with incidence of respiratory infections. Diarrhoea was more common in the short breast feeding group than in the long breast feeding group during the first year of life. We conclude that prolonging exclusive breast feeding from the median of 70 days to nine months did not contribute to the prevention of infantile atopy and respiratory tract infections.", "A randomized intervention trial to promote breast-feeding was carried out in southern Brazil. A group of 450 mothers and babies was visited at home 5, 10 and 20 days after birth and compared to a non-visited control group of the same size. Ninety-two per cent of the families visited received the three home visits planned. The evaluation of breast-feeding patterns and reasons for weaning took place 6 months after birth for both groups. Ninety-four per cent of the group visited and 92% of the non-visited controls group were traced on the occasion of the assessment. The intervention increased the duration of breast-feeding (median duration of 120 days in the group visited and 105 days in the controls; p = 0.03) and delayed the introduction of milk bottles (median age of introduction of 90 days in the group visited and 60 days in the controls; p = 0.01). Causes of weaning were classified as underlying, intermediate and immediate. The most common underlying cause of weaning was \"the baby cried too much\", which suggests that mothers should be taught about normal patterns of infant behaviour in the first weeks of life, particularly the need for crying, and the fact that this not necessarily reflects hunger.", "Long periods of exclusive as well as partial breast-feeding in poor communities are of considerable importance from a nutritional standpoint, as it is in these communities that malnutrition is predominant. Although benefits of exclusive breast feeding have been well documented, those for partial breast-feeding have not been examined. The present study in particular examines the effects of prolonged breast-feeding, i.e. exclusive breast-feeding beyond 6 months or partial breast-feeding up to 2-3 years, in terms of prevalent malnutrition and morbidity among rural children. A total of 395 children were observed for weight, height, information on duration of breast-feeding, age at weaning and morbidity in terms of recent illness in the 7 days prior to the day of visit. Exclusive breast-feeding beyond 6 months and up to 12 months appeared beneficial in terms of reduced morbidity. Beyond infancy, there was no evidence of any protective effect of partial breast-feeding. This could be due to poor lactational performance of mothers and their unawareness about it resulting in inadequate weaning foods being offered to partially breast-fed children. Significant differences in male and female children in the extent of malnutrition pointed towards discrimination against girls even in respect of exclusive breast-feeding. The study highlights the need for advocating proper weaning practices while recommending prolonged breast-feeding in poor communities.", "To determine whether an individualized, prenatal and postnatal, lactation consultant intervention resulted in increased cumulative intensity of breastfeeding up to 52 weeks.\n The randomized, nonblinded, controlled trial recruited women from prenatal care. Baseline prenatal interviews covered demographic data and breastfeeding experience, intention, and knowledge. Interviews at 1, 2, 3, 4, 6, 8, 10, and 12 months after birth collected data on weekly feeding patterns, infant illness, and infant health care use.\n Two community health centers serving low-income, primarily Hispanic and/or black women.\n The analytic sample included 304 women (intervention: n = 145; control: n = 159) with > or = 1 postnatal interview.\n Study lactation consultants attempted 2 prenatal meetings, a postpartum hospital visit, and/or home visits and telephone calls. Control subjects received the standard of care.\n Cumulative breastfeeding intensity at 13 and 52 weeks, based on self-reports of weekly feeding, on a 7-level scale.\n The intervention group was more likely to breastfeed through week 20 (53.0% vs 39.3%). Exclusive breastfeeding rates were low and did not differ according to group. In multivariate analyses, control subjects had lower breastfeeding intensity at 13 weeks (odds ratio [OR]: 1.90; 95% confidence interval [CI]: 1.13-3.20) and 52 weeks (OR: 2.50; 95% CI: 1.48-4.21). US-born control subjects had lowest breastfeeding intensity at 13 weeks (OR: 5.22; 95% CI: 2.43-11.22) and 52 weeks (OR: 5.25; 95% CI: 2.44-11.29). There were no significant differences in breastfeeding intensity among the US-born intervention, foreign-born intervention, and foreign-born control groups.\n This \"best-practices\" intervention was effective in increasing breastfeeding duration and intensity. Breastfeeding promotion should focus on US-born women and exclusive breastfeeding.", "Compared with preterm formula (PF), mother's milk (MM) is associated with lower rates of late-onset sepsis (LOS) and necrotizing enterocolitis (NEC) among premature infants. Because not all mothers of premature infants produce sufficient milk to supply their infants throughout hospitalization, we reasoned that pasteurized donor human milk (DM) would be a suitable alternative.\n Extremely premature infants (<30 weeks of gestation) whose mothers intended to breastfeed were assigned randomly to receive either pasteurized DM or PF if the supply of their own MM became insufficient during the study (birth to 90 days of age or hospital discharge). Infection-related events (LOS, NEC, meningitis, presumed sepsis, or urinary tract infection) that occurred after the attainment of a milk intake of 50 mL/kg, dietary intake, growth, skin-to-skin contact, and duration of hospital stay were compared. The primary analysis compared groups DM and PF on an intent-to-treat basis. If no differences were noted, then these groups were combined and compared with the reference group, group MM. If differences were noted, then the subsequent analyses compared each group with group MM.\n Of 243 infants, 70 (29%) received only MM; group DM included 81 infants and group PF included 92 infants. Because of poor weight gain, 17 infants (21%), all in group DM, were switched to PF. There were no differences in birth weight, gestational age, multiple births, and age at attainment of feeding of 50 mL/kg among groups. There were no differences between group DM and group PF in LOS and/or NEC, other infection-related events, hospital stay, or number of deaths. Group DM received a greater intake of milk and more nutritional supplements but had a slower rate of weight gain, compared with group PF. Compared with groups DM and PF, group MM had fewer episodes of LOS and/or NEC and total infection-related events and a shorter duration of hospital stay. Group MM also had fewer Gram-negative organisms isolated from blood cultures than did the other groups.\n In this randomized, blinded trial of feeding of extremely premature infants, we found that, as a substitute for MM, DM offered little observed short-term advantage over PF for feeding extremely premature infants. Advantages to an exclusive diet of MM were observed in terms of fewer infection-related events and shorter hospital stays.", "To determine if the addition of a multinutrient human milk fortifier to mother's milk while breastfeeding very preterm infants after hospital discharge is possible and whether it influences first-year growth.\n Of a cohort of 320 infants (gestational age: 24-32 weeks; birth weight: 535-2255 g), breastfed infants (65% [n = 207]) were randomly assigned shortly before hospital discharge to receive either unfortified (n = 102, group A) or fortified (n = 105, group B) mother's milk until 4 months' corrected age (CA). The remaining infants were bottle-fed with a preterm formula (group C). Follow-up was performed at term and at 2, 4, 6, and 12 months' CA.\n Mean duration of breastfeeding after term was not significantly different between groups A and B (11.8 and 10.6 weeks, respectively). Weight, length, and head circumference were not significantly different between groups A and B at 12 months' CA. Compared with groups A and B, infants in group C had a higher increase in weight z score until term and in length z score until 6 months' CA. At 12 months' CA, boys in group C were significantly longer and heavier compared with those in groups A and B, whereas girls in group C were longer and heavier compared with those in group A only. A higher protein intake was related to a higher serum urea nitrogen level and growth.\n Fortification of mother's milk after hospital discharge while breastfeeding very preterm infants was possible without influencing breastfeeding duration but did not significantly influence growth parameters at 1 year of age compared with unfortified mother's milk.", "To determine whether infants who are fed initially and advanced at 30 mL/kg per day (intervention) take fewer days to get to full feedings than those who are fed initially and advanced at 20 mL/kg per day (control), without increasing their incidence of feeding complications and necrotizing enterocolitis (NEC). We also examined whether these infants regain birth weight earlier, have fewer days of intravenous fluids, and a have shorter hospital stay.\n A randomized, controlled, single-center trial was conducted in a Neonatal Intensive Care Unit of a community-based county hospital in Houston, Texas. Infants between 1000 and 2000 g at birth, gestational age < or =35 weeks, and weight appropriate for gestational age were allocated randomly to feedings of expressed human milk or Enfamil formula starting and advanced at either 30 mL/kg per day or 20 mL/kg per day. Infants remained in the study until discharge or development of stage > or =IIA NEC.\n A total of 155 infants were enrolled: 72 infants in the intervention group and 83 in the control group. Infants in the intervention group achieved full-volume feedings sooner (7 vs 10 days, median), regained birth weight faster (11 vs 13 days, median), and had fewer days of intravenous fluids (6 vs 8 days, median). Three infants in the intervention group and 2 control infants developed NEC for an overall incidence of 3.2% (relative risk: 1.73; 95% confidence interval: 0.30-10.06).\n Among infants between 1000 and 2000 g at birth, starting and advancing feedings at 30 mL/kg per day seems to be a safe practice and results in fewer days to reach full-volume feedings than using 20 mL/kg per day. This intervention also leads to faster weight gain and fewer days of intravenous fluids.", "The influence of the breastfeeding pattern and several clinical variables upon the duration of postpartum amenorrhea was assessed in a group of healthy women selected for having had a normal pregnancy and delivery and being highly motivated for prolonged breastfeeding on demand. 676 women who were fully nursing at the second month postpartum entered the study. Supplements were administered to 11% and 48% of the infants by the end of the 3rd and 6th month, respectively. The first bleeding was experienced before the end of the sixth month postpartum by 57% of the cases. Supplementation had a strong negative influence while nursing frequency had a significant positive influence upon the length of amenorrhea. Notwithstanding, a frequency of 8+ suckling episodes per 24 h could not maintain amenorrhea in around half of the subjects. Age and parity had a moderate negative influence upon the risk of experiencing the first postpartum bleeding. Maternal weight and ponderal index, infant sex, birth weight and growth rate showed no significant influence upon the length of amenorrhea. In this urban population selected for having the highest motivation and best breastfeeding performance, the association of breastfeeding with amenorrhea was weak in comparison with what has been described for other populations. The risk of experiencing the first bleeding was reduced while fully breastfeeding with a high number of nursing episodes per day and night, particularly in older women with higher parity. But even in such situation 25% and 50% of the women had started to cycle by the end of the fifth and eight postpartum month." ]	Infants who are exclusively breastfed for six months experience less morbidity from gastrointestinal infection than those who are partially breastfed as of three or four months, and no deficits have been demonstrated in growth among infants from either developing or developed countries who are exclusively breastfed for six months or longer. Moreover, the mothers of such infants have more prolonged lactational amenorrhea. Although infants should still be managed individually so that insufficient growth or other adverse outcomes are not ignored and appropriate interventions are provided, the available evidence demonstrates no apparent risks in recommending, as a general policy, exclusive breastfeeding for the first six months of life in both developing and developed-country settings.
CD003348	[ "3338348", "10232210", "8576671", "3364765", "3324616", "3200596", "7082061", "2926558", "2407164", "1542838", "1307344", "1999793", "1890479", "3971682", "8513519", "9262274", "9854662", "11772793", "10733789", "7718370", "9661537", "8948744", "9104663", "9287573", "1378707", "7818065", "9249122", "9856712", "9876706", "7942878", "1758253", "7533484", "12488379", "7514506", "9390586", "8608069", "10669270", "1809429", "9879163", "8994466", "1758710", "2618915", "10389787", "12938592", "10593465", "2225288" ]	[ "Patient-controlled analgesia vs. conventional intramuscular analgesia following colon surgery.", "Preoperative PCA teaching program to manage postoperative pain.", "Cost-effectiveness analysis of patient-controlled analgesia, intramuscular q.i.d. injection and p.r.n. injection for postoperative pain relief.", "A statistical model for pain in patient-controlled analgesia and conventional intramuscular opioid regimens.", "Patient-controlled analgesia: a controlled trial.", "Patient-controlled analgesia: a randomized, prospective comparison between two commercially available PCA pumps and conventional analgesic therapy for postoperative pain.", "Patient-controlled analgesia: a new concept of postoperative pain relief.", "A study of pain management: patient controlled analgesia versus intramuscular analgesia.", "A prospective study of patient-controlled analgesia. Impact on overall hospital course.", "A randomized comparison of patient-controlled versus standard analgesic requirements in patients undergoing cholecystectomy.", "Patient-controlled versus conventional analgesia for postsurgical pain relief in adolescents.", "Patient-controlled analgesia in children and adolescents: a randomized, prospective comparison with intramuscular administration of morphine for postoperative analgesia.", "Pain control after cesarean birth. Efficacy of patient-controlled analgesia vs traditional therapy (IM morphine).", "Efficacy of patient-controlled versus conventional analgesia for postoperative pain.", "Comparison between patient-controlled analgesia and intramuscular meperidine after thoracotomy.", "How effective is patient-controlled analgesia? A randomized comparison of two protocols for pain relief during oocyte recovery.", "Pain management in cardiac surgery patients: comparison between standard therapy and patient-controlled analgesia regimen.", "The effects of three different analgesia techniques on long-term postthoracotomy pain.", "Patient-Controlled Analgesia Following Vertical Gastroplasty: a Comparison with Intramuscular Narcotics.", "Psychological characteristics and the effectiveness of patient-controlled analgesia.", "Nurse-administered subcutaneous morphine is a satisfactory alternative to intravenous patient-controlled analgesia morphine after cardiac surgery.", "[Patient-controlled postoperative analgesia in orthopedic surgery: epidural PCA versus intravenous PCA].", "Patient controlled analgesia and intramuscular injections: a comparisons of patient pain experiences and postoperative outcomes.", "Patient-controlled analgesia compared with nurse-controlled infusion analgesia after heart surgery.", "Epidural patient-controlled analgesia: an alternative to intravenous patient-controlled analgesia for pain relief after cesarean delivery.", "Patient-controlled analgesia: a comparison with nurse-controlled intravenous opioid infusions.", "Effect of the intensity of transcutaneous acupoint electrical stimulation on the postoperative analgesic requirement.", "Efficacy and costs of patient-controlled analgesia versus regularly administered intramuscular opioid therapy.", "Analgesia following major gynecological laparoscopic surgery--PCA versus intermittent intramuscular injection.", "Patient-controlled analgesia versus intramuscular analgesic therapy.", "[Efficiency of patient-controlled analgesia versus conventional analgesia in patients after thoracotomy].", "Intravenous versus epidural administration of hydromorphone. Effects on analgesia and recovery after radical retropubic prostatectomy.", "Comparison between patient-controlled analgesia and subcutaneous morphine in elderly patients after total hip replacement.", "Hydromorphone patient-controlled analgesia (PCA) after coronary artery bypass surgery.", "Epidural analgesia and intravenous patient-controlled analgesia result in similar rates of postoperative myocardial ischemia after aortic surgery.", "Impact of patient-controlled analgesia on required nursing time and duration of postoperative recovery.", "Patient-controlled versus nurse-controlled pain treatment after coronary artery bypass surgery.", "A comparison of patient-controlled analgesia and bolus PRN intravenous morphine in the intensive care environment.", "Music does not reduce alfentanil requirement during patient-controlled analgesia (PCA) use in extracorporeal shock wave lithotripsy for renal stones.", "A comparison of patient-controlled and fixed schedule analgesia after orthognathic surgery.", "Adolescents use patient-controlled analgesia effectively for relief from prolonged oropharyngeal mucositis pain.", "Patient-controlled analgesia in gynecologic oncology surgery.", "Ropivacaine epidural anesthesia and analgesia versus general anesthesia and intravenous patient-controlled analgesia with morphine in the perioperative management of hip replacement. Ropivacaine Hip Replacement Multicenter Study Group.", "A prospective randomized clinical trial on pain control after major abdominal surgery.", "Intraarticular, epidural, and intravenous analgesia after total knee arthroplasty.", "Reduction of postoperative morbidity following patient-controlled morphine." ]	[ "Though patient-controlled analgesia (PCA) has been in use for over a decade, it has been popularized only recently. Conventional techniques of intermittent intramuscular (IM) administration of analgesia have fallen short of meeting the needs of patients following major abdominal surgery. This has prompted a search for methods to improve postoperative pain management. Though PCA has been accepted in many hospitals, few studies comparing conventional IM administration of morphine with PCA have been performed. A prospective randomized study comparing IM- and PCA-administered morphine in 62 patients undergoing colon surgery was performed. A comparison of the efficacy of analgesia and extent of sedation using these approaches shows that PCA allows for analgesia with less sedation and less drug requirement than that of IM administration. No differences were noted in postoperative duration of ileus, duration of hospitalization, and total hospital costs. This study confirms the safety and efficacy of PCA, and should be considered the current optimal method of controlling pain following major colonic surgery.", "Patient-controlled analgesia (PCA) therapy was designed to provide patients with greater control in managing their pain. However, many patients continue to suffer from moderate to severe pain due to lack of knowledge about how to use PCA therapy. The results of this quasi-experimental study demonstrated that patients who received structured preoperative teaching had statistically significant higher knowledge regarding the use of PCA therapy and more positive attitudes toward using pain medicine. Patients who received the video teaching reported better pain control and satisfaction with pain management 4 and 8 hours following their surgical procedures.", "We conclude that the intravenous PCA method is a cost-effective technique. Although the PCA device is expensive, the cost-effectiveness analysis should give explicit figures for physicians and the hospital administrators to decide whether they should use the PCA instead of the conventional method.", "A statistical model was developed: 1) to compare the efficacy of patient-controlled analgesia (PCA) and traditional intramuscular (IM) opioids for pain relief in 40 patients after total knee replacement and, 2) to evaluate pain cycles associated with each technique. Hourly visual analog pain scores were subjected to two-way analysis of variance (ANOVA) and time-series analysis. Hourly verbal analog pain scores were used to determine predominant pain levels. According to ANOVA, PCA was no more effective than were IM opioids. Time-series analyses documented a complete cycle of pain every 5.3 hours in patients receiving IM opioids but no pain cycle with use of PCA. Analysis of PCA verbal analog scores demonstrated self-administration of opioids to \"moderate\" levels of pain relief with use of PCA, not to complete analgesia. These results suggest that certain patients may not envision complete postoperative analgesia as being possible. Hence, they self-administer opioids for pain relief with PCA according to their expectations. Population characteristics may modify PCA efficacy. These characteristics should be delineated and the use of PCA targeted to appropriate patients.", "Thirty-six patients undergoing lower abdominal surgery were included in a prospective randomized controlled study to compare the effects of patient-controlled analgesia (PCA) and a standard intramuscular/intravenous treatment (conventional analgesia, CA) of postoperative pain. Morphine was used in both groups. There were no significant differences between the two analgesic regimens in respect of linear analogue pain scores, verbal pain-relief scores, amount of morphine used or side-effects. No treatment-induced alterations in vital values were experienced.", "Two pumps, 'PA' and 'PB,' with different drug delivery characteristics were available at the time of this study for patient-controlled analgesia (PCA). PB purportedly produces a 'placebo effect' by emitting an audible signal whenever the patient depresses the trigger button. PA emits an audible signal only when the drug is successfully administered into the patient's intravenous line. In a prospective, randomized Latin squares cross-over study, the 2 pumps and conventional therapy were compared for efficacy and cost. Patients in both pump groups used less drug and perceived less pain than those on conventional therapy. However, statistically less anxiety and greater pain relief and patient and nursing satisfaction were reported with PA only. Daily cost including drug, pharmacy and nursing time, pump rental was 33%, PA, versus 23%, PB, more than conventional therapy. Purchase and amortization of the pumps decreases the cost. We conclude that PCA provides superior pain management at minimal additional cost.", "This report concerns evaluation of patient-controlled analgesia (PCA) in the form of two preliminary investigations. In the first study, the patient-controlled analgesia device, which consists of a pump linked to a timer so that patients can activate intravenous administration of morphine sulfate to themselves during the postoperative period, was used in seven morbidly obese patients. The amount of morphine used during the first 36 hours was found to vary between 32 and 185 mg, with a significant difference in drug usage when related to weight as well as to body surface area. In the second study, morbidly obese patients undergoing gastric bypass operations were prospectively randomized into 12 patients who used the PCA device in the postoperative period and 12 patients who were given standard intramuscular dosages of morphine sulfate. An analgesia and sedation scale was then used to compare the two groups. The patients in the PCA group were able to maintain a state of adequate analgesia without sleep with a significantly greater frequency than were those in the intramuscular injection group. On the basis of answers to a questionnaire given to the patient after 60 hours of morphine analgesia, it was apparent that the PCA group was much more satisfied with that form of postoperative analgesia. It would appear that PCA is an efficacious and safe method of providing for postoperative pain relief.", "A clinical study examining the efficacy of Patient Controlled Analgesia compared with Intramuscular Analgesia was conducted. Patient Controlled Analgesia (PCA) Therapy was used in a select group of patients after major abdominal surgery. Specific parameters monitored were: total amount of analgesia required, incidence of pulmonary complications, assessment of pain level and sedation, patient activity, nursing time required for administration, safety, cost-effectiveness of both modes of analgesia and length of hospital stay. A questionnaire survey of both patients and nursing staff was done to evaluate responses. Conventional pain management often is inadequate with PRN administration of analgesic drugs due to the unpredictable and uneven patient absorption rate and the individual pain intensity and tolerance. The patient experiences a repetitive cycle of pain and sedation. The patient on PCA therapy is able to titrate his analgesic medication very effectively and maintain a state of analgesia without sedation. He is more responsive and able to participate in the early postoperative rehabilitation phase. The transition to oral medication usually was accomplished at 48 hours postoperative.", "Previous studies have shown that patient-controlled analgesia (PCA) provides effective pain control in the postoperative patient. To determine the impact of PCA technology on the overall hospital course, we designed a randomized controlled study comparing patients receiving analgesia using PCA infusion (Abbott Lifecare, Abbott Laboratories; Chicago, IL) with patients receiving analgesia by traditional intramuscular or intravenous methods. All patients had undergone elective cholecystectomy. Sixty-nine patients completed the study, 35 received traditional postoperative analgesia, and 34 received analgesia using the PCA infuser. Comparison of both groups demonstrated no significant difference in postoperative bowel activity with both groups receiving liquids on the first postoperative day. There was no significant difference between the two groups with respect to postoperative length of stay (3.4 days for PCA vs 3.6 days for traditional). Patients demonstrated a wide range of analgesic requirement in the first 24 hours but the average of the total analgesic required was higher in the PCA group (average, 29.5 mg) than the traditional group (22.8 mg). Urinary complications occurred more commonly in the group of patients receiving traditional analgesia than in the group of patients receiving analgesia with the PCA device. When compared with patients receiving analgesia by traditional methods, patients receiving the PCA infusion required more analgesia with fewer urinary complications and similar postoperative length of stay.", "In the current study, 55 patients undergoing elective cholecystectomy were randomly allocated to receive postoperative analgesia (morphine sulfate) administered through either patient-controlled intravenous (PCA) or standard intramuscular (IM) routes. There were no significant differences in length of hospitalization or required dose of morphine sulfate. Patients randomized to PCA reported significantly improved subjective relief from pain and a smaller percentage of time in pain during each of the first two postoperative days. In addition, they reported less sedation and less interference with both postoperative breathing and pulmonary recovery than patients who received IM morphine. Theoretically, PCA regimens can deliver narcotic analgesia at a higher and more varied rate (with fewer side effects) compared with standard IM narcotic delivery, which is more limited by considerations of clinical doses. In PCA dosing, patients should experience less time in pain and sedation. The results of the current study support this premise.", "We performed a randomized nonblinded, cross-over comparison of patient-controlled analgesia (PCA) with conventional intramuscular analgesia in 10 adolescents (13-18 years) undergoing spinal fusion for idiopathic scoliosis. PCA use afforded more effective pain control (p < 0.02) on a 10-point linear pain intensity scale than did intramuscular injections, while causing an equal amount of sedation and no side effects. PCA appears to be a promising technique for providing postoperative pain relief in this group of adolescents. Further studies are needed to define its role for other pediatric conditions.", "A randomized, prospective trial of patient-controlled analgesia (PCA), that is, a method of analgesia administration involving a computer-driven pump activated by patients to receive small doses within defined limits was performed in 82 children and adolescents after major orthopedic surgery to compare (1) intramuscularly administered morphine, (2) PCA morphine and (3) PCA morphine with a low-dose continuous morphine infusion (PCA-plus). Patients receiving PCA and PCA-plus had lower pain scores and greater satisfaction than patients receiving intramuscularly administered morphine. The three groups used equal amounts of morphine and most measures of recovery were identical in the groups. In particular, PCA and PCA-plus did not increase the incidence of opioid-related complications, and patients receiving PCA-plus were less sedated than patients receiving intramuscular therapy. We conclude that PCA and PCA-plus are safe and effective methods of pain relief in children and adolescents after orthopedic surgery, are better accepted than intramuscular injections, and do not increase perioperative morbidity.", "A clinical trial compared the efficacy of a mechanical device to deliver patient-controlled analgesia (PCA) (n = 25) with intramuscularly administered morphine (n = 17) for postcesarean pain management. Hypotheses were: (1) patient-controlled administration of narcotics will be superior (increased satisfaction, reduced pain, decreased sedation, increased ambulation, decreased length of stay), and (2) functional vital capacity will increase post-operatively with PCA. No differences in demographic variables were identified (P = less than or equal to .001). Differences in satisfaction (greater in PCA group, P = less than or equal to .05), ambulation (greater in PCA group, P = less than or equal to .001), amount of medication used (greater in PCA group, P = less than or equal to .001), and sedation level (less in PCA group, P = less than or equal to .05) were identified. No differences in vital capacity were identified. The hypothesis related to the superiority of PCA was accepted, while the association between PCA and increased vital capacity was not supported. The use of mechanical PCA devices provides an effective and safe means of managing postcesarean pain.", "Patient-controlled i.v. administration and intramuscular administration of morphine sulfate were compared in a crossover study to determine their relative effectiveness in relieving postoperative pain. Twenty adult patients scheduled for abdominal surgery were randomly assigned to one of two groups; one group received i.v. morphine sulfate for 24 hours using a patient-controlled analgesia (PCA) device, after which they were given morphine sulfate i.m. for 24 hours. The treatment order was reversed for the other group. Amount of narcotic administered, respiratory rate, and levels of discomfort, activity, and sedation were assessed by the nursing staff every two hours. At the end of each 24-hour treatment phase, patients ranked their level of pain, amount of pain relief, level of sedation, ability to sleep, and ability to perform pulmonary toilet. Patients were also asked whether they preferred PCA or i.m. analgesic therapy for future surgery. Patients reported significantly less discomfort while using PCA than during i.m. morphine administration. No significant differences in amount of narcotic used, respiratory rate, nausea and vomiting, or levels of activity or sedation were noted for the two regimens. Patients' rankings of the two treatment modes did not differ significantly, but a majority of patients indicated a preference for future use of PCA. In these postoperative patients, administration of i.v. morphine sulfate by PCA was as safe as i.m. administration and possibly more effective in relieving pain.", "A prospective randomized controlled study was performed to assess the efficacy and safety of patient-controlled analgesia (PCA) in patients undergoing thoracotomy. This method was compared with a conventional pain management technique consisting of regularly scheduled im injections of analgesics. Forty adult patients were randomly assigned to receive intravenous PCA or im meperidine treatment over a 48-hr period after surgery. Care was taken to optimize analgesia in patients of both groups. The McGill Pain Questionnaire, visual analogue and verbal-numeric scales were administered at regular intervals to measure various components of the patients' pain experience, degree of pain relief, adverse side effects and overall treatment efficacy. Functional recovery after surgery was also examined. The results showed good and comparable analgesia with both pain-control methods. However, a greater number of patients receiving im injections required dosage adjustments than in the PCA group. Patients' and nurses' evaluations of overall treatment efficacy also favoured PCA treatment. There were no major group differences in the side effect profile. Recovery pattern was also comparable in the two groups except for the length of hospitalisation. There were fewer long-stay patients in the PCA than in the im group. Meperidine intake was similar in both groups but considerable interpatient variation was seen. In conclusion, PCA is a safe, effective and individualized treatment method for controlling pain after thoracotomy. There appears to be some clinical advantages of PCA over im dosing regimens for analgesia after thoracotomy.", "Although the conventional method of pain relief during outpatient oocyte recovery involves physician-administered drugs, patient-controlled analgesia (PCA) offers an alternative technique with the potential to give women more control over peroperative analgesia. We conducted a prospective randomized study to compare the effect of fentanyl administered either through a PCA delivery system or by a physician. Thirty-nine women were randomized to PCA during egg collection while 42 were allocated to receive intermittent doses administered by a physician. Pain was evaluated by means of a 100 mm linear analogue scale. The mean (SD) pain score in the PCA group was 38.5 (19.8) while in the other group it was 46.1 (21.3) (P = 0.1). In the PCA group, 64% of women felt very satisfied with their analgesia as compared with 57% in the non-PCA group (P = 0.6). Among the PCA users, 39% of demands were successful. Significantly more fentanyl (97.5 microg) was used in the PCA group than in the other group (84.6 microg) (P = 0.03). Though intraoperative PCA with fentanyl is an effective alternative to physician-administered techniques, many women still feel the need for more analgesia during the procedure.", "To compare standard nurse-based pain therapy with a patient-controlled analgesia (PCA) regimen.\n Prospective, randomized study.\n Single-institutional, clinical investigation in an urban, university-affiliated hospital.\n Sixty patients undergoing elective first-time cardiac surgery were included.\n In 30 patients, a standard analgesic regimen was used, and in 30 patients, a PCA regimen was used. The perioperative and postoperative management was similar for all patients.\n Degree of sedation, satisfaction, and pain (by visual analog scale [VAS]) was assessed within the first 3 postoperative days. Vital capacity (VC) and forced expiratory volume in 1 second (FEV1) were measured using a portable spirometry system. Cortisol and troponin T (TnT) plasma levels were also measured. The expectation of pain was similar in both groups, and the postoperative pain score was significantly lower in the PCA than in the standard group throughout the study period. Significantly more piritramid was used in the PCA (total, 75.6 +/- 33.4 mg) than in the standard group (total, 20.1 +/- 31.9 mg). VC and FEV1 were significantly lower in the standard group compared with the PCA patients. Cortisol and TnT plasma levels were similar in both groups. Frequency of side effects were similar for both groups.\n Because of the beneficial effects with regard to degree of pain and satisfaction, pain management using PCA systems can be recommended for cardiac surgery patients. It appears to be superior to standard nurse-based pain therapy.", "In this clinical, randomized, prospective study, we compared the effects of three different analgesia techniques (thoracic epidural analgesia [TEA] with and without preoperative initiation and IV patient-controlled analgesia [IV-PCA]) on postthoracotomy pain in 69 patients. In two groups, a thoracic epidural catheter was inserted preoperatively. Group Pre-TEA had bupivacaine and morphine solution preoperatively and intraoperatively. Postoperative analgesia was maintained with epidural PCA with a similar solution. Group Post-TEA, with no intraoperative medication, had the same postoperative analgesia as Group Pre-TEA plus the bolus dose. Group IV-PCA received only IV-PCA with morphine for postoperative analgesia. Pain was evaluated every 4 h during the first 48 h at rest, cough, and movement. Pre-TEA was associated with decreased pain compared with the other groups. Six months later, the patients were asked about their pain. The incidence and the intensity of pain were most frequent in Group IV-PCA (78%) and were the least in Group Pre-TEA (45%) (Group Pre-TEA versus Group IV-PCA, P = 0.0233; Group Pre-TEA versus Group IV-PCA, P = 0.014). Patients having pain on the second postoperative day had 83% chronic pain. TEA with preoperative initiation is a preferable method in preventing acute and long-term thoracotomy pain.\n Preoperatively initiated thoracic epidural analgesia has the most satisfying results in controlling postthoracotomy pain in the acute and long-term period, and it is associated with a decreased incidence (and intensity) of chronic pain compared with postoperative (epidural or IV) analgesia. Chronic pain has an incidence of 62%.", "BACKGROUND: patient-controlled analgesia PCA is a rapidly spreading approach to the management of post-operative pain. The suitability of this method for the morbidly obese patient undergoing bariatric surgery has not yet been determined. METHODS: in the present study we randomly compared two groups of patients undergoing silastic ring vertical gastroplasty. One group received PCA (12 patients) and the other (11 patients) received intermittent doses of pethidine intramuscularly. RESULTS: the cumulative morphine use during the first post-operative day was 52.71 +/- 1.83 mg by the PCA group and an equivalent of 24.55 +/- 3.42 mg morphine by the IM pethidine group (p = 0.0002). The analgesic and sedative effects by the PCA were found to be superior. There were no significant differences between the groups in the incidence of side-effects or complications, except a higher, unexplained incidence of wound infection in the PCA group. CONCLUSION: use of PCA in patients undergoing bariatric surgery has obvious advantages and appears to be a safe procedure.", "We have evaluated the level of state and trait anxiety, neuroticism, extroversion and coping style as predictors of the effectiveness of patient-controlled analgesia (PCA) in 110 patients undergoing total abdominal hysterectomy. After operation patients were allocated to receive pain control with either PCA or i.m. injections (IMI). Pain was assessed using the short form McGill pain questionnaire at 6, 18 and 24 h after operation, and by recording the amount of analgesic consumed in the first 24 h after surgery. Both state anxiety and coping style were significant predictors of postoperative pain, irrespective of the method of analgesia used. Patients using PCA experienced significantly better pain control than those receiving IMI. However, it was those with high levels of state anxiety who experienced the greatest reduction in pain with PCA. In addition to achieving better pain control, patients who received PCA used significantly less analgesia and were discharged earlier than patients who received IMI.", "There are no comparisons of i.v. patient controlled analgesia (i.v. PCA) versus nurse-administered subcutaneous (NA s.c.) morphine for acute postoperative pain. We undertook a prospective, randomized, controlled clinical trial of 80 cardiac surgical patients to compare i.v. PCA with NA s.c. morphine for postoperative pain control. Visual analog scale (VAS) pain scores at rest and with movement, daily verbal pain relief scores, and side effect profiles were not significantly different. Total morphine requirements in the two groups were not significantly different. A physiotherapist's evaluation of the effectiveness of analgesia for chest physiotherapy revealed no difference between the two groups. We conclude that NA s.c. morphine, administered as required (up to hourly), is a satisfactory alternative to i.v. PCA morphine after cardiac surgery. Implications: In a prospective, randomized study, we have shown that nurse-administered subcutaneous morphine is a satisfactory alternative to i.v. patient-controlled analgesia after cardiac surgery.", "To evaluate both effectiveness and incidence of side effects of two techniques of postoperative pain treatment: intravenous and epidural PCA.\n Prospective analysis of data from two groups of randomized patients.\n Orthopedic and trauma center.\n Figty ASA class II-III patients undergoing total hip replacement under combined Spinal-Epidural Anesthesia.\n Patients were divided into 2 groups who received different postoperative pain treatment. One group (group PCA) received a patient-controlled intravenous analgesia with morphine 30 mg and ketorolac 90 mg in 100 ml of saline (back-ground infusion 2-4 ml, according to body weith, bolus 1 ml, lockout 5 min, 4 h dose limit 40 ml). PCEA group received a patient-controlled epidural analgesia with morphine 4 mg and bupivacaine 0.125% 100 ml, (background infusion 3-4 ml, according to patient' height, bolus 1 ml, lockout 10 min, 4 h dose limit 25 ml). Postoperative pain intensity was evaluated, through 24 postoperative hours, by a verbal analogue scale (VPS = 0 to 3) and a total pain score (TOTPAR) was calculated for each patient at 6 and 24 postoperative hours. Side effects were recorded and their incidence was obtained for each group. Statistical data analysis was performed by one-way ANOVA and non-parametric tests for ordinal data. Nominal data were analyzed by chi 2 test. p < 0.05 was considered significant.\n Patient receiving PCEA showed a significant (p < 0.005) decrease of incident pain, while VPS at rest was similar in the two groups. TOTPAR VPS was lower (p < 0.05) in PCEA group both at 6 and 24 postoperative hours. Somnolence was observed more often in PCA patients (8% vs 2%; p 0.05), while no significant differences were noted among other side effects incidence.\n Our data show a better control of postoperative pain arising from total hip replacement during PCEA when compared to PCA. It should be emphasized that incident pain is far more decreased by PCEA, so that this technique is particularly indicated when an early postoperative mobilization is required.", "Despite relatively widespread use of various forms of patient controlled analgesia (PCA), there remain conflicting results in the literature as to the efficacy of PCA. This study was conducted to assess the efficacy and postoperative outcomes of intravenous PCA compared to intramuscular (IM) injections in 73 patients who received major abdominal surgery. These patients were randomly selected and randomly assigned preoperatively to receiving IM or PCA modes of analgesia postoperatively. The following factors were compared: amount of pain; amount of analgesia use; degree of patient satisfaction with pain control both while on parenteral analgesia and after switching to oral; length of time to first ambulation; and length of stay in hospital. Results of the study did not demonstrate a statistically significant difference in any of these, using a P-value of 0.01. The PCA patients took an average of 4.5 hours longer than the IM patients to ambulate postoperatively and the IM patients received at least three times as much antiemetic (P = 0.001). Locus of control was not found to be a major factor in satisfaction or pain levels. Subsequent meta-analyses have also failed to yield significant differences between IM and PCA groups except in patient satisfaction. It is recommended that expansion of PCA programmes with abdominal surgery patients be considered only in cases where there is fiscal advantage or where patient satisfaction can be a driving force.", "A randomized, controlled clinical trial was conducted on 66 patients undergoing elective cardiac surgery to compare patient-controlled analgesia (PCA) to nurse-controlled analgesia (NCA) with continuous morphine infusion. Hourly assessment of pain (at rest and on movement) using a visual analogue scale (VAS), of respiratory rate, and level of sedation took place for the 24 h following extubation. The incidence of nausea was also recorded. Mean pain scores were calculated, and peak pain and sedation scores, together with lowest respiratory rates, were identified. Morphine consumption was measured at 24 h. No significant differences were found between the groups' scores for pain or sedation. The PCA group had significantly lower respiratory rates (P = 0.02) and a lower incidence of nausea (P = 0.008). The PCA group also consumed significantly more morphine (P = 0.0001). The study suggests a beneficial effect from PCA after cardiac surgery in reducing nausea, compared to NCA. It confirms nurse-controlled infusion analgesia as an effective form of pain relief in an intensive care and high-dependency setting.", "Epidural administration of an opioid analgesic by means of a patient-controlled analgesia (PCA) system was compared with conventional intravenous PCA for pain relief after cesarean delivery. One hundred seventeen healthy women were randomly assigned to receive hydromorphone either intravenously (IV-PCA) or epidurally (EPI-PCA) after cesarean delivery with epidural bupivacaine for operative anesthesia. The hydromorphone requirements were 3.4 and 4.2 times more in the IV-PCA group on the first (P less than 0.01) and second (P less than 0.01) postoperative days, respectively. The mean number (+/- SD) of PCA demands during the first 24 h after the operation was 105 (+/- 88) for the IV-PCA group and 33 (+/- 48) for the EPI-PCA group (P less than 0.01). This difference was also significant 24-48 h after surgery. Although the EPI-PCA group utilized significantly less opioid medication, pain and sedation scores were similar in the two treatment groups; however, a significantly larger percentage of patients in the IV-PCA group (46% vs 22%) stated that they felt drowsy during the first postoperative day. Pruritus was reported more frequently in the EPI-PCA (67%) than in the IV-PCA (33%) group. Nausea was experienced by only 10% of patients in the IV-PCA and 6% in the EPI-PCA group. There was no evidence of postoperative respiratory depression, with minimal oxygen saturation values of 93% (+/- 3%) and 94% (+/- 1%) in the IV-PCA and EPI-PCA groups, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)", "Patient-controlled analgesia (PCA) with intravenous pethidine was compared with nurse-controlled pethidine infusions for pain relief in 200 patients after major abdominal or thoracic surgery. Pain, level of sedation, nausea and presence of other adverse effects, in addition to cumulative pethidine requirement, were measured for the first 24 hours after surgery. Both groups were similar for age, weight and type of surgery. There was no significant difference between the quality of analgesia achieved in both groups. The frequency and severity of adverse effects was also similar. The cumulative pethidine dose administered to both groups was identical. It is concluded that nurse-controlled opioid infusions are as effective as PCA and may be used as an alternative to PCA where this is either unavailable or unsuitable.", "Given the inherent side effects associated with both opioid and nonopioid analgesic drugs, a nonpharmacologic therapy that could decrease the need for analgesic medication would be valuable. We designed a sham-controlled study to assess the effect of the intensity of transcutaneous acupoint electrical stimulation (TAES) on postoperative patient-controlled analgesia (PCA) requirement for hydromorphone (HM), the incidence of opioid-related side effects, and the recovery profile after lower abdominal surgery. One hundred one healthy consenting women undergoing lower abdominal procedures with a standardized general anesthetic technique were randomly assigned to one of four postoperative analgesic treatment regimens: Group I (n = 26) PCA only; Group II (n = 25), PCA + sham-TAES (no electrical stimulation); Group III (n = 25), PCA + low-TAES (4-5 mA of electrical stimulation); Group IV (n = 25), PCA + high-TAES (9-12 mA of electrical stimulation). The PCA device was programmed to deliver HM, 0.2-0.4 mg intravenously boluses \"on demand,\" with a minimum lockout interval of 10 min. The TAES skin electrodes were placed at the Hegu acupoint on the nondominant hand and on both sides of the surgical incision. The TAES frequency was set in the dense-and-disperse mode, alternating at 2 Hz and 100 Hz every 3 s, with stimulation of the hand and incision alternated every 6 s. The patients in Groups II-IV were instructed to use TAES every 2 h for 30 min while awake. After discontinuation of PCA, oral pain medications were administered on demand. The postoperative PCA-HM requirement, pain scores, opioid-related side effects, and requirements for antiemetic and antipruritic medication were recorded. High-TAES decreased the HM requirement by 65% and reduced the duration of PCA therapy, as well as the incidence of nausea, dizziness, and pruritus. Low-TAES produced a 34% decrease in the HM requirement compared with only 23% in the \"sham\" TAES group. We conclude that high-TAES produced a significant decrease in the PCA opioid requirement and opioid-related side effects after low intraabdominal surgery.", "Many studies have shown the efficacy of patient-controlled analgesia (PCA). However, it is not clear whether PCA has clinical or economic benefits in addition to efficient analgesia. The current study was designed to evaluate these issues by comparing PCA with regularly administered intramuscular injections of opioids after hysterectomy.\n This prospective study included 126 patients who underwent abdominal hysterectomy and were randomly assigned to receive PCA or regularly timed intramuscular injections of morphine during a period of 48 h. Doses were adjusted to provide satisfactory analgesia in both treatment groups. Pain at rest and with movement, functional recovery, drug side effects, and patient satisfaction were measured using rating scales and questionnaires. The costs of PCA and intramuscular therapy were calculated based on personnel time and drug and material requirements.\n Comparable analgesia was observed with the two treatment methods, with no significant differences in the incidence of side effects or patient satisfaction. The medication dosage had to be adjusted significantly more frequently in the intramuscular group than in the PCA patients. The PCA did not favor a faster recuperation time compared with intramuscular therapy in terms of times to ambulation, resumption of liquid and solid diet, passage of bowel gas, or hospital discharge. The results of the economic evaluation, which used a cost-minimization model and sensitivity analyses, showed that PCA was more costly than regular intramuscular injections despite the fact that no costs for the pump were included in the analyses. Cost differences in nursing time favoring PCA were offset by drug and material costs associated with this type of treatment.\n Compared with regularly scheduled intramuscular dosing, PCA is more costly and does not have clinical advantages for pain management after hysterectomy. Because of the comparable outcomes, the general use of PCA in similar patients should be questioned.", "To compare the use of patient-controlled analgesia to intermittent intramuscular injections of morphine following major gynecological laparoscopic procedures in order to assess differences in level of pain, sedation, episodes of nausea and/or vomiting, hospitalization time and patient satisfaction with their postoperative analgesia.\n Seventy-two patients undergoing major gynecological laparoscopic surgery were randomized to receive either postoperative analgesia via intermittent intramuscular injection of morphine (Group 1) or patient controlled analgesia (PCA-Group 2). All patients received anesthesia via a standardized protocol. Postoperative pain levels were recorded via a 10 cm visual analogue scale, and sedation scores were recorded on a standard PCA form. Episodes of nausea and vomiting were also recorded on the same form.\n There were no statistically significant differences between intramuscular analgesia and PCA for any of the factors studied. Most significantly it was found that most patients ceased to require either form of parenteral analgesia within 24 hours of their procedure, regardless of the operating time.\n It is important for the surgeon to be aware of the effects of postoperative analgesia on his or her patients' level of satisfaction. We do not recommend the use of PCA analgesia following major laparoscopic gynecological surgery.", "The pharmacy and nursing time requirements, quality of postoperative pain control, and cost of patient-controlled analgesia (PCA) and intramuscular (i.m.) analgesic therapy were studied. All timings were conducted with a stopwatch on a single nursing unit that primarily receives gynecologic surgery patients. The various work elements involved in each type of therapy were timed individually. Both quality of analgesia and cost were evaluated in a prospective, randomized study in hysterectomy patients. I.M. patients received meperidine hydrochloride 75-100 mg every three to four hours as needed. PCA patients had access to morphine sulfate 1 mg or meperidine hydrochloride 10 mg, with a six-minute lockout period. The patients scored their pain every four hours. Direct costs for PCA were calculated as drug cost plus tubing cost plus form cost plus maintenance cost plus depreciation cost. Direct costs for i.m. therapy consisted of the cost of drugs. The total mean nursing time per patient was 16.9 minutes for PCA and 10.7 minutes for i.m. therapy. Pharmacy time per patient was 5.1 minutes longer for PCA than for i.m. therapy. Thirty-six hysterectomy patients (17 i.m. and 19 PCA) were enrolled in the study of pain control and cost. Among i.m. patients, 64% of the pain scores were mild or worse, compared with 40% for PCA patients. The median pain scores were moderate for i.m. patients and mild for PCA patients. Scores tended to be lower for PCA patients at 16 and 20 hours. Although equal numbers of patients in the two groups experienced nausea, i.m. patients needed more doses of antiemetics than PCA patients.(ABSTRACT TRUNCATED AT 250 WORDS)", "The patients received thoracotomy usually suffered from significant severe pain postoperatively, which accompanied with impaired pulmonary function or increased incidences of atelectasis and pneumonia. So adequate analgesia for those patients is indicated. The purpose of this study is to investigate the efficiency of patient-controlled analgesia (PCA) and determine whether it is better than conventional analgesia or not. Twenty-six patients, ASA physical status class I and II, were randomized into two groups: PCA and intramuscular (IM). The effect on pain relief was assessed by a visual analogue pain scale (VAPS) q 4 h postoperatively for two days. Forced vital capacity (FVC) and the questionnaire of nocturnal sleep disturbance by pain were evaluated preoperatively, the first, second postoperative mornings. As result of this study, the patients of PCA group get less pain than IM group after the first and second days of surgery. VAPS values are 3.7 +/- 1.1, 2.8 +/- 0.8 and 6.1 +/- 0.9, 5.3 +/- 1.1 respectively pertaining to PCA and IM groups (p less than 0.05). The patients of IM group get more disturbance of nocturnal sleep than PCA group at initial two nights of postoperation as well (p less than 0.05). It is manifest to look out the significant difference between these two groups in accordance with FVC ratio records of post-surgery vs presurgery at initial two days after surgery on the subject of respiratory function recovery. PCA group are 46.46 +/- 7.29%, 52.25 +/- 8.32% in a condition of more progress on lung function recovery than IM group of 38.13 +/- 10.25%, 42.15 +/- 7.82% (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)", "It remains unclear whether epidural administration of hydromorphone results in spinal analgesia or clinical benefit when compared with intravenous administration. Therefore, we undertook this study to determine whether epidural administration of hydromorphone resulted in decreased opioid requirement, improved analgesia, reduced side effects, more rapid return of gastrointestinal function, or shorter duration of hospital stay than intravenous administration.\n Sixteen patients undergoing radical retropubic prostatectomy were randomized in a double-blind manner to receive either intravenous or epidural hydromorphone via patient-controlled analgesia (PCA) for postoperative analgesia. All patients underwent a standardized combined epidural and general anesthetic and all received ketorolac for 72 h postoperatively. To decrease variability, patients were cared for according to a standardized protocol and were deemed ready for discharge according to prospectively defined criteria.\n Patients in the intravenous PCA group required approximately twice as much opioid than the epidural PCA group (P < 0.008), but there were no differences between groups in pain scores or patient satisfaction. Epidural administration resulted in a greater incidence of pruritus (P = 0.02). Gastrointestinal function recovered quickly in all patients with little variation, and there were no differences between groups. All patients were deemed ready for discharge by the third postoperative day, and removal of surgical drains was the last discharge criterion reached in all patients.\n Our results indicate that epidural administration of hydromorphone results in spinally mediated analgesia. However, epidural administration did not provide significant benefits in terms of postoperative analgesia, recovery of gastrointestinal function, or duration of hospitalization. Furthermore, we suggest that radical retropubic prostatectomy no longer be used as a model to assess the effects of analgesic technique on postoperative recovery, because control of discharge criteria revealed that hospital discharge was primarily dependent on removal of surgical drains.", "The goal of this study was to evaluate the effectiveness on postoperative pain, and cognitive impact, of patient-controlled analgesia (PCA) compared with subcutaneous (s.c.) injections of morphine in elderly patients undergoing total hip replacement (THR).\n Forty patients older than 70 yr were randomly assigned to two different postoperative analgesic techniques for 48 h: i.v. PCA morphine (dose, 1 mg; lockout interval, 8 min; PCA group) or regular s.c. morphine injections (SC group). Postoperative pain was assessed at rest and when moving, using a visual analogue scale (VAS) every 4 h. A Mini Mental Status (MMS) examination was used to assess cognitive functions before surgery, at 2 h, 24 h and 48 h after surgery, and at hospital discharge. Side-effects were also recorded systematically during the first 48 h after surgery.\n The PCA group showed significantly lower pain scores than the SC group both at rest and during mobilization. However, the clinical significance of pain scores was weak. There was no intergroup difference in postoperative MMS scores. The incidence of side-effects was similar in both groups.\n We conclude that in healthy elderly subjects undergoing THR, the flexibility of the analgesic regimen is more important than the route of administration with regard to efficacy, adverse effects and recovery of cognitive function.", "We conducted a study to compare the effectiveness of patient-controlled analgesia (PCA) technique to conventional analgesic therapy (CAT) after coronary artery bypass graft (CABG). The PCA group received hydromorphone 0.1 mg.hr-1 basal infusion and bolus doses of 0.2 mg Q 5 min (maximum 1.2 mg.hr-1) while the CAT group received morphine 2.5 mg iv Q 30 min prn until extubation followed by prn meperidine 1 mg.kg-1 im Q 4 hr or acetaminophen 325 mg with codeine 30 mg po (1 or 2 tablets) when oral intake was possible. The degree of pain was assessed using a Visual Analogue Scale (VAS) starting after extubation and every 6-8 hr for the next 60 hr. Holter monitoring was initiated one hour after patient arrival in the Intensive Care Unit (ICU) and continued for 72 hr. Other measured variables were pulmonary function, sedation, side effects and total opioid requirements. Results show that the day-to-day VAS pain score decreased in the PCA group (P < 0.001) while it remained unchanged in CAT patients. The PCA patients had lower VAS pain scores at extubation (P < 0.05). During the third postoperative day, the PCA group had a lower VAS pain score, a lower incidence of severe pain defined as a score > 5 on the VAS scale, and a reduced incidence of myocardial ischaemia (P < 0.01). However, there was no difference in the duration, severity, area under the curve (AUC), or heart rate during ischaemic events. Postoperative pulmonary function was abnormal in both groups (NS) with minimal recovery by the fourth day.(ABSTRACT TRUNCATED AT 250 WORDS)", "To assess the role of postoperative analgesia on myocardial ischemia after aortic surgery, we compared intravenous patient-controlled analgesia (PCA) with thoracic epidural analgesia (TEA). One hundred twenty-four patients were prospectively randomized to the PCA or TEA group. In the TEA group, a T6-7 or T7-8 epidural catheter was inserted before the induction of general anesthesia. Within 1 h of the end of surgery, analgesia and 24-h two-channel Holter monitoring were begun. Myocardial ischemia was defined as ST segment depression > or = 1 mm, 0.06 s after the J point, and lasting for more than 1 min. In the PCA group, a bolus of morphine, 0.05 mg/kg, was given, followed by 0.02 mg/kg of morphine on demand every 10 min. Bupivacaine 0.125% and fentanyl 10 microg/mL was used in the TEA group. Analgesics were titrated to maintain a visual analog scale score < or = 3. The overall incidence of myocardial ischemia was 18.4%-18.2% for TEA and 18.6% for PCA (P = not significant). There were no differences between the groups in the total duration of ischemia per patient (22.2 +/- 119.8 min for TEA and 20.5 +/- 99 min for PCA) and the number of episodes per patient (0.69 +/- 2.1 for TEA and 1.2 +/- 4.9 for PCA). Twenty-three patients had an adverse cardiac outcome, although there were no differences between the groups. The postoperative pain control was superior with TEA. In these patients undergoing elective aortic surgery, the use of postoperative TEA did not result in a lower incidence of early myocardial ischemia compared with intravenous PCA with morphine, despite better analgesia with TEA. Implications: Postoperative myocardial ischemia is associated with adverse cardiac outcome. Using Holter monitoring after aortic surgery, this study shows that the use of thoracic epidural analgesia with bupivacaine and fentanyl did not result in a lower incidence of myocardial ischemia compared with intravenous patient-controlled analgesia with morphine.", "Patient-controlled analgesia (PCA) offers effective postoperative pain management. However, the evidence of economic benefits associated with its use is lacking. Although suggestive, the potential economic advantages of PCA in saving nursing time and shortening hospital stay need objective documentation.\n This study compared the effects of morphine administered by PCA systems with intramuscular (i.m.) morphine injection on patient analgesic response, satisfaction, nursing time requirements, and postoperative recovery in 23 patients undergoing \"open\" cholecystectomy and 44 patients undergoing lumbar laminectomy and bony fusion. After the operation, patients in the PCA group received 1.5-2 mg morphine with a lockout of 5-10 minutes on demand, whereas those in the i.m. group received 0.15-0.2 mg/kg every 4 hours on demand. Visual analog scale (VAS) pain scores and satisfaction scores were evaluated at 4-hour intervals while nursing time spent on both analgesia-related and non-analgesia-related activities was recorded continuously by a team of independent observers on the ward. Recovery time profile for the return of bowel function, activities of daily living, ambulation without support, and length of hospital stay was also recorded.\n It was found that morphine consumption, VAS, and satisfaction scores were similar in both PCA and i.m. treatment groups following both types of surgery. However, the delay in nurse response to i.m. morphine request ranged from 27.2 +/- to 42.1 +/- 11.8 minutes. The demand of nursing time on analgesia administration was less with PCA. The magnitude of time saving was 10 min/patient/d in cholecystectomy patients and 13 min/patient/d in laminectomy patients. The speed of postoperative patient recovery was similar between the two analgesia groups. Length of hospital stay following cholecystectomy was shorter--92.0 +/- 5.9 hours with PCA versus 128.6 +/- 22.2 hours with i.m. (not statistically significant)--whereas that following laminectomy was not different.\n Data in this study have demonstrated some beneficial effects of PCA on nursing time requirements when it was used following cholecystectomy and lumbar laminectomy at the University of Toronto: however, the magnitude of these benefits was less than previously reported. The effects of PCA on postoperative recovery and hospital stay, however, were not significantly different from i.m. therapy.", "Pain after coronary artery bypass surgery persists for several days. A continuous intravenous infusion of an opioid adequately accomplishes good pain control in the intensive care unit, but it is often not suitable on the ordinary ward. Patient-controlled analgesia (PCA) with intermittent injections delivered by one of the new devices now available could be an alternative to conventional nurse-controlled analgesia (NCA) based on intermittent injections. The aim was to compare these two techniques with respect to efficacy and the amount of opioid used.\n Forty-eight patients randomly received PCA or NCA with ketobemidone following extubation after coronary artery bypass grafting. Drug consumption, pain assessment with the visual analogue score (VAS) and possible side effects were evaluated from extubation to the end of the second postoperative day.\n On the day of surgery the VAS scores did not differ between the groups. From the afternoon of the first postoperative day the VAS scores were higher in the NCA group with mean values at 3-4 out of 10 as compared with mean values around 2 in the PCA group (P<0.01). During the study period the patients in the PCA group received more ketobemidone as compared with the NCA group, 61.9+/-24.0 mg and 36.3+/-20.2 mg, respectively (P<0.01). Additional oral analgesics were used in 12 of the patients in the NCA group compared with none in the PCA group. The few side effects reported were equally distributed between the two groups.\n PCA treatment after coronary artery bypass surgery resulted in better pain treatment and the use of more opioid without an increase in side effects compared with traditional NCA treatment.", "We compared the use of patient-controlled analgesia (PCA) morphine and p.r.n. intravenous morphine in an intensive care unit setting. Thirty-eight patients scheduled for admission to the Surgical Intensive Care Unit (SICU) were prospectively randomized to either a PCA group or a p.r.n. intravenous morphine group. Assessments included pain and sedation scores, respiratory rates, pulse oximetry, and morphine utilization. PCA was found to be comparable in safety and efficacy to nurse-administered morphine in the intensive care environment. An unexpected finding was the higher initial morphine utilization seen in the patients utilizing PCA.", "To evaluate the impact of music on opioid requirements and pain levels during renal lithotripsy using alfentanil patient-controlled analgesia (PCA), we conducted a prospective, blinded, randomized controlled trial. Patients undergoing lithotripsy were instructed in PCA use and asked to rate their anxiety and select their preferred type of music. They were then premedicated with morphine and ketorolac and randomly allocated into two groups. Group 1 (n = 97) had music started 10 min before the procedure and maintained until 10 min after its conclusion. Group 2 (n = 96) had music begun at the conclusion of lithotripsy and continued for 10 min. Pain intensity, alfentanil requirement, side effects, quality of analgesia, patient satisfaction, and acceptance of the technique were evaluated. Demographics, alfentanil requirement, pain levels, side effects, quality of analgesia, and patient satisfaction were similar in both groups. The addition of music did not provide any benefit. This result raises the possibility that some nonpharmacologic therapies have minimal impact in settings where the painful stimulus is moderate to severe and adequate pharmacotherapy is available.", "The purpose of this prospective study was to compare the effectiveness of patient-controlled intravenous (i.v.) opioid analgesic administration (PCA) with fixed schedule and dosage oral/rectal administration of naproxen, and opioid analgesics intramuscularly/orally as needed (i.m./p.o. prn) for postoperative analgesia over a period of 48 to 56 hours after surgery.\n There were 75 orthognathic patients aged 25.73 +/- 8.01 years, subdivided into three study groups of 25: codeine group (8 males, 17 females); naproxen group (5 males, 20 females) and PCA group (8 male, 17 females). The degree of analgesia was assessed every 4 hours from 8:00 AM to 8:00 PM hours on days 1 and 2 postsurgery using a visual analog scale (VAS). Mean daily and mean overall VAS scores were treated as parametric data and were analyzed accordingly. Mean daily VAS scores also were categorized as comfort days when mean scores were less than 3.0 cm, and as discomfort days when mean scores were equal to or greater than 3.0 cm. ANOVA were used to analyze patient demographics, pain scores, surgical time, fentanyl used during general anaesthesia, analgesic morphine equivalents, and vital signs. Chi-square tests were used to analyze sex, comfort (discomfort) days, and nausea and vomiting. Mean VAS ratings were analyzed using independent t-tests.\n The three groups were matched in demographics, surgical time, fentanyl used, and sex. The PCA group used less than half the amount of morphine equivalent as the codeine group (P = .0001). Both the naproxen and the PCA groups were significantly more comfortable than the codeine group during day 1 and day 2 postsurgery. The codeine group had significantly more episodes of nausea than either the naproxen or the PCA groups.\n In patients undergoing orthognathic surgery, the naproxen and PCA regimens provided better analgesia than the codeine regimen.", "We compared patient-controlled analgesia (PCA) and continuous infusion (CI) morphine delivery in a randomized controlled trial in adolescents during oropharyngeal mucositis pain after bone marrow transplantation. Results from 20 patients who completed 7 or more days on study (10 PCA, 10 CI) were evaluated. The group means for age, weight and height were comparable. Daily measures were morphine intake, self-report of pain intensity and side effect scores. Over 10 study days, the mean cumulative morphine dose to subjects in each group was 4.94 mg/kg (PCA) vs. 12.17 mg/kg (CI); the difference is significant (P less than 0.01). No significant differences were found between the groups for patient ratings of pain intensity or side effect scores despite the large difference in mean morphine intake, but the PCA group tended to report less intense sedation and less difficulty concentrating. Adolescents can use PCA effectively and safely for 1-3 weeks. Morphine intake of adolescent patients using PCA morphine intake is significantly lower than that of similar patients receiving staff-controlled CI.", "A prospective comparison of conventional analgesia and patient-controlled analgesia using morphine was conducted. Each patient underwent a major gynecologic oncology procedure and was observed on the post-operative floor. All 192 patients were studied during the first three post-operative days. The findings suggest less total medication and less sedation with equal pain control in the patient-controlled analgesia group.", "The aim of our study was to compare epidural anesthesia and analgesia (EDA) with ropivacaine versus general anesthesia followed by IV patient-controlled analgesia with morphine (GA/PCA) after hip replacement regarding pain, side effects, and discharge from the postanesthesia care unit. After ethics committee approval, randomization, and informed consent, 90 patients were enrolled. In Group EDA, epidural anesthesia (ropivacaine 10 mg/mL, 15-25 mL) was followed by an epidural infusion (2 mg/mL, 4-6 mL/h for 24 h, plus top-up doses of 6-10 mL for 48 h). GA/PCA patients received general anesthesia (isoflurane/N2O/fentanyl) followed by IV patient-controlled analgesia with morphine postoperatively. Pain was assessed by using visual analog scales (0-100 mm) at rest and during physiotherapy. Pain at rest was less in the EDA (n = 43) group than in the GA/PCA (n = 45) group (at 10 h: 11.8+/-12.9 vs. 28.4+/-17.1 [P< 0.001]; at 24 h: 14.3+/-11.7 vs. 24.0+/-17 [P<0.01]; in 48 h: 14.3+/-9.3 vs. 21.1+/-17.4 [P = 0.1]). Whereas EDA patients were deemed ready for discharge from the postanesthesia care unit earlier than GA/PCA patients (5.6+/-8.9 vs. 39.7+/-41.5 min), the actual discharge time was comparable. The median time for first passage of flatus was shorter in the EDA group than in the GA/PCA group (26 vs. 47 h). Nausea and vomiting were more common in the GA/PCA group than in the EDA group (16% vs. 28% and 11% vs. 22%, respectively), whereas hypotension (11% vs. 4%) and bradycardia (14% vs. 2%) were less frequent. Under the conditions of the present study, EDA with ropivacaine provided pain control after hip replacement superior to that provided by IV patient-controlled analgesia with morphine, particularly during the first 24 h. Both approaches to pain management were equally safe.\n Compared with general anesthesia and postoperative IV patient-controlled analgesia with morphine, epidural anesthesia and analgesia with the new local anesthetic ropivacaine enables patients to be discharged sooner from a postanesthesia care unit and provides superior pain relief during the first 24 h after hip replacement.", "This study was conducted in order to investigate the advantages and limitations of four analgesic modalities: a) epidural morphine; b) intravenous morphine; c) patient controlled intravenous morphine (patient-controlled analgesia); and d) non-steroidal anti-inflammatory drugs. Eighty patients undergoing major abdominal surgical procedures were prospectively and randomly treated with one of the above-mentioned analgesic methods. Evaluation of pain perception was done using the visual analogue pain score and the simple descriptive scale 4 hours after the procedure, in the early morning on postoperative day 1 and in the afternoon on postoperative days 1, 2 and 3. The need for supplementary analgesia and the onset of complications, if any, were also evaluated for each patient. Patient-controlled intravenous morphine yielded the best analgesic effect over the entire period. Epidural morphine was more effective in the very early postoperative period compared to modalities (b) and (d). Non-steroidal anti-inflammatory drugs, on the other hand, were more effective on the later postoperative days. None of the patients in group C needed supplementary analgesia, as against 20% in group A, 55% in group B and 40% in group D. Patients with hypochondriasis scores > 70 or depression scores > 70 required supplementation of analgesia more often. Morphine proved to be the drug of choice. Drug titration may be modulated in relation to the psychological characteristics of the patient. The best drug titration modality, in fact, is patient-controlled analgesia.", "After total knee arthroplasty, patients regularly suffer from severe pain. It is unclear whether epidural or systemic pain therapy is superior in terms of postoperative pain relief, patients' comfort and side effects. A new therapeutic approach, intraarticular opioids, has been suggested with the detection of opioid receptors in inflamed tissue. This method has proven suitable for clinical use in small operations (e.g. knee arthroscopy). In this study, we compared epidural analgesia and intraarticular application of morphine plus \"on-demand\" intravenous analgesia to \"on-demand\" intravenous analgesia alone.\n Thirty-seven patients, scheduled for total knee arthroplasty, were randomly assigned to three treatment groups: in group 1 (EPI) patients received bolus doses of morphine via an epidural catheter; in group 2 (IA) an intraarticular bolus of 1 mg of morphine was applied at the end of the operation with subsequent use of a patient-controlled analgesia (PCA) pump; group 3 (Control), in which only PCA was provided, served as control for both analgesic procedures. Main outcome measures included visual analogue pain scales, total morphine consumption, and stress hormones.\n No statistically significant differences in visual analogue pain scales could be detected between the three groups. Application of intraarticular morphine did not reduce the amount of analgesics required for postoperative analgesia as compared to intravenous analgesia alone. Application of epidural morphine significantly suppressed beta-endorphine release, but did not significantly influence other stress hormones as compared to the control group.\n Epidural and intravenous analgesia after total knee arthroplasty are equivalent methods of pain relief. In major orthopaedic procedures, application of intraarticular morphine does not reduce analgesic requirements.", "The present study examined the impact of two methods of pain management on recovery in 38 women undergoing hysterectomy. One group received IV morphine in the recovery room and IM morphine on the ward on a PRN basis (PRN group). In the other group, a loading dose of morphine 8 mg IV was given when the patient first complained of pain and patient-controlled IV morphine (PCA) was initiated and continued for 48 h (PCA group). Both groups received similar amounts of morphine overall, differently distributed over time. The PCA patients received 8 mg.h-1 in the recovery room (approximately 2.5 hrs) and less thereafter. The PRN patients received approximately 2 mg.h-1 for the entire 48-hr period. Pain control was better throughout convalescence and less variable across time with PCA management. Minute ventilation also recovered faster and by day four was 25 per cent above the preoperative baseline in the PCA group. In addition, oral temperature became normal one day earlier, ambulation recovered more rapidly and patients were discharged from hospital earlier. The data suggest that early treatment with relatively high, self-titrated morphine doses may alter the course of the metabolic response to surgery." ]	This review provides evidence that PCA is an efficacious alternative to conventional systemic analgesia for postoperative pain control.
CD005071	[ "12876092", "12392866", "2304219", "769027" ]	[ "Factors associated with failure to publish large randomized trials presented at an oncology meeting.", "The end-of-study patient survey: methods influencing response rate in the AVID Trial.", "A cohort study of summary reports of controlled trials.", "An example of European multicenter trials: multispectral analysis of clozapine." ]	[ "Large clinical trials are the criterion standard for making treatment decisions, and nonpublication of the results of such trials can lead to bias in the literature and contribute to inappropriate medical decisions.\n To determine the rate of full publication of large randomized trials presented at annual meetings of the American Society of Clinical Oncology (ASCO), quantify bias against publishing nonsignificant results, and identify factors associated with time to publication.\n Survey of 510 abstracts from large (sample size, > or =200), phase 3, randomized controlled trials presented at ASCO meetings between 1989 and 1998. Trial results were classified as significant (P< or =.05 for the primary outcome measure) or nonsignificant (P>.05 or not reported), and the type of presentation and sponsorship were identified. Subsequent full publication was identified using a search of MEDLINE and EMBASE, completed November 1, 2001; the search was updated in November 2002, using the Cochrane Register of Controlled Trials. Authors were contacted if the searches did not find evidence of publication.\n Publication rate at 5 years; time from presentation to full publication.\n Of 510 randomized trials, 26% were not published in full within 5 years after presentation at the meeting. Eighty-one percent of the studies with significant results had been published by this time compared with 68% of the studies with nonsignificant results (P<.001). Studies with oral or plenary presentation were published sooner than those not presented (P =.002), and studies with pharmaceutical sponsorship were published sooner than studies with cooperative group sponsorship or studies for which sponsorship was not specified (P =.02). These factors remained significant in a multivariable model. The most frequent reason cited by authors for not publishing was lack of time, funds, or other resources.\n A substantial number of large phase 3 trials presented at an international oncology meeting remain unpublished 5 years after presentation. Bias against publishing nonsignificant results is a problem even for large randomized trials. Nonpublication breaks the contract that investigators make with trial participants, funding agencies, and ethics boards.", "Patient surveys are commonly distributed at the end of a multicenter clinical trial. This Antiarrhythmics Versus Implantable Defibrillators (AVID) substudy prospectively explored the relationship between methods used in distributing a survey and the quantity of responses received. AVID was a multicenter, randomized trial comparing survival in arrhythmia patients treated with antiarrhythmic drugs versus implantable defibrillators. At study termination, a patient satisfaction survey was mailed to the 664 surviving participants. Questions included reasons for study participation, study benefits and problems and quality of care. Survey mailings were stratified by four factors in a 2x2x2x2 factorial design: delivery mode (overnight vs. regular mail), certificate of appreciation, timing of administration (\"early\" vs. \"late\") and cover letter signed by a physician versus coordinator. Patients were randomly assigned to received one of 16 combinations of these four factors. Clinical characteristics and response rates were evaluated. Patients were more likely to return surveys delivered by overnight mail (75% vs. 68%, p=0.04), with no certificate of appreciation enclosed (75% vs. 68%, p=0.05) and administered close to the time of study closeout (79% vs. 72%, p=0.085). Compared to the 184 nonrespondents, the 456 (71%) respondents were older, Caucasian, lived with others, were high school graduates and less likely to have Medicare/Medicaid or HMO insurance (p<0.03). Physician recommendation was the most common reason cited for trial participation. Main benefits included increased knowledge of their medical condition and improved health. Reported problems included parking, transportation and excess clinic wait time. This randomized study demonstrated that methods of patient survey distribution affect the survey return rate. Additional studies should explore mechanisms for maximizing return rates.\n Copyright 2002 Elsevier Science Inc.", "Substantial numbers of clinical trials continue to be reported only in summary reports that present insufficient methodological details to permit informed judgments about the likely validity of the conclusions. Using a cohort of 176 controlled trials reported in summary form, we tested the hypotheses that they would be more likely to be followed by full reports if, on the basis of the information provided in the summary report, (1) the trial was judged to be methodologically sound, (2) the results favored the test treatment, and (3) the sample size was relatively large. The results of univariate and multivariate analyses provided support for only the third of these hypotheses. Investigators, as well as those who fund and sanction the conduct of clinical research, should make greater efforts to ensure that clinical trials are reported properly.", "nan" ]	The number of trials and participants is insufficient to draw final conclusions. A large multicenter study with adequate power is needed.
CD005298	[ "9084544", "8198263", "9380919" ]	[ "Prophylaxis against acid aspiration in regional anesthesia for elective cesarean section: a comparison between oral single-dose ranitidine, famotidine and omeprazole assessed with fiberoptic gastric aspiration.", "Intravenous administration of the proton pump inhibitor omeprazole reduces the risk of acid aspiration at emergency cesarean section.", "[Prophylaxis of intraoperative nausea and vomiting with sub-hypnotic dose of propofol during intradural anesthesia in cesarean section]." ]	[ "Acid aspiration syndrome is still an important cause which contributes to maternal mortality in obstetric anesthesia. In this study, we compared famotidine, ranitidine, omeprazole with placebo for prophylaxis against aspiration pneumonitis in elective Cesarean section under regional anesthesia.\n One hundred and sixty patients undergoing elective Cesarean section under spinal anesthesia were allocated randomly into four groups: Group P (n = 40) received placebo only; Group F (n = 40) received famotidine 40 mg Group R (n = 40) received ranitidine 300 mg; and Group O (n = 40) received omeprazole 40 mg. All drugs were given orally at least three hours before the patients entering the operating room. Gastric content was directly aspirated and measured respectively with a flexible fiberoscope under visualization and by a pH meter after delivery.\n Although these three drugs (F, R, and O) were all effective in controlling the secretion of gastric acid, from gastric analysis it was demonstrated that famotidine and ranitidine could be more defective to neutralize acidity than omeprazole (p < 0.05). Percentages of patients with pH < or = 2.5 in Groups P, F, R, and O were respectively 88%, 10%, 8%, and 21%, showing that the innate pH of gastric juice was far lower than expected. Patients receiving omeprazole in single oral dose regimen retained a greater gastric volume (> or = 0.4 ml/kg) than those who received famotidine or ranitidine (p < 0.005). From the criteria defining the patients \"at risk\" (pH < or = 2.5 and gastric volume > or = 0.4 ml/kg), it is speculated that all these three regimens could potentially reduce the incidence of patients with calculated risk.\n Our data demonstrated that parturients under regional anesthesia were at a higher risk of aspiration pneumonitis than generally thought. Single dose of ranitidine or famotidine administered orally three hours before surgery provided a more effective means to control and neutralize gastric secretion than omeprazole in parturients.", "This study documented gastric pH and volume, and the number of patients at risk for acid aspiration of gastric contents, in a group of mothers undergoing emergency cesarean section under general anesthesia. Patients were randomized in a double-blind fashion to receive omeprazole 40 mg intravenously or placebo at the time of decision to proceed to cesarean section. In addition, all patients received 10 mg intravenous metoclopramide and 30 mL of 0.3 M sodium citrate. Aspiration of gastric contents was undertaken immediately after endotracheal intubation (PI) and before tracheal extubation (PE). Patients with both pH < 3.5 and volume > 25 mL were deemed to be at risk of acid aspiration should regurgitation occur. Only cases where the study-drug-to-PI-aspiration interval was > 30 min were evaluated. There were 282 patients in the study group and 259 in the control group. PI, 11 patients (4.25%; 95% confidence interval [CI] 1.79-6.71) were at risk in the control group compared with 4 (1.42%; 95% CI 0.04-2.8) in the study group (P = 0.045). The omeprazole-to-PI-aspiration interval in these four cases was < or = 40 min. PE, 19 (7.3%; 95% CI 4.17-10.51) patients were at risk in the control group compared with 2 (0.7%; 95% CI 0-1.69) in the study group (P < 0.0001). Mean pH in patients receiving omeprazole was significantly higher (P < 0.001) than in the control group. Gastric volumes were significantly lower in the omeprazole group compared with the control group at both PI (P = 0.006) and PE (P = 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)", "To determine the preventive and therapeutic effect of 10 mg of propofol administered after delivery on the incidence of intraoperative nausea and vomiting (IONV) during intradural anesthesia for cesarean delivery.\n Controlled, randomized double blind study of 60 women (ASA I-II) receiving intradural anesthesia for elective or deferred emergency cesarean delivery. The propofol group received 10 mg i.v. immediately after fetal extraction. The control group received an equal volume of Intralipid. The presence of IONV after administration of the prophylactic bolus was treated with a second bolus, and if nausea had not subsided completely after two minutes, treatment was topped up with dehydro-benzoperidol.\n The control group included 31 women and the propofol group 29, of whom 3 were excluded. Control variables were similar in the two groups. There were no significant differences in the incidence and severity of IONV between the two groups (22.5 versus 23%). The top-up antiemetic drug was used in the same number of patients in each group.\n Although 10 mg propofol has been described as an effective direct antiemetic, episodes of IONV were neither prevented nor reversed by its use during intradural anesthesia for cesarean delivery." ]	There is no good evidence to support the routine administration of acid prophylaxis drugs in normal labour to prevent gastric aspiration and its consequences. Giving such drugs to women once a decision to give general anaesthesia is made, is assessed in another Cochrane review. [Note: The four citations in the awaiting classification section of the review may alter the conclusions of the review once assessed.]
CD003292	[ "18091051", "21041710", "16757720" ]	[ "Improved survival, quality of life, and quality-adjusted survival in breast cancer patients treated with efaproxiral (Efaproxyn) plus whole-brain radiation therapy for brain metastases.", "Adjuvant whole-brain radiotherapy versus observation after radiosurgery or surgical resection of one to three cerebral metastases: results of the EORTC 22952-26001 study.", "Stereotactic radiosurgery plus whole-brain radiation therapy vs stereotactic radiosurgery alone for treatment of brain metastases: a randomized controlled trial." ]	[ "To determine whether efaproxiral, an allosteric modifier of hemoglobin, improves quality of life and quality of survival in patients with primary breast cancer and brain metastases when used as an adjunct to whole-brain radiation therapy (WBRT).\n Patients with brain metastases from breast cancer were randomly assigned to receive WBRT and either efaproxiral or no efaproxiral. The primary endpoint for this analysis was quality of life and quality-adjusted survival. Quality of life was assessed prior to initiation of WBRT and periodically in follow-up using the Spitzer Quality of Life Index (SQLI).\n A subgroup of 106 eligible breast cancer patients with baseline SQLI were randomized into this study and represent the target population discussed in this report. Treatment, age, and SQLI were significant predictors of survival. The addition of efaproxiral to WBRT reduced the death rate by 46% (P = 0.0086). Quality of life was improved in the WBRT + efaproxiral arm compared with the WBRT alone arm (P = 0.019). Quality-adjusted survival was statistically significantly improved by the addition of efaproxiral to WBRT (P = 0.001).\n Survival, quality of life, and quality-adjusted survival were all improved in breast cancer patients with brain metastases receiving efaproxiral and WBRT compared with those receiving WBRT alone.", "This European Organisation for Research and Treatment of Cancer phase III trial assesses whether adjuvant whole-brain radiotherapy (WBRT) increases the duration of functional independence after surgery or radiosurgery of brain metastases.\n Patients with one to three brain metastases of solid tumors (small-cell lung cancer excluded) with stable systemic disease or asymptomatic primary tumors and WHO performance status (PS) of 0 to 2 were treated with complete surgery or radiosurgery and randomly assigned to adjuvant WBRT (30 Gy in 10 fractions) or observation (OBS). The primary end point was time to WHO PS deterioration to more than 2.\n Of 359 patients, 199 underwent radiosurgery, and 160 underwent surgery. In the radiosurgery group, 100 patients were allocated to OBS, and 99 were allocated to WBRT. After surgery, 79 patients were allocated to OBS, and 81 were allocated to adjuvant WBRT. The median time to WHO PS more than 2 was 10.0 months (95% CI, 8.1 to 11.7 months) after OBS and 9.5 months (95% CI, 7.8 to 11.9 months) after WBRT (P = .71). Overall survival was similar in the WBRT and OBS arms (median, 10.9 v 10.7 months, respectively; P = .89). WBRT reduced the 2-year relapse rate both at initial sites (surgery: 59% to 27%, P < .001; radiosurgery: 31% to 19%, P = .040) and at new sites (surgery: 42% to 23%, P = .008; radiosurgery: 48% to 33%, P = .023). Salvage therapies were used more frequently after OBS than after WBRT. Intracranial progression caused death in 78 (44%) of 179 patients in the OBS arm and in 50 (28%) of 180 patients in the WBRT arm.\n After radiosurgery or surgery of a limited number of brain metastases, adjuvant WBRT reduces intracranial relapses and neurologic deaths but fails to improve the duration of functional independence and overall survival.", "In patients with brain metastases, it is unclear whether adding up-front whole-brain radiation therapy (WBRT) to stereotactic radiosurgery (SRS) has beneficial effects on mortality or neurologic function compared with SRS alone.\n To determine if WBRT combined with SRS results in improvements in survival, brain tumor control, functional preservation rate, and frequency of neurologic death.\n Randomized controlled trial of 132 patients with 1 to 4 brain metastases, each less than 3 cm in diameter, enrolled at 11 hospitals in Japan between October 1999 and December 2003.\n Patients were randomly assigned to receive WBRT plus SRS (65 patients) or SRS alone (67 patients).\n The primary end point was overall survival; secondary end points were brain tumor recurrence, salvage brain treatment, functional preservation, toxic effects of radiation, and cause of death.\n The median survival time and the 1-year actuarial survival rate were 7.5 months and 38.5% (95% confidence interval, 26.7%-50.3%) in the WBRT + SRS group and 8.0 months and 28.4% (95% confidence interval, 17.6%-39.2%) for SRS alone (P = .42). The 12-month brain tumor recurrence rate was 46.8% in the WBRT + SRS group and 76.4% for SRS alone group (P<.001). Salvage brain treatment was less frequently required in the WBRT + SRS group (n = 10) than with SRS alone (n = 29) (P<.001). Death was attributed to neurologic causes in 22.8% of patients in the WBRT + SRS group and in 19.3% of those treated with SRS alone (P = .64). There were no significant differences in systemic and neurologic functional preservation and toxic effects of radiation.\n Compared with SRS alone, the use of WBRT plus SRS did not improve survival for patients with 1 to 4 brain metastases, but intracranial relapse occurred considerably more frequently in those who did not receive WBRT. Consequently, salvage treatment is frequently required when up-front WBRT is not used.\n umin.ac.jp/ctr Identifier: C000000412." ]	Surgery and WBRT may improve FIS but not overall survival. It may also reduce the proportion of deaths due to neurological cause. All these results were in a highly selected group of patients. Patients undergoing surgery were not reported to have any higher risk of adverse events than patients who only had WBRT.
CD007966	[ "3891946", "7612090", "2213261", "1408537", "10730039", "17429240", "17551656", "1297921" ]	[ "Randomized trial of prophylactic phototherapy in the infant with very low birth weight.", "Double phototherapy with high irradiance compared with single phototherapy in neonates with hyperbilirubinemia.", "A randomized, controlled application of the Wallaby phototherapy system compared with standard phototherapy.", "Double versus single phototherapy in low birth weight newborns.", "Double versus single phototherapy in term newborns with significant hyperbilirubinemia.", "Fiberoptic, conventional and combination phototherapy for treatment of nonhemolytic hyperbilirubinemia in neonates.", "Efficacy of new microprocessed phototherapy system with five high intensity light emitting diodes (Super LED).", "[A new device for phototherapy of neonatal jaundice]." ]	[ "Twenty-two preterm infants (birth weight 850 +/- 220 gm) were randomly assigned to receive phototherapy either soon after birth or after the serum bilirubin concentration reached 5 mg/dl. Infants receiving prophylactic phototherapy were placed under lights at a significantly earlier age and lower serum bilirubin concentration than infants in the routine group (P less than 0.001). There was no significant difference between groups in peak serum bilirubin concentration, age at which it peaked, rate of rise in serum bilirubin concentration, or serum bilirubin concentration at any time during the study. Infants assigned to the prophylactic phototherapy group were under lights for a significantly longer time than those in the routine group (P less than 0.05). There was a significant rise in both configurational and structural photo-isomers (P less than 0.005) independent of serum bilirubin concentration after phototherapy in all patients. These data suggest that the clinical course of hyperbilirubinemia is not altered in infants with very low birth weight receiving prophylactic phototherapy compared with infants with phototherapy begun at a bilirubin concentration of 5 mg/dl.", "The purpose of this study is to compare the effectiveness of double phototherapy versus single conventional phototherapy in decreasing serum bilirubin levels in jaundiced neonates. Forty-two preterm infants who were less than 37 weeks' gestational age and less than 2000 g birthweight with nonhemolytic jaundice were alternately assigned to double phototherapy (n = 19) (Biliblanket, Ohmeda with irradiance of 33 to 35 microW/cm2/nm in addition to single conventional phototherapy with combination of three or four special blue and white lamps with irradiance of 7 to 9 microW/cm2/nm) or to single conventional phototherapy (n = 23) based on elevated serum bilirubin levels in the first week of life. Phototherapy was initiated at specific bilirubin levels in three weight stratifications. The groups were similar in clinical characteristics at study entry. The decrease in serum bilirubin levels was very significant in the double phototherapy group at 8 hours after the therapy (-29 +/- 18.8 versus 8.5 +/- 27 mumol/L; P < 0.001), at 16 hours after the therapy (-49.6 +/- 15.4 versus 3.4 +/- 39 mumol/L; p < 0.001), and at 24 hours after therapy (-71.8 +/- 18.8 versus -3.4 +/- 32.5 mumol/L; p < 0.001) compared with the conventional phototherapy group. The time taken for bilirubin levels to fall below the threshold level was 55 +/- 41 hours in the single group and 14 +/- 6 hours in the double group (p < 0.001). Double phototherapy was well tolerated. The Biliblanket when used in conjunction with single conventional phototherapy resulted in a faster decrease of serum bilirubin.(ABSTRACT TRUNCATED AT 250 WORDS)", "The feasibility and efficacy of a fiberoptic blanket (Wallaby Phototherapy System) for the treatment of physiologic jaundice was compared with conventional phototherapy. Forty-two full-term infants with nonhemolytic jaundice were included in the study. Infants in the study group were treated with the fiberoptic blanket and the infants in the control group were placed under a standard phototherapy unit. Both the fiberoptic blanket and the standard phototherapy unit delivered an average irradiance of 7.0 +/- 0.5 muw/cm2/nm. Incremental changes in serial plasma bilirubin levels compared with the initial bilirubin concentration did not differ between the study and control groups. For infants whose initial plasma bilirubin concentration exceeded 200 mumol/L, a statistically significant difference was found in both study and control groups between the average bilirubin level at initiation of phototherapy and the average bilirubin level at termination of treatment. We conclude that phototherapy delivered by the fiberoptic blanket is safe and has efficacy comparable to that of conventional phototherapy, providing a convenient alternative phototherapy application strategy that obviates the need for eye patches and facilitates maternal handling of the infant during therapy.", "Conventional phototherapy systems that simultaneously irradiate the front and the back of the baby lower the serum bilirubin level more rapidly than one-sided systems, but they are impractical. Fiberoptic phototherapy makes it easy to administer conventional phototherapy from above while the infant lies on a fiberoptic phototherapy blanket. Newborns with birth weights less than 2500 g were randomly assigned to receive either single (n = 37) or double (n = 33) phototherapy. The groups were similar in clinical and laboratory characteristics. After 18 hours of therapy the serum bilirubin concentration declined by 31 +/- 11% in the double and 16 +/- 15% in the single phototherapy group (2.9 +/- 1.1 vs 1.6 +/- 1.4 mg/dL), and the difference in the total serum bilirubin levels after 18 hours of therapy was significant (double phototherapy group 7.1 +/- 2.7 mg/dL vs single phototherapy group 8.2 +/- 2.6 mg/dL). After 18 hours of treatment the serum bilirubin level was less than the phototherapy threshold level in 26 of 37 single phototherapy patients vs 32 of 33 double phototherapy patients. Double phototherapy was well tolerated. It is concluded that this type of double phototherapy is more effective than single phototherapy in low birth weight newborns. Double phototherapy may be useful when it is necessary to reduce an elevated serum bilirubin level as rapidly as possible or when the bilirubin level is rising with single phototherapy.", "The efficacy of double phototherapy, in the form of conventional phototherapy with special blue light plus fiberoptic phototherapy, was compared with conventional phototherapy consisting of special blue lamps alone in a relatively larger series of term newborns with significant hyperbilirubinemia. During the study period the sum of the average spectral irradiances in the double phototherapy group was significantly higher than that of the single phototherapy group (p < 0.05). Phototherapy was effective in decreasing bilirubin levels in both groups, but the response was greater in the double phototherapy group; the duration of exposure to phototherapy was significantly shorter (31.2 +/- 8.5 vs. 38.98 +/- 14.7 h, p < 0.05), and the overall bilirubin decline rate as mumol/l/h and per cent/h was significantly greater in the double phototherapy group (4.1 +/- 1.37 vs. 3.3 +/- 0.86 mumol/l/h, and 1.29 +/- 0.38 vs. 1.02 +/- 0.44 per cent/h, p < 0.05). In phototherapy treatment of term newborns with significant hyperbilirubinemia, double phototherapy provided more rapid and effective bilirubin reduction than conventional phototherapy alone due to higher spectral irradiance and larger body surface area exposed to phototherapy. The value of double phototherapy in the treatment of newborns with hemolytic hyperbilirubinemia remains to be determined.", "The objective of this prospective, randomized study was to compare the effectiveness of fiberoptic, conventional and a combination phototherapy in decreasing bilirubin concentrations in neonatal nonhemolytic hyperbilirubinemia. Forty-six infants who were 36 weeks' gestation and more were randomly assigned to fiberoptic phototherapy (n=16) (Biliblanket, Ohmeda), conventional daylight phototherapy (n=15) and combination phototherapy (n=15) (fiberoptic and conventional). The groups were similar in clinical characteristics at study entry in terms of birth weight, age and bilirubin concentration. There were no statistically significant differences in the duration of treatment among the three groups (P=0.83). There were also no statistically significant differences among the three groups in the serum bilirubin concentrations at 24 hours, 48 hours, end of phototherapy, and 24 hours postphototherapy. We concluded that the decrease in serum bilirubin concentration was comparable among fiberoptic, conventional and combination phototherapy groups.", "To evaluate the efficacy of a microprocessed phototherapy (PT) system with five high intensity light emitting diodes (Super LED) for the treatment of neonatal hyperbilirubinemia of premature infants.\n Randomized clinical trial using Super LED phototherapy in the study group and twin halogen spotlight phototherapy in the control group. A stratified blocked randomization, based on birth weight, was performed. The duration of phototherapy and the rate of decrease of total serum bilirubin (TSB) concentration in the first 24 hours of treatment were the main outcome measures.\n We studied 88 infants, 44 in the Super LED group and 44 in the halogen spotlight PT group. The demographic characteristics of the patients in both groups were similar. Infants in the Super LED group had a similar mean initial serum bilirubin level (10.1+/-2.4 mg%) to those receiving halogen spotlight treatment (10.9+/-2.0 mg%). After 24 hours of treatment, the decrease in total serum bilirubin levels was significantly greater in the Super LED group (27.9 vs. 10.7%, p<0.01) and duration of phototherapy was significantly shorter in this group (36.8 h vs. 63.8 h, p<0.01). After 24 hours of treatment, a significantly greater number of patients receiving Super LED phototherapy had reached serum bilirubin concentrations low enough to allow withdrawal of treatment (23 vs. 10, p<0.01).\n Our results demonstrate that the efficacy of Super LED phototherapy for treating hyperbilirubinemia in premature infants was significantly better than halogen phototherapy.", "The effectiveness of a new device for phototherapy in the treatment of nonhemolytic hyperbilirubinemia (Wallaby Phototherapy System) was evaluated. 46 healthy term infants, appropriate for gestational age and with serum bilirubin > 12 mg/dl in the first 3 days of life or > 15 mg/dl after 3rd day were randomly assigned to a treatment group (24 hours of light exposure with Wallaby Phototherapy System) and to a control group (any treatment for hyperbilirubinemia). Body temperature, weight, feeding and hydration were recorded during the study period. Serum bilirubin and haematocrit were done every 12 hours in all babies. In the treated group we found a decrease of 5.1% and of 7.8% at 12 and 24 hours, while an increase of 3.37% and of 2.9% at 12 and 24 hours was found in the control group. After 24 hours the serum bilirubin level was significantly lower in the treated group than in the control group (p < 0.05). No newborn of the treated group needed conventional phototherapy versus 4 control infants (17.4%). The conclusion of our study is that the Wallaby System is useful in the treatment of neonatal nonhemolytic hyperbilirubinemia even if its effectiveness for higher bilirubin levels has still to be tested." ]	Prophylactic phototherapy helps to maintain a lower serum bilirubin concentration and may have an effect on the rate of exchange transfusion and the risk of neurodevelopmental impairment. However, further well-designed studies are needed to determine the efficacy and safety of prophylactic phototherapy on long-term outcomes including neurodevelopmental outcomes.
CD002991	[ "20037682", "10095821", "9864001", "11001866", "11243949", "14682412", "3902388", "2920584", "2665584", "7032378", "9713447", "15363007", "10343624", "10556133", "9043535", "21917440", "8625660", "10581660", "10780760", "9925060", "19863361", "15894479", "1615177", "3514164", "10421835", "1729064", "7497762", "11948381", "12449158", "6383740", "2669554", "9364183", "12850128", "8924134", "12149529", "9771245", "7713201", "1514669", "12583942", "1426202", "10359405", "9519948", "10212082", "3885915", "8239103", "16507855", "8077885" ]	[ "Predictive value and utility of oral steroid testing for treatment of COPD in primary care: the COOPT study.", "The response to inhaled and oral steroids in patients with stable chronic obstructive pulmonary disease.", "An inhaled steroid improves markers of airway inflammation in patients with mild asthma.", "Additive effects of prednisolone and beclomethasone dipropionate in patients with stable chronic obstructive pulmonary disease.", "Systemic glucocorticoids in severe exacerbations of COPD.", "Short- and long-term efficacy of fluticasone propionate in subjects with early signs and symptoms of chronic obstructive pulmonary disease. Results of the DIMCA study.", "Effect of steroid therapy on exercise performance in patients with irreversible chronic obstructive pulmonary disease.", "A randomized controlled trial of methylprednisolone in the emergency treatment of acute exacerbations of COPD.", "High doses of inhaled corticosteroids in unstable chronic asthma. A multicenter, double-blind, placebo-controlled study.", "Steroid response in stable chronic obstructive pulmonary disease.", "Randomised controlled trial of inhaled corticosteroids in patients with chronic obstructive pulmonary disease.", "Does addition of inhaled steroid to combined bronchodilator therapy affect health status in patients with COPD?", "Long term effects of inhaled corticosteroids in chronic obstructive pulmonary disease: a meta-analysis.", "Effect of high dose inhaled steroid on cells, cytokines, and proteases in induced sputum in chronic obstructive pulmonary disease.", "The effects of combined intravenous and inhaled steroids (beclomethasone dipropionate) for the emergency treatment of acute asthma. The Asthma ED Study Group.", "Effect of adjunct fluticasone propionate on airway physiology during rest and exercise in COPD.", "Effects of long-term treatment with corticosteroids in COPD.", "Steroid reversibility test followed by inhaled budesonide or placebo in outpatients with stable chronic obstructive pulmonary disease. The Danish Society of Respiratory Medicine.", "Effects of inhaled steroids on methacholine-induced bronchoconstriction and gas trapping in mild asthma.", "The effect of high-dose inhaled beclomethasone dipropionate in patients with stable COPD.", "Effect of fluticasone propionate/salmeterol (250/50) on COPD exacerbations and impact on patient outcomes.", "Effects of inhaled HFA beclomethasone on pulmonary function and symptoms in patients with chronic obstructive pulmonary disease.", "Inhaled steroids in patients with bronchiectasis.", "Corticosteroids in COPD. A clinical trial and reassessment of the literature.", "A double-blind placebo-controlled study of the effect of inhaled beclomethasone dipropionate for 2 years in patients with nonasthmatic chronic obstructive pulmonary disease.", "Theophylline and salbutamol improve pulmonary function in patients with irreversible chronic obstructive pulmonary disease.", "Inhaled budesonide therapy for patients with stable COPD.", "A randomized trial of inhaled versus intravenous steroids in ventilator-dependent preterm infants.", "Dose reduction of inhaled corticosteroids under concomitant medication with montelukast in patients with asthma.", "Treatment of chronic obstructive pulmonary disease with corticosteroids. Comparison of daily vs alternate-day therapy.", "Comparison of dose-response effects of inhaled beclomethasone dipropionate and budesonide in the management of asthma.", "The efficacy of inhaled corticosteroids in the management of non asthmatic chronic airflow obstruction.", "Salmeterol & fluticasone 50 microg/250 microg bid in combination provides a better long-term control than salmeterol 50 microg bid alone and placebo in COPD patients already treated with theophylline.", "Early corticosteroid use in acute exacerbations of chronic airflow obstruction.", "Effects of fluticasone propionate in COPD patients with bronchial hyperresponsiveness.", "Treatment of acute asthmatic exacerbations with an increased dose of inhaled steroid.", "High-dose inhaled steroids in asthmatics: moderate efficacy gain and suppression of the hypothalamic-pituitary-adrenal (HPA) axis. Research Council of the Norwegian Thoracic Society.", "High-dose inhaled steroids in the management of asthma. A comparison of the effects of budesonide and beclomethasone dipropionate on pulmonary function, symptoms, bronchial responsiveness and the adrenal function.", "Combined salmeterol and fluticasone in the treatment of chronic obstructive pulmonary disease: a randomised controlled trial.", "Inhaled beclomethasone improves the course of asthma and COPD.", "Long-term effect of inhaled budesonide in mild and moderate chronic obstructive pulmonary disease: a randomised controlled trial.", "Multicentre randomised placebo-controlled trial of inhaled fluticasone propionate in patients with chronic obstructive pulmonary disease. International COPD Study Group.", "Randomised controlled study of early use of inhaled corticosteroid in preterm infants with respiratory distress syndrome.", "Early steroid therapy for respiratory failure.", "Intramuscular methylprednisolone acetate for the prevention of relapse in acute asthma.", "The effect of tiotropium on exacerbations and airflow in patients with COPD.", "No effect of high-dose inhaled steroids in pulmonary sarcoidosis: a double-blind, placebo-controlled study." ]	[ "The oral prednisolone test is widely used to distinguish chronic obstructive pulmonary disease (COPD) patients who might benefit from inhaled steroid treatment. Previous studies used selected patient groups that did not represent the large COPD population in primary care.\n The study included smokers and exsmokers with chronic bronchitis or COPD from primary care, who underwent prednisolone testing (30 mg for 14 days) before randomization in a three-year follow-up randomized controlled trial (COOPT Study). Spirometry was performed before and after the test. Responders and nonresponders were classified according to international criteria. Effectiveness of inhaled fluticasone relative to placebo was compared in terms of health status (Chronic Respiratory Disease Questionnaire), exacerbations, and postbronchodilator forced expiratory volume in one second (FEV(1)), using repeated measurement analysis.\n Two hundred eighty-six patients recruited from 44 primary care practices were randomized. Nine percent to 16% of the COPD population was classified as responder, depending on the international guideline criteria used. On average, responders did not reach the minimum clinically important difference in health status (0.29 points/year, P = 0.05), although a borderline significant effect of inhaled fluticasone was noted. Possible clinically relevant reductions in exacerbation rate (rate ratio 0.67) and FEV(1) decline (39 mL/year) occurred in responders, but did not reach statistical significance.\n Oral steroid testing identifies a limited proportion of COPD patients, but does not reveal any clinically relevant benefit from inhaled steroid treatment on health status. No significant effects on exacerbation rate and lung function decline occurred.", "A significant minority of patients with COPD have favourable response to corticosteroid treatment. In addition, the benefit of corticosteroid treatment may be outweighed by the side-effects. Long-term administration of inhaled steroids is a safe means of treatment. However, only a few studies have addressed the role of inhaled steroids in patients with COPD, with conflicting results.\n Forty-four patients with stable COPD were defined as 'responders to bronchodilators' (increase in FEV1 > or = 20% following administration of beta 2-agonist) (group A), and 124 as 'non-responders to bronchodilators' (group B). All patients were randomized to receive a 6-week course of either a daily dose of 800 micrograms of inhaled budesonide or placebo, separated by 4 weeks when no medication was taken; were randomized again to receive a 6-week course of either 1600 micrograms day-1 of inhaled budesonide, or 800 micrograms day-1 of inhaled budesonide plus placebo; and were randomized once again to receive a 6-week course of either 40 mg day-1 of prednisone or placebo. All stages were performed in a double-blind cross-over design.\n Following administration of 800 micrograms day-1 of inhaled budesonide, there was an increase in the mean FEV1 from 1.40 +/- 0.20 to 1.92 +/- 0.22 L (P < 0.001) and a significant decrease in inhaled beta 2 agonist consumption in group A. These changes remained almost stable during the increased dose of inhaled budesonide or during prednisone treatment. The mean FEV1 did not change during the placebo period, or in group B in either treatments.\n Treatment with inhaled steroids improved spirometry data and inhaled beta 2-agonist consumption in about one-quarter of patients with stable COPD, and this rate increased to about three-quarters in patients who responded to beta 2-agonist inhalation. There was no additional benefit in using a higher dose of inhaled budesonide or prednisone.", "Airway inflammation can be demonstrated in mildly asthmatic patients who are not treated with inhaled steroids. Current guidelines recommend that inhaled steroids should be introduced in mild asthmatics who use an inhaled beta2-agonist more than once daily. It was postulated that inhaled steroids can have anti-inflammatory effects in patients with even milder disease. The effect of 4 weeks of treatment with budesonide (800 microg twice daily by Turbohaler) was studied in 10 steroid-naive mildly asthmatic patients (forced expiratory volume in one second (FEV1) = 96+/-1.4% predicted) who required an inhaled beta2-agonist less than one puff daily, in a double-blind, placebo-controlled, crossover fashion. Spirometry, exhaled nitric oxide (NO), bronchial responsiveness (provocative concentration causing a 20% fall in FEV1 (PC20)), and sputum induction were performed before and after each treatment period. Following budesonide treatment, there were significant improvements in FEV1, and PC20, in association with a significant reduction in the percentage of eosinophils in induced sputum. Exhaled NO levels tended towards reduction, but the change was nonsignificant. There were also nonsignificant reductions in sputum eosinophil cationic protein and tumour necrosis factor-alpha levels. In conclusion inhaled budesonide can lead to improvements in noninvasive markers of airway inflammation, in association with a small improvement in lung function, even in mildly asthmatic patients who require an inhaled beta2-agonist less than once daily. This suggests a potential benefit of inhaled corticosteroids, even in relatively asymptomatic asthma.", "It remains unclear whether inhaled corticosteroids can produce the maximum benefits of corticosteroids in patients with chronic obstructive pulmonary disease (COPD). To assess the additive effects of 30 mg/day prednisolone to high-dose, inhaled beclomethasone dipropionate (BDP), we conducted a randomised double-blind, placebo-controlled cross-over trial. The study population consisted of 21 men with stable COPD. The mean age of the patients was 69.1 +/- 6.8 years, and FEV(1)was 0.86 +/- 0.28 l. Seventeen out of the 21 patients (81%) were considered susceptible to steroids in a previous trial (FEV(1)increased at least 15% from baseline after receiving 14 days of 30 mg/day prednisolone). All of the patients had been on 1600 microg/day BDP for more than 3 months. Spirometry was performed before the entry, and at the end of 3-week placebo and prednisolone periods. The peak expiratory flow (PEF), symptoms, and Guyatt's Chronic Respiratory Disease Questionnaire (CRQ) as a disease specific health-related quality of life over the last seven days of each period were also evaluated. Although a marginal increase in PEF was found during the prednisolone period, no significant differences in FEV(1), FVC, symptoms or CRQ scores were observed between the two treatment periods. We conclude that the therapeutic effects of steroid therapy may be achieved by the long-term use of high-dose, inhaled corticosteroid in some patients with stable COPD.\n Copyright 2000 Academic Press.", "This study aimed to compare the efficacies of 3-day and 10-day courses of methylprednisolone (MP) treatment in severe COPD exacerbations necessitating hospitalization for respiratory failure.\n Prospective, randomized, single-blind study.\n Tertiary-care center.\n Thirty-six patients were included in the study and randomized into two groups: group 1 received MP, 0.5 mg/kg q6h for 3 days, and group 2 was administered the same dosage of MP for the first 3 days, after which it was tapered and terminated on the tenth day. There was no difference between the groups for age, baseline FEV(1), PaO(2), PaCO(2), and pH levels. One patient in group 1 who developed pneumothorax and one patient in group 2 who had steroid-related psychosis could not complete the study.\n Both groups showed significant improvements in PaO(2) and FEV(1) levels, but these were more marked in group 2 (p = 0.012 and p = 0.019, respectively). There was a significant increase in FVC levels in group 2 only (p = 0.003). Group 2 also had a more marked improvement in dyspnea on exertion. There was no difference between the two groups with regards to other parameters, including pH, PaCO(2) levels, and other symptom scores. Six patients in group 1 and five patients in group 2 developed new exacerbations within the following 6 months. Hyperglycemia occurred in two patients in each group.\n In severe COPD exacerbations, a 10-day course of steroid treatment is more effective than a 3-day course in improving the outcome, but has no benefit in reducing exacerbation rates.", "Early treatment with inhaled corticosteroids may prevent progression of irreversible obstruction in COPD, especially in patients with bronchial hyperresponsiveness. We investigated the clinical effects of early introduction of inhaled steroids in subjects showing early signs and symptoms of COPD without a prior clinical diagnosis.\n Study subjects were detected in a general population screening and monitoring program. Those with a moderately accelerated annual FEV1 decline and persistent respiratory symptoms were invited to participate in a 2-year randomized controlled trial comparing fluticasone propionate DPI 250 microg b.i.d. with placebo. Pre- and post-bronchodilator (BD) FEV1, PC20 histamine, functional status (COOP/WONCA charts) and occurrence of exacerbations were periodically assessed. Subjects recorded respiratory symptoms. Post-BD FEV1 decline served as the main outcome. Multivariable repeated measurements analysis techniques were applied.\n 48 subjects were randomized (24 fluticasone, 24 placebo). After 3 months, the post-BD FEV1 had increased with 125 ml (SE = 68, P = 0.075) and the pre-BD FEV1 with 174 ml (SE 90, P = 0.059) in the fluticasone relative to the placebo group. The subsequent post-BD and pre-BD FEV1 decline were not beneficially modified by fluticasone treatment. There were no statistically significant differences in respiratory symptoms, functional status, or exacerbations favoring fluticasone. Subgroup analysis indicated that the presence of bronchial hyperresponsiveness modified the initial FEV1 response on fluticasone, but not the subsequent annual FEV1 decline.\n Early initiation of inhaled steroid treatment does not seem to affect the progressive deterioration of lung function or other respiratory health outcomes in subjects with early signs and symptoms of COPD. In subjects at risk for, or in an early stage of COPD, long-term inhaled steroid treatment should not be based on a single spirometric evaluation after 3 months.", "Many patients with irreversible chronic obstructive pulmonary disease (COPD) claim symptomatic improvement with steroid therapy, despite a lack of objective improvement in their spirometric data. To determine if steroids actually increase the exercise capacity of these individuals, 13 clinically stable patients (mean age, 63 +/- 4 years; 12 male patients) were given methylprednisolone (32 mg once daily) or placebo in a randomized double-blind crossover fashion. Spirometric data and minute ventilation, oxygen consumption (VO2), carbon dioxide production, and heart rate during incremental exercise were measured at each visit. Methylprednisolone did not produce a significant change in any of the measured parameters. Three patients had an increase in maximal VO2 of greater than 2 ml/kg/min during therapy with methylprednisolone, while two experienced a decline in maximal VO2 of similar magnitude. The change in exercise capacity was unrelated to the change in the forced expiratory volume in one second in individual patients (r = 0.08). We conclude that in the absence of any improvement in the usual tests of airway mechanics, steroid therapy does not improve exercise performance in patients with COPD.", "We conducted a randomized, controlled double-blind study to determine whether intravenous administration of methylprednisolone early in the therapy for acute exacerbations of COPD would improve pulmonary function in the Emergency Department and reduce the need for hospitalization. Ninety-six patients completed the study. All were at least 50 years of age and had no history of asthma. Patients received aminophylline and hourly administration of aerosolized isoetharine. Methylprednisolone (100 mg) or physiologic saline solution was given within one-half hour of arrival in the Emergency Department. Spirometry was performed initially and after the third and fifth aerosol treatments. We found no greater improvement in FEV1 in the group receiving the steroid (37 percent) than in the control group (43 percent; NS). There was also no difference in the rate of hospitalization (33 percent in the steroid-treated group vs 30 percent in the control group; NS). We conclude that early administration of methylprednisolone does not affect the emergency phase of treatment for acute exacerbations of COPD.", "In a multicenter, randomized, double-blind study, inhaled beclomethasone dipropionate (BDP) 1,500 micrograms/day was compared to placebo in 43 chronic asthmatic patients uncontrolled by inhaled salbutamol and oral theophylline. During the prestudy period, a test of maximal steroid reversibility with oral prednisolone 0.5 mg/kg/day for 14 days was performed. The therapeutic response was measured over an 8-wk period as the ability to maintain the clinical improvement and the optimal pulmonary function induced by prednisolone. During the study, severe asthma exacerbation occurred in one (5%) of the 21 patients who received BDP and in 15 (78%) of the 22 patients who received placebo (p less than 0.001). In patients who received BDP, FEV1 and peak expiratory flow (PEF) remained above the optimal postprednisolone value, with a trend to improvement during the 8-wk study period. In patients who received placebo, FEV1 and PEF decreased and remained below the optimal value. We conclude that, in chronic asthma, inhaled BDP 1,500 micrograms/day maintains the optimal pulmonary function in addition to the clinical benefit induced by a short course of oral corticosteroids.", "We compared a 2-week course of 32 mg/d methylprednisolone with placebo in a double-blind crossover trial in 46 well-characterized patients with stable chronic obstructive pulmonary disease. Placebo and steroid trials were separated by 2 weeks when no tablets were given. Response was assessed by measuring forced expiratory volume in 1 second (FEV1.0). Placebo responses were normally distributed (mean, 0.8% change in FEV1.0; range, -30% to 33%). Six patients showed a greater than 50% increase of FEV1.0 in response to steroid; a seventh showed a 36% increase and an eighth, a 29% increase. Because of these patients the group as a whole showed a significantly greater FEV1.0 after steroid than after placebo. The eight steroid responders did not differ from nonresponders in age, sex, smoking history, or duration and intensity of symptoms including wheeze. Baseline lung function and eosinophilia of blood or sputum did not differ between the two groups. Patients who responded to steroids also responded to inhaled beta agonists: Acute bronchodilator response averaged 25% in steroid responders and 13% in nonresponders, a difference that was statistically significant although there was overlap between the two groups.", "Inhaled corticosteroids are known to be beneficial for patients with asthma, but their role in treating patients with stable chronic obstructive pulmonary disease (COPD) remains controversial. A study was undertaken to determine whether inhaled corticosteroids are of functional benefit in patients who did not show improvement with a trial of oral corticosteroids.\n In phase I patients with stable COPD were given a two week course of oral placebo followed by two weeks of prednisone 40 mg per day in a single blind manner to distinguish between responders and non-responders to oral corticosteroids. In phase II a double blind, randomised, parallel group trial of inhaled budesonide 1600 micrograms per day versus placebo was carried out in 79 nonresponders to oral corticosteroids. The primary outcome measure was forced expiratory volume in one second (FEV1), and secondary outcome measures were exercise capacity, dyspnoea with exertion, quality of life, peak expiration flow rate, and respiratory symptoms.\n Randomisation allocated 39 subjects to inhaled corticosteroids and 40 to placebo. There was no difference in the change in FEV1 from baseline between the treatment and placebo groups; mean difference -12 ml (95% CI -88 to 63) at three months and -4 ml (95% CI -95 to 87) at six months. The proportion of patients with a 15% or greater improvement was no higher among those receiving inhaled corticosteroids than in the placebo group at any of the follow up visits. Changes in secondary outcomes were also no different.\n Inhaled corticosteroids, even at high doses, were of no physiological or functional benefit in these patients with advanced COPD.", "Withdrawal of corticosteroid is associated with a deterioration of health status in COPD. In this study the aim was to determine whether high dose inhaled corticosteroid improves quality of life in patients with COPD.\n In total, 38 male patients with moderate COPD were included in the study. Baseline quality of life scores were determined using a Turkish version of the St George's Respiratory Questionnaire (SGRQ). Patients were randomly divided into two groups. Group 1 consisted of 20 patients who received existing bronchodilator therapy plus inhaled corticosteroid (800 micro g budesonide) for 12 weeks, while 18 patients in group 2 received bronchodilator and placebo. The SGRQ was repeated after the treatment period.\n All patients were male and mean age was 67 +/- 8.2 years. Symptom, activity, impact, and total scores were assessed and a difference of four units with treatment was considered to be clinically significant. Total score and activity score were decreased by six units and eight units, respectively, in the placebo group while symptom and impact scores did not change significantly. Total scores and the three component scores improved significantly in the corticosteroid group compared to the placebo group (Deltatotal score: -22 in corticosteroid group, -6 in placebo group, P < 0.01).\n Inhaled corticosteroid improved quality of life scores in patients with COPD, without significant improvement in airflow obstruction parameters. Since improvement of health status is one of the important aims in COPD treatment, use of inhaled corticosteroids should be considered from this perspective.", "The role of inhaled corticosteroids in the long term management of chronic obstructive pulmonary disease (COPD) is still unclear. A meta-analysis of the original data sets of the randomised controlled trials published thus far was therefore performed. The main question was: \"Are inhaled corticosteroids able to slow down the decline in lung function (FEV1) in COPD?\"\n A Medline search of papers published between 1983 and 1996 was performed and three studies were selected, two of which were published in full and one in abstract form. Patients with \"asthmatic features\" were excluded from the original data. Ninety five of the original 140 patients treated with inhaled corticosteroids (81 with 1500 micrograms beclomethasone daily, six with 1600 micrograms budesonide daily, and eight with 800 micrograms beclomethasone daily) and 88 patients treated with placebo (of the initial 144 patients) were included in the analysis. The effect on FEV1 was assessed by a multiple repeated measurement technique in which points of time in the study and treatment effects (inhaled corticosteroids compared with placebo) were investigated.\n No baseline differences were observed (mean age 61 years, mean FEV1 45% predicted). The estimated two year difference in prebronchodilator FEV1 was +0.034 l/year (95% confidence interval (CI) 0.005 to 0.063) in the inhaled corticosteroid group compared with placebo. The postbronchodilator FEV1 showed a difference of +0.039 l/year (95% CI -0.006 to 0.084). No beneficial effect was observed on the exacerbation rate. Worsening of the disease was the reason for drop out in four patients in the treatment group compared with nine in the placebo group. In the treatment group six of the 95 subjects dropped out because of an adverse effect which may have been related to the treatment compared with two of the 88 patients in the placebo group.\n This meta-analysis in patients with clearly defined moderately severe COPD showed a beneficial course of FEV1 during two years of treatment with relatively high daily dosages of inhaled corticosteroids.", "Inhaled corticosteroids are widely prescribed for the treatment of stable chronic obstructive pulmonary disease (COPD), despite lack of proven efficacy. Because COPD involves airway inflammation and probable protease-antiprotease imbalance, we examined the effect of high dose fluticasone propionate on markers of activity of both pathogenetic mechanisms. Thirteen patients with COPD were treated with fluticasone propionate (500 microg twice a day) for 4 wk, delivered via MDI and spacer, in a double-blind crossover study. There was no clinical benefit in terms of lung function or symptom scores, and induced sputum inflammatory cells, percentage neutrophils, and IL-8 levels were unchanged. Sputum supernatant elastase activity, matrix metalloproteinase (MMP)-1, MMP-9, and the antiproteases secretory leukoprotease inhibitor (SLPI) and tissue inhibitor of metalloproteinase (TIMP)-1 were similarly unaffected by treatment. These results add to previous evidence that inhaled steroids have no anti-inflammatory action in stable COPD. Furthermore, inhaled steroids do not appear to redress the protease-antiprotease imbalance that is thought to be important in the pathogenesis of airway obstruction.", "To compare the efficacy of high-dose inhaled steroids in conjunction with IV steroids with that of IV steroids alone in the emergency treatment for acute asthma.\n A double-blind, placebo-controlled, randomized trial was conducted on 60 ED patients presenting with acute asthma. All patients received nebulized salbutamol, and IV methylprednisolone, 80 mg at baseline and 40 mg at 6 hours. In addition to the above therapy, the experimental group received beclomethasone dipropionate (BDP) 7 mg over 8 hours via a metered-dose inhaler (MDI) attached to a holding chamber, while the control group received a placebo administered in the same fashion. Patients were treated on the protocol for 12 hours with the primary outcome measure being the change in % predicted FEV1.\n Of 60 patients, 30 were randomized to BDP (age: 42 +/- 16 years; FEV1: 0.97 +/- 0.42 L) and 30 were randomized to placebo (age: 37 +/- 18 years; FEV1: 0.98 +/- 0.35 L). Spirometry and dyspnea measured by the Borg Scale improved significantly in both groups compared with baseline (p < 0.001). Changes in spirometry measures, dyspnea, and vital signs did not differ between treatment groups over the 12 hours of study (p > 0.05).\n Inhaled BDP added to the standard regimen of IV methylprednisolone, and beta-agonist did not further improve flow rates or dyspnea scores measured for up to 12 hours after presentation to the ED.", "Combination therapy with corticosteroid and long-acting β(2)-agonists (LABA) in a single inhaler is associated with superior effects on airway function and exercise performance in COPD compared with LABA monotherapy. The physiological effects of adding inhaled corticosteroid monotherapy to maintenance bronchodilator therapy (long-acting anticholinergics and LABA singly or in combination) in COPD are unknown.\n This was a randomized, double-blind, placebo-controlled, crossover study (NCT00387036) to compare the effects of inhaled fluticasone propionate 500 μg (FP500) twice-daily and placebo (PLA) on airway function during rest and exercise, measured during constant work rate cycle exercise at 75% of maximum incremental cycle work rate, in 17 patients with COPD (FEV(1) ≤ 70% predicted).\n After treatment with FP500 compared to PLA, there were significant increases in post-dose measurements of FEV(1) (+115 mL, P = 0.006) and the FEV(1)/FVC ratio (+2.5%, P = 0.017), along with decreases in plethysmographic residual volume (-0.32L; P = 0.031), functional residual capacity (-0.30L, P = 0.033), and total lung capacity (-0.30L, P = 0.027) but no changes in vital capacity or inspiratory capacity (IC). Post-treatment comparisons demonstrated a significant improvement in endurance time by 188 ± 362 s with FP500 (P = 0.047) with no concomitant increase in dyspnea intensity. End-inspiratory and end-expiratory lung volumes were reduced at rest and throughout exercise with FP500 compared with PLA (P < 0.05).\n Inhaled FP500 monotherapy was associated with consistent and clinically important improvements in FEV(1), static lung volumes, dynamic operating lung volumes, and exercise endurance when added to established maintenance long-acting bronchodilator therapy in patients with moderate to severe COPD.\n Copyright © 2011 Elsevier Ltd. All rights reserved.", "To determine the effectiveness of treatment with corticosteroids in patients with COPD.\n In this study, we investigated the effect of a 2-year treatment with corticosteroids on clinical symptoms and the decline of lung function in 58 nonallergic patients with COPD. Subjects were treated in a double-blind, randomized, placebo-controlled, parallel way with inhaled budesonide (bud), 1,600 micrograms/d; inhaled budesonide, 1,600 micrograms/d, plus oral prednisolone, 5 micrograms/d (bud + pred); or placebo (plac). Clinical assessment (history, physical examination, and spirometry) was carried out every 2 months. The rate of decline in FEV1 was assessed by calculating individual regression co-efficients from linear regression of FEV1 on time for each subject.\n Eleven patients dropped out. The number of withdrawals due to pulmonary problems was significantly higher in the plac group (n = 5 out of 18) than in the actively treated groups (n = 2 out of 40). Treatment with corticosteroids significantly reduced pulmonary symptoms. Median decline of FEV1 was 60 mL/yr in the plac group, 40 mL/yr in the bud + pred group, and 30 mL/yr in the bud group. Variation was large and differences were not statistically significant. No treatment effect was found on frequency or duration of exacerbations, possibly because of the high number of withdrawals due to pulmonary deterioration in the plac group. Treatment with a combination of inhaled plus oral corticosteroids was not more effective than inhaled corticosteroids alone. Morning plasma cortisol levels remained within the normal range in all three groups.\n Our study shows beneficial effects of long-term daily treatment with inhaled corticosteroids in patients with COPD with regard to symptoms and drop out due to pulmonary problems. Lung function decline tends to decrease during treatment with inhaled corticosteroids. The observed effects are limited but warrant further studies on the effectiveness of corticosteroids in larger numbers of patients with COPD.", "The aim of this study was evaluate the predictive value of a 2 week course of prednisolone on the effect of 6 months treatment with inhaled budesonide in patients with stable chronic obstructive pulmonary disease (COPD). Forty patients with stable COPD entered the study, and received prednisolone (37.5 mg o.d.) for 2 weeks. They were subsequently divided into steroid-irreversible and steroid-irreversible, using 15% of baseline as a dividing point. In each group patients were randomized to receive budesonide 400 micrograms b.i.d. or placebo for 6 months. During treatment with prednisolone, three patients dropped out because of side effects. Of the remaining 37, only two patients (5%) were reversible with prednisolone forced expiratory volume in 1s [(FEV1) > 15% of baseline], and among the steroid-irreversible, 26 patients were evaluated after 6 months treatment with either placebo or budesonide. No significant differences in spirometry values, symptoms, or number of exacerbations were found between these two groups. Reversibility with prednisolone is rarely seen in COPD. In outpatients with stable COPD and no signs of asthma or atopy, 2 weeks treatment with prednisolone seems to be of no value in choosing subsequent long-term therapy.", "According to a recent hypothesis, airway smooth muscle regulates airway calibre mostly at high lung volume, whereas the mucosa and adventitia dimensions dominate at low lung volumes. It was thought that if inhaled steroids decrease the thickness of airway wall in asthma, then forced vital capacity (FVC), which reflects the functional changes at low lung volume, should decrease less during induced bronchoconstriction than flow at high volume. The study was conducted in 31 mild asthmatics under control conditions and during a methacholine challenge before and after 4-weeks treatment with inhaled fluticasone dipropionate (1.5 mg daily, 16 patients) or placebo (15 patients). After fluticasone dipropionate treatment, control forced expiratory volume in one second (FEV1), and maximal flow at 50% of control FVC during forced expiration after a maximal (V'max,50) and a partial inspiration (V'p,50) significantly increased. During methacholine challenge, FVC decreased less than did FEV1 or V'max,50, and so did inspiratory vital capacity compared to V'p,50. Both the provocative dose of methacholine causing a 20% fall in FEV1 and the bronchodilator effect of deep inhalation significantly increased. The latter was assessed by means of the regression coefficient of all V'max,50 plotted against V'p,50. No significant changes in these parameters occurred after placebo. These data show that inhaled steroids remarkably blunt the occurrence of gas trapping during induced bronchoconstriction in mild bronchial asthma, possibly due to their effect on airway wall remodelling.", "The benefits of inhaled corticosteroids in the management of COPD are less apparent than they are in asthma therapy, and the potential for adverse systemic effects of high-dose inhaled corticosteroids has been recognized recently. It is therefore essential to know the maximal obtainable benefits in order to assess the risk/benefit ratio of this treatment.\n The aim of this study was to investigate the maximal obtainable benefits of high-dose inhaled corticosteroids, 3 mg/d of beclomethasone dipropionate (BDP), when used in combination with adequate doses of regular bronchodilators in patients with stable COPD.\n Thirty patients with stable COPD completed a randomized, double-blind, placebo-controlled cross-over trial with either 3 mg/d of BDP or with a matching placebo using a metered-dose inhaler with a spacer device for 4 weeks during each treatment period. All of the patients continued to inhale both 400 microg of salbutamol qid and 80 microg of ipratropium bromide qid.\n The mean prebronchodilator FEV1 was 0.97+/-0.35 L during the placebo period and 1.08+/-0.38 L during the BDP period (p < 0.001). While on BDP, five patients demonstrated a response in their FEV1 of more than 8.5% of the predicted value, which was above the range that covered 95% of the distribution of the placebo response. The mean absolute improvement in the FEV1 in these 5 objective responders was 0.34+/-0.10 L, compared to 0.06+/-0.09 L in the 25 objective nonresponders. Symptom scores for wheezing and dyspnea were significantly better with BDP than with placebo. Hoarseness and sore throat were associated more with BDP treatment.\n Although a considerable minority of patients benefited substantially from this treatment, the overall outcome does not seem to justify the widespread use of this treatment in the light of increasing recognition of the potential adverse systemic effects of high-dose inhaled corticosteroids.", "Prevention and treatment of COPD exacerbations are recognized as key goals in disease management. This randomized, double-blind, parallel-group, multicenter study evaluated the effect of fluticasone propionate/salmeterol 250 mcg/50 mcg (FSC 250/50) and salmeterol 50 mcg (SAL) twice-daily on moderate/severe exacerbations. Subjects received treatment with FSC 250/50 during a one month run-in, followed by randomization to FSC 250/50 or SAL for 52 weeks. Moderate/severe exacerbations were defined as worsening symptoms of COPD requiring antibiotics, oral corticosteroids and/or hospitalization. In 797 subjects with COPD (mean FEV(1) = 0.98L, 34% predicted normal), treatment with FSC 250/50 significantly reduced the annual rate of moderate/severe exacerbations by 30.4% compared with SAL (1.10 and 1.59 per subject per year, respectively, p < 0.001), the annual rate of exacerbations requiring oral corticosteroids by 34% (p < 0.001) and the annual rate of moderate/severe exacerbations requiring hospitalization by 36% (p = 0.043). Clinical improvements observed during run-in treatment with FSC 250/50 were better maintained over 52 weeks with FSC 250/50 compared to SAL. Statistically significant reductions in albuterol use, dyspnea scores, and nighttime awakenings and numerical benefits on quality of life were seen with FSC 250/50 compared with SAL. The incidence of adverse events was similar across groups. Pneumonia was reported more frequently with FSC 250/50 compared with SAL (7% vs. 2%). FSC 250/50 is more effective than SAL at reducing the rate of moderate/severe exacerbations. These data confirm the beneficial effect of FSC on the management of COPD exacerbations and support the use of FSC in patients with COPD.", "Chronic obstructive pulmonary disease is characterized by progressive airflow limitation and pulmonary inflammation. Inhaled corticosteroids (ICS) have been shown to be effective in the reduction of the number of exacerbations and the rate of deterioration in health status in patients with more advanced chronic obstructive pulmonary disease (COPD). Therefore current international guidelines recommend ICS for patients with severe COPD (FEV1 < 50%) with at least one exacerbation within the last year. We determined the short-term effect of the inhaled corticosteroid beclomethasone in HFA 134 formulation (Ventolair) on Health related Quality of Life (HRQOL), pulmonary function and the release of the cytokines Interleukin-10 (IL-10), Granulocyte-Macrophage Colony-stimulating Factor (GM-CSF), Interferon-gamma (IFN-gamma) and Macrophage Inflammatory Protein-1alpha (MIP-1alpha) from peripheral blood monocytes of patients with COPD (n = 11) in a 12 week double blind cross over placebo-controlled study. Baseline lung function and the St. George Respiratory Questionnaire (SGRQ) were performed at the start and the end of each treatment phase. Monocytes were separated from blood at the end of each treatment phase. The treatment with Ventolair) resulted in an increase of PEF from 4.92 to 5.53 l/s and a decrease of RV% TLC (% predicted) values from 144.52 to 131.36. Inhaled HFA beclomethasone did not affect the cytokine release of IL-10, IFN-gamma, GM-CSF and MIP-1alpha. All cytokines were measured using commercially available Enzyme Linked Immun Sorbent Assay (ELISA) kits. The symptom score of the St. George Respiratory Questionnaire significantly decreased from 55.12 to 47.77 units in the active period compared to the placebo period after the treatment with HFA beclomethasone. The present study shows that a short-term treatment with inhaled steroid beclomethasone in fine particle HFA formulation decreases the hyperinflation and improves the PEF and the COPD symptoms.", "The effect of inhaled beclomethasone diproprionate (1500 micrograms day-1) on symptoms, pulmonary function and sputum production was examined in a double-blind, placebo-controlled, cross-over study in 20 patients with bronchiectasis. An 18% reduction in daily sputum production (P less than 0.003) was observed on treatment with inhaled steroid compared to placebo. A small, significant, improvement in morning peak expiratory flow rate (P less than 0.03) and forced expiratory volume in 1 s (P less than 0.03) was seen but the absolute changes are unlikely to be of clinical importance. Symptom scores for cough improved significantly (P less than 0.02). Inhaled steroids may have a role in the management of bronchiectasis by reducing cough and sputum production.", "A placebo-controlled, double-blind cross-over trial was conducted to assess whether 16 men with chronic obstructive pulmonary disease (COPD) would benefit from orally taken corticosteroids. Two weeks of treatment with 40 mg of prednisone daily did not result in improvement of pulmonary symptoms or function in the group as a whole, although one patient had small improvement in airflow. The baseline spirometric data and beta-agonist responsiveness of the patients in the study were then compared to a reference population consisting of 264 men who fulfilled a criteria for chronic obstruction out of 730 men who comprised a systematic sample drawn from all patients referred for spirometry at three hospitals. Our study subjects and those of five similar trials of corticosteroids in COPD had more severe obstruction than this reference group. Furthermore, the proportion of steroid responders found in each study was inversely related to the baseline FEV1 of the patients examined. It appears that previous studies of corticosteroids in COPD may have overestimated the number of COPD patients who might benefit from corticosteroids, due to a bias resulting from the selection of severely obstructed subjects.", "Treatment of chronic obstructive pulmonary disease (COPD) with inhaled and oral corticosteroids is common, although their exact role is unclear. Previous studies suggest these drugs may reduce decline in lung function in this group of patients. We report a study investigating the effect of inhaled beclomethasone diproprionate (BDP) on lung function and symptoms in a group of patients with COPD. Treatment was given for 2 years, and the decline in FEV1 in individual patients calculated over this period. Ninety-eight patients were randomized for the study, 59 completing 2 years of treatment. Patients withdrawn had more severe airflow obstruction. Decline in FEV1, measured both prior to and after bronchodilator, was less in patients receiving inhaled BDP, although the differences failed to reach statistical significance except in a subgroup of patients with more severe airflow obstruction. Exacerbation rates were also reduced by inhaled BDP, but again the differences failed to reach conventional levels of statistical significance. The results of this study are consistent with previous published work, but further insight into the long-term role of corticosteroids in COPD await the publication of large studies which have recently been completed. Although the changes seen in this study and others are numerically small, the rate of decline in FEV1 returned to normal levels expected from age-related decline, and hence such treatment combined with other strategies may well have a significant role in the long-term treatment of this condition.", "To investigate the efficacy of bronchodilators in patients with irreversible chronic obstructive pulmonary disease (COPD), we conducted a double-blind, randomized, four-phase, crossover comparison between placebo, oral theophylline, inhaled salbutamol, and a combination of both drugs in 12 patients with stable COPD (mean age, 63 years) whose increase in forced expiratory volume in 1 s (FEV1) was less than or equal to 15 percent following 200 micrograms of inhaled salbutamol. Patients received two weeks of therapy with each of the test regimens. Both theophylline and salbutamol resulted in statistically significant improvement in FEV1, forced vital capacity (FVC), slow vital capacity (SVC), residual volume (RV), airway resistance (Raw), and maximum expiratory flow rate at 50 percent of vital capacity (V50). In most instances, there were no significant differences between theophylline and salbutamol. Combination therapy produced significantly greater improvement in FEV1, FVC, V50, Raw, and RV than either agent alone. The two drugs interacted in an additive fashion. Neither of the drugs, used singly, significantly reduced the severity or incidence of symptoms. The reduction in dyspnea and wheeze during combination therapy approached statistical significance (p = 0.06) and patient preference was significantly in favor of the combination regimen. None of the active treatments produced significantly more side effects than placebo. We conclude that theophylline and inhaled salbutamol produce significant, and approximately equal, improvement in pulmonary function in patients traditionally classified as suffering from \"irreversible\" COPD. The combination of theophylline and inhaled salbutamol generally results in additional improvement over that obtained with either drug used alone and this improvement is reflected by reduced symptomatology and treatment preference.", "A significant minority of patients with COPD have favorable response to corticosteroid treatment. In addition, the benefit of corticosteroid treatment may be outweighed by the side effects. Long-term administration of inhaled steroids is a safe means of treatment. We hypothesized that treatment with high-dose inhaled budesonide would improve clinical symptoms and pulmonary function in subjects with COPD, and that the response to inhaled beta 2-agonist will serve to individualize steroid responders. We compared a 6-week course of 800 micrograms/d inhaled budesonide with placebo, separated by 4 weeks when no medication was taken, in a double-blind crossover trial, in 8 patients responding to inhaled beta 2-agonist, and in 22 nonresponders with stable COPD. In six of eight \"responders to beta 2-agonist,\" there was a significant improvement in the FEV1 (defined as > or = 20%) following inhaled budesonide, as compared with placebo. In the 22 \"nonresponders to beta 2-agonist,\" there was no significant improvement in the mean FEV1 (1.41 +/- 0.1 L before, and 1.61 +/- 0.1 L after treatment) with inhaled budesonide or placebo. Over the 6-week course of treatment by either budesonide or placebo, the nonresponders reported similar beta 2-agonist consumption (4.8 +/- 0.2 and 5.0 +/- 0.1 puffs per patient per day, respectively). However, there was a significant difference between the two periods of treatment in the responders as for the mean daily number of beta 2-agonist inhalations (2.4 +/- 0.1 in the budesonide period as compared with 5.3 +/- 0.1 in the placebo period; p < 0.005). We conclude that treatment with inhaled steroids improved spirometry data and inhaled beta 2-agonist consumption in about 25% of patients with stable COPD, and this rate is increased to about 75% in patients who respond to beta 2-agonist inhalation.", "Intravenous steroids improve the respiratory course in ventilator-dependent preterm infants but have adverse effects. We hypothesized that inhaled steroids would be as effective, but with less systemic effects.\n We conducted a randomized, prospective trial comparing inhaled beclomethasone, either 400 or 800 microg/d, to intravenous dexamethasone in preterm infants dependent on conventional mechanical ventilation and supplemental oxygen at 2 weeks of age.\n Seventy-eight infants were randomized. By day three of therapy, the intravenous steroid group had significantly decreased ventilator and oxygen requirements compared to either inhaled group. The inhaled 800-microg/d group trended toward more rapid decreases in ventilator and oxygen requirements than the 400-microg/d group. By day 14, all groups had similar reductions in ventilator and oxygen requirements. The incidence of adverse effects did not differ between groups.\n In this small, randomized study, inhaled steroids conferred no advantages to intravenous steroids in the management of ventilator-dependent preterm infants.", "The present study aimed at comparing the effects of a dose reduction of inhaled corticosteroids on lung function, indirect measures of airway inflammation and clinical scores during treatment with a leucotriene receptor antagonist. In 50 patients (mean forced expiratory volume in one second (FEV1) 94% predicted), steroid doses (800 microg beclomethasone dipropionate) were first reduced to 50% and then to 25%, for 6 weeks each. One group received a placebo and the other group received montelukast (10 mg). The first reduction did not cause significant effects. During the second, FEV1 and peak expiratory flow decreased in both groups (p<0.001). Daytime symptoms were not altered with placebo but were reduced by montelukast (p<0.05). Night-time symptoms were slightly elevated with placebo (p<0.05) but not montelukast, as well as the use of supplemental salbutamol. Changes in provocative concentration of methacholine causing a 20% fall in FEV1 (PC20), sputum eosinophils and exhaled nitric oxide were mostly nonsignificant for both placebo and montelukast. These data demonstrate that a 75% reduction in the dose of steroid given to patients with asthma led to a deterioration in lung function not prevented by montelukast, whereas changes in clinical state seemed to favour montelukast treatment. It therefore appears that potential effects of montelukast, in the presence of low-dose steroids, could not be attributed to single indices of lung function or airway inflammation.", "We compared the efficacy of corticosteroid therapy initiated as an alternate-day regimen to that of a four-times-daily regimen in patients with stable chronic obstructive pulmonary disease. In this double-blind study, 44 patients with moderate to severe COPD (mean FEV1 740 +/- 310 ml) were hospitalized and randomly allocated to receive methylprednisolone, 8 mg qid, 64 mg qod, or placebo for a ten-day period. The mean FEV1 and FVC improved significantly to a comparable degree in both steroid-treated groups, but not in the placebo-treated group. Eight of the 29 steroid-treated patients (28 percent) had improved FEV1 of more than 25 percent compared with only one of the 15 placebo-treated patients. Those in the qod group also had notable improvement in SaO2. Although the correlation between the improvement after the administration of nebulized bronchodilators and that after corticosteroid therapy was significant, some patients had more than a 25 percent improvement in their FEV1 with corticosteroids, but less than a 10 percent improvement after nebulized bronchodilators. We conclude that a substantial proportion of all patients with stable COPD will have a greater than 25 percent improvement in their flow rates with corticosteroid administration. Since the response to a qod regimen is comparable to that of a qid regimen, and since the qod regimen is associated with fewer side effects, we recommend that a qod regimen be tried initially.", "The dose-response effects of inhaled beclomethasone dipropionate (BDP) and budesonide (BUD) administered b.i.d. with the aid of metered dose aerosols were studied in 128 patients (67 men and 61 women, mean age 53 years) suffering from asthma bronchiale. The study was designed as a multi-centre, double-blind, four-period cross-over study, followed by a single-blind double placebo period. BDP was administered in doses of 400 and 1000 micrograms, and BUD in doses of 400 and 800 micrograms. The results in terms of peak expiratory flow (PEF) in the morning and evening, daily symptoms score and use of inhaled beta 2-agonists did not reveal any clinically significant differences between the drugs or between high (800 micrograms BUD, 1000 micrograms BDP) and low (400 micrograms BUD/BDP) doses. However, statistically significant differences were recorded for the corresponding parameters when comparing the placebo with preceding steroid periods. Adverse effects consisting mainly of oropharyngeal candidiasis, hoarseness and cough occurred in 54 of 468 treatment months (12%). The carry-over effects of inhaled steroids are longer lasting than was previously assumed.", "The aims of this investigation were to evaluate the efficacy of regular inhaled beclomethasone in the control of symptoms and lung function with non-asthmatic smoking related obstructive pulmonary disease and to evaluate the relationship between clinical responses to a short course of oral prednisone and longer term outcomes using inhaled steroid.\n The study was a randomised, double blind, placebo controlled, crossover investigation in 18 patients. The active treatment was inhaled beclomethasone 1000 micrograms given twice daily for three months by metered dose inhaler. At the end of each treatment period, patients received oral prednisone 30 mg/day for ten days. The two treatment phases were separated by a one month washout interval. Peak flow rates, symptom scores and \"rescue\" bronchodilator use were recorded twice daily. Lung function (FEV1, FVC and lung volumes) and bronchial hyperresponsiveness (PC20 methacholine) were measured at monthly visits. The number of exacerbations requiring intervention therapy were also recorded.\n There were no consistent benefits attributable to beclomethasone. Lung function was not significantly better as a result of active treatment. Sputum production improved but other symptom scores were similar during active and placebo therapy. Three patients exhibited an increase in FEV1 of 15% or more during active treatment but did not do so when oral prednisone was administered immediately after the period of placebo treatment. A further three patients showed an improvement in FEV1 of 15% or more with oral prednisone but failed to improve during treatment with inhaled beclomethasone. The predictive value of the \"trial of steroid\" was 0% and 81.3% for positive and negative outcomes respectively.\n Our results indicate that in non-asthmatic chronic obstructive pulmonary disease inhaled corticosteroid fails to achieve significant improvements in either lung function or symptoms. The response to a \"trial of steroid\" using oral prednisone is not clinically helpful in selecting the small number of patients who may subsequently benefit from this form of therapy.", "Bronchodilator agents are central to the symptomatic management of Chronic Obstructive Pulmonary Disease (COPD), and long-acting inhaled bronchodilators are regarded as more convenient. The role of inhaled corticosteroids still remains controversial, but there is increasing evidence that they may improve FEV(1) and symptoms in the long-term.\n of the present small pilot study was to compare Salmeterol & Fluticasone (SM&FP) 50/250 microg bid via a single Diskus inhaler with SM 50 microg bid alone, and with placebo (P) in the treatment of moderate COPD.\n Eighteen moderate COPD patients (53-77 yr, mean basal FEV(1)=49.1% pred.+/-5.0 s.d.; mean FEV(1) reversibility=3.6% bsln+/-3.8 s.d.) treated with theophylline 400 mg/day and beta(2) short acting prn, were divided into three matched groups of six subjects according to a double-blind design, and treated with SM&FP 50/250 microcg, or SM 50 microcg alone, or P via Diskus inhaler bid for 52 weeks. In bsln, after 4, 12, 24, 36 and 52 weeks, FEV(1) (% pred), morning PEF (l/s), the daily symptom score, and the number of exacerbations (compared with the previous year) were considered. Statistics. t-test, anova in each treatment group, and anova among basal values and among the 52 week values were used, being p<0.05 accepted. Also changes (DeltaFEV(1)) from baseline were compared at different control times.\n The mean number of exacerbations/yr decreased from 3.5+/-0.8 to 1.16+/-0.75 s.d. exacerbation/yr in the SM&FP group (t-test p<0.001); from 3.0+/-0.89 to 2.3+/-0.81 s.d. in the SM group (t-test p=ns); and from 3.16+/-1.16 to 4.16+/-0.75 s.d. in the P group (t-test p=ns). Patients receiving SM&FP showed the highest mean improvement in FEV(1) (+7.3%+/-3.3 s.d.) over the baseline pre-treatment value after 36 weeks of treatment (anova p<0.001), being FEV(1) unchanged after 52 weeks of treatment in SM group (+0.33%+/-2.4 s.d.) and with a substantial decrease following P (-2.6%+/-1.2 s.d.) (anova p<0.001). Morning PEF (l/min) increased in subjects treated with SM&FP (anova p<0.001), while it remained unchanged in SM and P group (in both, anova p=ns). After 52 weeks of treatment, only subjects treated with SM&FP showed a reduction of the daily symptoms score from 3.6+/-0.7 to 2.0+/-0.2 s.d. (anova p=0.008). Daily beta(2) short acting prn consumption was reduced only in SM&FP group from 4.2+/-0.81 to 2.2+/-1.2 s.d. after 52 weeks (anova p<0.001).\n SM&FP 50/250 microcg regularly assumed in combination via a single Diskus inhaler for a 52 week period improves respiratory function (such as FEV(1), morning PEF), and and symptom score significantly in moderate COPD previously treated with theophylline, and at an higher extent than SM alone or P. The use of beta(2) short acting prn is also reduced, together with the number of exacerbations.", "To determine the benefit of early steroid use in acute exacerbations of chronic airflow obstruction in the ED, 113 patients with an average age of 66 years, acute or chronic dyspnea, an FEV1 of < 60% and FEV1/FVC ratio of < 60% were included in a randomized, double-blinded, interventional clinical trial. All patients received the same bronchodilator treatment. At 6 hours the steroid- treated group showed a 21.71 L/min improvement in PEFR (P < .05) and 0.14 L improvement in FEV1 (P < .05), while the nonsteroid group showed insignificant improvements of 5.52 L/min and 0.02 L, respectively. Of those patients receiving steroids, 22 achieved > 40% improvements in PEFR by 6 hours and 17 achieved similar results in FEV1, whereas of those not receiving steroids, 13 and 8, respectively, achieved improvements. Within 24 hours of observation in the ED, 16 patients receiving steroids were discharged and none relapsed within 2 weeks. Of those not receiving steroids, only 10 were discharged and 3 returned with exacerbations. Although early response to steroids in chronic airflow obstruction is variable, the overall medical and cost benefits justify their early use in acute exacerbations.", "Treatment of chronic obstructive pulmonary disease (COPD) with inhaled corticosteroids does not appear to be as effective as similar treatment of asthma. It seems that only certain subgroups of patients with COPD benefit from steroid treatment. A study was undertaken to examine whether inhaled fluticasone propionate (FP) had an effect on lung function and on indices of inflammation in a subgroup of COPD patients with bronchial hyperresponsiveness (BHR).\n Twenty three patients with COPD were studied. Patients had to be persistent current smokers between 40 and 70 years of age. Non-specific BHR was defined as a PC(20) for histamine of <or=8 mg/ml. Patients received either 2 x 500 microg FP or placebo for 6 months. Expiratory volumes were measured at monthly visits, BHR was determined at the start of the study and after 3 and 6 months, and bronchial biopsy specimens were taken at the start and after 6 months of treatment. Biopsy specimens from asymptomatic smokers served as controls.\n In contrast to asthma, indices of BHR were not significantly influenced by treatment with FP. Forced expiratory volume in 1 second (FEV(1)) showed a steep decline in the placebo group but remained stable in patients treated with FP. FEV(1)/FVC, and maximal expiratory flows at 50% and 25% FVC (MEF(50), MEF(25)) were significantly increased in the FP treated patients compared with the placebo group. Biopsy specimens were analysed for the presence of CD3+, CD4+, CD8+, MBP+, CD15+, CD68+, CD1a, and tryptase cells. FP treatment resulted in marginal reductions in these indices of inflammation.\n In patients with COPD and BHR, FP has a positive effect on indices of lung function compared with placebo. Bronchial inflammation analysed in bronchial biopsy specimens is only marginally reduced.", "To investigate the efficacy of an increased dose of inhaled steroid used within the context of an asthma self management plan for treating exacerbations of asthma.\n Randomised, double blind, placebo controlled, crossover trial.\n Twenty eight children aged 6-14 years with asthma of mild to moderate severity were studied for six months. Eighteen pairs of exacerbations were available for analysis, during which subjects took an increased dose of inhaled steroids or continued on the same dose.\n There was no significant difference between increasing inhaled steroids or placebo on morning or evening peak expiratory flow rates (PEFRs), diurnal peak flow variability, or symptom scores in the two weeks following an asthma exacerbation. Difference (95% confidence intervals) in baseline PEFR on days 1-3 were 3.4% (-3.5% to 10.4%) and -0.9% (-4.7% to 2.9%) for inhaled steroid and placebo, respectively. Spirometric function and the parents' opinion of the effectiveness of asthma medications at each exacerbation were also not significantly different between inhaled steroid or placebo.\n This study suggests that increasing the dose of inhaled steroids at the onset of an exacerbation of asthma is ineffective and should not be included in asthma self management plans.", "We wanted to evaluate the improvement in efficacy when increasing the daily dose of inhaled steroids and to compare the efficacy, safety, and tolerance of 1.6 mg beclomethasone dipropionate (BDP) with that of 2.0 mg fluticasone propionate (FP). The study was a randomized, double-blind, 3 month, multicentre study. One hundred and thirty four asthmatics currently using inhaled steroids (0.4-1.6 mg BDP or budesonide (BUD)) were stratified according to pretrial daily steroid use. Within each stratum they were randomized to either 1.6 mg BDP or 2.0 mg FP. A significant increase in the primary efficacy variables, i.e. mean morning and evening peak expiratory flow (PEF) (approximately 20 l.min-1) during the treatment period, was found for both treatments. No significant differences between the drugs were revealed for these primary or any other secondary efficacy variables (use of beta 2-agonists, symptom scores, and PEF, forced vital capacity (FVC), forced expiratory volume in one second (FEV1) recorded at the clinical visits). However, significant differences between treatments occurred regarding decrease of serum cortisol and adrenocorticotropic hormone. We conclude that, although both treatments gave statistically significant increases in efficacy parameters when compared with baseline, the increases were so small that they can be regarded as being clinically unimportant. Daily doses of BDP, 1.6 mg, and FP, 2.0 mg, had comparable effects on lung function. A suppression of the hypothalamic pituitary adrenal (HPA) axis was only found with a daily dose of 2 mg FP.", "The efficacy of budesonide (800 micrograms b.d.) and beclomethasone dipropionate (750 micrograms b.d.) in controlling the symptoms of asthma, pulmonary function, bronchial responsiveness to histamine, and adrenal function, was assessed in a double-blind, double-dummy cross-over study of 36 adult chronic asthmatic patients. The patients, the majority of whom were assessed to be affected to a severe degree, were insufficiently controlled in their current regimen of inhaled steroids and/or inhaled and oral bronchodilators. A 2 weeks baseline period preceded 6 weeks of treatment with each of the study drugs. Both treatment groups showed improvements from baseline in clinical assessment of lung function carried out after the first 6 weeks of treatment. No significant differences were seen throughout the entire 12 weeks study, when comparing the effects of the treatments on FEV1, FVC, PEF or the histamine PC20. Asthma severity, symptom score and inhaled bronchodilator use showed the same results after both treatments. It is concluded that inhalations of budesonide and beclomethasone dipropionate in high doses are equally potent in the treatment of severe asthma. There is no significant influence on the adrenal function and no significant side effects during a period equal to that of the present study.", "Inhaled long-acting beta2 agonists improve lung function and health status in symptomatic chronic obstructive pulmonary disease (COPD), whereas inhaled corticosteroids reduce the frequency of acute episodes of symptom exacerbation and delay deterioration in health status. We postulated that a combination of these treatments would be better than each component used alone.\n 1465 patients with COPD were recruited from outpatient departments in 25 countries. They were treated in a randomised, double-blind, parallel-group, placebo-controlled study with either 50 microg salmeterol twice daily (n=372), 500 microg fluticasone twice daily (n=374), 50 microg salmeterol and 500 microg fluticasone twice daily (n=358), or placebo (n=361) for 12 months. The primary outcome was the pretreatment forced expiratory volume in 1s (FEV1) after 12 months treatment' and after patients had abstained from all bronchodilators for at least 6h and from study medication for at least 12h. Secondary outcomes were other lung function measurements, symptoms and rescue treatment use, the number of exacerbations, patient withdrawals, and disease-specific health status. We assessed adverse events, serum cortisol concentrations, skin bruising, and electrocardiograms. Analysis was as predefined in the study protocol.\n All active treatments improved lung function, symptoms, and health status and reduced use of rescue medication and frequency of exacerbations. Combination therapy improved pretreatment FEV1 significantly more than did placebo (treatment difference 133 mL, 95% CI 105-161, p<0.0001), salmeterol (73 mL, 46-101, p<0.0001), or fluticasone alone (95 mL, 67-122, p<0.0001). Combination treatment produced a clinically significant improvement in health status and the greatest reduction in daily symptoms. All treatments were well tolerated with no difference in the frequency of adverse events, bruising, or clinically significant falls in serum cortisol concentration.\n Because inhaled long-acting beta2 agonists and corticosteroid combination treatment produces better control of symptoms and lung function, with no greater risk of side-effects than that with use of either component alone, this combination treatment should be considered for patients with COPD.", "The effects of inhaled beclomethasone dipropionate (BDP), 800 micrograms daily, on the long-term course of asthma and chronic obstructive pulmonary disease (COPD) were investigated in a prospective, controlled study, over three years. During the first two years, patients were treated with a bronchodilator only (salbutamol or ipratropium bromide). Fifty six patients (28 asthma, 28 COPD), with an unfavourable course of disease during bronchodilator therapy alone (an annual decline in forced expiratory volume in one second (FEV1) of > or = 80 ml.yr-1 in combination with at least one exacerbation.yr-1), were selected for additional treatment with inhaled beclomethasone dipropionate (BDP), 800 micrograms daily, during the third year. The FEV1 and provoking concentration of histamine producing a 20% fall in FEV1 (PC20-histamine) were assessed at six-monthly intervals. In asthma, the annual decline in prebronchodilator FEV1 of -158 ml.yr-1 during bronchodilator therapy alone was followed by a significant increase of 562 ml.yr-1 during months 1-6 of BDP treatment (p < 0.0005). During months 7-12 of BDP, the FEV1 declined slightly with -31 ml.yr-1, which was not statistically different from the annual decline before steroid therapy (p = 0.17). In COPD, the increase of 323 ml.yr-1 during months 1-6 of treatment with BDP was different from the annual decline of -156 ml.yr-1 before BDP (p < 0.05). The PC20-histamine improved by 308 doubling doses during 1-12 months of BDP in asthma (p < 0.05) but not in COPD.(ABSTRACT TRUNCATED AT 250 WORDS)", "Little is known about the long-term efficacy of inhaled corticosteroids in chronic obstructive pulmonary disease (COPD). We investigated the efficacy of inhaled budesonide on decline in lung function and respiratory symptoms in a 3-year placebo-controlled study of patients with COPD.\n We used a parallel-group, randomised, double-blind, placebo-controlled design in a singlecentre study, nested in a continuing epidemiological survey (the Copenhagen City Heart Study). Inclusion criteria were as follows: no asthma; a ratio of forced expiratory volume in 1 s (FEV1) and vital capacity of 0.7 or less; FEV1 which showed no response (<15% change) to 1 mg inhaled terbutaline or prednisolone 37.5 mg orally once daily for 10 days. 290 patients were randomly assigned budesonide, 800 microg plus 400 microg daily for 6 months followed by 400 microg twice daily for 30 months, or placebo for 36 months. The mean age of the participants was 59 years and the mean FEV1 2.37 L or 86% of predicted. The main outcome measure was rate of FEV1 decline. Analyses were by intention to treat.\n The crude rates of FEV1 decline were slightly smaller than expected (placebo group 41.8 mL per year, budesonide group 45.1 mL per year). The estimated rates of decline from the regression model did not differ significantly (49.1 mL vs 46.0 mL per year; difference 3.1 mL per year [95% CI -12.8 to 19.0]; p=0.7). Before the study, the minimum relevant difference was defined as 20 mL per year; this difference was outside the 95% CI. No effect of inhaled budesonide was seen on respiratory symptoms. 316 exacerbations occurred during the study period, 155 in the budesonide group and 161 in the placebo group. Treatment was well tolerated.\n Inhaled budesonide was of no clinical benefit in COPD patients recruited from the general population by screening. We question the role of long-term inhaled corticosteroids in the treatment of mild to moderate COPD.", "The efficacy of inhaled corticosteroids in the treatment of chronic obstructive pulmonary disease (COPD) remains controversial because of a lack of placebo-controlled studies. We compared the effect of inhaled fluticasone propionate with placebo in the treatment of patients with COPD.\n We used a randomised, double-blind, placebo-controlled design. We enrolled from 13 European countries, New Zealand, and South Africa, 281 outpatient current or ex-smokers, aged between 50 and 75 years. They had a forced expiratory volume in 1 s (FEV1) of between 35% and 90% of predicted normal values, a ratio of FEV1 to forced vital capacity of 70% or less and bronchodilator reversibility of less than 15%, as well as a history of chronic bronchitis. Patients were randomly assigned fluticasone propionate 500 microg (n=142) or placebo (n=139) twice daily via a metered-dose inhaler for 6 months. The main outcome measures were the number of patients who had at least one exacerbation by the end of treatment, the number and severity of exacerbations, clinic lung function, diary card symptoms and peak expiratory flow and 6 min walking distance.\n 51 (37%) patients in the placebo group compared with 45 (32%) in the fluticasone propionate group had had at least one exacerbation by the end of treatment (p=0.449). Significantly more patients had moderate or severe exacerbations in the placebo group than in the fluticasone propionate group (86% vs 60%, p<0.001). Diary-card and clinic morning peak expiratory flows improved significantly in the fluticasone propionate group (p<0.001, p=0.048, respectively), as did clinic FEV1 (p<0.001), forced vital capacity (p<0.001), and mid-expiratory flow (p=0.01). Symptom scores for median daily cough and sputum volume were significantly lower with fluticasone propionate treatment than with placebo (p=0.004 and p=0.016, respectively). At the end of treatment, patients on fluticasone propionate had increased their 6 min walking distance significantly more than those on placebo (p=0.032). Fluticasone propionate was tolerated as well as placebo, with few adverse effects and without a clinically important effect on mean serum cortisol concentration.\n Fluticasone propionate may be of clinical benefit in patients with COPD over at least 6 months. Inhaled corticosteroids may have an important role in the long-term treatment of COPD.", "To investigate the therapeutic efficacy of inhaled fluticasone propionate, started on day 1 of age, on ventilated preterm infants with respiratory distress syndrome.\n Starting within 24 hours of age, ventilated preterm infants (gestation < 32 weeks, birthweight < 1.5 kg) with respiratory distress syndrome were given a 14 day course (two puffs, 12 hourly) of either fluticasone propionate (250 microg/puff) (group 1, n=27) or placebo (group 2, n=26) with a metered dose inhaler-spacer device. Response to treatment was assessed by the rate of successful extubation by days 7 and 14 of age, changes in respiratory system mechanics, death, occurrence of chronic lung disease, and other neonatal complications.\n More infants in the treatment group were successfully extubated by 14 days of age than those in the placebo group (17/27 vs 8/26; p = 0.038). The treated infants also showed a more significant improvement in respiratory system compliance during the first 14 days of life. The two groups, however, did not differ significantly in their need for systemic steroids after day 14 of age, death, or the occurrence of chronic lung disease. The treatment was not associated with any increase in neonatal complications, including those attributable to steroid induced side effects.\n These results provide preliminary evidence that early treatment with inhaled corticosteroids may be beneficial to ventilated preterm infants with respiratory distress. Further study of its use in a large scale randomised trial is warranted.", "We performed a randomized double-blind trial to determine the usefulness of early methylprednisolone therapy for patients with pulmonary failure. We selected 81 acutely ill, mechanically ventilated patients at high risk for adult respiratory distress syndrome (ARDS). Thirty-nine patients received methylprednisolone, 30 mg/kg, every six hours for 48 hours; 42 patients received mannitol placebo. All patients were given a positive end-expiratory pressure of 5 cm H2O, monitored with pulmonary artery catheters, and treated for their primary disease processes. Twenty-five steroid-treated patients (64%) and 14 placebo-treated patients (33%) developed ARDS. Early infectious complications occurred in 30 steroid-treated patients (77%) and 18 placebo-treated patients (43%). There were no significant differences in factors predisposing to ARDS, ventilatory requirements, or days of intensive care. These results do not support the use of methylprednisolone for ARDS. Steroids failed to improve pulmonary function and were associated with an increased infection rate. Intensive pulmonary and general supportive care remain the preferred therapy for ARDS.", "To examine the hypothesis that an IM long-acting steroid injection will decrease the relapse rate of asthma patients.\n A randomized, single-blind, placebo-controlled trial.\n The emergency department of an urban academic medical center.\n Acute asthma patients aged 18 to 45 years who were treated successfully in the ED.\n Participants received either IM saline placebo or 240 mg methylprednisolone acetate suspension at the time of discharge. MEASUREMENTS AND MAIN OUTCOME: Relapse, defined as the need to seek nonroutine medical care for asthma within seven days of discharge, was the main outcome measure. Of 70 patients entered, 56 (80%) completed follow-up, including 30 in the steroid group and 26 in the placebo group. The groups had similar characteristics and peak expiratory flow values on arrival and at discharge. Relapse occurred in two steroid patients (6.7%) and eight placebo recipients (30.8%) (P < .05). There was one death in the placebo group. Reported side effects were similar.\n IM long-acting steroids reduced the rate of relapse in patients with acute asthma.", "This randomised, double-blind, parallel-group, 1-yr study compared the effect of tiotropium 18 microg once daily (n=500) and placebo (n=510) on exacerbations, associated health resource use (HRU) and airflow limitation in chronic obstructive pulmonary disease (COPD) patients. The mean+/-sd number of exacerbations during the past year was 2.14+/-1.40, the mean weekly morning peak expiratory flow (PEF) was 259.6+/-96.1 L.min-1 and the mean forced expiratory volume in one second (FEV1) was 1.37+/-0.45 L. Tiotropium significantly delayed the time to first exacerbation by approximately 100 days, reduced the proportion of patients experiencing more than one exacerbation by 17%, and decreased the number of exacerbations by 35% and exacerbation days by 37% versus placebo. Tiotropium also decreased HRU versus placebo, as indicated by the significant reductions in the use of concomitant respiratory medications, antibiotics and oral steroids, and the number of unscheduled physician contacts. Mean weekly morning PEF improved significantly with tiotropium versus placebo from week 1 until the end of the study. At the end of the study, tiotropium significantly improved trough (pre-dose) FEV1, forced vital capacity, slow vital capacity and inspiratory capacity versus placebo. In conclusion, tiotropium reduced exacerbations and associated health resource use, and improved airflow over 1 yr in chronic obstructive pulmonary disease patients.", "To evaluate whether inhaled steroids in high doses might be of therapeutic value in pulmonary sarcoidosis.\n Randomized, double blind and placebo controlled parallel study.\n The out-patient clinic of the Department of Pulmonary Medicine, Gentofte Hospital, Copenhagen, Denmark.\n Twenty-one untreated patients (17 males, 4 females, median age 33 years, range 21-65) and eight patients treated with systemic prednisolone. All patients had biopsy proven pulmonary sarcoidosis radiological stage I-III.\n Treatment with either inhaled budesonide 1.2 mg day-1-2.0 mg day-1 (n = 9) or placebo (n = 12) for 12 months.\n Clinical (cough, chest pain, dyspnoea) and paraclinical variables (chest X-ray, gallium scintigraphy, pulmonary function tests, and biochemical markers of disease activity: blood leukocytes, lymphocytes, serum (S-) angiotensin converting enzyme (ACE), S-1,25-OH-cholecalciferol, plasma (P-) calcium, P-immunoglobulins) were recorded before treatment, every three months during treatment, and 6 months after treatment had been discontinued.\n There were no significant differences between the recorded variables in the budesonide and placebo groups. In general, a regression of disease activity was observed in both groups. Two patients in the treatment group, treated with 2.0 mg budesonide/day, and two in the placebo group had progression in disease and were put on systemic steroids.\n Inhaled budesonide in doses of 1.2-2.0 mg day-1 had no recognizable therapeutic effect on pulmonary sarcoidosis." ]	Patients and clinicians should balance the potential benefits of inhaled steroids in COPD (reduced rate of exacerbations, reduced rate of decline in quality of life and possibly reduced rate of decline in FEV1) against the potential side effects (oropharyngeal candidiasis and hoarseness, and risk of pneumonia).
CD002963	[ "2358916", "3524234", "9215204", "2372330" ]	[ "Vibroacoustic stimulation and fetal heart rate in nonstress tests.", "Fetal acoustic stimulation testing. II. A randomized clinical comparison with the nonstress test.", "A randomized controlled trial of a new fetal acoustic stimulation test for fetal well-being.", "Effect of vibratory acoustic stimulation on the duration of fetal heart rate monitoring tests." ]	[ "Two methods of vibroacoustic stimulation were compared with traditional nonstress tests. Fetal heart rate tracings following stimulation had more accelerations and were of greater amplitude and duration than in the control group. The length of time required to obtain a reactive nonstress test was almost 15 minutes shorter when vibroacoustic stimulation was applied than when vibroacoustic stimulation was not used. Vibroacoustic stimulation elicited a heightened reactivity that persisted beyond the observation period in 30 of 45 (67%) of the experimental group subjects.", "Antepartum fetal heart rate testing, specifically the nonstress test, is of accepted value in the antenatal surveillance of high-risk pregnancies. Fetal rest-activity cycles coupled with arbitrary test intervals appear to lead to falsely nonreactive tests. Methods to alter fetal behavioral states have not been uniformly successful. A retrospective analysis of the adjunctive use of acoustic stimulation at our institution demonstrated a 50% reduction in the number of nonreactive tests. Consequently a prospective randomized clinical trial was undertaken to compare the standard nonstress test with the fetal acoustic stimulation test. Those patients randomized to the fetal acoustic stimulation test underwent transabdominal acoustic stimulation with a Model 5C electronic artificial larynx. The incidence of nonreactive tests was 14% in the control group and 9% in the study group (chi 2 = 11.09, p = 0.004). A significant reduction in testing time was also observed. The fetal acoustic stimulation test offers advantages over the traditional nonstress test by lowering the incidence of nonreactive tests and reducing testing time.", "Our purpose was to determine (1) whether a fetal acoustic stimulation test results in more palpable fetal movement compared with a mock test (control) and (2) whether palpated fetal movements after a fetal acoustic stimulation test are accompanied by a reactive nonstress test.\n In a randomized controlled trial we studied women seen in the labor and delivery suite for various indications. Women were excluded for multiple gestation, < 31 weeks' gestational age, treatment with magnesium sulfate or narcotics, or ruptured membranes. Informed consent was obtained from eligible women, who were then randomized to a test or control group. We placed an acoustic stimulator on the abdomen of each woman, but only the test group was stimulated. We assessed fetal movement by a grading system: 0 = no fetal movement felt by patient or tester, 1 = fetal movement felt by patient only, 2 = fetal movement felt by tester, 3 = visual movement seen by tester. A positive fetal acoustic stimulation test result was defined as one with any fetal movement felt or seen by the tester (grades 2 or 3). We then performed a nonstress test. We compared rates of a positive fetal acoustic stimulation test in the test and control groups with the chi 2 test. A p value < 0.05 was considered significant.\n We randomized 297 women to the test group and 280 women to the control (mock test) group. Of women tested with the fetal acoustic stimulation test. 81% had fetal movement by palpation or visualization (grades 2 or 3) compared with 19% of the control group (p < 0.0001, odds ratio 19.29, 95% confidence interval 12.42 to 30.07). Of the test group, 283 (95%) had a reactive nonstress test and 14 (5%) had nonreactive tests; the control group had 267 (95%) reactive and 13 (5%) nonreactive nonstress tests. Of 242 patients in the test group with a positive fetal acoustic stimulation test, 236 (98%) had a reactive nonstress test. Of those in the test group with fewer than three contractions per 10 minutes. 164 (89%) had a positive fetal acoustic stimulation test. Of these, 162 (99%) had a reactive nonstress test.\n The fetal acoustic stimulation test evokes significantly more palpated or visualized fetal movement than in controls. Palpated or visualized fetal movement after acoustic stimulation was almost always accompanied by a reactive nonstress test.", "The ability of vibratory acoustic stimulation to shorten the duration of antepartum fetal heart rate monitoring was investigated by a randomized controlled trial. Vibratory acoustic stimulation did not shorten the overall duration of testing. This failure to improve the performance of antepartum monitoring appeared to result from prolonged accelerations, which complicated one third of the tests in which vibratory acoustic stimulation was employed. Further investigation is warranted using less profound methods of fetal stimulation." ]	Vibroacoustic stimulation offers benefits by decreasing the incidence of non-reactive cardiotocography and reducing the testing time. Further randomized trials should be encouraged to determine not only the optimum intensity, frequency, duration and position of the vibroacoustic stimulation, but also to evaluate the efficacy, predictive reliability, safety and perinatal outcome of these stimuli with cardiotocography and other tests of fetal well-being. [Note: The eight citations in the awaiting classification section of the review may alter the conclusions of the review once assessed.]
CD007137	[ "19809023" ]	[ "Bovine lactoferrin supplementation for prevention of late-onset sepsis in very low-birth-weight neonates: a randomized trial." ]	[ "Sepsis is a common and severe complication in premature neonates, particularly those with very low birth weight (VLBW) (<1500 g). Whether lactoferrin, a mammalian milk glycoprotein involved in innate immune host defenses, can reduce the incidence of sepsis is unknown. In animal models, the probiotic Lactobacillus rhamnosus GG (LGG) enhances the activity of lactoferrin but has not been studied in human infants.\n To establish whether bovine lactoferrin (BLF), alone or in combination with LGG, reduces the incidence of late-onset sepsis in VLBW neonates.\n Prospective, multicenter, double-blind, placebo-controlled, randomized trial conducted in 11 Italian tertiary neonatal intensive care units. Patients were 472 VLBW infants enrolled from October 1, 2007, through July 31, 2008, and assessed until discharge for development of sepsis.\n Infants were randomly assigned to receive orally administered BLF (100 mg/d) alone (n = 153), BLF plus LGG (6 x 10(9) colony-forming units/d) (n = 151), or placebo (n = 168) from birth until day 30 of life (day 45 for neonates <1000 g at birth).\n First episode of late-onset sepsis, ie, sepsis occurring more than 72 hours after birth with isolation of any pathogen from blood or from peritoneal or cerebrospinal fluid.\n Demographic, clinical, and management characteristics of the 3 groups were similar, including type of feeding and intake of maternal milk. Incidence of late-onset sepsis was significantly lower in the BLF and BLF plus LGG groups (9/153 [5.9%] and 7/151 [4.6%], respectively) than in the control group receiving placebo (29/168 [17.3%]) (risk ratio, 0.34; 95% confidence interval, 0.17-0.70; P = .002 for BLF vs control and risk ratio, 0.27; 95% confidence interval, 0.12-0.60; P < .001 for BLF plus LGG vs control). The decrease occurred for both bacterial and fungal sepsis. No adverse effects or intolerances to treatment occurred.\n Compared with placebo, BLF supplementation alone or in combination with LGG reduced the incidence of a first episode of late-onset sepsis in VLBW neonates.\n isrctn.org Identifier: ISRCTN53107700." ]	Oral lactoferrin prophylaxis reduces the incidence of late-onset sepsis in infants weighing less than 1500 g and most effective in infants weighing less than 1000 g. There is no evidence of efficacy of oral lactoferrin (given alone) in the prevention of NEC in preterm neonates. Well designed, randomized trials should address dosing, duration, type of lactoferrin (bovine or human) prophylaxis in prevention of sepsis and NEC. The effect of exclusive maternal milk feeding should be clarified.
CD001842	[ "9033441", "11044540", "2866047", "14678373", "35296", "15077078", "26371", "16291357", "11597664", "19558807", "8335810", "10881251", "10735784", "6863097" ]	[ "Short-term regular beta 2-adrenergic agonists treatment is safe in mild asthmatics taking low doses of inhaled steroids.", "beta(2)-adrenergic agonists and pelvic floor exercises for female stress incontinence.", "Effect of beta-adrenergic blockers on the peripheral circulation in patients with peripheral vascular disease.", "A randomized crossover study to evaluate Ro 115-1240, a selective alpha1A/1L-adrenoceptor partial agonist in women with stress urinary incontinence.", "Selectivity of beta adrenoreceptor antagonist drugs assessed by histamine bronchial provocation.", "A comparison between oral antiarrhythmic drugs in the prevention of atrial fibrillation after cardiac surgery: the pilot study of prevention of postoperative atrial fibrillation (SPPAF), a randomized, placebo-controlled trial.", "A comparison of four beta-adrenoceptor antagonists in patients with asthma.", "Clinical impact of corticosteroid-induced adrenal suppression during treatment for acute lymphoblastic leukemia in children: a prospective observational study using the low-dose adrenocorticotropin test.", "Effects of the dual endothelin-receptor antagonist bosentan in patients with pulmonary hypertension: a randomised placebo-controlled study.", "[A comparative study of conventional dose and low dose adrenocorticotrophic hormone therapy for West syndrome].", "Short-term effects of early intravenous treatment with a beta-adrenergic blocking agent or a specific bradycardiac agent in patients with acute myocardial infarction receiving thrombolytic therapy.", "A 5-month, randomized, placebo-controlled trial of galantamine in AD. The Galantamine USA-10 Study Group.", "The hemodynamic and adrenergic effects of perioperative dexmedetomidine infusion after vascular surgery.", "Effect of beta-adrenergic blockade on hyperventilation and exercise tolerance in emphysema." ]	[ "Regular treatment with beta 2-adrenergic agonists is controversial in bronchial asthma. To investigate whether beta 2-adrenergic agonists can be used safely if associated with low doses of inhaled steroids, for a short period, without a deterioration of asthma control, we have examined 24 mild asthmatics. In a parallel, double-blind, placebo-controlled study, 1 week of run-in and run-out period framed 3 weeks of treatment. All patients received inhaled beclomethasone dipropionate (BDP 250 micrograms t.i.d.); after 1 week, 12 patients inhaled 400 micrograms of broxaterol and 12 patients received placebo t.i.d. FVC, FEV1, PD20-FEV1 methacholine, morning and evening PEF, and PEF amplitude % mean were measured before, during, and after treatment. No significant changes were noted in patients receiving inhaled broxaterol. There were no differences in symptoms and the use of rescue medication (salbutamol spray). We conclude that short-term regular treatment with beta 2-adrenergic agonists is not associated with a deterioration in asthma control in mild asthmatics inhaling low doses of steroids.", "We compared beta(2)-adrenergic agonist therapy with clenbuterol (DT) and physiological therapy (PT) in a randomized study to establish the first line therapy for stress incontinence (SI).\n The clinical efficacy of DT (group A), PT (group B), and a combination of DT and PT (group C) was investigated in 61 patients with SI by means of a 12-week randomized controlled study. The frequency and volume of SI and the patients' own impressions were used as the basis for the assessment of efficacy.\n The SI improvement rates in groups A, B, and C were 76.9, 52.6, and 89. 5%, respectively (P=0.0361). A significant therapeutic effect on the frequency of SI was observed in group B and group C at 2 weeks after the start of treatment (both P<0.05), and in all groups at 6 weeks (all P<0.01). The efficacy rates based on the patients' own impressions in groups A, B, and C were 84.6, 31.6, and 68.4%, respectively (P=0.0064).\n The beta(2)-adrenergic agonist appeared to be clinically useful as a drug of choice for SI.", "Beta-Adrenergic blockers have not been widely used in patients with peripheral vascular disease because these drugs have been reported to worsen the symptoms of intermittent claudication. To test this assumption we studied the effects of a beta 1-selective and a nonselective beta-adrenergic blocker on postexercise calf blood flow and symptoms of claudication in 19 patients with mild-to-moderate peripheral vascular disease. Subjects received placebo for 3 weeks, and then were randomized to 120 mg/day propranolol or 150 mg/day metoprolol with the use of a crossover design. Blood flow in the calf was measured by strain-gauge plethysmography at rest and immediately after exercise on a bicycle ergometer at a low and a high workload. The symptoms of claudication were monitored during bicycle exercise and by patient diaries maintained between visits. Maximal exercise heart rate was reduced an equivalent amount by metoprolol (19 beats/min) and propranolol (16 beats/min). Mean arterial pressure was reduced by propranolol at rest and by both drugs with exercise. Calf blood flow was not affected by either drug compared with placebo at rest or at either workload. In addition, the symptoms of claudication were not worsened by either drug. We conclude that despite evidence of beta 1-adrenergic blockade and a lowering of arterial pressure, neither beta-adrenergic blocker adversely affected the peripheral circulation.", "To investigate the potential therapeutic benefits of the selective alpha1A/1l-adrenoceptor partial agonist Ro 115-1240 in women with mild-to-moderate stress urinary incontinence (SUI).\n Thirty-seven women with mild-to-moderate SUI were enrolled in a randomized, placebo-controlled crossover study. Patients received 1.5 mg Ro 115-1240 twice daily or matching placebo for 2 or 4 weeks. Voiding diaries were used to record the number of SUI episodes, urge incontinence episodes and pads used. Sitting blood pressures and heart rate were recorded at each visit.\n Ro 115-1240 was associated with a significantly lower mean weekly number of SUI episodes than placebo (8.4 vs 6.0; P= 0.0079), a 28% relative improvement over placebo. There was also a significantly lower mean number of pads used and wet pads changed/week with Ro 115-1240 than with placebo (P = 0.0055 and 0.0066, respectively). The most frequently reported treatment-emergent adverse events were scalp tingling, headache, chills, piloerection, and pruritus. Generally these events were transient and mild to moderate. There was a slightly lower mean sitting heart rate with Ro 115-1240 than with placebo, but no difference in mean systolic or diastolic blood pressure between treatments.\n This study suggests that selective alpha1A/1l-adrenoceptor partial agonists have the potential to improve the symptoms of SUI with little or no cardiovascular effect. These results are encouraging and a randomized controlled trial of Ro 115-1240 in a larger population with SUI is warranted to substantiate these findings.", "In a double-blind, within-patient, randomized study, 12 mild asthmatics were given single oral doses of propranolol (80 mg), metoprolol (100 mg), timolol (10 mg), or placebo. Resting heart rate and forced expiratory volume in one sec (FEV1) were measured before and 90 min after treatment. Nonspecific bronchial reactivity was measured by inhaled histamine at 90 min. Following each active drug, resting heart rate changed to a similar extent and to a greater degree than after placebo (p less than 0.01). Changes in FEV1 were small and not different from those after placebo. In contrast, after each active drug, bronchial reactivity increased more than after placebo. The degree of reactivity with each active drug was similar but the differences from corresponding placebo values were significant (p less than 0.05). We conclude that, in mild asthmatics, nonspecific bronchial reactivity is a more sensitive index of airway effects than resting FEV1. Moreover, in the context of this study, since the beta-blockers were given in doses likely to induce equivalent cardiac beta-blockade, there is no evidence to suggest that any one of them is more \"cardioselective\" than the others.", "Atrial fibrillation (AF) frequently occurs after cardiac surgical procedures, and beta-blockers, sotalol, and amiodarone may reduce the frequency of AF after open heart surgery. This pilot trial was designed to test whether each of the active oral drug regimens is superior to placebo for prevention of postoperative AF and whether there are differences in favor of 1 of the preventive strategies.\n We conducted a randomized, double-blinded, placebo-controlled trial in which patients undergoing cardiac surgery in the absence of heart failure and without significant left ventricular dysfunction (n = 253; average age, 65 +/- 11 years) received oral amiodarone plus metoprolol (n = 63), metoprolol alone (n = 62), sotalol (n = 63), or placebo (n = 65). Patients receiving combination therapy (amiodarone plus metoprolol) and those receiving sotalol had a significantly lower frequency of AF (30.2% and 31.7%; absolute difference, 23.6% and 22.1%; odds ratios [OR], 0.37 [95% CI, 0.18 to 0.77, P <.01 vs placebo] and 0.40 [0.19 to 0.82, P =.01 vs placebo]) compared with patients receiving placebo (53.8%). Treatment with metoprolol was associated with a 13.5% absolute reduction of AF (P =.16; OR, 0.58 [0.29 to 1.17]. Treatment effects did not differ significantly between active drug groups. Adverse events including cerebrovascular accident, postoperative ventricular tachycardia, nausea, and dyspepsia, in hospital death, postoperative infections, and hypotension, were similar among the groups. Bradycardia necessitating dose reduction or drug withdrawal occurred in 3.1% (placebo), 3.2% (combined amiodarone and metoprolol; P =.65 vs placebo), 12.7% (sotalol; P <.05 vs placebo), and 16.1% (metoprolol; P <.05 vs placebo). Patients in the placebo group had a nonsignificantly longer length of hospital stay as compared with the active treatment groups (13.1 +/- 8.9 days vs 11.3 +/- 7; P =.10), with no significant difference between the active treatment groups.\n Oral active prophylaxis with either sotalol or amiodarone plus metoprolol may reduce the rate of AF after cardiac surgery in a population at high risk for postoperative AF. Treatment with metoprolol alone resulted in a trend to a lower risk for postoperative AF.", "1 Cardiovascular and airways response to two non-cardioselective beta-adrenoceptor blocking drugs, propranolol and pindolol (with partial agonist activity) and two cardioselective beta-adrenoceptor blocking drugs, acebutolol (with partial agonist activity) and atenolol, were compared in twelve patients with asthma. 2 All four drugs produced a significant reduction in resting pulse rate and prevented the increase in heart rate following inhaled isoprenaline (1,500 microgram). 3 Seven patients in clinical remission showed no significant bronchoconstrictor response to any of the drugs. In the remaining five patients, bronchoconstriction was greatest following propranolol (mean reduction in FEV1 26.6%) and least following atenolol (mean reduction in FEV1 6.5%). 4 The bronchodilator response to inhaled isoprenaline was blocked by propranolol and pindolol but not by acebutolol and atenolol. 5 Partial agonist activity did not appear to be clinically useful.", "To investigate how frequently adrenal function fails to recover after corticosteroid therapy in children with acute lymphoblastic leukemia and to explore the clinical impact of slow adrenal recovery without steroid substitution.\n Low-dose (1 microg) adrenocorticotropic hormone tests were performed before and after steroid courses and during infectious episodes in 24 children. Test results were not available during the study.\n All 13 patients tested before treatment had normal adrenal responses. Adrenal suppression was found in 8 (47%) of 17 patients 5 days after discontinuation of a 5-week induction course of prednisolone and in 1 (20%) of 5 patients 7 days after a 3-week intensification course of dexamethasone, both courses being tapered over 9 days, as well as in all 13 patients tested 2 days after a 1-week prednisolone course. Clinically significant manifestations of adrenal suppression were noted in 3 (12%) patients. Of 204 scheduled tests, 131 were performed.\n High-dose glucocorticoid therapy may cause adrenal suppression lasting more than 1 week in children with acute lymphoblastic leukemia, even after tapering the dose. We suggest steroid replacement during stress episodes within 1 to 2 weeks after discontinuation and thereafter testing adrenal function selectively in accordance with symptoms.", "Endothelin 1, a powerful endogenous vasoconstrictor and mitogen, might be a cause of pulmonary hypertension. We describe the efficacy and safety of bosentan, a dual endothelin-receptor antagonist that can be taken orally, in patients with severe pulmonary hypertension.\n In this double-blind, placebo-controlled study, 32 patients with pulmonary hypertension (primary or associated with scleroderma) were randomly assigned to bosentan (62.5mg taken twice daily for 4 weeks then 125 mg twice daily) or placebo for a minimum of 12 weeks. The primary endpoint was change in exercise capacity. Secondary endpoints included changes in cardiopulmonary haemodynamics, Borg dyspnoea index, WHO functional class, and withdrawal due to clinical worsening. Analysis was by intention to treat.\n In patients given bosentan, the distance walked in 6 min improved by 70 m at 12 weeks compared with baseline, whereas it worsened by 6 m in those on placebo (difference 76 m [95% CI 12-139], p=0.021). The improvement was maintained for at least 20 weeks. The cardiac index was 1.0 L min(-1) m(-2) (95% CI 0.6-1.4, p<0.0001) greater in patients given bosentan than in those given placebo. Pulmonary vascular resistance decreased by 223 dyn s cm(-)(5) with bosentan, but increased by 191 dyn s cm(-5) with placebo (difference -415 [-608 to -221], p=0.0002). Patients given bosentan had a reduced Borg dyspnoea index and an improved WHO functional class. All three withdrawals from clinical worsening were in the placebo group (p=0.033). The number and nature of adverse events did not differ between the two groups.\n Bosentan increases exercise capacity and improves haemodynamics in patients with pulmonary hypertension, suggesting that endothelin has an important role in pulmonary hypertension.", "The efficacy and adverse effects of conventional dose and low dose adrenocorticotrophic hormone (ACTH) therapy for West syndrome (WS) were compared in order to identify a low effective dose with few adverse effects.\n A prospective randomized controlled study was conducted. Thirty children with cryptogenic (n=8) or symptomatic (n=22) WS were enrolled. They were randomly assigned to receive either conventional dose or low dose ACTH therapy. For the conventional dose group, ACTH 50 IU per day was administered for 2 weeks and tapered to zero over the subsequent 2 weeks. For the low dose group, 0.4 IU/kg per day was injected for 2 weeks. After seizures were fully controlled, ACTH was tapered to zero over the subsequent 2 weeks. If there was an absence of an effective response in the low dose group, the dosage was increased to 1 IU/kg per day for the next 2 weeks and then tapered to zero over 2 weeks. Both effectiveness and adverse effects were compared between the two groups.\n There were no significant differences in the good initial responses between the conventional and the low dose groups, which were 53% and 60%, respectively (P> 0.05). EEG findings after ACTH therapy, the rate of relapse of spasms, and the interval to relapse were not different between the two groups (P> 0.05). The long-term outcomes were assessed in the initial 8 responders, and there were no significant differences between the two groups (follow-up duration>12 months). The rates of good efficacy and disappearance of the hypsarrhythmia were significantly higher in the cryptogenic WS group than in the symptomatic WS group (P<0.05). The incidence of ACTH therapy related-adverse effects in the conventional dose group (93%) was significantly higher than in the low dose group (20%) (P<0.01). The mild brain shrinkage was observed in one patient from the conventional dose group.\n The short-term and long-term therapeutic effects of ACTH between 50 IU/d and 0.4 IU/kg/d doses are similar. ACTH therapy is more effective for cryptogenic WS than symptomatic WS. To reduce adverse effects, ACTH therapy should start with a low dose (0.4 IU/ kg each day).", "This study was conducted to explore mechanisms that could explain the possible clinical benefit of early administration of a beta 1-selective adrenoreceptor blocking agent or a bradycardiac drug as adjunct to thrombolysis in acute myocardial infarction.\n The effects of beta-blockers given concomitantly with thrombolytic therapy in patients with acute myocardial infarction have not been fully examined. The potential role of specific bradycardiac agents lacking negative inotropism as an alternative to beta-blockers in this setting has never been studied in humans.\n In a double-blind study, we examined the effects of early intravenous and continued oral administration of a beta-blocker (atenolol), a specific bradycardiac agent (alinidine) or placebo on left ventricular function, late coronary artery patency, infarct size, exercise capacity and incidence of arrhythmias.\n A total of 292 patients with acute myocardial infarction of < or = 5 h duration and without contraindications to thrombolytic or beta-blocker therapy were studied. Of these, 100 were allocated to treatment with atenolol (5 to 10 mg intravenously followed by 25 to 50 mg orally every 12 h), 98 to alinidine (20 to 40 mg intravenously followed by 20 to 40 mg orally every 8 h) and 94 to placebo. All patients received 100 mg of alteplase over 3 h and full intravenous heparinization. No significant differences in coronary artery patency, global ejection fraction or regional wall motion were observed at 10 to 14 days among the three groups. Likewise, enzymatic and scintigraphic infarct size were also very similar. Neither atenolol nor alinidine was associated with a significant reduction in the incidence of arrhythmias during the 1st 24 h. No significant differences in clinical events were observed, with the exception of a greater incidence of nonfatal pulmonary edema in the atenolol group (6% vs. 1% in the alinidine group and 0% in the placebo group, p = 0.021).\n In the absence of contraindications, the administration of a beta-blocker or a specific bradycardiac agent together with thrombolytic therapy was safe. In this limited number of patients, these agents did not appear to enhance myocardial salvage or preservation of left ventricular function or to reduce the incidence of major arrhythmias in the early phase of infarction.", "To investigate the efficacy and tolerability of galantamine, using a slow dose escalation schedule of up to 8 weeks, in 978 patients with mild to moderate AD.\n A 5-month multicenter, placebo-controlled, double-blind trial. Following a 4-week placebo run-in, patients were randomized to one of four treatment arms: placebo or galantamine escalated to final maintenance doses of 8, 16, or 24 mg/day. Outcome measures included the cognitive subscale of the AD Assessment Scale (ADAS-cog), the Clinician's Interview-Based Impression of Change plus Caregiver Input (CIBIC-plus), the AD Cooperative Study Activities of Daily Living inventory, and the Neuropsychiatric Inventory. Standard safety evaluations and adverse event monitoring were carried out.\n After 5 months, the galantamine-placebo differences on ADAS-cog were 3.3 points for the 16 mg/day group and 3.6 points for the 24 mg/day group (p < 0.001 versus placebo, both doses). Compared with placebo, the galantamine 16- and 24-mg/day groups also had a significantly better outcome on CIBIC-plus, activities of daily living, and behavioral symptoms. Treatment discontinuations due to adverse events were low in all galantamine groups (6 to 10%) and comparable with the discontinuation rate in the placebo group (7%). The incidence of adverse events in the galantamine groups, notably gastrointestinal symptoms, was low and most adverse events were mild.\n Galantamine 16 and 24 mg/day significantly benefits the cognitive, functional, and behavioral symptoms of AD as compared with placebo. Slow dose escalation appears to enhance the tolerability of galantamine, minimizing the incidence and severity of adverse events.", "We tested dexmedetomidine, an alpha(2) agonist that decreases heart rate, blood pressure, and plasma norepinephrine concentration, for its ability to attenuate stress responses during emergence from anesthesia after major vascular operations. Patients scheduled for vascular surgery received either dexmedetomidine (n = 22) or placebo (n = 19) IV beginning 20 min before the induction of anesthesia and continuing until 48 h after the end of surgery. All patients received standardized anesthesia. Heart rate and arterial blood pressure were kept within predetermined limits by varying anesthetic level and using vasoactive medications. Heart rate, arterial blood pressure, and inhaled anesthetic concentration were monitored continuously; additional measurements included plasma and urine catecholamines. During emergence from anesthesia, heart rate was slower with dexmedetomidine (73 +/- 11 bpm) than placebo (83 +/- 20 bpm) (P = 0.006), and the percentage of time the heart rate was within the predetermined hemodynamic limits was more frequent with dexmedetomidine (P < 0.05). Plasma norepinephrine levels increased only in the placebo group and were significantly lower for the dexmedetomidine group during the immediate postoperative period (P = 0.0002). We conclude that dexmedetomidine attenuates increases in heart rate and plasma norepinephrine concentrations during emergence from anesthesia.\n The alpha(2) agonist, dexmedetomidine, attenuates increases in heart rate and plasma norepinephrine concentrations during emergence from anesthesia in vascular surgery patients.", "Ventilation, heart rate, and arterial blood gas tensions were measured at rest and during incremental exercise in 10 patients with emphysema after intravenous placebo or 7 mg metoprolol. Metoprolol reduced heart rate by 14% (P less than 0.001) and ventilation by 11% (P less than 0.01), but there was no significant difference in arterial O2 or CO2 tension (Pao2 and PaCO2, respectively). Metoprolol increased the time to exhaustion on a cycle ergometer (P less than 0.05) but did not improve the 12-min walking distance. A double-blind randomized crossover comparison of 4 wk treatment with atenolol (100 mg/day), metoprolol (100 mg/day), or matched placebo was performed in 12 patients with emphysema. Both beta-adrenoceptor antagonists reduced resting heart rate by 33% (P less than 0.001) and resting minute ventilation by 11% (P less than 0.025). There was no change in resting or exercise Pao2 or Paco2. During steady-state exercise on a cycle ergometer, atenolol and metoprolol reduced ventilation by 14 and 4%, respectively. This was accompanied by 11 and 5% reductions in O2 consumption (P less than 0.05) and 13 and 6% falls in CO2 production (P less than 0.05). There were no significant changes in tests of exercise tolerance, but forced expiratory volume in 1 s and forced vital capacity were reduced during beta 1-adrenergic blockade. beta 1-Blocking drugs reduce hyperventilation in emphysema by reducing pulmonary gas exchange without a change in arterial blood gas tensions. Increased airflow obstruction prevents this reduction being of therapeutic value." ]	There was weak evidence to suggest that use of an adrenergic agonist was better than placebo treatment. There was not enough evidence to assess the effects of adrenergic agonists when compared to or combined with other treatments. Further larger trials are needed to identify when adrenergics may be useful. Patients using adrenergic agonists may suffer from minor side effects, which sometimes cause them to stop treatment. Rare but serious side effects, such as cardiac arrhythmias and hypertension, have been reported.
CD004749	[ "16893677", "15249261" ]	[ "What factors are associated with the integration of evidence retrieval technology into routine general practice settings?", "Providing a web-based online medical record with electronic communication capabilities to patients with congestive heart failure: randomized trial." ]	[ "Information retrieval systems have the potential to improve patient care but little is known about the variables which influence clinicians' uptake and use of systems in routine work.\n To determine which factors influenced use of an online evidence retrieval system.\n Computer logs and pre- and post-system survey analysis of a 4-week clinical trial of the Quick Clinical online evidence system involving 227 general practitioners across Australia.\n Online evidence use was not linked to general practice training or clinical experience but female clinicians conducted more searches than their male counterparts (mean use=14.38 searches, S.D.=11.68 versus mean use=8.50 searches, S.D.=9.99; t=2.67, d.f.=157, P=0.008). Practice characteristics such as hours worked, type and geographic location of clinic were not associated with search activity. Information seeking was also not related to participants' perceived information needs, computer skills, training nor Internet connection speed. Clinicians who reported direct improvements in patient care as a result of system use had significantly higher rates of system use than other users (mean use=12.55 searches, S.D.=13.18 versus mean use=8.15 searches, S.D.=9.18; t=2.322, d.f.=154 P=0.022). Comparison of participants' views pre- and post- the trial, showed that post-trial clinicians expressed more positive views about searching for information during a consultation (chi(2)=27.40, d.f.=4, P< or =0.001) and a significantly greater number reported seeking information between consultations as a result of having access to an online evidence system in their consulting rooms (chi(2)=9.818, d.f.=2, P=0.010).\n Clinicians' use of an online evidence system was directly related to their reported experiences of improvements in patient care. Post-trial clinicians positively changed their views about having time to search for information and pursued more questions during clinic hours.", "It is possible to provide patients with secure access to their medical records using the Internet. Such access may assist patients in the self-management of chronic diseases such as heart failure.\n To assess how a patient-accessible online medical record affects patient care and clinic operations. The SPPARO (System Providing Access to Records Online) software consisted of a web-based electronic medical record, an educational guide, and a messaging system enabling electronic communication between the patient and staff.\n A randomized controlled trial was conducted in a specialty practice for patients with heart failure. Surveys assessing doctor-patient communication, adherence, and health status were conducted at baseline, 6 months, and 1 year. Use of the system, message volume, utilization of clinical services, and mortality were monitored.\n One hundred and seven patients were enrolled (54 intervention and 53 controls). At 12 months, the intervention group was not found to be superior in self-efficacy (KCCQ self-efficacy score 91 vs. 85, p=0.08), but was superior in general adherence (MOS compliance score 85 vs. 78, p=0.01). A trend was observed for better satisfaction with doctor-patient communication. The intervention group had more emergency department visits (20 vs. 8, p=0.03), but these visits were not temporally related to use of the online medical record. There were no adverse effects from use of the system.\n Providing patients with congestive heart failure access to an online medical record was feasible and improved adherence. An effect on health status could not be demonstrated in this pilot study." ]	Overall there was insufficient evidence to support or refute the use of electronic retrieval of healthcare information by healthcare providers to improve practice and patient care.
CD000218	[ "1396198", "6350957", "1411848", "1098732", "343312", "7018164", "2606014", "769913", "9166304", "9524997", "10819810", "9132982", "322823", "4939601", "8014510", "12139216", "16014845", "10326116", "11098194", "6995193", "6401550", "356372", "8937280", "2076717", "11355564" ]	[ "Treatment of symptomatic trichomoniasis among adult women using oral nitroimidazoles.", "Single oral dose of ornidazole in women with vaginal trichomoniasis.", "Split-dose metronidazole or single-dose tinidazole for the treatment of vaginal trichomoniasis.", "Treatment of trichomoniasis in the female. A comparison of metronidazole and nimorazole.", "Treatment of intestinal amoebiasis and vaginal trichomoniasis with panidazole and its comparison with metronidazole.", "A double-blind study of the value of treatment with a single dose tinidazole of partners to females with trichomoniasis.", "Comparison of four nitroimidazole compounds for treatment of symptomatic amoebiasis in Kenya.", "Two-day treatment of trichomoniasis in the female. Comparison of metronidazole and nimorazole.", "The minimum single oral metronidazole dose for treating trichomoniasis: a randomized, blinded study.", "A pilot study of metronidazole vaginal gel versus oral metronidazole for the treatment of Trichomonas vaginalis vaginitis.", "A randomized trial of intravaginal nonoxynol 9 versus oral metronidazole in the treatment of vaginal trichomoniasis.", "Multicenter comparison of clotrimazole vaginal tablets, oral metronidazole, and vaginal suppositories containing sulfanilamide, aminacrine hydrochloride, and allantoin in the treatment of symptomatic trichomoniasis.", "First experiences with single-dose treatment of vaginal trichomoniasis with carnidazole (R 25831).", "Nitrimidazine compared with metronidazole in the treatment of vaginal trichomoniasis.", "A double-blind placebo-controlled trial of single-dose intravaginal versus single-dose oral metronidazole in the treatment of trichomonal vaginitis.", "Nitazoxanide compared with quinfamide and mebendazole in the treatment of helminthic infections and intestinal protozoa in children.", "Tolerance and efficacy of combined diethylcarbamazine and albendazole for treatment of Wuchereria bancrofti and intestinal helminth infections in Haitian children.", "A double-'blind' placebo-controlled study of nitazoxanide in the treatment of cryptosporidial diarrhoea in AIDS patients in Mexico.", "Comparative Study of the Efficacy and Tolerability of Secnidazole Suspension (single dose) and Tinidazole Suspension (two days dosage) in the Treatment of Amebiasis in Children.", "A double-blind controlled clinical trial of carnidazole and tinidazole in the treatment of vaginal trichomoniasis.", "Single dose oral treatment in urinary schistosomiasis: a double blind trial.", "[Single-dose treatment with ornidazole (Tiberal) in vaginal trichomoniasis. A controlled clinical study in general practice].", "Randomised trial of efficacy of benznidazole in treatment of early Trypanosoma cruzi infection.", "Comparative study of aminosidine, etophamide and nimorazole, alone or in combination, in the treatment of intestinal amoebiasis in Kenya.", "The effect of different anthelmintic treatment regimens combined with iron supplementation on the nutritional status of schoolchildren in KwaZulu-Natal, South Africa: a randomized controlled trial." ]	[ "Successful treatment of infections with Trichomonas vaginalis (TV) is difficult because of many confounding factors such as poor abstinence from sex during chemotherapy, lack of standardised chemotherapy, difficulties in understanding transmission patterns and low detection rates among infected individuals. The purpose of this study was to establish the present efficacy of the available drugs at their recommended single or double dosages for Kenya. Adult symptomatic females (age 17-39 years) with positive High Vaginal Swabs but without pregnancy were recruited into the study; and asked to swallow one of the following medicine: nimorazole 2G (Naxogin Farmitalia Carlo Erba, Italy), nimorazole 4G in two equally divided doses 24 hours apart (2GBD), nimorazole 3G, tinidazole 2G (Fasigyn, Pfizer Ltd) and ornidazole 1.5G (Tiberal, Roche, Switzerland). All patients were reviewed 48 hours after the drugs administration and 24 hours after the last dose for the group which received nimorazole 2GBD. 153 patients were recruited into the study. 121 came for follow up out of which 49 were dropped from the study for involvement in sexual intercourse leaving only 72 for the final analysis. Clinical cure was 100% for the group receiving nimorazole 2GBD and nimorazole 3G. Parasitological cure was highest for the group on nimorazole 2GBD (100%) and lowest for the group on tinidazole (50%). Instruction to avoid sex during treatment were withheld from patients. This made it easier during the follow up to pick out and drop from the study those who had had sexual contact.", "Fifty-nine women with trichomonal vaginitis were randomly allocated to receive treatment with a single oral dose of either 0.5, 1.0, or 1.5 g of ornidazole. One week after treatment, a parasitologic cure was observed in 100% of patients treated with 1.5 g, in 95% of patients treated with 1.0 g, and in 65% of patients given 0.5 g. At the one-month follow-up visit, the cure rate remained at 100% for the 1.5-g dose group but dropped to 85 and 45% in the 1.0- and 0.5-g dose groups, respectively. The disappearance of symptomatic complaints was also dose related: the clinical cure was 100, 85, and 40% at the first follow-up visit and 89, 80, and 30% at the second follow-up visit. Adverse effects of mild or moderate severity were reported by 13 patients. These were encountered mostly in the 1.5- and the 1.0-g dose groups. The most frequent adverse effects were dizziness and gastrointestinal distress. Laboratory safety test did not reveal any significant toxicity. This study confirms that single-dose treatment of trichomoniasis with an oral dose of 1.5 or 1.0 g of ornidazole is effective and well tolerated.", "In a double-blind, randomized, controlled trial, efficacy and safety of a single-day split dose of 1.6 g of metronidazole were compared with a single 2-g dose of tinidazole in the treatment of vaginal trichomoniasis. Women with symptomatic vaginal trichomoniasis were randomly assigned to one of the two treatment groups. There were 67 women in the group treated with the single-day split dose and 65 in group treated with the single dose. There was no significant difference between the two groups in terms of clinical characteristics (age, weight, and length of follow-up period). The cure rates, using trypticase yeast extract iron serum (TYI) medium to confirm microbiologic cure, were 98.5% and 100% for the groups treated with a single-day split dose and with a single dose, respectively. The side effects were minimal and did not warrant any treatment. The differences in the results were not statistically significant. We recommend that the single-day split dose of 1.6 g of metronidazole regimen be given as an alternative drug for vaginal trichomoniasis. Its advantages include being highly effective, significantly less expensive, and with minimal side effects.", "The effectiveness of metronidazole (Flagyl) and nimorazole (Naxogin) has been compared by using these drugs in the recommended dosage in alternate patients in a series of 218 consecutive cases of vaginal trichomoniasis. Follow-up tests in 100 patients treated with metronidazole and 97 treated with nimorazole indicated cure-rates of 95 and 82 per cent. respectively. Male consorts were examined and given treatment on epidemiological grounds in about 70 per cent. of both treatment groups. Both drugs were free from significant side-effects. The causes of treatment failure in trichomoniasis are discussed and the desirability of relating dosage to the patient's body-weight is suggested. This factor may be especially important in deciding the dosage given on epidemiological grounds to the male consorts. It may also be an important advantage in the current trend of treating trichomoniasis in both sexes with larger doses over a much shorter time.", "A dose range study in 18 patients suffering from intestinal amoebiasis and treated with doses of panidazole between 1.0 and 2.0 g per day for six days revealed that the best therapeutic results were obtained with the higher dose. This dose was then compared with metronidazole, at the same dose, in a clinical trial in 100 patients with intestinal amoebiasis. Cure rates were 68% and 80% for the two drugs respectively. In 100 cases of vaginal trichomoniasis treated with panidazole at the dose of 1.0 g per day for seven days in half of the patients and for 10 days in the other half, we obtained 50% and 60% cure rates. The results of our studies with both amoebiasis and trichomoniasis were not superior to those obtained with metronidazole and other nitroimidazole derivatives. Side effects were found in 74% of the patients treated for amoebiasis and in 46% of the cases treated for trichomoniasis. No toxic effects were revealed by haematological, biochemical and renal function tests nor by cardiovascular studies.", "Tinidazole 2 g single oral dose was given to 137 females with positive trichomonal cultures. On a random basis the same dose of tinidazole was given to half the sexual partners, and matching placebo to the other half. One to two weeks after treatment 5 females had positive cultures, indicating a primary cure rate of 96.4%. At an average of 2 months after treatment and 6 weeks after resuming sexual activity, 118 females were reexamined; 17 had a positive culture, giving an overall relapse rate of 14.4%. The relapse rate with tinidazole-treated partner was 5.1%, and with placebo-treated partner 23.7% (p equals 0.01). The definitive cure rate after a single dose of tinidazole 2 g was in females with treated partner 91.8% and with untreated partner 72.6%. It is concluded that a single dose of tinidazole is an effective treatment for females with trichomoniasis but to avoid relapse it is necessary to treat the sexual partner too.", "Four antiamoebic drugs currently used in many Kenyan hospitals and health centres were compared for their efficacy on symptomatic luminal amoebiasis in Kiambu, Kilifi, and Machakos hospitals during this study. The drugs were; the brand metronidazole (Flagyl, May & Baker, Kenya Ltd.), the generic metronidazole (Metrozol, Cosmos Ltd., Nairobi, Kenya), the brand tinidazole (Fasigyn, Pfizer Laboratories Ltd.) and the generic tinidazole (Tynazole Laboratory and Allied Equipments, Kenya Ltd). Clinical cure was achieved in all individuals receiving any of the four drugs. Parasitological cure was better for those receiving either Flagyl or Fasigyn, than those receiving the generic counterparts. Both parasitological and clinical cures were achieved in about 50% of all those who received either Flagyl or Fasigyn. It appears that Flagyl and Fasigyn are not as efficacious as previously reported but are still much better than their generic counterparts for the treatment of symptomatic Entamoeba histolytica infections.", "A comparison has been made of the efficiency of a 2-day course of metronidazole (Flagyl) with that of a similar course of nimorazole (Naxogin) in the treatment of trichomoniasis. Of the 105 consecutive patients treated, 72 were finally included in the study (38 on metronidazole and 34 on nimorazole). Follow-up tests indicated an overall cure rate of 84-3 per cent. in those given Flagyl and 85-3 per cent. in those given Naxogin. Consorts were treated in just over 55 per cent. of cases in both groups. An attempt has been made to classify the recurrences as either 'primary' treatment failures or re-infections. Although both drugs were effective in the majority of cases, 'primary' treatment failure appeared to be commoner in the group receiving metronidazole. It is emphasized that the total dose of metronidazole was substantially lower than that recommended by the manufacturers.", "To identify the minimum effective single oral dose of metronidazole for trichomoniasis.\n Women attending an inner-city sexually transmitted disease clinic who had Trichomonas vaginalis vaginitis diagnosed by microscopy were recruited for this randomized, double-blind study. Subjects were given a 0.5-, 1-, 1.5-, or 2-g single oral dose of metronidazole, taken under direct observation. Demographic information, symptoms, and clinical findings were collected from patient interviews, and physical examinations were conducted at the time of enrollment and at the follow-up visit. The primary outcome measure was treatment success at the follow-up visit, established by negative culture and microscopy.\n Three (1.8%) of the 167 women enrolled were excluded because of vomiting after taking metronidazole, and 66 (40%) of the 164 remaining subjects did not return for the follow-up visit. No associations were found between the proportion of subjects lost to follow-up and the characteristics of these subjects across assignment groups. The treatment success ratio was highest in subjects who received the 1.5-g dose (23, 85%), followed by the 2-g (16, 84%), 1-g (18, 62%), and the 0.5-g dose (8, 35%).\n A single 1.5-g dose of metronidazole has efficacy equivalent to a single 2-g dose for the treatment of T vaginalis vaginitis.", "Trichomonas vaginalis is a common sexually transmitted pathogen. In the United States, oral metronidazole is the only officially sanctioned treatment option.\n This study was undertaken to compare the efficacy and safety of 0.75% metronidazole vaginal gel with that of oral metronidazole for the treatment of trichomonal vaginitis.\n Women with trichomoniasis were enrolled in this randomized, open-label pilot study of 0.75% metronidazole vaginal gel twice daily for 7 days compared with 7 days of generic oral metronidazole, 250 mg, three times daily. Patients were seen for follow-up visits 5 to 7 days and 21 to 28 days after the last dose of medication.\n Using culture for test of cure, trichomonal infection was eliminated in all 15 women treated with oral metronidazole and 7 (44%) of 16 women treated with intravaginal metronidazole. Adverse events were similar, except that there were more taste-related adverse events in the oral metronidazole group. Significant reductions in genitourinary symptoms were seen in both the oral and intravaginal groups.\n This study has shown that 0.75% metronidazole vaginal gel is not effective as a single agent for the treatment of trichomoniasis. Future studies may define a role for metronidazole gel for symptomatic relief in patients intolerant of oral medication or as adjunctive treatment with oral metronidazole for the management of patients infected with metronidazole-resistant strains of T. vaginalis.", "This study was undertaken to investigate the efficacy of nonoxynol 9 suppositories in the treatment of vaginal trichomoniasis.\n In this prospective comparison trial 46 women with documented motile trichomonads found on a wet preparation were randomly assigned to one of two treatment arms: (1) a single oral dose of 2 g metronidazole and (2) a single 150-mg nonoxynol 9 suppository placed intravaginally for 3 consecutive nights. Cure was determined by a repeated wet preparation examination. After its first year, the study was terminated because of the poor efficacy of the nonoxynol 9 suppositories.\n Results were available for 33 patients. Three of 17 patients treated with nonoxynol 9 had negative wet preparation results at retest (17.6% cure rate). All 16 patients treated with metronidazole had negative wet preparation results (100% cure rate). All women with nonoxynol 9 failures who were evaluated after treatment with 2 g metronidazole had negative wet preparation results.\n Intravaginal nonoxynol 9 at the tested dose and by the tested method of delivery was not an effective cure for vaginal trichomoniasis.", "Trichomonas vaginalis is a common vaginal pathogen. Oral metronidazole is the drug of choice for the treatment of trichomoniasis. Oral metronidazole, however, may cause unpleasant side effects and is contraindicated during the first trimester of pregnancy. In vitro studies and preliminary clinical data have suggested that intravaginal clotrimazole may be effective against this pathogen.\n To compare the efficacy of clotrimazole vaginal tablets, oral metronidazole, and vaginal suppositories containing sulfanilamide, aminacrine, and allantoin (AVC suppositories) in the treatment of women with symptomatic trichomoniasis.\n In a multicenter, open-label trial conducted in 1982 and 1983, 168 symptomatic women with microscopically evident vaginal trichomoniasis were randomized to receive any of 2 g of metronidazole as a single oral dose, two 100-mg clotrimazole vaginal tablets once a day for 7 days, or vaginal suppositories containing 1.05 g of sulfanilamide, 14 mg of aminacrine hydrochloride, and 140 mg of allantoin (AVC suppositories) twice a day for 7 days. Wet mounts and cultures were repated at 1 to 2 and 4 to 6 weeks after completion of treatment.\n The number of patients who had positive cultures after treatment were 40/45 (88.9%) in the clotrimazole group, 35/43 (81.4%) in the AVC suppository group, and 9/45 (20%) in the metronidazole group (P < 0.001). All treatments were associated with a reduction in reported symptoms. Oral metrohidazole was more effective in reducing symptoms than either of the topical preparations. Adverse events, mostly mild or moderate in severity, were reported by 7 (14.6%) of 48 patients who had received oral metronidazole and 4 (7.8%) of 51 women who used AVC suppositories. There were no adverse events reported by the 50 women who used clotrimazole vaginal tablets.\n Oral metronidazole was more effective in eradicating T. vaginalis than clotrimazole vaginal tablets or AVC vaginal suppositories. All three regimens reduced symptoms; oral metronidazole was more effective in reducing symptoms than either topical preparation.", "This paper reports the results of treating 152 women with carnidazole, a new trichomonacidal drug. They were divided into two groups. The first comprised 91 patients who were treated with 2 g, while the second group comprised 61 patients who were treated with 1-5 g carnidazole in a single oral dose. Defaulter rates were 6-6% for the first group and 13-1% for the second. Of the remaining 85 patients in the first group, 76 (89-5%) were negative at the first follow-up one to three weeks after treatment, three (3-5%) were considered to be treatment failures, and six (7-0%) were considered to be reinfected. Of 53 women treated with 1-5 g, 39 (73-6%) were negative at first follow-up, eight (15-1%) were considered to be treatment failures, and six (11-3%) were considered to be reinfected. The difference between the number of patients cured in both groups is statistically significant. Fourteen patients experienced side-effects, but these were of little significance. Carnidazole given in a single oral dose of 2 g in 16 women did not cause consistent changes in any of the haematological and biochemical parameters studied.", "A new substituted nitroimidazole, nitrimidazine (Naxogin), is compared with the established drug, metronidazole (Flagyl), for the treatment of vaginal trichomoniasis in a randomized double-blind trial. Nitrimidazine cured 39 (68%) out of 57 patients and showed no undesirable effects other than nausea in one patient. Metronidazole cured 51 (89%) out of 57 patients and also caused nausea in one patient; this cure rate corresponds with that previously reported in other trials. In the recommended dosage nitrimidazine is inferior to metronidazole, but is sufficiently effective to be useful in cases of intolerance to metronidazole.", "Since metronidazole is a mutagen in vitro, there is concern about the widespread systemic use of this drug in women with trichomoniasis, particularly those who are pregnant. A randomized, double-blind, placebo-controlled trial compared a single 2-g intravaginal dose of metronidazole cream with a single 2-g oral dose of metronidazole in patients with a culture positive for Trichomonas organisms. Of the 302 preenrollment cultures completed, 94 (31%) were positive. Sixty-one patients were enrolled in the study. Each received either oral placebo and intravaginal metronidazole or intravaginal placebo and oral metronidazole. Follow-up cultures were done on posttreatment day 3-5. Of the 53 evaluatable patients, 14 (50%) of 28 in the intravaginal group and 22 (88%) of 25 in the oral group were microbiologically cured (P = .0037). Single-dose intravaginal metronidazole is inferior to single-dose oral metronidazole and cannot be relied on as an alternative therapy.", "The present study was carried out to evaluate the effectiveness of nitazoxanide compared with that of quinfamide, mebendazole, or both in the treatment of intestinal protozoa and helminthic infections. A total of 677 stool specimens from children aged 2-12 years living in 3 communities of Colima, México, were analyzed in order to detect the presence of cysts, trophozoites, eggs, or larvae of intestinal protozoa or helminths. A total of 275 infected children were enlisted in a double-blind controlled study and randomly assigned to one of 2 treatment groups: Group A, nitazoxanide (200 mg for 3 days) and Group B, quinfamide (100 mg for 1 day), mebendazole (200 mg for 3 days), or both. A posttreatment fecal examination was conducted on Day 14 from treatment initiation. In Group A (n = 143), the parasitosis eradication rate was superior to that of Group B (n = 132). However, there was no significant difference between the 2 groups (P > 0.05).", "This randomized, placebo-controlled trial investigated the tolerance, efficacy, and nutritional benefit of combining chemotherapeutic treatment of intestinal helminths and lymphatic filariasis. Children were infected with Ascaris (30.7%), Trichuris (53.4%), and hookworm (9.7%) with 69.9% having more than one of these parasites. A total of 15.8% of the children had Wuchereria bancrofti microfilariae. Children were randomly assigned treatment with placebo, albendazole (ALB), diethylcarbamazine (DEC), or combined therapy. The combination of DEC/ALB reduced microfilarial density compared with placebo, ALB, or DEC (P < or = 0.03). Albendazole and DEC/ALB reduced the prevalence of Ascaris, Trichuris, and hookworm more than placebo or DEC (P < or = 0.03). Among Trichuris-infected children, those receiving ALB and DEC/ALB demonstrated greater gains in weight compared with placebo (P < or = 0.05). Albendazole and DEC/ALB were equally efficacious in treating intestinal helminths and for children with W. bancrofti microfilaremia, DEC/ALB was more effective than DEC, with no increase in severity of adverse reactions.", "Sixty-six patients with human immunodeficiency virus infection and diarrhoea caused by Cryptosporidium parvum were enrolled in a double-'blind' placebo-controlled study to evaluate the safety and efficacy of nitazoxanide in the treatment of cryptosporidiosis related to the acquired immune deficiency syndrome. Patients were randomly assigned to one of 3 treatment groups and received either 500 mg twice daily of nitazoxanide, 1000 mg twice daily of nitazoxanide, or placebo orally for 14 d; the patients on nitazoxanide then crossed over to placebo while the placebo patients crossed over to nitazoxanide therapy at either the high or low dose depending on their randomization. Three post-treatment faecal examinations were conducted on days 15, 22 and 29 following initiation of treatment: patients were considered 'cured' if none revealed any C. parvum oocysts. Both doses of nitazoxanide produced parasitological cure rates superior to the placebo responses (12/19 [63%, P = 0.016] for patients receiving 1 g/d and 10/15 [67%, P = 0.013] for those receiving 2 g/d). Parasitological cure was correlated with the complete resolution of the diarrhoeal syndrome in 19 of the 22 treated patients who were considered parasitologically cured (86%). Both doses of nitazoxanide were well tolerated by the patients.", "Amebiasis caused by Entamoeba histolytica may be considered the most aggressive parasitic disease affecting human intestine, causing acute amoebic colitis and extra-intestinal diseases of high morbidity and mortality. 5-nitroimidazoles are the drugs of choice. In this multicenter, open and random clinical trial, the efficacy and tolerability of secnidazole suspension in a single oral dose of 1ml/kg was compared with 0.5ml/kg doses of tinidazole suspension given for 2 consecutive days to 303 Entamoeba histolytica-positive children aged 2 to 13. Patients with extra-intestinal complications were excluded from the study. Clinical and parasitological follow-up using the Faust and Kato-Katz method were carried out 7, 14, and 21 days after treatment. Clinical improvement/cure was observed in 93% of the patients in the secnidazole group and 91% in the tinidazole group. Parasitological success was reported for 77% and 63% of the secnidazole and tinidazole patients, respectively, showing a significant statistical difference between the two groups (p=0.007). Both drugs were well tolerated, and the adverse effects reported were mild, consisting mainly of digestive disturbances. This comparative study showed that a single oral dose of 1ml/kg of secnidazole produced a significantly higher parasitological cure rate than 2 doses of tinidazole. Secnidazole is a safe and effective drug for the treatment of uncomplicated intestinal amebiasis.", "A double-blind controlled clinical trial of the new, not yet commercially available drug, carnidazole and tinidazole, was carried out in 77 women with a proven vaginal trichomoniasis. 39 patients and their sexual partners received a single dose of 2 g of carnidazole and the other 38 couples were treated in the same manner with tinidazole. The cure rate was 100% and 95% respectively. The side-effects were higher in the carnidazole group, although they were mild and well-tolerated by the patients and their partners. The history of the disease and its treatment are also briefly reviewed.", "A double blind trial of three oral preparations given in single doses for the treatment of Schistosoma haematobium infection was carried out in schoolchildren; selection was biased towards those who excreted large quantities of eggs. Praziquantel 40 mg/kg was the most effective drug giving a greater than 97% reduction in egg output six months after treatment; combined treatment with niridazole 25 mg/kg and metrifonate 10 mg/kg gave a reduction of greater than 92% and metrifonate 10 mg/kg alone a reduction of greater than 86%. Fewer children continued to have moderate to heavy infections (excretion greater than 124 ova/10 ml urine) six months after treatment with praziquantel (5%) and the combined regimen (7%) than with metrifonate (16%). Though our findings show that praziquantel appears to be the most effective and convenient drug available for individuals with S haematobium infection, the combined regimen is a cheaper alternative for treatment where cost is important and parasitological cure not an essential objective.", "nan", "Benznidazole, a nitroimidazole derivative, has been recommended for the treatment of acute and congenital Trypanosoma cruzi infection (Chagas' disease). We have examined the safety and efficacy of this drug in the treatment of the early chronic phase of T cruzi infection.\n Between 1991 and 1995, we carried out a randomised, double-blind, placebo-controlled trial in a rural area of Brazil with endemic Chagas' disease. 82% of 2434 schoolchildren (aged 7-12 years) identified in a census were screened for antibodies to T cruzi by indirect immunofluorescence, indirect haemagglutination, and ELISA. 130 were positive in all tests and were randomly assigned benznidazole (7.5 mg/kg daily for 60 days by mouth) or placebo. The primary endpoint for efficacy was the disappearance of specific antibodies (negative seroconversion) by the end of 3-year follow-up. The secondary endpoint was the reduction of antibody titres on repeated serological tests. One child moved away from the area just after randomisation and was excluded from the analyses. Insecticidal measures were taken throughout the trial to reduce the risk of reinfection.\n Minor side-effects requiring no specific medication were recorded in a small proportion of individuals. On a chemiluminescent ELISA with purified trypomastigote glycoconjugate, serum from all participants was positive at the beginning of the trial. At the end of follow-up, 37 (58%) of the 64 benznidazole-treated participants and 3 (5%) of those who received placebo were negative for T cruzi antibodies. The efficacy of benznidazole treatment estimated by intention to treat was 55.8% (95% CI 40.8-67.0). At the end of follow-up, children who received benznidazole had five-fold lower geometric mean titres by indirect immunofluorescence than placebo-treated children (196[147-256] vs 1068[809-1408], p < 0.00001).\n The trial showed that a 60-day course of benznidazole treatment of early chronic T cruzi infection was safe and 55.8% effective in producing negative seroconversion of specific antibodies. The results are very encouraging and justify the recommendation of treatment for seropositive children as public health policy.", "417 patients suffering from intestinal amoebiasis were randomly allocated to 6 different treatment groups in a controlled study in 3 District Hospitals in Kenya. The patients received either aminosidine (A), etophamide (E), nimorazole (N), or the combinations NA, NE, EA. Treatment in all cases was given twice daily for 5 days. Before and after treatment, rectosigmoidoscopy was done in each patient, and stool examination with characterization of invasive (IF) and non invasive (NIF) forms of amoeba was done daily throughout treatment, and on Days 15, 30 and 60 of follow-up. Clinical cure was good after all the treatments, varying from 90 to 100%; parasitological cure at the end of treatment was 100% in the NA and EA treatments groups, and 98% in A group. The incidence of relapses was nil in the EA group, followed by 3% in NA and 6% in A groups. Anatomical cure (healing of ulcers) was 97.8% in the NA group, 95.5% in the N group and 88.5% in the A group. Drug tolerance was excellent or good after all the treatments, except that the EA combination produced diarrhoea in 76.5% of patients. Overall analysis of the findings, including tolerance of the various treatments, showed that aminosidine either alone or in combination with nimorazole gave the best results. Ulcers seen on rectosigmoidoscopy were more common in patients excreting invasive forms of amoebae in their stools.", "A randomized controlled trial in KwaZulu-Natal (South Africa) of 428 primary-school pupils (stratified into 6 groups by age, sex and intervention) measured the effect of different anthelmintic treatments and iron supplementation regimens provided twice at 6-monthly intervals for 1 year (1996/97). Half the pupils received iron supplementation (ferrous fumarate 200 mg weekly for 10 weeks). Pupils received 2 anthelmintic regimens, either (i) albendazole 400 mg plus praziquantel 40 mg/kg or (ii) albendazole 400 mg on 3 consecutive days plus praziquantel 40 mg/kg or (iii) placebo. Baseline prevalences of Ascaris 55.9%, Trichuris 83.6%, hookworm spp. 59.4%, were reduced after 12 months for single-dose albendazole treatment to Ascaris 17.4% (P < 0.005), Trichuris 61.5% (NS), hookworm spp. 0% (P < 0.005), and for triple-dose albendazole treatment to Ascaris 14.8% (P < 0.005), Trichuris 25.0% (P < 0.01), hookworm 0% (P < 0.005). Schistosoma haematobium 43.4% was reduced among treated groups to 8.3% (P < 0.005). There were no significant changes in the anthropometry of the different treatment groups at either 6 or 12 months post treatment. Twelve months after treatment there was a significant increase in haemoglobin levels (P = 0.02) among pupils receiving triple-dose albendazole, praziquantel and ferrous fumarate; pupils receiving no anthelmintic treatment showed a significant decrease as did pupils who received triple-dose albendazole and praziquantel but no iron. Regular 6-monthly anthelmintic treatment significantly reduced the prevalence of Ascaris, hookworm spp. and S. haematobium infections (P < 0.05). Triple-dose treatment for Trichuris was significantly more effective than a single dose of albendazole 400 mg (P = 0.002). In areas with schistosomiasis, hookworm infection and high prevalence of Trichuris infection, combination treatment with praziquantel, triple-dose albendazole, plus iron supplementation, is likely to improve pupils' health and haemoglobin levels." ]	Parasitological cure can be achieved by single oral dose of nitroimidazole. Further research should focus on developing effective partner treatment strategies to prevent reinfections and reduce trichomoniasis prevalence.
CD005230	[ "1350338", "6227304", "769630", "17689192", "1532760", "10208073", "12825916", "15726029", "17459741", "16627548", "3524727", "16719602" ]	[ "Hypnosis or cognitive behavioral training for the reduction of pain and nausea during cancer treatment: a controlled clinical trial.", "Hypnosis compared to relaxation in the outpatient management of chronic low back pain.", "Acupuncture for chronic shoulder pain. An experimental study with attention to the role of placebo and hypnotic susceptibility.", "Hypnosis in the management of persistent idiopathic orofacial pain--clinical and psychosocial findings.", "Randomised clinical trial of manipulative therapy and physiotherapy for persistent back and neck complaints: results of one year follow up.", "Clinical hypnosis versus cognitive behavioral training for pain management with pediatric cancer patients undergoing bone marrow aspirations.", "Clinical hypnosis in the alleviation of procedure-related pain in pediatric oncology patients.", "Long-term follow-up of a randomized clinical trial assessing the efficacy of medication, acupuncture, and spinal manipulation for chronic mechanical spinal pain syndromes.", "A randomised controlled study of reflexology for the management of chronic low back pain.", "Treatment of non-cardiac chest pain: a controlled trial of hypnotherapy.", "A controlled study of acupuncture in neck pain.", "Randomized clinical trial of local anesthetic versus a combination of local anesthetic with self-hypnosis in the management of pediatric procedure-related pain." ]	[ "Few controlled clinical trials have tested the efficacy of psychological techniques for reducing cancer pain or post-chemotherapy nausea and emesis. In this study, 67 bone marrow transplant patients with hematological malignancies were randomly assigned to one of four groups prior to beginning transplantation conditioning: (1) hypnosis training (HYP); (2) cognitive behavioral coping skills training (CB); (3) therapist contact control (TC); or (4) treatment as usual (TAU; no treatment control). Patients completed measures of physical functioning (Sickness Impact Profile; SIP) and psychological functioning (Brief Symptom Inventory; BSI), which were used as covariates in the analyses. Biodemographic variables included gender, age and a risk variable based on diagnosis and number of remissions or relapses. Patients in the HYP, CB and TC groups met with a clinical psychologist for two pre-transplant training sessions and ten in-hospital \"booster\" sessions during the course of transplantation. Forty-five patients completed the study and provided all covariate data, and 80% of the time series outcome data. Analyses of the principal study variables indicated that hypnosis was effective in reducing reported oral pain for patients undergoing marrow transplantation. Risk, SIP, and BSI pre-transplant were found to be effective predictors of inpatient physical symptoms. Nausea, emesis and opioid use did not differ significantly between the treatment groups. The cognitive behavioral intervention, as applied in this study, was not effective in reducing the symptoms measured.", "Chronic low back pain (CLBP) presents a problem of massive dimensions. While inpatient approaches have been evaluated, outpatient treatment programs have received relatively little examination. Hypnosis and relaxation are two powerful techniques amenable to outpatient use. Seventeen outpatient subjects suffering from CLBP were assigned to either Self-Hypnosis (n = 9) or Relaxation (n = 8) treatments. Following pretreatment assessment, all subjects attended a single placebo session in which they received minimal EMG feedback. One week later the subjects began eight individual weekly treatment sessions. Subjects were assessed on a number of dependent variables at pretreatment, following the placebo phase, one week after the completion of treatment, and three months after treatment ended. Subjects in both groups showed significant decrements in such measures as average pain rating, pain as measured by derivations from the McGill Pain Questionnaire, level of depression, and length of pain analog line. Self-Hypnosis subjects reported less time to sleep onset, and physicians rated their use of medication as less problematic after treatment. While both treatments were effective, neither proved superior to the other. The placebo treatment produced nonsignificant improvement.", "One half of 42 subjects treated for painful shoulders received classic acupuncture, and one half received a placebo in which the needles did not penetrate the skin. Half of each of these groups was treated in a positive setting to encourage the subject, and half in a negative setting designed to keep encouragement at a minimum. All patients were independently rated for susceptibility to hypnosis. Although range of motion did not improve, the majority of patients reported significant improvement in shoulder discomfort to a blind evaluator after treatment; placebo and acupuncture groups did not differ in this respect, however. The positive and negative settings did not affect treatment outcome. In all groups, those who were not rated as highly susceptible to hypnosis tended to fail to achieve the highest levels of relief, but such differences were not statistically significant.", "This controlled and patient blinded study tested the effect of hypnosis on persistent idiopathic orofacial pain (PIOP) in terms of clinical and psychosocial findings. Forty-one PIOP were randomized to active hypnotic intervention or simple relaxation as control for five individual 1-h sessions. Primary outcome was average pain intensity scored three times daily in a pain diary using visual analogue scale (VAS). Secondary outcome measures were pain quality assessed by McGill pain questionnaire (MPQ), psychological symptoms assessed by symptom check list (SCL), quality of life assessed by SF36, sleep quality, and consumption of analgesic. Data were compared between groups before and after treatment using ANOVA models and paired t-tests. The change in VAS pain scores from baseline to the last treatment (t4) was (33.1+/-7.4%) in the hypnosis group and (3.2+/-5.4%) in the control group (P<0.03). In the hypnosis group, highly hypnotic susceptible patients had greater decreases in VAS pain scores (55.0+/-12.3%) when compared to less susceptible patients (17.9+/-6.7%) (P<0.02). After the last treatment there were also statistically significant differences between groups in perceived pain area (MPQ) and the use of weak analgesics (P<0.03). There were no statistically significant changes in SCL or SF36 scores from baseline to t4. In conclusion, hypnosis seems to offer clinically relevant pain relief in PIOP, particularly in highly susceptible patients. However, stress coping skills and unresolved psychological problems need to be included in a comprehensive management plan in order also to address psychological symptoms and quality of life.", "To compare the effectiveness of manipulative therapy, physiotherapy, treatment by the general practitioner, and placebo therapy in patients with persistent non-specific back and neck complaints.\n Randomised clinical trial.\n Primary health care in the Netherlands.\n 256 patients with non-specific back and neck complaints of at least six weeks' duration who had not received physiotherapy or manipulative therapy in the past two years.\n At the discretion of the manipulative therapists, physiotherapists, and general practitioners. Physiotherapy consisted of exercises, massage, and physical therapy (heat, electrotherapy, ultrasound, shortwave diathermy). Manipulative therapy consisted of manipulation and mobilisation of the spine. Treatment by general practitioners consisted of drugs (for example, analgesics), advice about posture, home exercises, and (bed)rest. Placebo treatment consisted of detuned shortwave diathermy (10 minutes) and detuned ultrasound (10 minutes).\n Changes in severity of the main complaint and limitation of physical functioning measured on 10 point scales by a blinded research assistant and global perceived effect measured on a 6 point scale by the patients.\n Many patients in the general practitioner and placebo groups received other treatment during follow up. Improvement in the main complaint was larger with manipulative therapy (4.5) than with physiotherapy (3.8) after 12 months' follow up (difference 0.9; 95% confidence interval 0.1 to 1.7). Manipulative therapy also gave larger improvements in physical functioning (difference 0.6; -0.1 to 1.3). The global perceived effect after six and 12 months' follow up was similar for both treatments.\n Manipulative therapy and physiotherapy are better than general practitioner and placebo treatment. Furthermore, manipulative therapy is slightly better than physiotherapy after 12 months.", "A randomized controlled trial was conducted to compare the efficacy of clinical hypnosis versus cognitive behavioral (CB) coping skills training in alleviating the pain and distress of 30 pediatric cancer patients (age 5 to 15 years) undergoing bone marrow aspirations. Patients were randomized to one of three groups: hypnosis, a package of CB coping skills, and no intervention. Patients who received either hypnosis or CB reported less pain and pain-related anxiety than did control patients and less pain and anxiety than at their own baseline. Hypnosis and CB were similarly effective in the relief of pain. Results also indicated that children reported more anxiety and exhibited more behavioral distress in the CB group than in the hypnosis group. It is concluded that hypnosis and CB coping skills are effective in preparing pediatric oncology patients for bone marrow aspiration.", "This prospective controlled trial investigated the efficacy of a manual-based clinical hypnosis intervention in alleviating pain in 80 pediatric cancer patients (6-16 years of age) undergoing regular lumbar punctures. Patients were randomly assigned to 1 of 4 groups: direct hypnosis with standard medical treatment, indirect hypnosis with standard medical treatment, attention control with standard medical treatment, and standard medical treatment alone. Patients in the hypnosis groups reported less pain and anxiety and were rated as demonstrating less behavioral distress than those in the control groups. Direct and indirect suggestions were equally effective, and the level of hypnotizability was significantly associated with treatment benefit in the hypnosis groups. Therapeutic benefit degraded when patients were switched to self-hypnosis. The study indicates that hypnosis is effective in preparing pediatric oncology patients for lumbar puncture, but the presence of the therapist may be critical.", "To assess the long-term benefits of medication, needle acupuncture, and spinal manipulation as exclusive and standardized treatment regimens in patients with chronic (>13 weeks) spinal pain syndromes.\n Extended follow-up (>1 year) of a randomized clinical trial was conducted at the multidisciplinary spinal pain unit of Townsville's General Hospital between February 1999 and October 2001.\n Of the 115 patients originally randomized, 69 had exclusively been treated with the randomly allocated treatment during the 9-week treatment period (results at 9 weeks were reported earlier). These patients were followed up and assessed again 1 year after inception into the study reapplying the same instruments (ie, Oswestry Back Pain Index, Neck Disability Index, Short-Form-36, and Visual Analogue Scales). Questionnaires were obtained from 62 patients reflecting a retention proportion of 90%. The main analysis was restricted to 40 patients who had received exclusively the randomly allocated treatment for the whole observation period since randomization.\n Comparisons of initial and extended follow-up questionnaires to assess absolute efficacy showed that only the application of spinal manipulation revealed broad-based long-term benefit: 5 of the 7 main outcome measures showed significant improvements compared with only 1 item in each of the acupuncture and the medication groups.\n In patients with chronic spinal pain syndromes, spinal manipulation, if not contraindicated, may be the only treatment modality of the assessed regimens that provides broad and significant long-term benefit.", "The use of complementary and alternative medicine (CAM) for the management of chronic low back pain (CLBP) continues to rise. However, questions regarding the efficacy of many CAM therapies for CLBP remain unresolved. The present study investigated the effectiveness of reflexology for CLBP. A pragmatic randomised controlled trial was conducted. N=243 patients were randomised to one of three groups: reflexology, relaxation, or non-intervention (usual care). All completed a questionnaire booklet before and after the treatment phase, and at six months follow up. This measured their general health status, pain, functioning, coping strategies and mood. After adjusting for pre-treatment scores repeated measures ANCOVA found no significant differences between the groups pre and post treatment on the primary outcome measures of pain and functioning. There was a main effect of pain reduction, irrespective of group. Trends in the data illustrated the pain reduction was greatest in the reflexology group. Thus, the current study does not indicate that adding reflexology to usual GP care for the management of CLBP is any more effective than usual GP care alone.", "Non-cardiac chest pain (NCCP) is an extremely debilitating condition of uncertain origin which is difficult to treat and consequently has a high psychological morbidity. Hypnotherapy has been shown to be effective in related conditions such as irritable bowel syndrome where its beneficial effects are long lasting.\n This study aimed to assess the efficacy of hypnotherapy in a selected group of patients with angina-like chest pain in whom coronary angiography was normal and oesophageal reflux was not contributory.\n Twenty eight patients fulfilling the entry criteria were randomised to receive, after a four week baseline period, either 12 sessions of hypnotherapy or supportive therapy plus placebo medication over a 17 week period. The primary outcome measure was global assessment of chest pain improvement. Secondary variables were a change in scores for quality of life, pain severity, pain frequency, anxiety, and depression, as well as any alteration in the use of medication.\n Twelve of 15 (80%) hypnotherapy patients compared with three of 13 (23%) controls experienced a global improvement in pain (p = 0.008) which was associated with a significantly greater reduction in pain intensity (p = 0.046) although not frequency. Hypnotherapy also resulted in a significantly greater improvement in overall well being in addition to a reduction in medication usage. There were no differences favouring hypnotherapy with respect to anxiety or depression scores.\n Hypnotherapy appears to have use in this highly selected group of NCCP patients and warrants further assessment in the broader context of this disorder.", "Twenty-five out-patients with chronic neck pain participated in a prospective, randomized trial of acupuncture versus placebo transcutaneous nerve stimulation. A single-blind, non-cross-over design incorporated several outcome measures in an attempt to determine any particular facet of pain that responded to acupuncture. No significant difference between the two treatments was found either post-treatment or at follow-up. Whilst the small population studied limits the conclusions that may be drawn, these findings suggest that acupuncture may have no greater effect than that of a powerful placebo.", "A prospective controlled trial was conducted to compare the efficacy of an analgesic cream (eutectic mixture of local anesthetics, or EMLA) with a combination of EMLA with hypnosis in the relief of lumbar puncture-induced pain and anxiety in 45 pediatric cancer patients (age 6-16 years). The study also explored whether young patients can be taught and can use hypnosis independently as well as whether the therapeutic benefit depends on hypnotizability. Patients were randomized to 1 of 3 groups: local anesthetic, local anesthetic plus hypnosis, and local anesthetic plus attention. Results confirmed that patients in the local anesthetic plus hypnosis group reported less anticipatory anxiety and less procedure-related pain and anxiety and that they were rated as demonstrating less behavioral distress during the procedure. The level of hypnotizability was significantly associated with the magnitude of treatment benefit, and this benefit was maintained when patients used hypnosis independently.\n 2006 APA, all rights reserved" ]	There was weak evidence to support the use of hypnosis, psychotherapy, acupuncture, chiropractic and medicinal herbs but it was provided in each case by single small trials, some of dubious methodological rigour. Robust randomised trials are required with efficacy, cost-effectiveness and adverse effects clearly reported.
CD003887	[ "2681348", "11994337", "8359791" ]	[ "Acceleration of growth in Turner syndrome patients treated with growth hormone: summary of three-year results.", "Growth hormone and low dose estrogen in Turner syndrome: results of a United States multi-center trial to near-final height.", "Psychological aspects of the Canadian randomized controlled trial of human growth hormone and low-dose ethinyl oestradiol in children with Turner syndrome. The Canadian Growth Hormone Advisory Group." ]	[ "In 1983, a multicenter, collaborative, prospective study was begun to investigate the efficacy of human growth hormone (hGH), alone and in combination with oxandrolone, in girls with Turner syndrome. While subjects in the control group grew 3.8 cm/yr (-0.1 SD for untreated Turner patients), subjects receiving hGH alone grew 6.6, 5.4 and 4.6 cm/yr in years 1-3, respectively (+3.1, +2.0, +1.4 SD). Subjects in the combination therapy group grew 9.8, 7.4 and 6.1 cm/yr (+6.6, +4.3, +3.0 SD). Turner subjects in both treatment groups showed increased in Bayley-Pinneau predicted adult heights and in Turner projected adult heights.", "A cardinal clinical feature of Turner syndrome (TS) is linear growth failure resulting in extreme short stature: the median adult height of untreated women with TS is 143 cm, 20 cm (8 in.) below that of the general female population. In the largest multicenter, randomized, long-term, dose-response study conducted in the United States, 232 subjects with TS received either 0.27 or 0.36 mg/kg.wk of recombinant human GH with either low dose ethinyl E2 or oral placebo. The study was placebo-controlled for both GH and estrogen for the first 18 months and remained placebo-controlled for estrogen for its duration. The near-final height of the 99 subjects whose bone age was at least 14 yr was 148.7 +/- 6.1 cm after 5.5 +/- 1.8 yr of GH started at a mean age of 10.9 +/- 2.3 yr; this represents an average increase of 1.3 +/- 0.6 SD scores from baseline (TS standard). Height was greater than 152.4 cm (60 in.) in 29% of subjects compared with the expected 5% of untreated patients. Mean near-final heights of subjects who received the lower GH dose, with or without estrogen, were 145.1 +/- 5.4 and 149.9 +/- 6.0 cm, respectively; those who received the higher GH dose with or without estrogen achieved mean near-final heights of 149.1 +/- 6.0 and 150.4 +/- 6.0 cm, respectively. Factors that most impacted outcome were younger age, lower bone age/chronological age ratio, lower body weight, and greater height SD score at study entry. This study demonstrates significant GH-induced improvement in height SD score, with correction of height to within the normal channels for a significant number of patients, and provides evidence of a GH dose-response effect. These data also indicate that early administration of estrogen, even at relatively low doses, does not improve gain in near-final height in patients with TS.", "Preliminary results are presented after 2 years of the Canadian long-term multicentre study on the impact of hormone therapy on the final height, sexual development and psychological status of girls with Turner syndrome. Girls entering the study were randomized either to be treated with recombinant human growth hormone or to act as controls. Both groups received oestrogen replacement therapy in the same dose and format at the age of 13 years. However, for the purposes of the psychological study at this time, children receiving oestrogen were excluded from analysis. Girls treated with GH for a period of 2 years showed a significant increase in growth rate, which declined with continued treatment, while the growth rate in the control group remained constant throughout. There was a correlation between the higher growth rate and the girls' perceptions of themselves as more intelligent, more attractive, having more friends, greater popularity and experiencing less teasing than the untreated group. Growth rate was not correlated with family or school functioning." ]	Recombinant human growth hormone (hGH) doses between 0.3 to 0.375 mg/kg/wk increase short-term growth in girls with Turner syndrome by approximately three (two) cm in the first (second) year of treatment. Treatment in one trial increased final height by approximately six cm over an untreated control group. Despite this increase, the final height of treated women was still outside the normal range. Additional trials of the effects of hGH carried out with control groups until final height is achieved would allow better informed decisions about whether the benefits of hGH treatment outweigh the requirement of treatment over several years at considerable cost.
CD004069	[ "16616557", "3755517" ]	[ "Vitamin C and vitamin E in pregnant women at risk for pre-eclampsia (VIP trial): randomised placebo-controlled trial.", "Vitamin D supplementation in pregnancy: a controlled trial of two methods." ]	[ "Oxidative stress could play a part in pre-eclampsia, and there is some evidence to suggest that vitamin C and vitamin E supplements could reduce the risk of the disorder. Our aim was to investigate the potential benefit of these antioxidants in a cohort of women with a range of clinical risk factors.\n We did a randomised, placebo-controlled trial to which we enrolled 2410 women identified as at increased risk of pre-eclampsia from 25 hospitals. We assigned the women 1000 mg vitamin C and 400 IU vitamin E (RRR alpha tocopherol; n=1199) or matched placebo (n=1205) daily from the second trimester of pregnancy until delivery. Our primary endpoint was pre-eclampsia, and our main secondary endpoints were low birthweight (<2.5 kg) and small size for gestational age (<5th customised birthweight centile). Analyses were by intention to treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN 62368611 .\n Of 2404 patients treated, we analysed 2395 (99.6%). The incidence of pre-eclampsia was similar in treatment placebo groups (15% [n=181] vs 16% [n=187], RR 0.97 [95% CI 0.80-1.17]). More low birthweight babies were born to women who took antioxidants than to controls (28% [n=387] vs 24% [n=335], 1.15 [1.02-1.30]), but small size for gestational age did not differ between groups (21% [n=294] vs 19% [n=259], 1.12 [0.96-1.31]).\n Concomitant supplementation with vitamin C and vitamin E does not prevent pre-eclampsia in women at risk, but does increase the rate of babies born with a low birthweight. As such, use of these high-dose antioxidants is not justified in pregnancy.", "A randomized study was conducted to evaluate the effects of single-dose and daily vitamin D supplementation in pregnant women during the last trimester of a winter pregnancy in the Northwest of France. The women were divided into three randomized groups: one (N = 21) was given a vitamin D2 supplement of 1000 IU/day during the last three months of pregnancy, one (N = 27) was given a single oral dose of 5 mg at the seventh month of pregnancy, and one (N = 29) acted as a control. Venous plasma samples were obtained at delivery from the women and from cord blood, and levels of calcium, 25-OHD, and 1,25(OH)2D were determined. No significant difference in plasma calcium concentration was found among the three groups, but within each group plasma calcium concentrations were higher in the cord samples than in the respective maternal samples. The levels of the two metabolites measured were consistently lower in the cord samples than in the respective maternal samples. Cord 25-OHD concentrations correlated with those of maternal plasma. No significant modification of maternal calciuria or of the birth weight of term infants was observed. 25-OHD concentrations were greater in maternal and cord plasma from treated mothers, but only a slight difference was observed between the supplemented groups. 1,25(OH)2D concentrations were not significantly different in the three groups. A single 5-mg dose of vitamin D given orally at the seventh month of pregnancy provides effective prophylaxis in the authors' region." ]	The data are too few to say if vitamin E supplementation either alone or in combination with other supplements is beneficial during pregnancy. [Note: The 24 citations in the awaiting classification section of the review may alter the conclusions of the review once assessed.]
CD008191	[ "17846102", "11074227", "11087767", "9169246", "12633121", "16968574", "15178953" ]	[ "A double-blind comparison of citalopram and risperidone for the treatment of behavioral and psychotic symptoms associated with dementia.", "Placebo-controlled comparison of the selective serotonin reuptake inhibitors citalopram and sertraline.", "Treatment of agitation in AD: a randomized, placebo-controlled clinical trial.", "A double-blind comparison of trazodone and haloperidol for treatment of agitation in patients with dementia.", "A randomized placebo-controlled trial of risperidone for the treatment of aggression, agitation, and psychosis of dementia.", "A comparative, randomized, double-blind study of trazodone prolonged-release and sertraline in the treatment of major depressive disorder.", "Frontotemporal dementia: a randomised, controlled trial with trazodone." ]	[ "To compare citalopram and risperidone for the treatment of psychotic symptoms and agitation associated with dementia, with a priori hypotheses that risperidone would be more efficacious for psychosis and citalopram for agitation.\n A 12-week randomized, controlled trial in nondepressed patients with dementia hospitalized because of behavioral symptoms (N = 103) was conducted at the University of Pittsburgh Medical Center. Participants were consecutively recruited on an inpatient unit if they had at least one moderate to severe target symptom (aggression, agitation, hostility, suspiciousness, hallucinations, or delusions). Once they improved sufficiently, they were discharged to nursing homes, personal care homes, or residential homes for continued treatment. Planned pre-post and mixed model analyses of the main outcome measures of Neurobehavioral Rating Scale and Side Effect Rating Scale at baseline and at weekly/biweekly intervals were conducted.\n Completion rates did not differ for citalopram and risperidone (overall completion rate: 44%). Agitation symptoms (aggression, agitation, or hostility) and psychotic symptoms (suspiciousness, hallucinations, or delusions) decreased in both treatment groups but the improvement did not differ significantly between the two groups. There was a significant increase in side effect burden with risperidone but not with citalopram such that the two groups differed significantly.\n No statistical difference was found in the efficacy of citalopram and risperidone for the treatment of either agitation or psychotic symptoms in patients with dementia. These findings need to be replicated before citalopram or other serotonergic antidepressants can be recommended as alternatives to antipsychotics for the treatment of agitation or psychotic symptoms associated with dementia.", "Previous comparative studies of the selective serotonin reuptake inhibitors (SSRIs) have rarely included a placebo control group and have rarely demonstrated significant between-group differences. The study reported on here was a placebo-controlled comparison of the antidepressant effects of two SSRIs, citalopram and sertraline.\n Three hundred twenty-three patients with DSM-IV-defined major depressive disorder were randomized to 24 weeks of double-blind treatment with citalopram (20-60 mg/day), sertraline (50-150 mg/day), or a placebo. The primary efficacy measure was the Hamilton Depression Rating Scale (HAMD) and the primary statistical analysis was an analysis of variance comparing the change from baseline to the last observation carried forward in each treatment group.\n Both citalopram and sertraline produced significantly greater improvement than placebo on the HAMD, the Montgomery-Asberg Depression Rating Scale, and the Clinical Global Impression Scale. Significant improvement was observed at earlier timepoints in the citalopram group than the sertraline group; however, sertraline treatment was associated with increased gastrointestinal side effects and a tendency toward early discontinuation, and analyses that excluded early dropouts revealed similar acute efficacy for the two active treatments. The Hamilton Anxiety Scale demonstrated a significant anxiolytic effect of citalopram, but not sertraline, relative to placebo.\n This study confirms the antidepressant efficacy of two SSRIs, citalopram and sertraline. It is hypothesized that the more consistent evidence of antidepressant activity that was observed early in treatment in the citalopram group was related to more pronounced antianxiety effects and better tolerability upon initiation of therapy.", "Treatment of agitation is a crucial problem in the care of patients with AD. Although antipsychotic and antidepressant medications and behavior management techniques (BMT) have each been used to treat agitation, clinical trials of these treatments have been characterized by small sample sizes and uncontrolled treatment designs.\n To compare haloperidol, trazodone, and BMT with placebo in the treatment of agitation in AD outpatients.\n A total of 149 patients with AD and their caregivers participated in a randomized, placebo-controlled, multicenter trial. Blind assessment was conducted at baseline and after 16 weeks of treatment. The three active treatments were haloperidol, trazodone, and BMT. The Alzheimer's Disease Cooperative Study Clinical Global Impression of Change was the primary outcome measure. Secondary outcomes included patient agitation, cognition, and function, and caregiver burden.\n Thirty-four percent of subjects improved relative to baseline. No significant differences on outcome were obtained between haloperidol (mean dose, 1.8 mg/d), trazodone (mean dose, 200 mg/d), BMT, or placebo. Significantly fewer adverse events of bradykinesia and parkinsonian gait were evident in the BMT arm. No other significant difference in adverse events was seen. Symptoms did not respond differentially to the different treatments.\n Comparable modest reductions in agitation occurred in patients receiving haloperidol, trazodone, BMT, and placebo. More effective pharmacologic, nonpharmacologic, and combination treatments are needed.", "The authors compared the efficacy and side effects of trazodone and haloperidol for treating agitated behaviors associated with dementia. Twenty-eight elderly patients with dementia and agitated behaviors were randomly assigned to double-blind treatment with either trazodone (50-250 mg/day) or haloperidol (1-5 mg/day) for 9 weeks. There was no significant difference in improvement between the medication groups. Adverse effects, however, were more common in the group treated with haloperidol. Improvement in individual areas suggested that repetitive, verbally aggressive, and oppositional behaviors responded preferentially to trazodone, whereas symptoms of excessive motor activity and unwarranted accusations responded preferentially to haloperidol. These results indicate that moderate doses of trazodone and haloperidol are equally effective for treatment of overall agitated behaviors in patients with dementia, but specific symptoms may respond preferentially to a particular agent.", "This randomized, double-blind, placebo-controlled trial examined the efficacy and safety of risperidone in the treatment of aggression, agitation, and psychosis in elderly nursing-home patients with dementia.\n Elderly patients with a DSM-IV diagnosis of dementia of the Alzheimer's type, vascular dementia, or a combination of the 2 (i.e., mixed dementia) and significant aggressive behaviors were randomized to receive, for a period of 12 weeks, a flexible dose of either placebo or risperidone solution up to a maximum of 2 mg/day. Outcome measures were the Cohen-Mansfield Agitation Inventory (CMAI), the Behavioral Pathology in Alzheimer's Disease (BEHAVE-AD) rating scale, and the Clinical Global Impression of Severity (CGI-S) and of Change (CGI-C) scales.\n A total of 345 patients were randomized to treatment with risperidone or placebo, and 337 patients received at least one dose of study drug. The trial was completed by 67% of patients in the placebo group and 73% of patients in the risperidone group. The mean +/- SE dose of risperidone was 0.95 +/- 0.03 mg/day. The primary endpoint of the study, the difference from baseline to endpoint in CMAI total aggression score, showed a significant reduction in aggressive behavior for risperidone versus placebo (p <.001). A similar improvement was also seen for the CMAI total non-aggression subscale (p <.002) and for the BEHAVE-AD total (p <.001) and psychotic symptoms subscale (p =.004). At endpoint, the CGI-S and the CGI-C scores indicated a significantly greater improvement with risperidone compared with placebo (p <.001). Overall, 94% and 92% of the risperidone and placebo groups, respectively, reported at least 1 adverse event. Somnolence and urinary tract infection were more common with risperidone treatment, whereas agitation was more common with placebo. There was no significant difference in the number of patients who reported extrapyramidal symptoms between the risperidone (23%) and placebo (16%) groups.\n Treatment with low-dose (mean = 0.95 mg/day) risperidone resulted in significant improvement in aggression, agitation, and psychosis associated with dementia.", "To evaluate the efficacy and safety of trazodone prolonged-release compared with sertraline in the treatment of patients with major depression.\n A total of 122 patients aged 19-64 years were enrolled in this multicenter, double-blind, double-dummy, randomized, comparator-controlled study. Patients received 7 days of single-blind placebo treatment followed by 6 weeks of double-blind treatment with trazodone prolonged-release 150-450 mg/day (n = 62) or sertraline 50-100 mg/day (n = 60).\n Efficacy was evaluated by mean changes from baseline in the Hamilton Depression Rating scale (HAM-D), Montgomery Asberg Depression Rating Scale, Hamilton Anxiety Rating scale, and the Clinical Global Impression-Global Improvement/Severity scores; and by the rates of patients responding to treatment and considered to be in remission. Time to onset of efficacy and safety were assessed.\n Trazodone and sertraline were equally effective in reducing depressive symptoms and promoting remission, and had similar onset times. In the Intent-to-Treat population, there were no significant differences in favor of trazodone at study endpoint in all efficacy measures, while a statistically significant difference was detected in the Per-Protocol population on HAM-D and in the percentage of responders. Analysis of HAM-D factors (anxiety/somatization, cognitive disturbance, retardation, and sleep disturbance) indicated that sleep disturbances were significantly less evident for patients taking trazodone at study endpoint. Adverse drug reactions, mostly of mild intensity, were reported in 42% of trazodone-treated patients (mainly of the nervous system) and 43% of sertraline-treated patients (mainly gastrointestinal). One event was considered to be serious: a patient treated with trazodone 450 mg/day showed moderate anxiety/tremor/insomnia and was hospitalized. Treatment was discontinued; the patient made a full recovery.\n This study showed that after 6 weeks, trazodone and sertraline were not different in reducing symptoms of depression and in producing disease remission. Tolerability profiles reflected the differing pharmacological properties of these antidepressants. Trazodone may be a therapeutic option in the treatment of patients with major depression showing prevalent sleep disturbances.", "Behavioural troubles due to frontotemporal dementia (FTD) are difficult to treat. The serotonergic system is associated with frontal lobes, the degeneration of which contributes to FTD. Trazodone increases the extracellular 5-HT levels in the frontal cortex. In a randomised, double-blind, placebo-controlled cross-over study, we investigated the effect of trazodone. There was a significant decrease in the Neuropsychiatry Inventory (NPI) total score with trazodone (p = 0.028) in the 26 evaluable patients. A decrease of more than 50% in the NPI score was observed in 10 patients with trazodone. This improvement was mainly based on the improvement of 4 items of the scale (irritability, agitation, depressive symptoms and eating disorders). The Mini-Mental State Examination was not modified and trazodone was well tolerated. Results of this first placebo-controlled trial suggest that trazodone is an effective treatment for the behavioural symptoms of FTD.\n Copyright 2004 S. Karger AG, Basel" ]	Currently there are relatively few studies of antidepressants for the treatment of agitation and psychosis in dementia. The SSRIs sertraline and citalopram were associated with a reduction in symptoms of agitation when compared to placebo in two studies. Both SSRIs and trazodone appear to be tolerated reasonably well when compared to placebo, typical antipsychotics and atypical antipsychotics. Future studies involving more subjects are required to determine if SSRIs, trazodone, or other antidepressants are safe and effective treatments for agitation and psychosis in dementia.
CD002275	[ "11843764", "9189040", "21562253" ]	[ "Immunoglobulin treatment versus plasma exchange in patients with chronic moderate to severe myasthenia gravis.", "Clinical trial of plasma exchange and high-dose intravenous immunoglobulin in myasthenia gravis. Myasthenia Gravis Clinical Study Group.", "Comparison of IVIg and PLEX in patients with myasthenia gravis." ]	[ "The purpose of this study was to compare the efficacy of high-dose intravenous immunoglobulin (IVIG) treatment with plasma exchange in patients suffering from moderate to severe myasthenia gravis (MG) in a stable phase. There are no controlled studies comparing IVIG with plasma exchange in patients who despite immunosuppressive treatment have persistent incapacitating MG symptoms. This was a controlled crossover study. Twelve patients with generalized moderate to severe MG on immunosuppressive treatment for at least 12 months were included. The patients were evaluated clinically using a quantified MG clinical score (QMGS) before and at follow-up visits after each treatment. One week after the treatments, the patients who received plasma exchange treatment showed a significant improvement in QMGS compared to baseline but although some improvement was seen after IVIG this did not reach statistical significance. Four weeks after both plasma exchange and IVIG treatments, there was a significant improvement in QMGS compared to baseline. One week and 4 weeks after treatment, no significant difference between the 2 treatments was found. Both treatments have a clinically significant effect 4 weeks out in patients with chronic MG, but the improvement has a more rapid onset after plasma exchange than after IVIG.", "We have conducted a trial to randomly assess the efficacy and tolerance of intravenous immunoglobulin (i.v.Ig) or plasma exchange (PE) in myasthenia gravis (MG) exacerbation and to compare two doses of i.v.Ig. Eighty-seven patients with MG exacerbation were randomized to receive either three PE (n = 41), or i.v.Ig (n = 46) 0.4 gm/kg daily further allocated to 3 (n = 23) or 5 days (n = 23). The main end point was the variation of a myasthenic muscular score (MSS) between randomization and day 15. The MSS variation was similar in both groups (median value, +18 in the PE group and +15.5 in the i.v.Ig group, p = 0.65). Similar efficacy, although slightly reduced in the 5-day group was observed with both i.v.Ig schedules. The tolerance of i.v.Ig was better than that of PE with a total of 14 side effects observed in 9 patients, 8 in the PE group and 1 in the i.v.Ig group (p = 0.01). Although our trial failed to show a pronounced difference in the efficacy of both treatments, it exhibited a very limited risk for i.v.Ig. i.v.Ig is an alternative for the treatment of myasthenic crisis. The small sample sizes in our trial, however, could explain why a difference in efficacy was not observed. Further studies are needed to compare PE with i.v.Ig and to determine the optimal dosage of i.v.Ig.", "Both IV immunoglobulin (IVIg) and plasma exchange (PLEX) are immunomodulatory treatments used to treat patients with myasthenia gravis (MG), but the choice of which treatment to administer to patients is limited due to lack of evidence from adequately powered, masked, randomized, standardized trials.\n We randomized 84 patients with moderate to severe MG defined as a Quantitative Myasthenia Gravis Score for disease severity (QMGS) of >10.5 and worsening weakness to IVIg (Gamunex®, Talecris Biotherapeutics) 1 g/kg/day for 2 consecutive days or PLEX (Caridian Spectra) 1.0 plasma volume exchanges for 5 exchanges. The patients were evaluated at day 14 after treatment for the primary efficacy parameter of change in QMGS and secondary clinical and electrophysiologic parameters and were followed for a total of 60 days.\n Both IVIg and PLEX reduced the QMGS, and IVIg was comparable to PLEX in efficacy. The dropout rate was the same for both treatment arms and both treatments were well-tolerated. The presence of acetylcholine receptor antibodies and greater baseline disease severity predicted a better response to therapy. The postintervention status revealed that the same proportion of patients improved with treatment: 69% on IVIg and 65% on PLEX. The duration of improvement was similar with both treatments.\n IVIg has comparable efficacy to PLEX in the treatment of patients with moderate to severe MG. Both treatments are well-tolerated, and the duration of effect is comparable. Either treatment may be offered to patients depending on availability of resources. Classification of evidence: This study provides Class I evidence that IVIg and PLEX have comparable efficacy and are equally tolerated in adult patients with moderate to severe MG within 2 weeks of treatment.\n Copyright © 2011 by AAN Enterprises, Inc." ]	No adequate RCTs have been performed to determine whether plasma exchange improves the short- or long-term outcome for chronic myasthenia gravis or myasthenia gravis exacerbation. However, many studies with case series report short-term benefit from plasma exchange in myasthenia gravis, especially in myasthenic crisis. In severe exacerbations of myasthenia gravis one RCT did not show a significant difference between plasma exchange and intravenous immunoglobulin. Further research is need to compare plasma exchange with alternative short-term treatments for myasthenic crisis or before thymectomy and to determine the value of long-term plasma exchange for treating myasthenia gravis.
CD000031	[ "16517193", "16246996", "12365880", "17632223", "18441375", "17530112", "9337378", "17577801", "17624979", "11694208", "11377644", "12079730", "15534159", "10053177", "18096137", "20308641", "19934280", "9707377", "14581254", "19884613", "15364675", "12171809", "14982688", "10707439", "15764422", "17889314", "21574208", "9778204", "15317642", "15876899", "11199956", "17290726", "17558827", "19995670", "16649873", "12610193", "16908788", "14749158", "15682300", "11560455", "20008701", "14632962", "17763111", "16820546", "11068974", "12182272", "19395688", "12714026", "21475970", "21403011", "16820547", "15514412", "15899687", "12859700", "12215235", "15301658", "12359680", "7586937", "17145253" ]	[ "A controlled trial of nortriptyline, sustained-release bupropion and placebo for smoking cessation: preliminary results.", "Efficacy of bupropion and nortriptyline for smoking cessation among people at risk for or with chronic obstructive pulmonary disease.", "Psychological intervention and antidepressant treatment in smoking cessation.", "A 12-week double-blind, placebo-controlled study of bupropion sr added to high-dose dual nicotine replacement therapy for smoking cessation or reduction in schizophrenia.", "Nortriptyline plus nicotine replacement versus placebo plus nicotine replacement for smoking cessation: pragmatic randomised controlled trial.", "A randomized trial of smoking cessation. Medication versus motivation.", "A comparison of sustained-release bupropion and placebo for smoking cessation.", "Bupropion and cognitive-behavioral treatment for depression in smoking cessation.", "A randomized trial of bupropion and/or nicotine gum as maintenance treatment for preventing smoking relapse.", "A pilot trial of bupropion added to cognitive behavioral therapy for smoking cessation in schizophrenia.", "Smoking cessation in patients with chronic obstructive pulmonary disease: a double-blind, placebo-controlled, randomised trial.", "A placebo controlled trial of bupropion for smoking cessation in schizophrenia.", "A randomized trial of nortriptyline combined with transdermal nicotine for smoking cessation.", "A controlled trial of sustained-release bupropion, a nicotine patch, or both for smoking cessation.", "A placebo-controlled trial of bupropion combined with nicotine patch for smoking cessation in schizophrenia.", "Bupropion and cognitive behavioral therapy for weight-concerned women smokers.", "Effectiveness of pharmacotherapy and behavioral interventions for smoking cessation in actual clinical practice.", "Nortriptyline and cognitive-behavioral therapy in the treatment of cigarette smoking.", "Effectiveness of bupropion sustained release for smoking cessation in a health care setting: a randomized trial.", "A randomized placebo-controlled clinical trial of 5 smoking cessation pharmacotherapies.", "Bupropion for smoking cessation: a randomized trial.", "Stopping smoking: a prospective, randomized, double-blind study comparing nortriptyline to placebo.", "A multicenter, randomized, double-blind, placebo-controlled, 6-month trial of bupropion hydrochloride sustained-release tablets as an aid to smoking cessation in hospital employees.", "The effects of fluoxetine combined with nicotine inhalers in smoking cessation--a randomized trial.", "Double-blind placebo-controlled trial of fluoxetine in smoking cessation treatment including nicotine patch and cognitive-behavioral group therapy.", "Bupropion and nicotine patch as smoking cessation aids in alcoholics.", "Smoking cessation in primary care - a randomized controlled trial of bupropione, nicotine replacements, CBT and a minimal intervention.", "A randomized trial of nortriptyline for smoking cessation.", "Efficacy of bupropion and predictors of successful outcome in a sample of French smokers: a randomized placebo-controlled trial.", "A double-blind placebo-controlled trial of bupropion sustained-release for smoking cessation in schizophrenia.", "A preliminary study of bupropion sustained-release for smoking cessation in patients with chronic posttraumatic stress disorder.", "Randomized comparison of a nicotine inhaler and bupropion for smoking cessation and relapse prevention.", "Bupropion and cognitive-behavioral therapy for smoking cessation in women.", "Preliminary effects of bupropion and the promoter region (HTTLPR) serotonin transporter (SLC6A4) polymorphism on smoking behavior in schizophrenia.", "Extended treatment with bupropion SR for cigarette smoking cessation.", "Nicotine patch therapy based on smoking rate followed by bupropion for prevention of relapse to smoking.", "Smoking cessation with varenicline, a selective alpha4beta2 nicotinic receptor partial agonist: results from a 7-week, randomized, placebo- and bupropion-controlled trial with 1-year follow-up.", "Effects of sustained-release bupropion among persons interested in reducing but not quitting smoking.", "Naltrexone reduces the relative reinforcing value of nicotine in a cigarette smoking choice paradigm.", "Sustained-release bupropion for pharmacologic relapse prevention after smoking cessation. a randomized, controlled trial.", "Comparative effectiveness of 5 smoking cessation pharmacotherapies in primary care clinics.", "Double-blind comparison of fluoxetine and nortriptyline in the treatment of moderate to severe major depression.", "Efficacy of bupropion alone and in combination with nicotine gum.", "Varenicline, an alpha4beta2 nicotinic acetylcholine receptor partial agonist, vs sustained-release bupropion and placebo for smoking cessation: a randomized controlled trial.", "Nicotine patch and paroxetine for smoking cessation.", "Multicenter trial of fluoxetine as an adjunct to behavioral smoking cessation treatment.", "Sustained-release bupropion for hospital-based smoking cessation: a randomized trial.", "Bupropion SR for smoking cessation in smokers with cardiovascular disease: a multicentre, randomised study.", "Effects of contingency management and bupropion on cigarette smoking in smokers with schizophrenia.", "Bupropion for smoking cessation in patients with acute coronary syndrome.", "Efficacy of varenicline, an alpha4beta2 nicotinic acetylcholine receptor partial agonist, vs placebo or sustained-release bupropion for smoking cessation: a randomized controlled trial.", "Extended nortriptyline and psychological treatment for cigarette smoking.", "Bupropion SR vs placebo for smoking cessation in health care professionals.", "A multicentre, randomized, double-blind, placebo-controlled, 1-year study of bupropion SR for smoking cessation.", "Bupropion for the treatment of nicotine dependence in spit tobacco users: a pilot study.", "Randomized clinical trial of the efficacy of bupropion combined with nicotine patch in the treatment of adolescent smokers.", "A randomized trial of sertraline as a cessation aid for smokers with a history of major depression.", "A reversible monoamine oxidase A inhibitor (moclobemide) facilitates smoking cessation and abstinence in heavy, dependent smokers.", "Bupropion for smokers hospitalized with acute cardiovascular disease." ]	[ "Cognitive behavior therapy (CBT) constitutes the basis of smoking cessation programs. Quitting rates are usually increased by the concomitant use of CBT and pharmacotherapy. There are studies showing the efficacy of bupropion and nortriptyline compared to placebo, but there is just one published comparison between these drugs, unfortunately with low power to detect significant differences. This study was designed to compare the efficacy of bupropion, nortriptyline and placebo in a group of smokers who also received intensive counseling therapy. We conducted a double blind, double-dummy, placebo-controlled trial for smoking cessation that lasted 9 weeks. Patients were randomized to receive nortriptyline 75 mg/day (52 subjects), bupropion 300 mg/day (53 subjects) or placebo (51 subjects). All smokers also received the same intensive cognitive behavior therapy. The target day for quitting smoking was usually day 10. Intensive counseling was provided at baseline, weekly during treatment, and at 10, 13, 16, 20 and 26 weeks. Abstinence was defined as continuous when the subject was not smoking since the target-quitting day (self-report) and had an expired carbon monoxide concentration of 10 ppm or less.\n The sustained abstinence rates at 6 months were 21.6% in the placebo group, 30.8% in the nortriptyline group (p = 0.40), and 41.5% in the bupropion group (p = 0.05). The odds ratio was not statistically different for smokers using nortriptyline or bupropion (OR 1.60; 95% CI 0.66-3.86; p = 0.35). The most common adverse events were dry mouth and drowsiness in the nortriptyline group and dry mouth and insomnia in the bupropion group.\n Treatment with CBT + bupropion resulted in a better 6-month rate of smoking cessation compared to CBT+nortriptyline or CBT + placebo. Abstinence rate in the nortriptyline group was not statistically different from patients in the bupropion or placebo group.", "The observations that smokers with chronic obstructive pulmonary disease (COPD) are at increased risk of depression and that nicotine may have antidepressant effects and regulate mood provide a rationale for the use of antidepressant drugs for smoking cessation in patients with COPD. No clinical trial has studied the efficacy of bupropion hydrochloride and nortriptyline hydrochloride for smoking cessation in this patient population, to our knowledge.\n In a placebo-controlled double-dummy randomized trial, 255 adults at risk for COPD or with COPD were prescribed sustained-release bupropion (bupropion SR) (150 mg twice daily) or nortriptyline (75 mg once daily) for 12 weeks. All patients received smoking cessation counseling. The main outcome measure was prolonged abstinence from smoking from week 4 to week 26 after the target quit date.\n The use of bupropion SR and nortriptyline resulted in higher prolonged abstinence rates compared with placebo, although only the difference between bupropion SR and placebo was statistically significant (differences with placebo, 13.1% [95% confidence interval, 1.2%-25.1%] for bupropion SR and 10.2% [95% confidence interval, -1.7% to 22.2%] for nortriptyline). In patients with COPD, bupropion SR and nortriptyline seem efficacious in achieving prolonged abstinence (differences with placebo, 18.9% [95% confidence interval, 3.6%-34.2%] for bupropion SR and 12.9% [95% confidence interval, -0.8% to 26.4%] for nortriptyline). In participants at risk for COPD, no statistically significant differences with placebo in prolonged abstinence rates were found.\n Bupropion SR treatment is an efficacious aid to smoking cessation in patients with COPD. Nortriptyline treatment seems to be a useful alternative.", "Sustained-release bupropion hydrochloride and nortriptyline hydrochloride have been shown to be efficacious in the treatment of cigarette smoking. It is not known whether psychological intervention increases the efficacy of these antidepressants. This study compared both drugs with placebo. It also examined the efficacy of these 2 drugs and placebo with and without psychological intervention.\n This was a 2 (medical management vs psychological intervention) x 3 (bupropion vs nortriptyline vs placebo) randomized trial. Participants were 220 cigarette smokers. Outcome measures were biologically verified abstinence from cigarettes at weeks 12, 24, 36, and 52.\n Psychological intervention produced higher 7-day point-prevalence rates of biochemically verified abstinence than did medical management alone. With the use of point-prevalence abstinence, both nortriptyline and bupropion were more efficacious than placebo. On rates of 1-year continuous abstinence, the 2 drugs did not differ from each other or from placebo. Psychological intervention did not differ from medical management alone on rates of 1-year continuous abstinence.\n Both nortriptyline and bupropion are efficacious in producing abstinence in cigarette smokers. Similarly, psychological intervention produces better abstinence rates than simple medical management. Both drugs, and psychological intervention, have limited efficacy in producing sustained abstinence. The data also suggest that combined psychological intervention and antidepressant drug treatment may not be more effective than antidepressant drug treatment alone.", "The objective of this study was to examine whether there is a benefit of adding bupropion SR to high-dose combination nicotine replacement therapy (NRT) and weekly group cognitive behavioral therapy (CBT) for smoking reduction or cessation in schizophrenia. Fifty-one adult smokers with schizophrenia were randomly assigned to a 12-week trial of bupropion SR 300 mg/d or placebo added to transdermal nicotine patch, nicotine polacrilex gum, and CBT. The treatment goal was smoking cessation. The primary outcome measure was biochemically confirmed 7-day point-prevalence of 50% to 100% smoking reduction at week 12. Secondary outcomes were biochemically confirmed tobacco abstinence and change from baseline in expired air carbon monoxide (CO) and psychiatric symptoms. Subjects on bupropion + NRT had a greater rate of 50% to 100% smoking reduction at weeks 12 (60% vs. 31%; P = 0.036) and 24, a lower expired air CO in the treatment and follow-up periods, (F = 13.8; P < 0.001) and a greater continuous abstinence rate at week 8, before NRT taper, (52% vs. 19%; P = 0.014). However, relapse rates in subjects on bupropion + dual NRT were 31% during NRT taper (weeks 8-12) and 77% at the 12-month follow-up. Abstinence rates did not differ by treatment group at weeks 12 (36% vs. 19%), 24 (20% vs. 8%), or 52 (12% vs. 8%). Because abstinence rates were high during treatment with combination pharmacotherapy and relapse rates were very high during taper and after discontinuation of treatment, study of longer term treatment with combination pharmacotherapy and CBT for sustained abstinence is warranted in those who attain initial abstinence with this intervention.", "To test the efficacy of nortriptyline plus nicotine replacement therapy compared with placebo plus nicotine replacement therapy for smoking cessation.\n Pragmatic randomised controlled trial.\n National Health Service stop smoking service clinics.\n 901 people trying to stop smoking.\n Participants chose their nicotine replacement product, including combinations of nicotine replacement therapy, and received behavioural support. Nortriptyline was started one to two weeks before quit day, with the dose increased from 25 mg to 75 mg daily for eight weeks and reduced if not tolerated.\n Primary outcome was prolonged confirmed abstinence at six months. Secondary outcomes were prolonged abstinence at 12 months, drug use, severity of side effects, nicotine withdrawal symptoms, and urges to smoke.\n 72 of 445 (16%) people using nortriptyline and 55 of 456 (12%) using placebo achieved prolonged abstinence at six months (relative risk 1.34, 95% confidence interval 0.97 to 1.86). At 12 months the corresponding values were 49 (11%) for nortriptyline and 40 (9%) for placebo (1.26, 0.84 to 1.87). 337 (79%) people in the nortriptyline arm and 325 (75%) in the placebo arm were taking combination treatment on quit day, median 75 mg per day in both groups. More people in the nortriptyline arm than in the placebo arm took lower doses. The nortriptyline arm had noticeably higher severity ratings for dry mouth and constipation than the placebo arm, with slightly higher ratings for sweating and feeling shaky. Both groups had similar urges to smoke, but nortriptyline reduced depression and anxiety. Overall, withdrawal symptom scores did not differ.\n Nortriptyline and nicotine replacement therapy are both effective for smoking cessation but the effect of the combination is less than either alone and evidence is lacking that combination treatment is more effective than either alone. Trial registration Current Controlled Trials ISRCTN57852484.", "A prospective randomized study was undertaken to assess the effectiveness and side effect profiles of nicotine patch and bupropion therapies for smoking cessation.\n Three hundred and fifty patients were referred to our smoking cessation program in the Department of Pulmonary Diseases, Gaziantep University between September 2002 and July 2003. Of these, only 131 patients fulfilled the trial criteria. We randomized the patients into nicotine patch (n=50), bupropion (n=50) and control groups (n=31). Cases were followed up for 24 weeks. Questionnaires including the Fagerstrom test for nicotine dependence and Beck Depression Inventory were carried out at initial evaluation. Declaration of quitting and exhaled carbon monoxide level less than 10 ppm was accepted as success criteria.\n Success rates were 26% for nicotine patch group, 26% for bupropion and 16% for control group at the end of the 24th week (p=0.56). Beck depression inventory scores did not differ significantly between the groups, however none of the cases with scores greater than 13 succeeded regardless of the group. Mean body weight at baseline and change at 6 months did not differ significantly between the groups. Sleep disturbance was significantly more common in nicotine patch and bupropion groups than the control group (p=0.008).\n The present study reinforces the role of medical doctors and importance of close follow up in smoking cessation, and directed counseling is quite as effective as pharmacologic therapy and is the sole approach without any adverse effects.", "Trials of antidepressant medications for smoking cessation have had mixed results. We conducted a double-blind, placebo-controlled trial of a sustained-release form of bupropion for smoking cessation. We excluded smokers with current depression, but not those with a history of major depression. The 615 subjects were randomly assigned to receive placebo or bupropion at a dose of 100, 150, or 300 mg per day for seven weeks. The target quitting date (or \"target quit date\") was one week after the beginning of treatment. Brief counseling was provided at base line, weekly during treatment, and at 8, 12, 26, and 52 weeks. Self-reported abstinence was confirmed by a carbon monoxide concentration in expired air of 10 ppm or less.\n At the end of seven weeks of treatment, the rates of smoking cessation as confirmed by carbon monoxide measurements were 19.0 percent in the placebo group, 28.8 percent in the 100-mg group, 38.6 percent in the 150-mg group, and 44.2 percent in the 300-mg group (P<0.001). At one year the respective rates were 12.4 percent, 19.6 percent, 22.9 percent, and 23.1 percent. The rates for the 150-mg group (P=0.02) and the 300-mg group (P=0.01) -- but not the 100-mg group (P=0.09) -- were significantly better than those for the placebo group. Among the subjects who were continuously abstinent through the end of treatment, the mean absolute weight gain was inversely associated with the dose (a gain of 2.9 kg in the placebo group, 2.3 kg in 100-mg and 150-mg groups, and 1.5 kg in the 300-mg group; P= 0.02). No effects of treatment were observed on depression scores as measured serially by the Beck Depression Inventory. Thirty-seven subjects stopped treatment prematurely because of adverse events; the frequency was similar among all groups.\n A sustained-release form of bupropion was effective for smoking cessation and was accompanied by reduced weight gain and minimal side effects. Many participants in all groups were smoking at one year.", "This study is a randomized, double-blind, placebo-controlled clinical trial examining the effects of an intensive cognitive-behavioral mood management treatment (CBTD) and of bupropion, both singularly and in combination, on smoking cessation in adult smokers. As an extension of our previous work, we planned to examine the synergistic effects of CBTD and bupropion on smoking cessation outcomes in general and among smokers with depression vulnerability factors. Participants were 524 smokers (47.5% female, M (age) = 44.27 years) who were randomized to one of four 12-week treatments: (a) standard, cognitive-behavioral smoking cessation treatment (ST) plus bupropion (BUP), (b) ST plus placebo (PLAC), (c) standard cessation treatment combined with cognitive-behavioral treatment for depression (CBTD) plus BUP, and (d) CBTD plus PLAC. Follow-up assessments were conducted 2, 6, and 12 months after treatment, and self-reported abstinence was verified biochemically. Consistent with previous studies, bupropion, in comparison with placebo, resulted in better smoking outcomes in both intensive group treatments. Adding CBTD to standard intensive group treatment did not result in improved smoking cessation outcomes. In addition, neither CBTD nor bupropion, either alone or in combination, was differentially effective for smokers with single-past-episode major depressive disorder (MDD), recurrent MDD, or elevated depressive symptoms. However, findings with regard to recurrent MDD and elevated depressive symptoms should be interpreted with caution given the low rate of recurrent MDD and the low level of depressive symptoms in our sample. An a priori test of treatment effects in smokers with these depression vulnerability factors is warranted in future clinical trials.", "To investigate the efficacy of maintenance treatment with bupropion and/or nicotine gum for reducing smoking relapse.\n A 48-week study was conducted at a university-based smoking cessation clinic between February 2001 and October 2005. A total of 588 smokers received bupropion and nicotine patch in 8 weeks of open-label treatment (OLT); 289 abstainers during the last 4 weeks of OLT were randomized in double-blind placebo-controlled fashion to one of four arms for 16 weeks of maintenance treatment (MT) followed by 24 weeks of non-treatment follow-up (NTFU).\n Bupropion (300 mg/day) and 2 mg nicotine gum, used alone or combined, and comparable placebo pill and placebo gum. Behavioral counseling at all visits.\n Time to relapse (TTR) from randomization. Relapse is defined as the first 7 consecutive days of smoking. Abstinence verified by carbon monoxide <or= 8 parts per million.\n TTR was longer with extended active treatments compared to placebo (median days to relapse: bupropion + placebo = 136, nicotine + placebo = 98, bupropion + nicotine = 90, double placebo = 71). Hazard ratios (HR) for relapse were statistically significant for bupropion + placebo versus double placebo during MT (HR = 0.59, 95% CI = 0.37-0.92) and to the end of NTFU (HR = 0.66, 95% CI = 0.42-0.96). However, bupropion's advantage dissipated upon stopping the drug. Gum use was low, preventing a valid assessment; but analysis restricted to gum users suggested a weak effect of extended nicotine gum.\n Maintenance treatment with bupropion exerted a modest benefit for preventing smoking relapse; the optimum duration of bupropion treatment was unclear. Further research is needed to ascertain the merits of extended use of nicotine gum, other nicotine replacement agents and other treatments known to aid smokers for preventing relapse once abstinence is achieved.", "The purpose of this study was to investigate the effect of adding sustained-release (SR) bupropion to cognitive behavioral therapy (CBT) on smoking behavior and stability of psychiatric symptoms in patients with schizophrenia. We conducted a 3-month, double-blind, placebo-controlled trial of bupropion SR, 150 mg/day, added to a concurrent CBT program with 3-month follow-up in 19 stable outpatients with schizophrenia who wanted to quit smoking. Eighteen subjects completed the trial. Bupropion treatment was associated with significantly greater reduction in smoking, as measured by self-report verified by expired-air carbon monoxide (6/9 subjects, 66%), than placebo (1/9 subjects, 11%) during the 3-month active treatment period and the 3-month follow-up period. One subject in the bupropion group (11%) and no subjects in the placebo group achieved sustained tobacco abstinence for the 6-month trial. Bupropion treatment was associated with improvement in negative symptoms and greater stability of psychotic and depressive symptoms, compared with placebo, during the quit attempt. Subjects in the bupropion group experienced significant weight loss, compared with those on placebo during the smoking cessation attempt. These data suggest that bupropion SR, 150 mg/day, combined with CBT, may facilitate smoking reduction in patients with schizophrenia while stabilizing psychiatric symptoms during a quit attempt.", "Tobacco smoking is associated with chronic obstructive pulmonary disease (COPD) in more than 80% of cases. Our aim was to investigate the effect of sustained-release bupropion (amfebutamone) (SR) in promoting abstinence from smoking in patients with COPD.\n In a double-blind, randomised, placebo-controlled trial 404 individuals with mild or moderate COPD who smoked 15 or more cigarettes per day, were assigned bupropion SR (150 mg twice daily) or placebo for 12 weeks. All patients received smoking cessation counselling. Study medication was taken for 1 week before patients attempted to stop smoking. The primary efficacy endpoint was the complete and continuous abstinence from smoking from the beginning of week 4 to the end of week 7. Participants were followed up at month 6. Analysis was by intention to treat.\n All patients were chronic smokers with a smoking history of about 51 pack-years. Continuous smoking abstinence rates from week 4 to 7 were significantly higher in participants receiving bupropion SR than in those receiving placebo (28% [57/204] vs 16% [32/200], p=0.003). Continuous abstinence rates from weeks 4 to 12 (18% [36/204] vs 10% [20/200]) and weeks 4 to 26 (16% [32/204] vs 9% [18/200]) were also higher in participants receiving bupropion SR than in those taking placebo (p<0.05). Furthermore, symptoms of tobacco craving and withdrawal were attenuated in those receiving bupropion SR. Seven individuals discontinued study medication because of adverse events.\n Bupropion SRis a well-tolerated and effective aid to smoking cessation in people with mild to moderate COPD.", "Schizophrenic patients have high rates of cigarette smoking compared with the general population. We compared sustained-release (SR) bupropion with placebo for smoking cessation in patients with schizophrenic disorders. We also examined how antipsychotic class predicts smoking cessation outcomes with bupropion.\n Thirty-two subjects meeting DSM-IV criteria for schizophrenia or schizoaffective disorder and nicotine dependence were randomized to bupropion SR (BUP, 300 mg/day) or placebo (PLA). Outcomes included treatment retention, smoking abstinence rates, expired breath carbon monoxide (CO) levels, psychotic symptoms, and medication side effects.\n Bupropion significantly increased trial endpoint 7-day point prevalence smoking abstinence rates compared with placebo [BUP, 8/16 (50.0%), PLA, 2/16 (12.5%); chi(2) = 5.24, df = 1, p <.05], and reduced CO levels during the trial [Medication x Time interaction; Z = 3.09, p <.01]. Positive schizophrenia symptoms were not altered by BUP, but negative symptoms were significantly reduced. Atypical antipsychotic drug treatment enhanced smoking cessation responses to BUP. Major side effects were dry mouth, gastrointestinal symptoms, headache, and insomnia.\n Our results suggest that 1) BUP enhances smoking abstinence rates compared with PLA in nicotine-dependent schizophrenic smokers; 2) BUP is well-tolerated and safe for use in these patients; and 3) atypical antipsychotics may enhance smoking cessation outcomes with BUP.", "Smoking cessation rates with current therapy are suboptimal. Tricyclic antidepressants improve cessation rates. We hypothesized that addition of nortriptyline hydrochloride to transdermal nicotine would enhance cessation rates.\n We conducted a randomized, double-blind, placebo-controlled trial at a Department of Veterans Affairs medical center. Subjects were aged 18 to 65 years, smoked 10 or more cigarettes per day, and did not have current major depression. Nortriptyline hydrochloride or matched placebo was started at 25 mg 14 days before quit day, titrated to 75 mg/d as tolerated, and continued for 12 weeks after quit day. Transdermal nicotine (21 mg/d) was started on quit day and continued for 8 weeks. The behavioral intervention consisted of 12 brief, individual visits. Withdrawal symptoms were measured by means of a daily diary, and smoking cessation was defined as self-reported abstinence, expired carbon monoxide level of 9 ppm or less, and a 6-month urine cotinine level less than 50 ng/mL (284 nmol/L).\n A total of 158 patients were randomized (79 to nortriptyline and 79 to placebo). There was no significant reduction in withdrawal symptoms. The cessation rates at 6 months were 23% (18/79) and 10% (8/79), respectively (absolute difference, 13%; 95% confidence interval, 1.3%-24.5%; P = .052). Nortriptyline caused frequent side effects, including dry mouth (38%) and sedation (20%).\n Nortriptyline combined with transdermal nicotine resulted in an increased cessation rate with little effect on withdrawal symptoms. This combination may represent an option for smokers in whom standard therapy has failed.", "Use of nicotine-replacement therapies and the antidepressant bupropion helps people stop smoking. We conducted a double-blind, placebo-controlled comparison of sustained-release bupropion (244 subjects), a nicotine patch (244 subjects), bupropion and a nicotine patch (245 subjects), and placebo (160 subjects) for smoking cessation. Smokers with clinical depression were excluded. Treatment consisted of nine weeks of bupropion (150 mg a day for the first three days, and then 150 mg twice daily) or placebo, as well as eight weeks of nicotine-patch therapy (21 mg per day during weeks 2 through 7, 14 mg per day during week 8, and 7 mg per day during week 9) or placebo. The target day for quitting smoking was usually day 8.\n The abstinence rates at 12 months were 15.6 percent in the placebo group, as compared with 16.4 percent in the nicotine-patch group, 30.3 percent in the bupropion group (P<0.001), and 35.5 percent in the group given bupropion and the nicotine patch (P<0.001). By week 7, subjects in the placebo group had gained an average of 2.1 kg, as compared with a gain of 1.6 kg in the nicotine-patch group, a gain of 1.7 kg in the bupropion group, and a gain of 1.1 kg in the combined-treatment group (P<0.05). Weight gain at seven weeks was significantly less in the combined-treatment group than in the bupropion group and the placebo group (P<0.05 for both comparisons). A total of 311 subjects (34.8 percent) discontinued one or both medications. Seventy-nine subjects stopped treatment because of adverse events: 6 in the placebo group (3.8 percent), 16 in the nicotine-patch group (6.6 percent), 29 in the bupropion group (11.9 percent), and 28 in the combined-treatment group (11.4 percent). The most common adverse events were insomnia and headache.\n Treatment with sustained-release bupropion alone or in combination with a nicotine patch resulted in significantly higher long-term rates of smoking cessation than use of either the nicotine patch alone or placebo. Abstinence rates were higher with combination therapy than with bupropion alone, but the difference was not statistically significant.", "Individuals with schizophrenia smoke at higher rates (58%-88%) than the general population (approximately 22%), and have difficulty quitting. We determined whether the combination of sustained-release (SR) bupropion (BUP) with the transdermal nicotine patch (TNP) was well-tolerated and superior to placebo (PLO)+TNP for smoking cessation in schizophrenia.\n A 10-week, double-blind, placebo-controlled trial of BUP (300 mg/day) in combination with TNP (21 mg/24h) for 58 outpatient smokers with schizophrenia was conducted. Primary outcome measures were continuous smoking abstinence in the last 4 weeks of the trial (Days 43-70) and 7-day point prevalence abstinence at 6 months post-target quit date (TQD) (week 26).\n Smokers assigned to the BUP+TNP group (n = 29) were more likely to achieve continuous smoking abstinence (8/29, 27.6%) than the PLO+TNP group (n = 29, 1/29, 3.4%) [Fisher's Exact Test, p < .05]; at 6-months post-TQD, 4/29 (13.8%) versus 0/29 (0.0%) achieved 7-day point prevalence smoking abstinence (p = .11). Neither bupropion SR nor smoking abstinence significantly altered the positive or negative symptoms of schizophrenia. The combination was well-tolerated in smokers with schizophrenia.\n Combination therapy with bupropion SR+TNP versus placebo+TNP is well-tolerated and significantly improved short-term smoking abstinence in smokers with schizophrenia.", "We previously documented that cognitive behavioral therapy for smoking-related weight concerns (CONCERNS) improves cessation rates. However, the efficacy of combining CONCERNS with cessation medication is unknown. We sought to determine if the combination of CONCERNS and bupropion therapy would enhance abstinence for weight-concerned women smokers.\n In a randomized, double-blind, placebo-controlled trial, weight-concerned women (n = 349; 86% white) received smoking cessation counseling and were randomized to 1 of 2 adjunctive counseling components: CONCERNS or STANDARD (standard cessation treatment with added discussion of smoking topics but no specific weight focus), and 1 of 2 medication conditions: bupropion hydrochloride sustained release (B) or placebo (P) for 6 months. Rates and duration of biochemically verified prolonged abstinence were the primary outcomes. Point-prevalent abstinence, postcessation weight gain, and changes in nicotine withdrawal, depressive symptoms, and weight concerns were evaluated.\n Women in the CONCERNS + B group had higher rates of abstinence (34.0%) and longer time to relapse than did those in the STANDARD + B (21%; P = .05) or CONCERNS + P (11.5%; P = .005) groups at 6 months, although rates of prolonged abstinence in the CONCERNS + B and STANDARD + B groups did not differ significantly at 12 months. Abstinence rates and duration did not differ in the STANDARD + B group (21% and 19%) compared with the STANDARD + P group (10% and 7%) at 6 and 12 months, respectively. There were no differences among abstinent women in postcessation weight gain or weight concerns, although STANDARD + B produced greater decreases in nicotine withdrawal and depressive symptoms than did STANDARD + P.\n Weight-concerned women smokers receiving the combination of CONCERNS + B were most likely to sustain abstinence. This effect was not related to differences in postcessation weight gain or changes in weight concerns. Trial Registration clinicaltrials.gov Identifier: NCT00006170.", "This study evaluated the effectiveness of behavioral interventions (brief counseling, nonspecific psychological support in groups - NSGS and cognitive behavioral group therapy - CBGT) in combination with bupropion SR for smoking cessation in the field, through a smoking cessation clinic.\n Two-hundred-and-five smokers were enrolled in a 19-week course during 2007/ 2008, and were randomly assigned to: bupropion SR combined with brief counseling (group A), bupropion SR combined with NSGS (group B), bupropion SR combined with CBGT (group C), or CBGT as the only approach (group D).\n Continuous abstinence rates at the end of therapy were 53.2% for group A, 62.9% for group B, 50.0% for group C, and 22.2% (p < 0.05) for group D. Sustained abstinence rates in 12 months were 29.6%, 28.1%, 34.3% and 19.4% (p > 0.05), respectively.\n Bupropion SR is an effective aid for smoking cessation in clinical practice. NSGT increased the chances for success at the end of therapy when combined with bupropion SR, while CBGT as monotherapy was less effective compared with the approaches including pharmacotherapy. It is suggested that smoking cessation interventions in real-life healthcare settings should be implemented through comprehensive programs using pharmacotherapy where applicable, combined with NSGT, and integrated by specialized healthcare professionals.", "A history of major depressive disorder (MDD) predicts failure to quit smoking. We determined the effect of nortriptyline hydrochloride and cognitive-behavioral therapy on smoking treatment outcome in smokers with a history of MDD. The study also addressed the effects of diagnosis and treatment condition on dysphoria after quitting smoking and the effects of dysphoria on abstinence.\n This was a 2 (nortriptyline vs placebo) x 2 (cognitive-behavioral therapy vs control) x 2 (history of MDD vs no history) randomized trial. The participants were 199 cigarette smokers. The outcome measures were biologically verified abstinence from cigarettes at weeks 12, 24, 38, and 64. Mood, withdrawal, and depression were measured at 3, 5, and 8 days after the smoking quit date.\n Nortriptyline produced higher abstinence rates than placebo, independent of depression history. Cognitive-behavioral therapy was more effective for participants with a history of depression. Nortriptyline alleviated a negative affect occurring after smoking cessation. Increases in the level of negative affect from baseline to 3 days after the smoking quit date predicted abstinence at later assessments for MDD history-negative smokers. There was also a sex-by-depression history interaction; MDD history-positive women were less likely to be abstinent than MDD history-negative women, but depression history did not predict abstinence for men.\n Nortriptyline is a promising adjunct for smoking cessation. Smokers with a history of depression are aided by more intensive psychosocial treatments. Mood and diagnosis interact to predict relapse. Increases in negative affect after quitting smoking are attenuated by nortriptyline.", "The efficacy of bupropion hydrochloride sustained release (SR) (Zyban) for smoking cessation has been evaluated in clinical trials that included frequent in-person behavioral counseling, but not in actual practice settings.\n To determine the differential effectiveness of 2 doses of bupropion SR in combination with behavioral interventions of minimal to moderate intensity in an actual practice setting.\n Open-label randomized trial, with 1 year of follow-up.\n A large health system (Group Health Cooperative) based in Seattle.\n Adult smokers (N = 1524) interested in quitting smoking.\n Participants were randomly assigned to receive 1 of 4 combinations of bupropion SR (150 or 300 mg) and behavioral counseling (minimal or moderate intensity).\n The primary outcome measure was self-reported point-prevalence 7-day nonsmoking status at 3 and 12 months following the target quit date. Secondary outcomes included adverse and abstinence effects reported since beginning treatment with bupropion SR.\n At 3 months, a significantly higher rate of nonsmoking was observed among those receiving the larger bupropion SR dose (P=.005). At 12 months, moderate intensity counseling was associated significantly with a higher rate of nonsmoking (P=.001). At 3 months, the higher dose was associated with a significantly increased frequency of self-reported symptoms such as difficulty sleeping (P=.02), difficulty concentrating (P=.02), shakiness/tremor (P=.002), and gastrointestinal problems (P=.005)and a decreased frequency of reported desire to smoke (P=.001).\n In this actual practice setting, the combination of bupropion SR and minimal or moderate counseling was associated with 1-year quit rates of 23.6% to 33.2%. This suggests that existing health care systems can substantially decrease tobacco use rates among their enrollees if they provide these modest interventions.", "Little direct evidence exists on the relative efficacies of different smoking cessation pharmacotherapies, yet such evidence is needed to make informed decisions about their clinical use.\n To assess the relative efficacies of 5 smoking cessation pharmacotherapy interventions using placebo-controlled, head-to-head comparisons.\n A randomized, double-blind, placebo-controlled clinical trial.\n Two urban research sites.\n One thousand five hundred four adults who smoked at least 10 cigarettes per day during the past 6 months and reported being motivated to quit smoking. Participants were excluded if they reported using any form of tobacco other than cigarettes; current use of bupropion; having a current psychosis or schizophrenia diagnosis; or having medical contraindications for any of the study medications.\n Participants were randomized to 1 of 6 treatment conditions: nicotine lozenge, nicotine patch, sustained-release bupropion, nicotine patch plus nicotine lozenge, bupropion plus nicotine lozenge, or placebo. In addition, all participants received 6 individual counseling sessions.\n Biochemically confirmed 7-day point-prevalence abstinence assessed at 1 week after the quit date (postquit), end of treatment (8 weeks postquit), and 6 months postquit. Other outcomes were initial cessation, number of days to lapse, number of days to relapse, and latency to relapse after the first lapse.\n All pharmacotherapies differed from placebo when examined without protection for multiple comparisons (odds ratios, 1.63-2.34). With such protection, only the nicotine patch plus nicotine lozenge (odds ratio, 2.34, P < .001) produced significantly higher abstinence rates at 6-month postquit than did placebo.\n While the nicotine lozenge, bupropion, and bupropion plus lozenge produced effects that were comparable with those reported in previous research, the nicotine patch plus lozenge produced the greatest benefit relative to placebo for smoking cessation.", "Bupropion hydrochloride is recommended for smoking cessation; however, there have been relatively few clinical trials examining its efficacy.\n A total of 244 current smokers were enrolled in an outpatient randomized blinded smoking cessation trial conducted at the San Francisco Veterans Affairs Medical Center, San Francisco, Calif. Of the 244 participants, 121 received a 7-week course of bupropion and 123 received placebo. All participants received 2 months of transdermal nicotine replacement therapy and 3 months of cognitive-behavioral counseling. We determined on-medication treatment, end-of-medication treatment, 3-month, 6-month, and 1-year quit rates.\n During treatment with bupropion vs placebo, there was a trend toward increased quit rates among participants randomized to bupropion; the self-reported end-of-medication treatment quit rates were 64% for the bupropion group vs 57% for the placebo group (P =.23). The trend favoring bupropion persisted at 3 months of follow-up (P =.12) but was not apparent at 6 months and 1 year of follow-up (both P>.78). The 12-month quit rates, validated by either saliva cotinine or spousal proxy, were 22% in the bupropion group and 28% in the placebo group (P =.31). Based on biochemical validation, 19% of the bupropion group vs 24% of the placebo group had quit smoking by 1 year (P =.36).\n In this randomized blinded trial of mostly veteran participants, the addition of a brief 7-week bupropion trial to treatment with nicotine replacement therapy and counseling did not significantly increase smoking cessation rates.", "The administration of antidepressant drugs was shown to positively affect the rate of smoking cessation. This study evaluates the efficacy of nortriptyline in an antismoking program.\n A possible randomized double-blind study that included 144 patients who were randomized to receive nortriptyline, 75 mg/d (68 patients), or placebo (76 patients), during 6 consecutive weeks. All patients attended behavioral group orientation for 5 weeks. The rate of success, complications, adherence to the regime, and factors of pretreatment prognosis were evaluated (multivariate analysis).\n The groups were balanced in relation to the characteristics of the patients on entering the study. Patients receiving nortriptyline showed significantly higher cessation rate (55.9%) compared to the group receiving placebo (23.3%; p < 0.001). In a univariate analysis on prognosis factors influencing the rate of cessation in our study, the Fagerström test results (p = 0.005) and nortriptyline (p < 0.001) were identified. Logistic regression showed that a Fagerström test score of < 7 (odds ratio [OR], 3.1; 95% confidence interval [CI], 1.47 to 6.7; p = 0.003) and nortriptyline use (OR, 4.1; 95% CI, 2 to 8.3; p < 0.001) were independent factors impacting the rate of success for smoking cessation. No significant complications were observed in the nortriptyline group.\n This study showed that nortriptyline significantly increases the smoking cessation rate in chronic smokers, as compared to the placebo group, without any significant side effects.", "Despite changes in smoking behavior, one-third of the Danish population continues to smoke. Many of these smokers are hospital employees. This 6-month, multicenter, parallel group, randomized, double-blind, placebo-controlled study evaluated treatment with bupropion hydrochloride sustained release (Zyban) compared with placebo as an aid to smoking cessation in health care workers. A total of 336 hospital employees who smoked at least 10 cigarettes daily were randomized (2:1) to 7 weeks of treatment with bupropion (n=222) or placebo (n=114). All participants were motivated to quit smoking and received behavioral counseling. Continuous smoking abstinence during weeks 4-7 was the primary endpoint, and long-term smoking abstinence was among the secondary endpoints. Of the original participants, 212 completed the 6-month trial. Continuous smoking abstinence at week 7 was achieved by 43% in the bupropion group and 18% in the placebo group, p<.001. After 26 weeks, 18% and 7%, respectively, were continuously abstinent, p=.008. Side-effects were frequent but simple and reversible in both groups, and generally consistent with the findings of previous studies. Dizziness, insomnia, and pruritus appeared more frequently in the bupropion group than in the placebo group. Bupropion was effective as an aid to smoking cessation in a broad group of hospital employees in Denmark.", "Nicotine replacement therapy (NRT) is an established aid in stopping smoking, while the role of antidepressants remains uncertain. Antidepressants added to NRT might improve abstinence rates. Our aim was to determine the efficacy of nicotine inhaler and fluoxetine vs. nicotine inhaler and placebo in attempts to quit smoking.\n A randomized, double-blind, placebo-controlled trial.\n A smoker's cessation clinic.\n One hundred volunteers smoking 10 cigarettes/day or more.\n Subjects were instructed to start taking a daily dose of 10 mg of fluoxetine or placebo 16 days before stopping smoking, then 20 mg 10 days before quitting, continuing for up to at least 3 months. Subjects were instructed to use 6-12 units per day of nicotine inhalers after stopping smoking for up to 6 months.\n Continuous abstinence rates recorded at various time points up to 12 months from the quit date.\n The sustained abstinence rate for the inhaler-fluoxetine group was 54%, 40%, 29% and 21% after 1.5, 3, 6 and 12 months, respectively, compared to 48%, 40%, 32% and 23% for the inhaler-placebo group. The differences were not significant at any time point. Abstinence up to 3 months was more likely in older smokers, those with a lower Beck Depression Inventory Score (BDI), lower Fagerström Test of Nicotine Dependence (FTND) score and no history of alcoholism. Fluoxetine appeared to increase abstinence rates among high BDI smokers compared to high BDI smokers assigned placebo. Serum levels of nicotine during treatment in the inhaler-fluoxetine group were lower than in the inhaler-placebo group so that fluoxetine may have reduced inhaler use through a common site of action.\n We found no evidence that fluoxetine treatment when used as an adjunct to NRT in unselected smokers is effective, but there may be an advantage to using it in depressed smokers.", "Smoking cessation attempts are often complicated by dysphoria/depression, weight gain, craving, and other nicotine withdrawal symptoms. Fluoxetine's antidepressant and anorectant properties, along with its capacity to attenuate compulsive behavior, suggest that this medication might facilitate smoking cessation treatment. We examined the effect of fluoxetine on smoking cessation in the context of a program that included group cognitive-behavioral therapy (six weeks) and transdermal nicotine patch(ten weeks). In a double-blind randomized trial of fluoxetine for smoking cessation, 150 daily smokers were assigned to placebo (n=48), 20 mg (n=51), or 40 mg fluoxetine (n=51). Fluoxetine did not significantly improve smoking cessation rates, either for those with or without major depressive disorder(MDD)histories or elevated current depression. Our results suggest that fluoxetine may moderate withdrawal symptoms, even if that was not manifested in improved smoking cessation rates. Our results, however, clearly favor the use of fluoxetine if weight gain is a major clinical obstacle to smoking cessation.", "This is a double-blind placebo-controlled study of sustained-release bupropion as a smoking cessation aid in alcoholics undergoing treatment for their alcoholism. Participants (N=58) were enrolled within 1 week of entry into alcohol treatment from community and Veterans Affairs Substance Use Disorder programs. All participants received nicotine patch and were invited to attend a smoking cessation lecture and group. Cigarette smoking and alcohol outcomes were measured at 6 months. Bupropion when added to nicotine patch did not improve smoking outcomes. One third of participants on bupropion reported discontinuing the drug during weeks 1-4. Participants reported cigarette outcomes with nicotine patch that are similar to those seen in the general population. All study participants significantly reduced cigarette use. Comorbid affective disorder or antipersonality disorder did not affect outcomes. Alcohol outcomes were improved in those who discontinued cigarettes.", "Smoking cessation has been shown to be effective in randomized controlled trials. It is unclear though, whether interventions also work in routine primary care.\n In 167 primary care settings we conducted a randomized four-armed smoking cessation trial to examine the efficacy of a minimal intervention (MI; n = 81), cognitive-behavioral therapy (CBT; n = 175), bupropion (BUP; n = 108) and nicotine replacements (NRT; n = 103). Overall, 467 current smokers were enrolled. Abstinence rates at the end of treatment (12 weeks) were 32.8% for MI patients, 34.8% for CBT, 35.3% for NRT, and 46.5% for BUP patients (ITT, intention to treat) (no differential effects). Retention rates were highest in the BUP group (59.3%) and lowest in the NRT group (50.5%). Completer findings were: MI, 56.4%; CBT, 64%; BUP, 79.3%; NRT, 69.2% (LOCF, lost to follow-up). No serious adverse events occurred during or after the medication phase. At 12-month follow-up continuous abstinence rates were: BUP, 29.0%; CBT, 20.9%; NRT, 29.6%; MI, 29.6%.\n Our findings suggest that established smoking cessation treatments are effective when applied by non-specialist primary care physicians. Our data supports a structured, multimodal treatment structure as core ingredient of successful smoking cessation in primary care.\n Copyright © 2011 John Wiley & Sons, Ltd.", "Smoking cessation rates with current therapy are suboptimal. One class of drugs that may improve cessation is the tricyclics.\n To add nortriptyline hydrochloride to a behavioral smoking cessation program to enhance cessation rates and reduce withdrawal symptoms.\n We conducted a randomized, double-blind, placebo-controlled trial at an affiliated Department of Veterans Affairs Medical Center and an Army Medical Center. Subjects were aged 18 through 70 years, smoked 10 or more cigarettes per day, and were without current major depression. Nortriptyline hydrochloride or matched placebo was started at 25 mg before bed 10 days prior to quit day and titrated to 75 mg/d or to the maximal tolerated dose. The behavioral intervention consisted of 2 group sessions and 12 individual follow-up visits. Withdrawal symptoms were measured using a daily diary, and smoking cessation was defined as self-reported abstinence, expired carbon monoxide of 9 ppm or less, and a 6-month urine cotinine level of less than 50 ng/mL.\n A total of 214 patients were randomized (108 to nortriptyline and 106 to placebo). There was a significant reduction in several withdrawal symptoms including anxious/tense, anger/irritability, difficulty concentrating, restlessness, and impatience by day 8 after quit day in the nortriptyline group. The cessation rate at 6 months was 15 (14%) of 108 and 3 (3%) of 106, respectively (P = .003; absolute difference, 11%; 95% confidence interval, -18% to -4%). Nortriptyline caused frequent adverse effects, including dry mouth (64%) and dysgeusia (20%).\n We conclude that nortriptyline led to an increased short-term cessation rate compared with placebo. In addition, there were significant, but relatively small, reductions in withdrawal symptoms. Nortriptyline may represent a new therapeutic approach to smoking cessation.", "Previous published studies assessed the efficacy of bupropion in smoking cessation only in North American populations of smokers. Results of therapeutic drug trials are not always directly applicable in other populations.\n To confirm the efficacy of bupropion in smoking cessation in European smokers.\n A multi-centre, randomized, double-blind placebo-controlled trial.\n Seventy-four smoking cessation out-patient clinics in France.\n The study included 509 smokers motivated to quit smoking. Intervention Subjects were randomized to either slow-release bupropion 150 mg b.i.d. (B) or to placebo (Pl) in a 2 : 1 ratio, treated for 7 weeks, and followed-up for 26 weeks.\n Main outcome measure: 6 months' point prevalence abstinence, determined by self-report and expired air carbon monoxide measurement. Secondary outcome measures: weeks 4-7 and weeks 4-26 continuous abstinence rates, craving, withdrawal symptoms, weight and cigarette consumption in smokers unable to quit. Adverse events were recorded systematically.\n Six months' point prevalence abstinence rates were 31% and 16%[odds ratio = 2.3, confidence interval (CI) 95%: 1.4-3.7] in the B and Pl groups, respectively. Continuous abstinence rates were 41% (B) and 21% (P) with OR = 2.5 (CI 95%: 1.6-3.9) for weeks 4-7, and 25% (B) and 13% (P) with OR = 2.2 (CI 95%: 1.3-3.6) for weeks 4-26, respectively. Craving decreased significantly more with B than with Pl during treatment period, but there was no difference for total withdrawal symptoms score. Abstinent subjects gained significantly less weight at week 7 with B than with Pl. Low level of nicotine dependence, high motivation, absence of smoking-related disease, long duration of previous quit attempts, male gender, low level of current alcohol problems and living as a couple were predictive of successful cessation. With the exception of marital status, no interaction was observed between any of these predictive factors and the efficacy of bupropion. More of those who continued smoking in the B group than the P group reduced their consumption by at least 50%.\n Sustained-release bupropion is efficacious as an aid to smoking cessation in European smokers. No outcome predictors were identified that might indicate that certain subgroups of smokers would benefit more than others from treatment with bupropion.", "The objective of this study was to examine the efficacy of bupropion for smoking cessation in patients with schizophrenia. Adults with schizophrenia who smoked more than 10 cigarettes per day and wished to try to quit smoking were recruited from community mental health centers, enrolled in a 12-week group cognitive behavioral therapy intervention, and randomly assigned to receive either bupropion sustained-release 300 mg/d or identical placebo. Fifty-three adults, 25 on bupropion and 28 on placebo, were randomized, completed at least 1 postbaseline assessment and were included in the analysis. The primary outcome measures were 7-day point prevalence abstinence in the week after the quit date (week 4) and at the end of the intervention (week 12). Subjects in the bupropion group were significantly more likely to be abstinent for the week after the quit date (36% [9/25] vs. 7% [2/28], P = 0.016) and at end of the intervention (16% [4/25] vs. 0%, P = 0.043). Subjects in the bupropion group also had a higher rate of 4-week continuous abstinence (weeks 8-12) (16% [4/25] vs. 0%, P = 0.043) and a longer duration of abstinence (4.2 [3.2] weeks vs. 1.8 [0.96] weeks, t = 2.30, P = 0.037). The effect of bupropion did not persist after discontinuation of treatment. Subjects in the bupropion group had no worsening of clinical symptoms and had a trend toward improvement in depressive and negative symptoms. We conclude that bupropion does not worsen clinical symptoms of schizophrenia and is modestly effective for smoking cessation in patients with schizophrenia. The relapse rate is high after treatment discontinuation.", "This study was conducted to evaluate the effect of bupropion sustained-release (SR) on smoking cessation in patients with chronic posttraumatic stress disorder (PTSD). Fifteen veterans with chronic PTSD who desired to stop smoking enrolled in a 12-week double-blind evaluation of bupropion SR and placebo. Patients were randomly assigned in a 2:1 ratio to receive either bupropion SR or placebo. Bupropion SR was initiated at 150 mg daily for 3 or 4 days and increased to a final dose of 150 mg twice daily (300 mg daily total). Ten patients received bupropion SR and five received placebo. Nine of the patients who received bupropion SR were already being treated with at least one other psychotropic medication. One of the ten patients did not complete the study because of medication side effects. Eighty percent of patients receiving bupropion SR successfully stopped smoking by the end of week 2, and 6 (60%) of these 10 maintained smoking cessation at the study endpoint (week 12). At the 6-month follow-up, 40% of the patients (4 of 10) who received bupropion SR maintained smoking cessation. One (20%) of the five patients who received placebo stopped smoking and maintained smoking cessation at the 6-month follow-up. Bupropion SR was generally well-tolerated in combination with other psychotropic medications. Bupropion SR may be effective in helping patients who desire to quit smoking and who also have a concomitant anxiety disorder, such as PTSD.", "To compare the combination of a nicotine inhaler and bupropion to either treatment alone for initiating smoking abstinence and relapse prevention.\n Smokers were randomized to receive a nicotine inhaler, bupropion, or both for 3 months. At 3 months, smoking-abstinent study participants were randomized to their initial medications or placebo. Participants who were smoking at 3 months were randomized to an alternative treatment regimen or placebo. This study was conducted from July 2001 to January 2003.\n A total of 1700 smokers were randomized to treatment (phase 1) for 3 months. Among the 941 study participants eligible for randomization to the phase 2 trial, 837 continued in the study. For the phase 2 trial, 405 smoking-abstinent participants were randomized to relapse prevention for 9 additional months, and 432 smokers were randomized to re-treatment for an additional 3 months. At the end of the initial 3 months of treatment (phase 1), 82 (14%) of 566, 145 (26%) of 567, and 194 (34%) of 567 study participants receiving a nicotine inhaler, bupropion, or both, respectively, were abstinent from smoking. Of the 405 smoking-abstinent participants at the end of 3 months, the bupropion group had more smokers than the placebo group (mean No. of smokers, 1.5 vs 1.1; P < .001), and the nicotine inhaler group had higher smoking abstinence rates at 12 months than the placebo group. Those receiving combination therapy had reduced rates of relapse to smoking for the first 3 months of relapse prevention, but this difference disappeared after the initial 3 months. Of the 432 study participants who were smoking at the end of 3 months and who received an alternative treatment regimen, the 223 smokers initially assigned to a nicotine inhaler were more likely to stop smoking at 6 months if they were re-treated with bupropion instead of placebo (8 [7%] of 111 vs 0 [0%] of 112; P = .003), and the 209 smokers initially treated with bupropion and re-treated with a nicotine inhaler did not have significantly higher smoking abstinence rates (6 [6%] of 104 vs 3 [3%] of 105; P = -.50).\n Combined therapy with a nicotine inhaler and bupropion increased smoking abstinence rates. Continuation of the initial combination therapy does not appear to prevent relapse to smoking. Timing of re-treatment and alternative approaches to relapse prevention should be further examined.", "Gender data for bupropion suggest that it may be a particularly effective smoking cessation medication for women. It is not known whether the efficacy of this pharmacotherapy differs as a function of the psychotherapy with which it is administered. This study used a two level factorial design to examine the independent and interactive effects of medication (bupropion 300 mg/day vs. placebo) and psychotherapy (cognitive-behavioral therapy [CBT] vs. supportive therapy [ST]). In addition to testing the hypothesis that bupropion with CBT would be most effective of all the treatments, we examined medication compliance and its role in the efficacy of bupropion. Participants were 154 women, aged at least 30 years and smoking more than 10 cigarettes/day. Compliance with study medication was assessed using Medication Event Monitoring Systems (MEMS) over 7 weeks of treatment. Psychological interventions were delivered in 60-min weekly group sessions. Longitudinal analysis of abstinence outcomes from end of treatment (EOT) through 12 months after treatment revealed a significant interaction of medication and therapy. Higher abstinence rates at EOT and 3-, 6-, 9-, and 12-month follow-ups were observed when bupropion was delivered concurrently with CBT (44%, 24%, 30%, 23%, 17%) rather than with ST (18%, 1%, 8%, 5%, 2%). The bupropion-CBT combination, however, was not clearly superior to placebo, regardless of therapy assignment. Higher rates of medication compliance were positively predictive of abstinence, and this effect was most evident in the placebo condition. Findings provide only modest support for CBT as the preferred type of intensive therapy in conjunction with bupropion in women.", "In the current study, we investigated how individual variants in the serotonin promoter gene, previously associated with smoking cessation and linked to anxiety-related personality traits, were associated with individual differences in responsiveness to bupropion and cognitive behavioral therapy (CBT) in a clinical population. We hypothesize that subjects with the long allele may be less responsive to treatment. Altogether 61 schizophrenic patients (46 M, 15 F) on stable neuroleptic medication were initially enrolled in a smoking reduction program (prospective, double-blind, placebo-controlled) including cognitive behavioral therapy plus placebo or CBT plus bupropion. Additionally, subjects were genotyped for a polymorphism in the serotonin transporter (SLC6A4). Thirty-two subjects (23 M, 9 F) completed a 14-week course of treatment. While both groups of subjects demonstrated significant reductions in smoking behavior due to CBT, subjects receiving bupropion did not show significant differences in smoking behavior when compared to placebo. In addition, analysis by SPSS repeated measures multivariate showed a significant sex by SLC6A4 genotype interaction on the number of cigarettes smoked. Only male subjects with at least one short promoter region allele (short/short and short/long combined) showed a reduction in cigarette consumption as a result of treatment. This study provides preliminary evidence of how polymorphisms in the serotonin transporter can be informative in predicting individual responses to smoking reduction therapy.", "The authors present results of a randomized clinical trial of the efficacy of extended treatment with bupropion SR in producing longer term cigarette smoking cessation. Adult smokers (N = 362) received open-label treatment (11 weeks) that combined relapse prevention training, bupropion SR, and nicotine patch followed by extended treatment (14 weeks) with bupropion SR or matching placebo. Abstinence percentages were relatively high (week 11: 52%; week 25: bupropion, 42%; placebo, 38%; week 52: bupropion, 33%; placebo, 34%), but bupropion SR did not surpass placebo. Gender and baseline craving level were identified as significant, independent moderators of treatment response. Men were more likely to abstain than women (week 11: 59% vs. 43%, p = .001; week 25: 48% vs. 31%, p = .001; week 52: 39% vs. 27%, p = .01). Because most smokers suffer relapse with any current cessation treatment, the comparatively high abstinence percentages achieved in this trial are of interest.\n Copyright 2006 APA", "To determine whether (1) tailored nicotine patch therapy that is based on smoking rate can be carried out in a multisite oncology investigative group practice setting, (2) long-term use of bupropion reduces the rate of relapse to smoking in smokers who stop smoking with nicotine patch therapy, and (3) bupropion can initiate smoking abstinence among smokers who have failed to stop smoking after nicotine patch therapy. Participants and\n Fourteen North Central Cancer Treatment Group sites recruited generally healthy adult smokers from the general population for nicotine patch therapy and based the patch dosage on smoking rates. At completion of nicotine patch therapy, nonsmoking participants were eligible to be assigned to bupropion or placebo for 6 months (for relapse prevention). and smoking participants were eligible to be assigned to bupropion or placebo for 8 weeks of treatment.\n Of 578 subjects, 31% were abstinent from smoking at the end of nicotine patch therapy. Of those subjects not smoking at the end of nicotine patch therapy who entered the relapse prevention phase, 28% and 25% were not smoking at 6 months (the end of the medication phase) for bupropion and placebo, respectively (P =.73). For those still smoking at the end of nicotine patch therapy, 3.1% and 0.0% stopped smoking with bupropion or placebo, respectively (P =.12).\n Tailored nicotine patch therapy for the general population of smokers can be provided in a multisite oncology investigative group setting. Bupropion did not reduce relapse to smoking in smokers who stopped smoking with nicotine patch therapy. Bupropion did not initiate abstinence among smokers who failed to stop smoking with nicotine patch therapy.", "Currently available smoking cessation therapies have limited success rates. Varenicline tartrate is a novel, selective nicotinic receptor partial agonist developed specifically for smoking cessation. This study evaluated the efficacy, tolerability, and safety of 3 varenicline doses for smoking cessation. Bupropion hydrochloride was included as an active control.\n A phase 2, multicenter, randomized, double-blind, placebo-controlled study of healthy smokers (18-65 years old). Subjects were randomized to varenicline tartrate, 0.3 mg once daily (n = 128), 1.0 mg once daily (n = 128), or 1.0 mg twice daily (n = 127), for 6 weeks plus placebo for 1 week; to 150-mg sustained-release bupropion hydrochloride twice daily (n = 128) for 7 weeks; or to placebo (n = 127) for 7 weeks.\n During the treatment phase, the continuous quit rates for any 4 weeks were significantly higher for varenicline tartrate, 1.0 mg twice daily (48.0%; P<.001) and 1.0 mg once daily (37.3%; P<.001), than for placebo (17.1%). The bupropion rate was 33.3% (P = .002 vs placebo). The carbon monoxide-confirmed continuous quit rates from week 4 to week 52 were significantly higher in the varenicline tartrate, 1.0 mg twice daily, group compared with the placebo group (14.4% vs 4.9%; P = .002). The bupropion rate was 6.3% (P = .60 vs placebo). Discontinuation owing to treatment-emergent adverse events was 15.9% for bupropion, 11.2% to 14.3% for varenicline, and 9.8% for placebo. No dose-related increases occurred in adverse events for varenicline.\n Varenicline tartrate demonstrated both short-term (1 mg twice daily and 1 mg once daily) and long-term efficacy (1 mg twice daily) vs placebo. Varenicline was well tolerated and may provide a novel therapy to aid smoking cessation.", "To determine whether sustained-release bupropion promotes smoking reduction leading to smoking cessation among persons who wish to reduce their amount of smoking, but who are unwilling to quit or who perceive themselves as being unable to quit.\n Current smokers were assigned randomly to receive either sustained-release bupropion (150 mg twice daily) or matching placebo. During an initial 6-month smoking reduction phase, those who were willing to quit entered a 7-week cessation phase, during which study medication was continued.\n Four-week continuous abstinence rates were 14% (41/295) in the bupropion group and 8% (25/299) in the placebo group (P = 0.02) during treatment. However, this benefit did not continue after treatment was stopped; subsequent continuous abstinence rates were 7% (20/295) in the bupropion group and 5% (16/299) in the placebo group (P = 0.50). Similar proportions of subjects entered the cessation phase in both treatment groups (38% [n = 113] of those in the bupropion group and 34% [n = 101] of those in the placebo group), although the time until a cessation attempt was shorter for those taking bupropion (median, 64 days vs. 118 days, P = 0.008). The extent of smoking reduction (measured by urinary cotinine concentrations) among the 327 subjects who did not enter the cessation phase was significantly greater (P <0.05) in those treated with bupropion during the reduction treatment phase, but not during the month 12 follow-up visit (P = 0.25).\n Sustained-release bupropion, when used in smokers initially not willing to make a cessation attempt, can help sustain smoking reduction while subjects are on active medication, reduce the time until the next cessation attempt, and increase short-term abstinence rates. However, these benefits were modest and not sustained after bupropion was discontinued.", "Human behavioral pharmacology studies can examine how medications that target different neurotransmitter systems influence different aspects of smoking. Naltrexone and bupropion have been shown to alter ad lib smoking behavior; however, medication effects on nicotine reward in a cigarette choice paradigm have yet to be investigated.\n This study explored the effects of an acute dose of naltrexone, bupropion, or placebo on the relative reinforcing value of nicotine from cigarette smoking using new nicotine and de-nicotinized (Quest, 0.6 and 0.05 mg = \"denicotinized\") cigarettes.\n In a double-blind, within-subjects design, 26 dependent smokers participated in three experimental cigarette smoking sessions following pretreatment with either naltrexone (50 mg), bupropion (300 mg), or placebo. After medication administration and 2 h of monitored deprivation from cigarettes and food, participants rated their responses to the initial exposure to the cigarettes and then participated in four choice sessions over a 2-h period during which they could take four puffs from either cigarette.\n The relative reinforcing value of nicotine, as measured by the number of nicotine puffs chosen out of 16, was significantly lower following naltrexone compared to placebo. There were no effects of an acute dose of bupropion on nicotine choices.\n These results suggest that naltrexone may reduce the relative reinforcing effects of nicotine via cigarette smoking and support ongoing investigation of opioid antagonists as potential smoking cessation pharmacotherapies.", "Smoking relapse is common after successful pharmacologic treatment for smoking cessation. No previous studies have examined long-term drug therapy used expressly for prevention of smoking relapse.\n To evaluate the efficacy of bupropion to prevent smoking relapse.\n Randomized, placebo-controlled trial.\n 784 healthy community volunteers who were motivated to quit smoking and who smoked at least 15 cigarettes per day.\n The participants received open-label, sustained-release bupropion, 300 mg/d, for 7 weeks. Participants who were abstinent throughout week 7 of open-label treatment were randomly assigned to receive bupropion, 300 mg/d, or placebo for 45 weeks and were subsequently followed for an additional year after the conclusion of the medication phase. Participants were briefly counseled at all follow-up visits. At the end of open-label bupropion treatment, 461 of 784 participants (58.8%) were abstinent from smoking.\n Self-reported abstinence was confirmed by an expired air carbon monoxide concentration of 10 parts per million or less.\n The point prevalence of smoking abstinence was significantly higher in the bupropion group than in the placebo group at the end (week 52) of drug therapy (55.1% vs. 42.3%, respectively; P = 0.008) and at week 78 (47.7% vs. 37.7%; P = 0.034) but did not differ at the final (week 104) follow-up visit (41.6% vs. 40.0%). The median time to relapse was significantly greater for bupropion recipients than for placebo recipients (156 days vs. 65 days; P = 0.021). The continuous abstinence rate was higher in the bupropion group than in the placebo group at study week 24 (17 weeks after randomization) (52.3% vs. 42.3%; P = 0.037) but did not differ between groups after week 24. Weight gain was significantly less in the bupropion group than in the placebo group at study weeks 52 (3.8 kg vs. 5.6 kg; P = 0.002) and 104 (4.1 kg vs. 5.4 kg; P = 0.016).\n In persons who stopped smoking with 7 weeks of bupropion treatment, sustained-release bupropion for 12 months delayed smoking relapse and resulted in less weight gain.", "Randomized efficacy clinical trials conducted in research settings may not accurately reflect the benefits of tobacco dependence treatments when used in real-world clinical settings. Effectiveness trials (eg, in primary care settings) are needed to estimate the benefits of cessation treatments in real-world use.\n A total of 1346 primary care patients attending routine appointments were recruited by medical assistants in 12 primary care clinics. Patients were randomly assigned to 5 active pharmacotherapies: 3 monotherapies (nicotine patch, nicotine lozenge, and bupropion hydrochloride sustained release [SR]) and 2 combination therapies (patch + lozenge and bupropion SR + lozenge). Patients were referred to a telephone quit line for cessation counseling. Primary outcomes included 7-day point prevalence abstinence at 1 week, 8 weeks, and 6 months after quitting and number of days to relapse.\n Among 7128 eligible smokers (> or =10 cigarettes per day) attending routine primary care appointments, 1346 (18.9%) were enrolled in the study. Six-month abstinence rates for the 5 active pharmacotherapies were the following: bupropion SR, 16.8%; lozenge, 19.9%; patch, 17.7%; patch + lozenge, 26.9%; and bupropion SR + lozenge, 29.9%. Bupropion SR + lozenge was superior to all of the monotherapies (odds ratio, 0.46-0.56); patch + lozenge was superior to patch and bupropion monotherapies (odds ratio, 0.56 and 0.54, respectively).\n One in 5 smokers attending a routine primary care appointment was willing to make a serious quit attempt that included evidence-based counseling and medication. In this comparative effectiveness study of 5 tobacco dependence treatments, combination pharmacotherapy significantly increased abstinence compared with monotherapies. Provision of free cessation medications plus quit line counseling arranged in the primary care setting holds promise for assisting large numbers of smokers to quit. Trial Registration clinicaltrials.gov Identifier: NCT00296647.", "Depression is an international public health problem. Impairment in social and occupational functioning, increased comorbidity with other psychiatric and medical conditions, and an increased risk of mortality are a few of its consequences. Some psychiatrists have the impression that selective serotonin re-uptake inhibitors may not work as well as tricyclic anti-depressants in severe depression and/or melancholia. On the contrary, there is a general belief that selective serotonin re-uptake inhibitors are superior to the tricyclic anti-depressants in having fewer side-effects, particularly cardiovascular effects. The objective of this double-blind study was to compare the efficacy and safety of fluoxetine and nortriptyline in patients with moderate to severe major depression.\n A total of 48 adult outpatients who met the Diagnostic and Statistical Manual of Mental Disorders (DSM IV), forth edition for major depression, based on the structured clinical interview for DSM IV participated in the trial. Patients had a baseline Hamilton Rating Scale for Depression score of at least 20. In this double-blind, single-center trial, patients were randomly assigned to receive nortriptyline 150 mg/day (group 1) or fluoxetine 60 mg/day (group 2) for 6-weeks. The outcome of the two groups was assessed using Hamilton Depression Rating Scale, a side-effect checklist and a regular ECG assessment.\n The results suggest that the efficacy of nortriptyline is superior to fluoxetine in this group of major depressed patients. No significant differences were observed between dropout rates in the two groups but anti-cholinergic side-effects were significantly more frequent with nortriptyline than with fluoxetine but there was no significant difference in cardiovascular effects in particular QTc prolongation.\n The results of the current study suggest that nortriptyline was more effective than fluoxetine in the treatment of moderate to severe depression. A larger study is warranted.", "In this double-blind, placebo-controlled smoking cessation treatment study, 608 participants were randomly assigned to receive active bupropion and active 4-mg gum (AA, n = 228), active bupropion and placebo gum (AP, n = 224), or placebo bupropion and placebo gum (PP, n = 156). Relative to the PP group, the AA and AP groups were each significantly more likely to be abstinent at 1 week, end of treatment, and 6 months but not at 12 months postquit. After the first week postquit there were no differences in abstinence rates between the AA and AP groups. We found no significant individual difference variables that moderated outcome beyond 1 week postquit.", "The alpha4beta2 nicotinic acetylcholine receptors (nAChRs) are linked to the reinforcing effects of nicotine and maintaining smoking behavior. Varenicline, a novel alpha4beta2 nAChR partial agonist, may be beneficial for smoking cessation.\n To assess efficacy and safety of varenicline for smoking cessation compared with sustained-release bupropion (bupropion SR) and placebo.\n Randomized, double-blind, parallel-group, placebo- and active-treatment-controlled, phase 3 clinical trial conducted at 19 US centers from June 19, 2003, to April 22, 2005. Participants were 1025 generally healthy smokers (> or =10 cigarettes/d) with fewer than 3 months of smoking abstinence in the past year, 18 to 75 years old, recruited via advertising.\n Participants were randomly assigned in a 1:1:1 ratio to receive brief counseling and varenicline titrated to 1 mg twice per day (n = 352), bupropion SR titrated to 150 mg twice per day (n = 329), or placebo (n = 344) orally for 12 weeks, with 40 weeks of nondrug follow-up.\n Primary outcome was the exhaled carbon monoxide-confirmed 4-week rate of continuous abstinence from smoking for weeks 9 through 12. A secondary outcome was the continuous abstinence rate for weeks 9 through 24 and weeks 9 through 52.\n For weeks 9 through 12, the 4-week continuous abstinence rates were 44.0% for varenicline vs 17.7% for placebo (odds ratio [OR], 3.85; 95% confidence interval [CI], 2.70-5.50; P<.001) and vs 29.5% for bupropion SR (OR, 1.93; 95% CI, 1.40-2.68; P<.001). Bupropion SR was also significantly more efficacious than placebo (OR, 2.00; 95% CI, 1.38-2.89; P<.001). For weeks 9 through 52, the continuous abstinence rates were 21.9% for varenicline vs 8.4% for placebo (OR, 3.09; 95% CI, 1.95-4.91; P<.001) and vs 16.1% for bupropion SR (OR, 1.46; 95% CI, 0.99-2.17; P = .057). Varenicline reduced craving and withdrawal and, for those who smoked while receiving study drug, smoking satisfaction. No sex differences in efficacy for varenicline were observed. Varenicline was safe and generally well tolerated, with study drug discontinuation rates similar to those for placebo. The most common adverse events for participants receiving active-drug treatment were nausea (98 participants receiving varenicline [28.1%]) and insomnia (72 receiving bupropion SR [21.9%]).\n Varenicline was significantly more efficacious than placebo for smoking cessation at all time points and significantly more efficacious than bupropion SR at the end of 12 weeks of drug treatment and at 24 weeks.\n clinicaltrials.gov Identifier: NCT00141206.", "Smokers (N = 224) were randomized to 1 of 3 groups: (a) transdermal system (TNS) + placebo; (b) TNS + paroxetine (20 mg); (c) TNS + paroxetine (40 mg). Assignment to treatment was double-blind. Nicotine patch (TNS) treatment was provided for 8 weeks; paroxetine or placebo was provided for 9 weeks. Abstinence rates at Weeks 4, 10, and 26 were as follows: (a) TNS + placebo: 45%, 36%, and 25%; (b) TNS + paroxetine (20 mg): 48%, 33%, and 21%; (c) TNS + paroxetine (40 mg): 57%, 39%, and 27%. The differences were not statistically significant. The combined treatment was more effective in reducing both craving and depression symptoms associated with smoking cessation. A subgroup analysis comparing compliant participants was also conducted. Abstinence rates at Weeks 4, 10, and 26 were as follows: (a) TNS + placebo: 46%, 35%, and 24%; (b) TNS + paroxetine (20 mg): 64%, 43%, and 33%; (c) TNS + paroxetine (40 mg): 74%, 51%, and 38%. The differences between paroxetine groups and placebo at Week 4 were statistically significant. Although paroxetine may add value to the current standard of care in excess of potential risk, more conclusive evidence is needed.", "The authors evaluated the efficacy of fluoxetine hydrochloride (Prozac; Eli Lilly and Company, Indianapolis, IN) as an adjunct to behavioral treatment for smoking cessation. Sixteen sites randomized 989 smokers to 3 dose conditions: 10 weeks of placebo, 30 mg, or 60 mg fluoxetine per day. Smokers received 9 sessions of individualized cognitive-behavioral therapy, and biologically verified 7-day self-reported abstinence follow-ups were conducted at 1, 3, and 6 months posttreatment. Analyses assuming missing data counted as smoking observed no treatment difference in outcomes. Pattern-mixture analysis that estimates treatment effects in the presence of missing data observed enhanced quit rates associated with both the 60-mg and 30-mg doses. Results support a modest, short-term effect of fluoxetine on smoking cessation and consideration of alternative models for handling missing data.", "Bupropion is a first-line pharmacological aid for smoking cessation; however, no clinical trials have been conducted in a general population of hospitalized smokers.\n We enrolled 85 smokers in a hospital-based randomized smoking cessation trial conducted at the San Francisco Veterans Affairs Medical Center. A total of 42 participants received a 7-week course of sustained-release bupropion and 43 participants received placebo. All participants received cognitive-behavioral counseling. We screened 14,997 patients, of whom 25% were current smokers. Of the 536 smokers who met the entry criteria, 451 opted not to enroll. We determined on-medication, end-of-medication, 3-month, and 6-month smoking cessation rates.\n At the end of 7 weeks of drug treatment, self-reported quit rates were equivalent in the bupropion and placebo arms, 37% versus 33%, respectively (p = .82). The validated quit rates for the bupropion and placebo groups were 27% versus 29%, respectively (p = 1.00). At 6 months, the self-reported quit rates were 29% in the bupropion group and 41% in the placebo group (p = .36). In a comparison of 6-month quit rates, validated either by salivary cotinine or by spousal proxy, we found nonsignificantly higher quit rates in the placebo group than in the bupropion group, 31% versus 15% (p = .12).\n The addition of sustained-release bupropion to counseling did not increase quit rates, but the study was underpowered. Because of the secular trend toward shorter hospital stays, recruitment was very difficult, raising questions regarding the feasibility of future hospital-based smoking cessation trials and interventions.", "To investigate the safety and efficacy of bupropion sustained release (bupropion SR) in promoting abstinence from smoking in subjects with cardiovascular disease (CVD).\n Six hundred twenty-nine subjects with CVD who smoked >/=10 cigarettes/day were randomised in a double-blind, multicentre study to receive bupropion SR (150 mg twice daily) or placebo for 7 weeks, with a follow-up of 52 weeks. Primary efficacy endpoint: continuous abstinence from smoking from weeks 4 to 7. Secondary endpoints: continuous abstinence (weeks 4-12, 4-26 and 4-52) and weekly point prevalence abstinence. All participants received brief motivational support. Safety was evaluated throughout the study.\n Continuous smoking abstinence rates from weeks 4 to 7 were significantly higher in subjects receiving bupropion SR compared with placebo (43 vs. 19%, odds ratio [OR]=3.27, 95% confidence interval [CI] 2.24-4.84; P<0.001). Continuous abstinence rates from weeks 4 to 26 and 4 to 52 continued to be more than double for bupropion SR compared with placebo (27 vs. 11%; 22 vs. 9%, P<0.001). Weekly point prevalence abstinence was significantly higher for participants who received bupropion SR compared with placebo at weeks 3, 7, 26 and 52 (P<0.001). In both groups, there were no clinically significant changes in blood pressure and heart rate throughout the treatment phase. Overall, 6% of the participants (n=36) discontinued study medication due to an adverse event (bupropion SR, n=17; placebo, n=19).\n After 7 weeks of bupropion SR treatment, more than twice as many smokers with CVD had quit smoking at 1 year compared with placebo. The safety profile of bupropion SR was similar to that previously observed in general smoking populations.", "Individuals with schizophrenia have high smoking-related morbidity and mortality rates and need powerful and innovative smoking cessation interventions.\n This proof-of-concept study investigated the feasibility and initial efficacy of combining a contingency management intervention with bupropion to reduce smoking in people with schizophrenia.\n Using a double-blind, placebo-controlled, between-groups design, 57 non-treatment-seeking participants were randomized to receive 300 mg/day bupropion or placebo. One week later, participants were randomized to a contingency management (CM) intervention in which reductions in urinary cotinine levels were reinforced, or a non-contingent reinforcement (NR) condition in which session attendance was reinforced, regardless of cotinine level. Over the 22-day study period, participants visited the laboratory approximately three times per week to provide urine samples for analysis of cotinine levels, to give breath samples for analysis of carbon monoxide (CO) levels, and to report number of cigarettes smoked per day, nicotine withdrawal symptoms, cigarette craving, and psychiatric symptoms.\n Cotinine and CO levels significantly decreased during the study period in participants randomized to the CM condition, but not the NR condition. Bupropion did not reduce cotinine levels or increase the efficacy of CM. Cigarette craving and psychiatric symptom levels significantly decreased during the study in all groups.\n The results of this study indicate the efficacy and feasibility of this CM intervention for reducing smoking in individuals with schizophrenia.", "Smokers hospitalized with acute coronary syndrome (ACS) are at high risk for subsequent ischemic events. Nevertheless, over two-thirds of patients continue to smoke after an acute myocardial infarction. Bupropion hydrochloride has proven efficacy as a smoking cessation aid, but data regarding its safety and efficacy in ACS patients are limited.\n In a double-blind, randomized controlled trial, we compared the safety and efficacy of 8 weeks of treatment with bupropion slow-release (SR) or placebo for smokers hospitalized with ACS as an adjunct to nurse-led hospital- and telephone-based support. Primary efficacy outcome was smoking abstinence at 1 year. Primary safety outcome was clinical events at 1 year.\n A total of 151 patients were enrolled; all but 2 completed follow-up. Abstinence rates at 3 months were 45% and 44% in the bupropion SR and placebo groups, respectively (P = .99); 37% vs 42% (P = .61) at 6 months; and 31% vs 33% (P = .86) at 1 year. On multivariate analysis, an invasive procedure performed during index hospitalization was an independent predictor for smoking abstinence at 1 year (odds ratio [OR], 4.2; 95% confidence interval [CI], 1.22-14.19). Presence of adverse effects attributed to treatment was a negative predictor for smoking cessation (OR, 0.23; 95% CI, 0.07-0.78). Treatment with bupropion SR was not associated with an increase in clinical events or change in blood pressure or body mass index, but dizziness was more common compared with placebo (14% vs 1.4%; P = .005).\n In hospitalized patients with ACS who received continuous, intensive nurse counseling about smoking cessation, bupropion did not increase the rates of smoking abstinence.", "Varenicline, a partial agonist at the alpha4beta2 nicotinic acetylcholine receptor, has the potential to aid smoking cessation by relieving nicotine withdrawal symptoms and reducing the rewarding properties of nicotine.\n To determine the efficacy and safety of varenicline for smoking cessation compared with placebo or sustained-release bupropion (bupropion SR).\n A randomized, double-blind, placebo-controlled trial conducted between June 2003 and March 2005 at 14 research centers with a 12-week treatment period and follow-up of smoking status to week 52. Of 1413 adult smokers who volunteered for the study, 1027 were enrolled; 65% of randomized participants completed the study.\n Varenicline titrated to 1 mg twice daily (n = 344) or bupropion SR titrated to 150 mg twice daily (n = 342) or placebo (n = 341) for 12 weeks, plus weekly brief smoking cessation counseling.\n Continuous abstinence from smoking during the last 4 weeks of treatment (weeks 9-12; primary end point) and through the follow-up period (weeks 9-24 and 9-52).\n During the last 4 weeks of treatment (weeks 9-12), 43.9% of participants in the varenicline group were continuously abstinent from smoking compared with 17.6% in the placebo group (odds ratio [OR], 3.85; 95% confidence interval [CI], 2.69-5.50; P<.001) and 29.8% in the bupropion SR group (OR, 1.90; 95% CI, 1.38-2.62; P<.001). For weeks 9 through 24, 29.7% of participants in the varenicline group were continuously abstinent compared with 13.2% in the placebo group (OR, 2.83; 95% CI, 1.91-4.19; P<.001) and 20.2% in the bupropion group (OR, 1.69; 95% CI, 1.19-2.42; P = .003). For weeks 9 through 52, 23% of participants in the varenicline group were continuously abstinent compared with 10.3% in the placebo group (OR, 2.66; 95% CI, 1.72-4.11; P<.001) and 14.6% in the bupropion SR group (OR, 1.77; 95% CI, 1.19-2.63; P = .004). Treatment was discontinued due to adverse events by 10.5% of participants in the varenicline group, 12.6% in the bupropion SR group, and 7.3% in the placebo group. The most common adverse event with varenicline was nausea, which occurred in 101 participants (29.4%).\n Varenicline is an efficacious, safe, and well-tolerated smoking cessation pharmacotherapy. Varenicline's short-term and long-term efficacy exceeded that of both placebo and bupropion SR.\n clinicaltrials.gov Identifier: NCT00143364.", "Accepted treatments for cigarette smoking rarely achieve abstinence rates of >35% at 1 year. Low rates may reflect failure to provide extended and multifocal treatment for this complex and chronic addiction. Using a chronic disease model of smoking, the authors undertook a study to determine the effects of long-term antidepressant and psychological treatment.\n One hundred sixty smokers of > or =10 cigarettes/day were randomly assigned to one of four treatment conditions in a two-by-two (nortriptyline versus placebo by brief versus extended treatment) design. All subjects received 8 weeks of a transdermal nicotine patch, five group counseling sessions, and active or placebo treatment. Interventions for subjects in brief treatment ended at this point. Subjects in extended treatment continued taking drug or placebo to week 52 and received an additional 9 monthly counseling sessions, with checkup telephone calls midway through each session. Subjects were assessed at baseline and weeks 12, 24, 36, and 52. The principal outcome variables were repeated abstinence at each assessment after the first over a 1-year period and a point prevalence of 7 days of abstinence.\n At week 52, point-prevalence abstinence rates with missing subjects imputed as smokers were 30% for placebo brief treatment, 42% for placebo extended treatment, 18% for active brief treatment, and 50% for active extended treatment. With missing subjects omitted, these rates were 32%, 57%, 21%, and 56%, respectively.\n Comprehensive extended treatments that combine drug and psychological interventions can produce consistent abstinence rates that are substantially higher than those in the literature.", "To evaluate bupropion SR for smoking cessation in physicians and nurses.\n This double-blind prospective 26-center, 12-country trial randomized 687 subjects to smoking cessation counselling with bupropion SR or placebo for 7 weeks. The participants were followed for 52 weeks.\n Bupropion SR was superior to placebo (50% vs 40%, P=0.013) on the 4-week primary outcome variable. Due to a high placebo response in this health care population, statistical differences were not maintained after treatment was discontinued.\n Bupropion SR is effective and well tolerated in health care professionals. Relapse prevention measures are needed to attain long-term abstinence.", "Bupropion sustained release (bupropion SR) has been shown to increase smoking cessation success rates in the US studies.\n To determine whether bupropion SR, in combination with counselling, is effective for smoking cessation in a multi-country study.\n This randomized, double-blind, placebo-controlled trial enrolled 707 smokers. A total of 527 received bupropion SR 300 mg daily for 7 weeks and 180 received placebo. A total of 11 clinic visits and 10 telephone contacts were scheduled, during the course of 1 year. Seven-week and 12-month abstinence rates were the study outcomes.\n Both continuous and weekly point prevalence smoking abstinence rates were significantly higher in the bupropion SR group compared with placebo. The continuous abstinence rate from weeks 4 to 7 was 46% in the bupropion SR group compared with 23% in the placebo group [odds ratio (OR) = 2.82; 95% confidence interval (CI) 1.89-4.28; P < 0.001). At month 12, the continuous abstinence rates were 21% for the bupropion SR group and 11% for the placebo group (OR = 2.19; 95% CI 1.29-3.86, P = 0.002). For most nicotine-withdrawal symptoms small changes were measured. Adverse events were higher for the bupropion SR group compared with placebo (insomnia 24% vs. 15%; dry mouth 13% vs. 5%).\n Bupropion SR in combination with counselling increased the abstinence rate compared with placebo, and was well tolerated.", "Few pharmacological therapies have been shown to increase abstinence rates among spit tobacco (ST) users. Bupropion has been shown to be effective in increasing abstinence rates among smokers but has not been studied in ST users. Sixty-eight adult (aged > or = 18 years old) regular users of ST who were motivated to stop using ST were enrolled in a randomized, double-blind, placebo-controlled pilot study of bupropion sustained release (SR) or placebo for 12 weeks. The primary endpoint was 1-week, biochemically confirmed point-prevalence tobacco abstinence rate at the end of treatment (week 12). Nicotine withdrawal symptoms and weight change were assessed. At the end of 12 weeks of therapy, the point-prevalence tobacco abstinence rate was 44% in the bupropion group and 26% in the placebo group (p = 0.064). At 24 weeks following initiation of medication, the point-prevalence abstinence rate was 29% for both groups. After 7 weeks of medication, subjects on bupropion reported significantly less (p< or = 0.034) nicotine withdrawal than placebo. The mean weight change from baseline to end of treatment was +0.7 +/- 1.9 kg for bupropion and +4.4 +/- 2.4 kg for placebo (p = 0.03). The 6-month weight change for continuously abstinent subjects was 3.4 +/- 3.6 kg in the bupropion group and 6.2 +/- 5.0 kg in the placebo group (p = 0.49). Bupropion may increase abstinence rates in ST users and appears to attenuate weight gain during ST abstinence. Larger randomized, controlled trials of bupropion for ST users are needed.", "Adolescent smokers (N = 211) were randomized to 1 of 2 groups: (a) nicotine patch plus bupropion SR (sustained release; 150 mg per day) or (b) nicotine patch plus placebo. Group skills training sessions were conducted each week by research staff. Abstinence rates at Weeks 10 and 26 were as follows: (a) patch plus bupropion, 23% and 8%, (b) patch plus placebo, 28% and 7%. Despite the lack of a treatment effect, a large majority of adolescents in both treatment groups reduced their consumption to a few cigarettes per day or less and maintained this reduction over time. Similarly, an examination of survival curves revealed that by the end of treatment many had managed to avoid a return to daily smoking. These findings are encouraging and suggest new avenues for research. For example, treatments of the kind examined in this report, augmented by extended maintenance therapies, may yield higher long-term success rates.", "Evidence that major depression can be a significant hindrance to smoking cessation prompted this examination of the usefulness of sertraline as a cessation aid for smokers with a history of major depression. Specifically, sertraline's efficacy for smoking abstinence and its effects on withdrawal symptoms were evaluated.\n The study design included a 1-week placebo washout, a 9-week double-blind, placebo-controlled treatment phase followed by a 9-day taper period, and a 6-month drug-free follow-up. One hundred thirty-four smokers with a history of major depression were randomly assigned to receive sertraline (N=68) or matching placebo (N=66); all received intensive individual cessation counseling during nine clinic visits.\n Sertraline treatment produced a lower total withdrawal symptom score and less irritability, anxiety, craving, and restlessness than placebo. However, the abstinence rates did not significantly differ between treatment groups: 28.8% (19 of 66) for placebo and 33.8% (23 of 68) for sertraline at the end of treatment and 16.7% (11 of 66) for placebo and 11.8% (eight of 68) for sertraline at the 6-month follow-up. No moderating effects of single or recurrent major depression, depressed mood at baseline, nicotine dependence level, or gender were observed.\n Sertraline did not add to the efficacy of an intensive individual counseling program in a double-blind, placebo-controlled study. However, given that the end-of-treatment abstinence rate for the placebo group was much higher than expected, it is unclear whether a ceiling effect of the high level of psychological intervention received by all subjects prevented an adequate test of sertraline.", "To assess the effectiveness of moclobemide on smoking cessation and abstinence in heavy, dependent smokers. There is a strong association between smoking and depression, especially in dependent smokers. It was hypothesized that smoking is a self-medication to treat depression. Cigarette smoke has monoamine oxidase (MAO)-inhibitory properties, and smokers have lower MAO activity than non-smokers.\n We used a randomized, double-blind, placebo-controlled parallel-group study. Placebo or moclobemide, 400 mg/day for 2 months and 200 mg/day during the third month, was given. Main outcome measures were self-reported and biochemically verified (plasma cotinine levels, < 20 ng/ml) abstinence rate. Secondary outcome measures were withdrawal symptoms, Montgomery-Asberg Depression Rating Scale, Hamilton anxiety rating scores, platelet MAO-B activity, and plasma dihydroxyphenylglycol as a measure of MAO-A activity.\n Eighty-eight smokers were randomized to receive moclobemide (n = 44) or placebo (n = 44). The continuous self-reported abstinence rate was higher with moclobemide than with placebo (intention-to-treat analysis until the end point, 6 months: p < 0.05; until the end of follow-up, 1 year: p = 0.09). The abstinence rate according to plasma cotinine levels showed a trend to effectiveness of moclobemide (end point: p = 0.13; follow-up: p = 0.12). Platelet MAO-B activity increased after smoking cessation but without a significant difference. Plasma dihydroxyphenylglycol levels did not change in the placebo group but decreased dose dependently in the moclobemide group. No difference occurred for withdrawal symptoms, Montgomery-Asberg Depression Rating Scale, and Hamilton anxiety scores. Cessation of moclobemide had no adverse effect. More subjects reported insomnia with moclobemide (n = 16) than with placebo (n = 3).\n In this preliminary study, the reversible, selective MAO inhibitor moclobemide facilitated smoking cessation in highly dependent smokers. Further studies with substantially more smokers are needed to evaluate the role of MAO inhibitors in smoking cessation and abstinence in smokers with high nicotine dependence.", "Smoking cessation after myocardial infarction reduces cardiovascular mortality, but many smokers cannot quit despite state-of-the-art counseling intervention. Bupropion is effective for smoking cessation, but its safety and efficacy in hospitalized smokers with acute cardiovascular disease is unknown.\n A five-hospital randomized double-blind placebo-controlled trial assessed the safety and efficacy of 12 weeks of sustained-release bupropion (300 mg) or placebo in 248 smokers admitted for acute cardiovascular disease, primarily myocardial infarction and unstable angina. All subjects had smoking counseling in the hospital and for 12 weeks after discharge. Cotinine-validated 7-day tobacco abstinence, cardiovascular mortality, and new cardiovascular events were assessed at 3 months (end-of-treatment) and 1 year.\n Validated tobacco abstinence rates in bupropion and placebo groups were 37.1% vs 26.8% (OR 1.61, 95% CI, 0.94-2.76; P=.08) at 3 months and 25.0% vs 21.3% (OR, 1.23, 95% CI, 0.68-2.23, P=.49) at 1 year. The adjusted odds ratio, after controlling for cigarettes per day, depression symptoms, prior bupropion use, hypertension, and length of stay, was 1.91 (95% CI, 1.06-3.40, P=.03) at 3 months and 1.51 (95% CI, 0.81-2.83) at 1 year. Bupropion and placebo groups did not differ in cardiovascular mortality at 1 year (0% vs 2%), in blood pressure at follow-up, or in cardiovascular events at end-of-treatment (16% vs 14%, incidence rate ratio [IRR]1.22 (95% CI: 0.64-2.33) or 1 year (26% vs 18%, IRR 1.56, 95% CI 0.91-2.69).\n Bupropion improved short-term but not long-term smoking cessation rates over intensive counseling and appeared to be safe in hospitalized smokers with acute cardiovascular disease." ]	The antidepressants bupropion and nortriptyline aid long-term smoking cessation but selective serotonin reuptake inhibitors (e.g. fluoxetine) do not. Evidence suggests that the mode of action of bupropion and nortriptyline is independent of their antidepressant effect and that they are of similar efficacy to nicotine replacement. Adverse events with both medications appear to be rarely serious or lead to stopping medication.
CD001203	[ "17055767", "16269638", "15827910", "9550512", "15774435", "15066200" ]	[ "Effectiveness of physiotherapy in Parkinson's disease: the feasibility of a randomised controlled trial.", "Facilitation of sensory and motor recovery by thermal intervention for the hemiplegic upper limb in acute stroke patients: a single-blind randomized clinical trial.", "Efficacy of a physical therapy program in patients with Parkinson's disease: a randomized controlled trial.", "Effect of a therapeutic intervention for the hemiplegic upper limb in the acute phase after stroke: a single-blind, randomized, controlled multicenter trial.", "Comparison of Bobath based and movement science based treatment for stroke: a randomised controlled trial.", "An outreach intervention to implement evidence based practice in residential care: a randomized controlled trial [ISRCTN67855475]." ]	[ "To study the feasibility of a large randomised controlled trial (RCT) evaluating the effectiveness of physiotherapy in Parkinson's disease (PD), 173 patients were asked to participate in a study with random allocation to best practice physiotherapy, or to no physiotherapy. The primary outcome measures were the Parkinson's disease questionnaire-39, the Parkinson activity scale, and a patient preference outcome scale (PPOS). Only 14% of the patients could be included in the study. The PPOS showed the largest effect size (0.74) with a significant group effect (p<0.05). Specific alterations to the study design to ensure successful RCTs in this field are recommended.", "Thermal stimulation (TS) is commonly used in orthopedic rehabilitation, but the role of TS in the facilitation of sensorimotor recovery in hemiplegic patients remains unknown. This study addressed the issue of TS intervention in the facilitation of functional outcomes.\n Forty-six stroke survivors were randomly assigned to standard rehabilitation treatment and standard treatment plus TS (30 minutes daily for 6 weeks). Twenty-nine patients completed the experiment. Six measures, including Brunnstrom stage, modified motor assessment scale, grasping strength, angles of wrist extension and flexion, sensation by monofilament, and muscle tone by modified Ashworth scale, were performed weekly to evaluate sensory and motor functional outcomes.\n The performance of Brunnstrom stage and wrist extension and sensation were improved significantly after TS intervention. Recovery rates of 6 measures after TS were significantly higher than those of the control, except for grasping. Similar muscle tones were found in both groups.\n TS on the paretic hand significantly enhances the recovery of several aspects of sensory and motor functions in hemiplegic stroke patients.", "To investigate the effects of a physical therapy (PT) program in groups of people with Parkinson's disease (PD).\n Randomized controlled trial with a crossover design.\n Two outpatient rehabilitation clinics in Boston and Amsterdam, respectively.\n Sixty-eight subjects diagnosed with typical, idiopathic PD, Hoehn and Yahr stage II or III, and stable medication use.\n Group A received PT and medication therapy (MT) for the first 6 weeks, followed by MT only for the second 6 weeks. Group B received only MT for the first 6 weeks and PT and MT for the second 6 weeks.\n The Sickness Impact Profile (SIP-68), the mobility portion of the SIP-68, the Unified Parkinson's Disease Rating Scale (UPDRS), and comfortable walking speed (CWS) at baseline, 6-week, 12-week, and 3-month follow-up.\n At 6 weeks, differences between groups were significant for the SIP mobility ( P =.015; effect size [ES]=.55), for CWS ( P =.012; ES=.49), for the activities of daily living (ADL) section of the UPDRS ( P =.014; ES=.45), and for the total UPDRS ( P =.007; ES=.56). The total SIP and the mentation and motor sections of the UPDRS did not differ significantly between groups. Significant differences were found at 3 months compared with baseline for CWS, the UPDRS ADL, and total scores.\n People with PD derive benefits in the short term from PT group treatment, in addition to their MT, for quality of life related to mobility, CWS, and ADLs; long-term benefits were found in CWS, UPDRS ADL, and total scores but varied between groups.", "Arm function recovery is notoriously poor in stroke patients. The effect of treatment modalities, particularly those directed at improving upper limb function, has been studied primarily in chronic stroke patients. The purpose of this study was to investigate the effect of a specific therapeutic intervention on arm function in the acute phase after stroke.\n In a single-blind, randomized, controlled multicenter trial, 100 consecutive patients were allocated to either an experimental group that received an additional treatment of sensorimotor stimulation or to a control group. The intervention was applied for 6 weeks. Patients were evaluated for level of impairment (Brunnström-Fugl-Meyer test) and disability (Action Research Arm test, Barthel Index) before, midway, and after the intervention period and at follow-up 6 and 12 months after stroke.\n Patients in the experimental group performed better on the Brunnström-Fugl-Meyer test than those in the control group throughout the study period, but differences were significant only at follow-up. Results on the Action Research Arm test and Barthel Index revealed no effect at the level of disability. The effect of the therapy was attributed to the repetitive stimulation of muscle activity. The treatment was most effective in patients with a severe motor deficit and hemianopia or hemi-inattention. No adverse effects due to the intervention were found.\n Adding a specific intervention during the acute phase after stroke improved motor recovery, which was apparent 1 year later. These results emphasize the potential beneficial effect of therapeutic interventions for the arm.", "Bobath based (BB) and movement science based (MSB) physiotherapy interventions are widely used for patients after stroke. There is little evidence to suggest which is most effective. This single-blind randomised controlled trial evaluated the effect of these treatments on movement abilities and functional independence.\n A total of 120 patients admitted to a stroke rehabilitation ward were randomised into two treatment groups to receive either BB or MSB treatment. Primary outcome measures were the Rivermead Motor Assessment and the Motor Assessment Scale. Secondary measures assessed functional independence, walking speed, arm function, muscle tone, and sensation. Measures were performed by a blinded assessor at baseline, and then at 1, 3, and 6 months after baseline. Analysis of serial measurements was performed to compare outcomes between the groups by calculating the area under the curve (AUC) and inserting AUC values into Mann-Whitney U tests.\n Comparison between groups showed no significant difference for any outcome measures. Significance values for the Rivermead Motor Assessment ranged from p = 0.23 to p = 0.97 and for the Motor Assessment Scale from p = 0.29 to p = 0.87.\n There were no significant differences in movement abilities or functional independence between patients receiving a BB or an MSB intervention. Therefore the study did not show that one approach was more effective than the other in the treatment of stroke patients.", "The aim of this project was to assess whether outreach visits would improve the implementation of evidence based clinical practice in the area of falls reduction and stroke prevention in a residential care setting.\n Twenty facilities took part in a randomized controlled trial with a seven month follow-up period. Two outreach visits were delivered by a pharmacist. At the first a summary of the relevant evidence was provided and at the second detailed audit information was provided about fall rates, psychotropic drug prescribing and stroke risk reduction practices (BP monitoring, aspirin and warfarin use) for the facility relevant to the physician. The effect of the interventions was determined via pre- and post-intervention case note audit. Outcomes included change in percentage patients at risk of falling who fell in a three month period prior to follow-up and changes in use of psychotropic medications. Chi-square tests, independent samples t-test, and logistic regression were used in the analysis.\n Data were available from case notes at baseline (n = 897) and seven months follow-up (n = 902), 452 residential care staff were surveyed and 121 physicians were involved with 61 receiving outreach visits. Pre-and post-intervention data were available for 715 participants. There were no differences between the intervention and control groups for the three month fall rate. We were unable to detect statistically significant differences between groups for the psychotropic drug use of the patients before or after the intervention. The exception was significantly greater use of \"as required\" antipsychotics in the intervention group compared with the control group after the pharmacy intervention (RR = 4.95; 95%CI 1.69-14.50). There was no statistically significant difference between groups for the numbers of patients \"at risk of stroke\" on aspirin at follow-up.\n While the strategy was well received by the physicians involved, there was no change in prescribing patterns. Patient care in residential settings is complex and involves contributions from the patient's physician, family and residential care staff. The project highlights challenges of delivering evidence based care in a setting in which there is a paucity of well controlled trial evidence but where significant health outcomes can be attained." ]	This review highlights major methodological problems and sources of heterogeneity that not only hamper the comparability of trials but also preclude a conclusion on the efficacy of BR in the adjunct treatment of PD patients with motor complications.
CD002240	[ "11113837", "8813983", "3234607", "9797593", "8957948", "16541716", "12674840", "15670265", "2299491", "23577991", "3989196", "10378599", "19966605", "18450876", "14598248", "6525357", "15678233", "11433088", "2209296" ]	[ "Lack of benefit of laxatives as adjunctive therapy for functional nonretentive fecal soiling in children.", "Biofeedback training in treatment of childhood constipation: a randomised controlled study.", "Biofeedback training for patients with myelomeningocele and fecal incontinence.", "Randomised controlled trial of biofeedback training in persistent encopresis with anismus.", "Randomised trial of biofeedback training for encopresis.", "[Usefulness of biofeedback treatment in children with chronic functional constipation].", "Efficiency of biofeedback therapy for chronic constipation in children.", "A randomized-controlled trial comparing an educational intervention alone vs education and biofeedback in the management of faecal incontinence in women.", "Modulation of abnormal defecation dynamics by biofeedback treatment in chronically constipated children with encopresis.", "A prospective randomized trial comparing four biofeedback techniques for patients with faecal incontinence.", "Biofeedback treatment of fecal incontinence in geriatric patients.", "A prospective, randomized study comparing the effect of augmented biofeedback with sensory biofeedback alone on fecal incontinence after obstetric trauma.", "Randomized controlled trial shows biofeedback to be superior to pelvic floor exercises for fecal incontinence.", "Behavioral therapy for childhood constipation: a randomized, controlled trial.", "Randomized controlled trial of biofeedback for fecal incontinence.", "A components analysis of biofeedback in the treatment of fecal incontinence.", "Assessment of the effectiveness of biofeedback in children with dyssynergic defecation and recalcitrant constipation/encopresis: does home biofeedback improve long-term outcomes.", "The effect of anorectal manometry on the outcome of treatment in severe childhood constipation: a randomized, controlled trial.", "Investigation of mode of action of biofeedback in treatment of fecal incontinence." ]	[ "To determine whether the combination of laxative treatment and biofeedback therapy (BF) is more effective for management of functional nonretentive fecal soiling than biofeedback therapy alone.\n In a prospective nonblinded study, 48 children were randomized in 2 groups: treatment with oral laxatives (LAX) and 5 sessions of BF (BF + LAX) or 5 sessions of BF alone (BF) during a treatment intervention period of 7 weeks. Biofeedback was performed with perfused manometry catheters and rectal balloon distension. Training focused on awareness of balloon distension and instruction in correct defecation dynamics. Successful treatment was defined as <1 encopresis episode per 2 weeks.\n At the end of the intervention period, the number of encopresis episodes was significantly decreased in both groups: from 7 (2 to 24) to 2 (0 to 17) in the BF group and from 7 (3 to 25) to 2 (0 to 14) in the BF + LAX group. However, children given BF alone had significantly higher success rates than children treated with BF and additional oral laxatives (44% to 11%).\n There is no additional effect of laxative treatment in functional nonretentive fecal soiling. Children treated with BF in combination with laxatives showed a significantly lower success percentage compared with those treated with BF alone. These results suggest that children with functional nonretentive fecal soiling should be treated differently from children with constipation and encopresis.", "Because abnormal defaecation dynamics, which can be modified by biofeedback, are considered to be the underlying problem in constipation, biofeedback training may be a useful treatment for constipation. This treatment has mainly been studied in uncontrolled trials. We evaluated defaecation dynamics and clinical outcome in chronically constipated children in a randomised study comparing conventional treatment and conventional treatment with biofeedback training.\n Patients, 5 to 16 years old, were referred to the Academic Medical Center in Amsterdam by general practitioners, school doctors, paediatricians, and psychiatrists. They had to fulfil at least two of four criteria for paediatric constipation and were included if they had been treated medically for at least one month before randomisation. Patients had a medical history, abdominal and rectal examination, and anorectal manometry at the start and end of the 6-week intervention period. The conventional group received laxative treatment with additional dietary advice, toilet training, and maintenance of a diary of bowel habits. The biofeedback group received the same conventional treatment and additionally five biofeedback training sessions. During the first 3 weeks, patients visited the outpatient clinic weekly; two subsequent visits were twice monthly.\n 94 patients were randomised to conventional treatment (CT) and 98 to conventional treatment with additional biofeedback training (CT+BF). Normal defaecation dynamics increased in the CT group from 41% to 52% (not significant) and in the CT+BF group from 38% to 86% (p = 0.001). At 6 weeks, more patients in the CT+BF group showed normal defaecation dynamics, compared to the CT group (p < 0.001). This result was unaltered by controlling for baseline status in a logistic regression model. At 1 year, successful treatment (defaecation frequency > or = 3/week, soiling and/or encopresis < 2/month, and no laxatives) was accomplished in 59% of the CT and 50% of the CT+BF group (p = 0.24). The results were maintained after 1 1/2 years follow-up. No association was found between achievement of normal defaecation dynamics and clinical outcome.\n Additional biofeedback training compared to conventional therapy did not result in higher success rates in chronically constipated children. Furthermore, achievement of normal defaecation dynamics was not associated with success: abnormal defaecation dynamics seem not to play a crucial role in the pathogenesis of childhood constipation. Intensive conventional laxative treatment should remain the first choice in chronically constipated children.", "This study evaluated the efficacy of biofeedback training for fecal in continence in patients with myelomeningocele. 12 patients were randomized to receive conventional treatment alone, or in conjunction with biofeedback. Anorectal manometric functions were evaluated before and after treatment, six and 12 months later. 16 control children were also studied. Three of eight patients in the biofeedback group and three of the four given conventional treatment alone reported greater than or equal to 75 per cent improvement in frequency of soiling 12 months later. Biofeedback training did not improve anal squeeze, rectal sensation or continence of rectal infused saline. The number of patients who improved in both treatment groups was not different.", "Paradoxical external anal sphincter contraction during attempted defecation (anismus) is thought to be an important contributor to chronic faecal retention and encopresis in children. Biofeedback training can be used to teach children to abolish this abnormal contraction.\n A randomised controlled trial in medical treatment resistant and/or treatment dependent children with anismus using surface electromyographic (EMG) biofeedback training to determine whether such training produces sustained faecal continence. Up to four sessions of biofeedback training were conducted at weekly intervals for each patient. Anorectal manometry was performed before randomisation and six months later. Parents of patients completed the \"child behaviour checklist\" (CBCL) before randomisation and at follow up.\n Sixty eight children underwent anorectal manometry and EMG. Of these, 29 had anismus (ages 4-14 years) and were randomised to either EMG biofeedback training and conventional medical treatment (BFT) (n = 14) or to conventional medical treatment alone (n = 15). All but one child were able to learn relaxation of the external anal sphincter on attempted defecation. At six months' follow up, laxative free remission had been sustained in two of 14 patients in the BFT group and in two of 15 controls (95% confidence interval (CI) on difference, -24% to 26%). Remission or improvement occurred in four of 14 patients in the BFT group and six of 15 controls (95% CI on difference, -46% to 23%). Of subjects available for repeat anorectal manometry and EMG at six months, six of 13 in the BFT group still demonstrated anismus v 11 of 13 controls (95% CI on difference, -75% to -1%). Of the four patients in full remission at six months, only one (in the BFT group) did not exhibit anismus. Rectal hyposensitivity was not associated with remission or improvement in either of the groups. Mean CBCL total behaviour problem scores were not significantly different between the BFT and control groups, but there was a significant improvement in CBCL school scale scores in the BFT group, and this improvement was significantly greater than that seen in the control group.\n The result of this study, together with those reported in other controlled trials, argues against using biofeedback training in children with encopresis.", "To evaluate biofeedback training in children with encopresis and the effect on psychosocial function.\n Prospective controlled randomised study. PATIENT INTERVENTIONS: A multimodal treatment of six weeks. Children were randomised into two groups. Each group received dietary and toilet advice, enemas, oral laxatives, and anorectal manometry. One group also received five biofeedback training sessions.\n Successful treatment was defined as less than two episodes of encopresis, regular bowel movements, and no laxatives. Psychosocial function after treatment was assessed using the Child Behaviour Checklist.\n Children given laxatives and biofeedback training had higher success rates than those who received laxatives alone (39% v 19%) at the end of the intervention period. At 12 and 18 months, however, approximately 50% of children in each group were successfully treated. Abnormal behaviour scores were initially observed in 35% of children. Most children had improved behaviour scores six months after treatment. Children with an initial abnormal behaviour score who were successfully treated had a significant improvement in their behavioural profiles.\n Biofeedback training had no additional effect on the success rate or behaviour scores. Psychosocial problems are present in a subgroup of children with encopresis. The relation between successful treatment and improvement in behavioural function supports the idea that encopresis has an aetiological role in the occurrence and maintenance of behavioural problems in children with encopresis.", "About 2/3 of constipated children present anal-rectal dyssynergy (ARD) with paradoxical contraction of the external anal sphincter (EAS) during defecation.\n The aim of our study was to answer the question whether additional treatment with biofeedback training (BF) is more effective than traditional treatment. MATERIALS, METHODS: We assessed chronically constipated children who fulfilled the criteria of ARD: recto-sigmoid transit time in Hinton's test with radio-paque markers at least 28.8 h, paradoxical EAS contraction during defecation trials (anorectal manometry). The study included 22 constipated children (16 boys and 6 girls), aged 5 to 14 years (mean 8.1 +/- SD 2.8). Children were randomly divided in two groups. In group I at the start of the study children had four day-by-day sessions of BF training based on the anorectal manometry and the surface EMG. Children from group II received only traditional treatment. The follow-up was 6 months. Improvement was estimated based on manometric data, number and quality of stools.\n In the group I after one month, more manometric parameters, significantly improved as compared to the II group. During the observation period the number of stools increased and their quality improved in both groups. There was no statistically significant difference between the groups in terms of the above mentioned symptoms.\n Treatment with BF can improve rectal sensation and particularly defecation dynamics, faster than the traditional method. There is no significant effect of additional BF treatment on such objective symptoms as the number and quality of stools.", "Chronic constipation is a common disorder in childhood. The underlying mechanisms responsible for chronic constipation remain unknown. Conventional methods of treatment often fail to produce satisfactory results. Favorable effects of biofeedback treatment for constipation have been suggested, however, with variable results reported in the literature. The main aim of the study was to evaluate biofeedback versus conventional therapeutic protocol in the treatment of chronic constipation over a short period of time (3 months). Forty-nine children with chronic idiopathic constipation, 24 allocated to conventional and 25 to biofeedback therapy were included in the study. Thorough history data on bowel function and symptoms, anorectal status and manometric testing were collected before and after treatment. Follow up consisted of a structured interview. Mean age was 94 and 92 months in the children treated by the conventional and biofeedback method, respectively. The initial prevalence of abnormal defecation dynamics was 58% and 56% in the group children allocated to conventional and biofeedback therapy, respectively. The difference was not statistically significant. After the treatment, the values of rectal sensation threshold, critical volume, and recto-anal inhibitory reflex volume were significantly higher, and the prevalence of abnormal defecation dynamics was significantly lower in the group on biofeedback therapy. Biofeedback is an effective method of treatment for chronic constipation in children in short term. Therapeutic results are especially favorable in the recovery of abnormal anorectal dynamics and manometric parameters. There is no clear evidence for long-term benefits of biofeedback therapy.", "Biofeedback (BF) training is an accepted therapy in the treatment of faecal incontinence (FI) despite a paucity of data demonstrating benefit. This study aims to determine whether BF has any specific effect above and beyond an educational intervention. Twenty-three women with regular and frequent idiopathic FI were randomized to education and pelvic exercise vs education and BF therapy. Complete data is available for 18 women. Overall, 61% of participants demonstrated a complete response. There was no difference in response rate between treatment arms. Women with FI demonstrate a good response to treatment with education and exercise and education plus BF thus questioning the specific effect of BF.", "To determine whether outcome in chronically constipated and encopretic children with abnormal defecation dynamics could be improved with biofeedback training, we randomly assigned patients, 5 to 16 years of age, to receive conventional treatment alone (n = 19) or conventional plus biofeedback treatment (n = 22) and evaluated physiologic outcome at 7 months and clinical outcome at 7 and 12 months. Eighty-six percent of patients learned normal defecation dynamics with up to six biofeedback sessions. At 7 months, 13% of conventionally treated and 77% of biofeedback-treated patients had normal defecation dynamics (p less than 0.01); one conventionally treated (5%) and 12 biofeedback-treated patients (55%) had recovered (p less than 0.01). Learning normal defecation dynamics was correlated with clinical recovery (p less than 0.01). At 7 months, 11% of patients with normal defecation dynamics after biofeedback treatment had abnormal defecation dynamics, and 71% of the biofeedback-treated patients with normal defecation dynamics recovered. At 12 months, 16% of conventionally treated and 50% of biofeedback-treated patients had recovered (p less than 0.05). Balloon defecation did not improve significantly in those who learned normal defecation dynamics. Therefore the ability to defecate balloons is apparently not dependent on the normal function of the external and sphincter and pelvic floor muscles alone. Biofeedback treatment is complementary to a good conventional therapeutic regimen in patients with abnormal defecation dynamics.", "The aim of this study was to compare four methods of biofeedback therapy for patients with faecal incontinence (FI).\n All patients with FI who were ineligible for surgical management were prospectively randomized using a computer generated randomization method into one of four protocols: 1, out-patient intra-anal electromyographic biofeedback training (EMG); 2, EMG plus intrarectal balloon training (BT); 3, EMG plus a home trainer (HT); and 4, EMG, BT and HT. All patients received weekly, 1 h, out-patient biofeedback training. Success for patients with FI was measured by a reduction in incontinent episodes (days/week). In all instances, patients maintained a daily log in which documentation was recorded regarding each bowel evacuation.\n Forty patients were randomized into one of the four groups. Six patients withdrew after one session and were not included in the analysis. Therefore, 34 patients (23 female and 11 male) with a mean incontinence score of 12 (range 7-14) were randomized to one of the four groups (n=8, 8, 8, and 10, respectively). There was a statistically significant reduction in incontinent episodes for all groups. However, there were no significant differences in treatment outcome found in comparisons among the four groups.\n Biofeedback therapy significantly improves FI. Moreover, EMG training was as effective alone as was the addition of HT, BT or both for the treatment of FI.", "Eighteen fecally incontinent geriatric patients were first treated for constipation as a possible cause of incontinence, and the 13 who remained incontinent were provided sphincter biofeedback training. Half the patients were instructed to perform 50 sphincter exercises per day for a four-week period prior to the start of biofeedback training to determine whether such exercises would improve bowel control in the absence of biofeedback training. Sphincter exercises alone did not produce clinical improvements and did not significantly increase the strength of sphincter contractions. Biofeedback training did significantly augment sphincter strength and was associated with greater than 75 per cent decreases in incontinence for 10 (77 per cent) of the patients. Improvements were maintained in 60 per cent at six months and in 42 per cent at one year. Thus biofeedback training appears to be of specific value in the treatment of fecal incontinence in geriatric patients.", "This study was designed to compare prospectively the effects of augmented biofeedback with those of sensory biofeedback alone on fecal incontinence and anorectal manometry after obstetric trauma.\n A consecutive cohort of 40 females with impaired fecal continence after obstetric anal sphincter injury were recruited from a dedicated perineal clinic. Patients were randomly assigned to receive either augmented biofeedback or sensory biofeedback alone. All patients were assessed before and after twelve weeks of biofeedback training, using a fecal continence questionnaire and anorectal manometry.\n Thirty-nine of 40 females recruited completed the study. Continence scores improved in both treatment groups, but the results were better for those who received augmented biofeedback. Anorectal manometry was unchanged by sensory biofeedback, whereas anal resting and squeeze pressures increased with augmented biofeedback. No change in anal vector symmetry was observed in either group.\n Augmented biofeedback training is superior to sensory biofeedback alone in the treatment of impaired fecal continence after obstetric trauma.", "This study aimed to compare manometric biofeedback with pelvic floor exercises for the treatment of fecal incontinence in a randomized controlled trial controlling for nonspecific treatment effects.\n After excluding patients who were adequately treated with medication, education, and behavioral strategies (21%), 108 patients (83 females; average age, 59.6 years) underwent either pelvic floor exercises alone (n = 63) or manometric biofeedback plus pelvic floor exercises (n = 45). Patients in both groups were taught behavioral strategies to avoid incontinence.\n At three-month follow-up, biofeedback patients had significantly greater reductions on the Fecal Incontinence Severity Index (P = 0.01) and fewer days with fecal incontinence (P = 0.083). Biofeedback training increased anal canal squeeze pressure more than pelvic floor exercises did (P = 0.014) and with less abdominal tension during squeeze (P = 0.001). Three months after training 76% of patients treated with biofeedback vs. 41% patients treated with pelvic floor exercises (chi-squared = 12.5, P < 0.001) reported adequate relief. Before treatment, the groups did not differ on demographic, physiologic, or psychologic variables, symptom severity, duration of illness, quality-of-life impact, or expectation of benefit. At 12-month follow-up, biofeedback patients continued to show significantly greater reduction in Fecal Incontinence Severity Index scores (F = 4.83, P = 0.03), and more patients continued to report adequate relief (chi-squared = 3.64, P = 0.056).\n This investigation provides definitive support for the efficacy of biofeedback. Biofeedback training resulted in greater reductions in fecal incontinence severity and days with fecal incontinence. Biofeedback was also more effective than pelvic floor exercises alone in producing adequate relief of fecal incontinence symptoms in patients for whom conservative medical management had failed.", "It has been suggested that the addition of behavioral interventions to laxative therapy improves continence in children with functional fecal incontinence associated with constipation. Our aim was to evaluate the clinical effectiveness of behavioral therapy with laxatives compared with conventional treatment in treating functional constipation in childhood.\n In this randomized, controlled trial conducted in a tertiary hospital in The Netherlands, 134 children aged 4 to 18 years with functional constipation were randomly assigned to 22 weeks (12 visits) of either behavioral therapy or conventional treatment. Primary outcomes were defecation frequency, fecal incontinence frequency, and success rate. Success was defined as defecation frequency of > or = 3 times per week and fecal incontinence frequency of < or = 1 times per 2 weeks irrespective of laxative use. Secondary outcomes were stool-withholding behavior and behavior problems. Outcomes were evaluated at the end of treatment and at 6-months follow-up. All of the analyses were done by intention to treat.\n Defecation frequency was significantly higher for conventional treatment. Fecal incontinence frequency showed no difference between treatments. After 22 weeks, success rates did not differ between conventional treatment and behavioral therapy (respectively, 62.3% and 51.5%), nor did it differ at 6 months of follow-up (respectively, 57.3% and 42.3%). The proportion of children withholding stools was not different between interventions. At follow-up, the proportion of children with behavior problems was significantly smaller for behavioral therapy (11.7% vs 29.2%).\n Behavioral therapy with laxatives has no advantage over conventional treatment in treating childhood constipation. However, when behavior problems are present, behavioral therapy or referral to mental health services should be considered.", "Behavioral treatment (biofeedback) has been reported to improve fecal incontinence but has not been compared with standard care.\n A total of 171 patients with fecal incontinence were randomized to 1 of 4 groups: (1) standard care (advice); (2) advice plus instruction on sphincter exercises; (3) hospital-based computer-assisted sphincter pressure biofeedback; and (4) hospital biofeedback plus the use of a home electromyelogram biofeedback device. Outcome measures included diary, symptom questionnaire, continence score, patient's rating of change, quality of life (short-form 36 and disease specific), psychologic status (Hospital Anxiety and Depression scale), and anal manometry.\n Biofeedback yielded no greater benefit than standard care with advice (53% improved in group 3 vs. 54% in group 1). There was no difference between the groups on any of the following measures: episodes of incontinence decreased from a median of 2 to 0 per week (P < 0.001). Continence score (worst = 20) decreased from a median of 11 to 8 (P < 0.001). Disease-specific quality of life, short-form 36 (vitality, social functioning, and mental health), and Hospital Anxiety and Depression scale all significantly improved. Patients improved resting, squeeze, and sustained squeeze pressures (all P < 0.002). These improvements were largely maintained 1 year after finishing treatment.\n Conservative therapy for fecal incontinence improves continence, quality of life, psychologic well-being, and anal sphincter function. Benefit is maintained in the medium term. Neither pelvic floor exercises nor biofeedback was superior to standard care supplemented by advice and education.", "Fecal incontinence is a socially disabling symptom for which rectosphincteric biofeedback has been reported to be dramatically effective. The most commonly employed biofeedback procedure incorporates three separate and potentially effective components: exercise of the external sphincter muscle, training in discrimination of rectal sensations, and training synchrony of the internal and external sphincter responses. This paper reports the results of single case experiments employed with eight incontinent patients to examine the contributions of each of these components. All eight patients improved, but only one required the biofeedback procedure as it was originally described. Three responded to sensory discrimination training, one to exercise training, and one to the training of synchronous sphincteric responses; three recovered independently of the effects of biofeedback. Despite the achievement of continence, the rectosphincteric reflexes following treatment continued to be abnormal in every case. These findings suggest that the character of the external sphincter response to rectal distension is an unreliable index of sphincter function and that exercise and sensory discrimination training procedures are effective for some cases of fecal incontinence.", "The purpose of this study was to determine whether biofeedback benefits children with dyssynergic defecation and constipation/encopresis, and whether home biofeedback improves long-term outcomes. Thirty-six patients with chronic constipation who had failed at least 6 months of conventional treatment and demonstrated dyssynergic defecation at anorectal manometry were randomized to biofeedback in the laboratory alone (group 1, n=24) or in the laboratory and at home (group 2, n=12) and followed up at 2, 4, and a mean of 44 months. Thirty patients were available for long-term follow-up. Bowel movements increased in all from a mean of 1.4/week to 5.1, 5.8, and 5.1 per week at 2 months, 4 months, and long-term, respectively (p < or = 0.001). Soiling decreased in all from a mean of 5.5/week to 0.6, 0.1, and 1 per week at 2 months, 4 months, and long-term, respectively (p < or = 0.001). Laxative use decreased from a mean of 4.1 days/week to 0.6, 0.3, and 0.7 per week at 2 months, 4 months, and long-term, respectively (p < or = 0.001). Twenty-seven of 30 parents ranked their satisfaction a mean of 2.2 (range 1-excellent to 3-good). There were no significant differences in outcomes between the laboratory alone group and the laboratory plus home group. Biofeedback is beneficial for some children with chronic constipation and dyssynergic defecation. Supplemental home biofeedback does not improve long-term outcomes.", "Approximately 50% of constipated children contract rather than relax the external sphincter complex during a defecation attempt. Although biofeedback training (BF) is able to change this defecation behavior, there is no additional effect of BF to conventional treatment (CT) on clinical outcome compared with CT alone. It has been postulated that the absence of a significant difference between these 2 treatment options might be because of a therapeutic, \"demystifying\" effect of performing anorectal manometry in conventionally treated children, necessary to obtain basal manometric data. The objective of this prospective, controlled, randomized study was to evaluate the effect of CT with 2 anorectal manometry sessions compared with CT alone (dietary advice, diary, toilet training, oral laxatives, and enemas) on clinical outcome.\n A total of 212 constipated children (143 boys) who were visiting a referral pediatric gastroenterologic practice were randomized prospectively to CT alone (115 patients) or to CT combined with 2 manometry sessions (CTM; 97 patients). Patients were included in the study when they fulfilled at least 2 of the 4 following criteria: stool frequency fewer than 3 per week, 2 or more soiling and/or encopresis episodes per week, periodic passage of very large amounts of stool every 7 to 30 days, or a palpable rectal or abdominal fecal mass. CT comprises dietary advice, a daily diary, toilet training, and oral laxative treatment preceded by rectal disimpaction with enemas on 3 consecutive days. During both manometries, the child and the parent could watch the tracing on the computer screen. No explanation was given to either the child or the parents during the procedure. When the procedure was finished, the tracings were clarified. Successful treatment was defined as a defecation frequency of 3 or more per week and fewer than 1 soiling/encopresis episode per 2 weeks and no use of laxatives.\n Only 4 and 2 children from the CT and CTM groups showed no soiling and/or encopresis, whereas 76% and 65%, respectively, reported the periodic passage of large stools. In 26% and 30% of the patients, a rectal scybalum was found on physical examination. The success rates at 6, 26, 52, and 104 weeks' follow-up were 4%, 24%, 32%, and 43% and 7%, 22%, 30%, and 35% in the CT and CTM group, respectively. No significant difference in success percentage was observed between the 2 groups at any time of follow-up with relative risks (CT/CTM) and 95% confidence intervals, respectively, of 0.55 (0.16-1.89), 1.13 (0.67-1.89), 1.07 (0.69-1.65), and 1.23 (0.81-1.85). A significant increase in defecation frequency was observed between the first (intake) and second visits, which was sustained at all subsequent visits and stages of follow-up in both groups (not significant). Also in relation to the first visit, a significant decrease in encopresis episodes was shown and a further slow but significant decrease at 52 weeks of follow-up in both groups. The manometric data obtained from the CTM group showed a low percentage of children with normal defecation dynamics, namely 28%, which (significantly) increased to 38% at the last manometry.\n Anorectal manometry combined with CT compared with CT alone did not result in higher success rates in chronically constipated children. Therefore, anorectal manometry has no additional demystifying or educational effect on clinical outcome in chronically constipated children. This observation together with the observation in the current and previous studies that no correlation was found between (achievement of) normal defecation dynamics and success and that no relation was observed between volume of urge or critical volume and success leaves no diagnostic or therapeutic role for anorectal manometry in chronic constipated children, except its use as a diagnostic test to exclude Hirschsprung's disease. A simple CT is successful in 30% of severely constipated children who are referred to a tertiary hospital, underscoring the importance of long-lasting and adequate laxative treatment.", "A study was carried out in 25 incontinent patients to evaluate some of the factors thought to be responsible for the success of retraining for fecal incontinence. Subjects were initially allocated to one of two groups; one group was trained to perceive small rectal volumes (active retraining), the other group carried out the same maneuvers but were not given any information or instruction. Active sensory retraining reduced the sensory threshold from 32 +/- 8 to 7 +/- 2 ml (P less than 0.001), corrected any sensory delay that was present (P less than 0.004), and reduced the frequency of incontinence from 5 +/- 1 to 1 +/- 1 episodes per week (P less than 0.01). Sham retraining caused a modest reduction in the sensory threshold (from 29 +/- 9 to 20 +/- 8; P less than 0.05) but did not significantly reduce the frequency of incontinence. Subsequent strength and coordination training did not significantly improve continence, although at the end of the study, 50% of patients had no incontinent episodes at all and 76% of patients had reduced the frequency of incontinence episodes by more than 75%. This improvement in continence was not associated with any change in sphincter pressures or in the continence to rectally infused saline but was associated with significant improvements in rectal sensation. The functional improvement was sustained over a period of two years in 16 of the 22 patients available for follow-up. In conclusion, the results support the use of retraining in the management of fecal incontinence and suggest that retraining may work by enhancing rectal sensitivity and instilling confidence." ]	There is no evidence that biofeedback training adds any benefit to conventional treatment in the management of functional faecal incontinence in children. There was not enough evidence on which to assess the effects of biofeedback for the management of organic faecal incontinence. There is some evidence that behavioural interventions plus laxative therapy, rather than laxative therapy alone, improves continence in children with functional faecal incontinence associated with constipation.
CD003171	[ "12648639", "12353900", "17318205", "17202203" ]	[ "Morphological and functional results of AcrySof intraocular lens implantation in children: prospective randomized study of age-related surgical management.", "Posterior continuous curvilinear capsulorhexis with and without optic capture of the posterior chamber intraocular lens in the absence of vitrectomy.", "Posterior capsule opacification after extra capsular cataract extraction in Indian rural population: foldable acrylic vs poly (methyl-methacrylate) intraocular lenses a randomized clinical trial.", "Long-term results of sealed capsule irrigation using distilled water to prevent posterior capsule opacification: a prospective clinical randomised trial." ]	[ "To evaluate the prevalence and severity of posterior capsule opacification (PCO) in pediatric eyes with a foldable acrylic AcrySof (Alcon) intraocular lens (IOL) and age-related surgical methods.\n Department of Ophthalmology, University of Vienna, Medical School, Vienna, Austria.\n This prospective randomized study comprised 50 eyes of 34 children aged between 2 and 16 years. Eyes of children between 2 and 5.9 years were consecutively randomized to Group 1a (primary posterior capsulotomy and anterior vitrectomy) or Group 1b (optic capture in addition). Eyes of children between 6 and 16 years were consecutively randomized to Group 2a (primary posterior capsulotomy without anterior vitrectomy), Group 2b (optic capture in addition), or Group 2c (in-the-bag IOL implantation without opening the posterior capsule). Main outcome parameters were the incidence and severity of PCO formation, early postoperative complications, pigmented cell deposits on the IOL surface, and cataract morphology.\n The visual axis was clear at the last follow-up in all eyes in Groups 1a, 1b, 2a, and 2b except in 1 eye in Group 1a. Sixty-percent of eyes in Group 2c had PCO. The incidence of early postoperative complications was significantly higher in eyes that developed PCO than in those that maintained a clear visual axis. There was no evidence that cataract morphology influenced PCO rates.\n The AcrySof IOL was well tolerated in pediatric eyes. Optic capture was not necessary to ensure a clear visual axis. Primary posterior capsulotomy should be performed in preschool and uncooperative children and in eyes expected to have relatively high postoperative inflammation. Implanting the AcrySof in the bag and leaving the posterior capsule intact is acceptable for school children and juveniles with isolated developmental cataract.", "To evaluate the efficacy of posterior continuous curvilinear capsulorhexis (PCCC) with optic capture of the posterior chamber intraocular lens (PC IOL) in the absence of vitrectomy in preventing secondary opacification of the visual axis following pediatric cataract surgery.\n Thirty-four eyes of 28 children with congenital or developmental cataract, aged 1.5 to 12 years (mean, 6.39 years), were included in this prospective, randomized study. Anterior continuous curvilinear capsulorhexis (ACCC) with PCCC without optic capture of the PC IOL was performed in group A (18 eyes) and ACCC with PCCC with optic capture of the PC IOL was performed in group B (16 eyes). None of the eyes underwent anterior vitrectomy. Secondary opacification of the visual axis, visual acuity, and possible complications were observed and analyzed.\n The follow-up period ranged from 8 to 28 months (mean, 17.5 months). All 16 eyes (100%) in group B had a clear visual axis at the end of follow-up. Eight eyes (44.4%) in group A had significant opacification of the visual axis. The difference between the two groups was statistically significant (P = .0011). No eye in group B required secondary intervention, whereas all 8 eyes in group A with significant secondary opacification required secondary intervention. There was no statistically significant difference in other complications such as anterior chamber reaction, fibrin formation, lenticular precipitates, and posterior synechiae. The final best-corrected visual acuity at the end of follow-up was comparable in the two groups (P > .05).\n PCCC with optic capture of the PC IOL prevents secondary opacification of the visual axis even in the absence of vitrectomy.", "To compare the performance of single-piece acrylic vspoly (methylmethacrylate) intraocular lenses (IOL) on the development of posterior capsule opacification (PCO) after conventional extra capsular cataract extraction (ECCE).\n One hundred and eighty-two eyes of 91 patients with bilateral senile cataract undergoing ECCE were prospectively randomized to receive a single-piece Alcon AcrySof SA60AT IOL or a single-piece EPOCH polymethylmethacrylate IOL in the first eye to have surgery. At 1, 6 and 12 months post-operative follow-up, digital retro illumination images of the posterior capsule were taken for PCO assessment semi-objectively using PCO (POCO automated analysis software) system. Relationship of anterior capsule contact (total off and partial cover) on optic for PCO was analyzed.\n The AcrySof IOL was associated with less PCO than EPOCH lens at 6 months (10.01+/-8.75% vs 32.26+/-27.44%; P<0.001) and 1-year (11.65+/-10.55% vs 38.38+/-29.62%; P<0.001) follow-up. The EPOCH IOL showed a remarkably significant difference on development of PCO with anterior capsule overlap on IOL optic (total off and part on) 1 year (P<0.039), whereas no such difference was observed with the AcrySof IOL (P=0.197).\n The AcrySof IOL led to significantly less PCO than the EPOCH IOL post-operatively after extracapsular cataract extraction.", "We investigated long-term safety and efficacy of sealed capsule irrigation (SCI) during cataract surgery to prevent posterior capsule opacification (PCO).\n One eye of each of 17 patients (mean age: 70.1+/-9.7 years) who presented with bilateral cataracts was randomly chosen for SCI treatment. After phacoemulsification, the capsular bag was vacuum sealed with the PerfectCapsule device (Milvella) followed by SCI using distilled water for two minutes. No vacuum loss occurred during irrigation. Each patient's fellow eye served as a control. One hydrophilic acrylic intraocular lens model was implanted in all eyes. Five patients had to be excluded due to deep anterior chamber, small pupil or unilateral surgery. Follow-up examinations took place one day and one, three, six, 12 and 24 months after surgery. We evaluated safety parameters, anterior capsule (AC) overlapping and PCO.\n Postoperatively, mean best corrected visual acuity, pachymetry, endothelial cell count, intraocular pressure, AC overlapping and PCO showed no statistically significant difference between SCI and the control group (p>0.05, Wilcoxon test).\n SCI is a safe procedure and enables the specific pharmacological targeting of lens epithelial cells inside the capsular bag. Using distilled water, however, it is not possible to reduce PCO development significantly. Thus, alternative substances should be evaluated." ]	Evidence exists for the care of children with congenital or developmental bilateral cataracts to reduce the occurrence of visual axis opacification. Further randomised trials are required to inform modern practice about other concerns including the timing of surgery, age for implantation of an intraocular lens and development of long-term complications such as glaucoma and retinal detachment.
CD003059	[ "8464671", "3935013" ]	[ "Failure of cromolyn sodium to reduce the incidence of bronchopulmonary dysplasia: a pilot study. The Neonatal Cromolyn Study Group.", "A controlled study of education for improving compliance with cromolyn sodium (Intal): the importance of physician-patient communication." ]	[ "This prospective, randomized, blinded clinical trial was conducted to test whether therapy with cromolyn sodium might decrease the incidence or severity of bronchopulmonary dysplasia when given to newborns with respiratory distress syndrome. Cromolyn (20 mg) or placebo was aerosolized to intubated newborns with respiratory distress syndrome every 6 hours, beginning on the first day of intubation. Patients were stratified by birth weight less than 1000 g and 1000 to 2000 g; primary outcome success was defined as survival to 30 days without oxygen dependence. Of 10 patients enrolled who were less than 1000 g birth weight, there were no treatment successes, preventing outcome analysis. The study was discontinued after 28 patients of 1000 to 2000 g birth weight had been studied, at which time it had been found with 95% confidence, with a power of .80, that cromolyn sodium did not decrease by 50% the incidence of bronchopulmonary dysplasia. Severity of bronchopulmonary dysplasia was also similar, with 4 patients in the treatment group and 3 in the placebo group receiving mechanical ventilation at 30 days. Possible reasons for this study outcome include (1) a delivered dose too small to produce a clinical effect; (2) the start of therapy too late to prevent the onset of inflammation; (3) inadequate effect of cromolyn on polymorphonuclear cells in vivo; or (4) development of bronchopulmonary dysplasia through factors unaffected by the actions of cromolyn.", "The effectiveness of an educational program to increase compliance with cromolyn sodium was assessed in 31 children and adolescents 6 to 17 years of age. Patients were randomly assigned to an education or noneducation group. A standard education program regarding asthma and asthma medications was provided to the education group during four monthly visits. At each visit, all patients were assessed in terms of knowledge of asthma and medications, asthma-related symptoms, and pulmonary function. Patients were also asked to self-rate their compliance. The education program increased the patients' knowledge of cromolyn, and appeared to result in increased cromolyn compliance. Post-hoc analyses, however, suggested that increased compliance did not correspond to improved medical status unless the quality of management (by physician and parents) of the child's asthma was taken into account. These results suggest that inadequate management of asthma in children may be a more serious problem than patient noncompliance." ]	There is currently no evidence from randomised trials that cromolyn sodium has a role in the prevention of CLD. Cromolyn sodium cannot be recommended for the prevention of CLD in preterm infants.
CD004923	[ "8270972", "10819701", "16139656", "11896107", "18359433", "15520472", "15663589", "17565936", "22030384", "363136", "16509835", "11145492", "16192581" ]	[ "Transdermal clonidine for ameliorating tamoxifen-induced hot flashes.", "Oral clonidine in postmenopausal patients with breast cancer experiencing tamoxifen-induced hot flashes: a University of Rochester Cancer Center Community Clinical Oncology Program study.", "Gabapentin for hot flashes in 420 women with breast cancer: a randomised double-blind placebo-controlled trial.", "Phase III evaluation of fluoxetine for treatment of hot flashes.", "A randomized controlled trial of relaxation training to reduce hot flashes in women with primary breast cancer.", "The impact of the Women's Health Initiative study on incident clonidine use in Ontario, Canada.", "The effect of tibolone in postmenopausal women receiving tamoxifen after surgery for breast cancer: a randomised, double-blind, placebo-controlled trial.", "Black cohosh and fluoxetine in the treatment of postmenopausal symptoms: a prospective, randomized trial.", "Effects of tibolone on climacteric symptoms and quality of life in breast cancer patients--data from LIBERATE trial.", "Menopausal hot flushes: a double blind comparison of placebo, ethinyl oestradiol and norgestrel.", "Randomized, double-blind, placebo-controlled, crossover study of sertraline (Zoloft) for the treatment of hot flashes in women with early stage breast cancer taking tamoxifen.", "Venlafaxine in management of hot flashes in survivors of breast cancer: a randomised controlled trial.", "Paroxetine is an effective treatment for hot flashes: results from a prospective randomized clinical trial." ]	[ "To determine the efficacy of transdermal clonidine for alleviating tamoxifen-induced hot flashes in women with a history of breast cancer.\n A randomized, double-blind, crossover design was used in this prospective study. Women with a history of breast cancer who were receiving tamoxifen and suffering from hot flashes were potentially eligible for this protocol study.\n Clonidine did reduce hot-flash frequency to a degree that was statistically impressive (P < .0001), but clinically moderate (20% reduction from baseline). It also decreased hot-flash severity (P = .02, 10% reduction from baseline). Clonidine was related to increased mouth dryness (P < .001), constipation (P < .02), itchiness under the patch (P < .01), and drowsiness (P < .05).\n Better means are needed to alleviate hot flashes among patients in whom estrogen therapy is contraindicated.", "Hot flashes are the most frequently reported side effect of tamoxifen treatment. Although hormones are an effective treatment, their safety is questionable in women with breast cancer. It is therefore important to evaluate nonhormonal treatments for hot flashes.\n To evaluate the effectiveness of oral clonidine for control of hot flashes associated with tamoxifen therapy in postmenopausal women with breast cancer.\n Randomized, double-blind, placebo-controlled clinical trial.\n University of Rochester Cancer Center Community Clinical Oncology Program.\n 194 postmenopausal women with breast cancer who were receiving adjuvant tamoxifen therapy.\n Oral clonidine hydrochloride, 0.1 mg/d, or placebo for 8 weeks.\n In a daily diary, patients recorded number, duration, and severity of hot flashes and overall quality-of-life score (on a 10-point scale) during a 1-week baseline period and during the 4th, 8th, and 12th weeks of the study.\n Patients in the placebo and treatment groups were similar in age, duration of tamoxifen use, reported frequency and duration of hot flashes at baseline, and dropout rates. One hundred forty-nine patients completed 12 weeks of follow-up. The mean decrease in hot flash frequency was greater in the clonidine group than in the placebo group after 4 weeks of treatment (37% compared with 20% [95% CI for difference, 7% to 27%]) and 8 weeks of treatment (38% compared with 24% [CI for difference, 3% to 27%]). Patients receiving clonidine were more likely than patients receiving placebo to report difficulty sleeping (41% compared with 21%; P = 0.02). A significant difference was seen in the mean change in quality-of-life scores (0.3 points in the clonidine group compared with -0.2 points in the placebo group; P = 0.02) at 8 weeks, although the median difference was 0 in both groups.\n Oral clonidine, 0.1 mg/d, is effective against tamoxifen-induced hot flashes in postmenopausal women with breast cancer.", "Most women receiving systemic therapy for breast cancer experience hot flashes. We undertook a randomised, double-blind, placebo-controlled, multi-institutional trial to assess the efficacy of gabapentin in controlling hot flashes in women with breast cancer.\n 420 women with breast cancer who were having two or more hot flashes per day were randomly assigned placebo, gabapentin 300 mg/day, or gabapentin 900 mg/day by mouth in three divided doses for 8 weeks. Each patient kept a 1-week, self-report diary on the frequency, severity, and duration of hot flashes before the start of the study and during weeks 4 and 8 of treatment. Analyses were by intention to treat.\n Evaluable data were available on 371 participants at 4 weeks (119 placebo, 123 gabapentin 300 mg, and 129 gabapentin 900 mg) and 347 at 8 weeks (113 placebo, 114 gabapentin 300 mg, and 120 gabapentin 900 mg). The percentage decreases in hot-flash severity score between baseline and weeks 4 and 8, respectively were: 21% (95% CI 12 to 30) and 15% (1 to 29) in the placebo group; 33% (23 to 43) and 31% (16 to 46) in the group assigned gabapentin 300 mg; and 49% (42 to 56) and 46% (34 to 58) in the group assigned gabapentin 900 mg. The differences between the groups were significant (p=0.0001 at 4 weeks and p=0.007 at 8 weeks by ANCOVA for overall treatment effect, adjusted for baseline values); only the higher dose of gabapentin was associated with significant decreases in hot-flash frequency and severity.\n Gabapentin is effective in the control of hot flashes at a dose of 900 mg/day, but not at a dose of 300 mg/day. This drug should be considered for treatment of hot flashes in women with breast cancer.", "Hot flashes can be a prominent problem in women with a history of breast cancer. Given concerns regarding the use of hormonal therapies in such patients, other nonhormonal means for treating hot flashes are required. Based on anecdotal information regarding the efficacy of fluoxetine and other newer antidepressants for treating hot flashes, the present trial was developed.\n This trial used a double-blinded, randomized, two-period (4 weeks per period), cross-over methodology to study the efficacy of fluoxetine (20 mg/d) for treating hot flashes in women with a history of breast cancer or a concern regarding the use of estrogen (because of breast cancer risk). Eligible patients had to have reported that they averaged at least 14 hot flashes per week; they could have received tamoxifen or raloxifene as long as they were on a stable dose. The major outcome measure was a bivariate construct representing hot flash frequency and hot flash score, analyzed by a classic sums and differences cross-over analysis.\n Eighty-one randomized women began protocol therapy. By the end of the first treatment period, hot flash scores (frequency x average severity) decreased 50% in the fluoxetine arm versus 36% in the placebo arm. Cross-over analysis demonstrated a significantly greater marked hot flash score improvement with fluoxetine than placebo (P =.02). The results were not adjusted for potential confounding influences, including age and tamoxifen use. The fluoxetine was well tolerated.\n This dose of fluoxetine resulted in a modest improvement in hot flashes.", "Hot flashes are experienced by about 52% of perimenopausal women. After breast cancer, this may increase to 70%. The use of hormone replacement therapy is not recommended in women who have had breast cancer; therefore, alternatives are required to help relieve hot flashes. This study was conducted to assess the efficacy of relaxation training in reducing the incidence of hot flashes in women with primary breast cancer. This was a randomized controlled trial of 150 women with primary breast cancer who experienced hot flashes. The intervention group received a single relaxation training session and was instructed to use practice tapes on a daily basis at home for one month; the control group received no intervention. Outcomes were incidence and severity of flashes using a diary and validated measures of anxiety and quality of life. The incidence and severity of hot flashes, as recorded by diaries, each significantly declined over one month (P<0.001 and P=0.01, respectively), compared with the control group. Distress caused by flashes also significantly declined in the treatment group over one month (P=0.01), compared with the control group. There were no significant differences between the treatment group and the control group at three months and no changes in anxiety or quality-of-life measures. Relaxation may be a useful component of a program of measures to relieve hot flashes in women with primary breast cancer.", "Following publication of the Women's Health Initiative (WHI) study, many women discontinued use of estrogen replacement therapy. There is some evidence that the antihypertensive agent clonidine can reduce the frequency of hot flashes associated with menopause.\n To determine the impact of the WHI study on incident use of clonidine in elderly women in Ontario, Canada.\n Retrospective, population-based administrative database design. Data on all residents of Ontario over the age of 65 years were included. Time series methods were used to analyze change in incident clonidine use following publication of the WHI study.\n Following publication of the WHI study, incident use of clonidine increased substantially among elderly women in Ontario, Canada. Similar trends were not observed for incident use of other antihypertensive medications.\n During a period of time in which a large proportion of women discontinued estrogen replacement therapy, incident use of clonidine increased. There is some evidence that a small number of women may have sought alternative relief from menopausal symptoms using other pharmacological therapies.", "To assess the effects of tibolone on climacteric symptoms, endometrium and serum lipid/lipoproteins in postmenopausal women receiving tamoxifen after surgery for breast cancer.\n Double-blind, randomised, placebo-controlled, multicentre pilot study.\n Hospital outpatient clinic.\n Seventy postmenopausal women receiving tamoxifen following surgery for early breast cancer.\n Women received 20 mg/day oral tamoxifen plus either 2.5 mg/day oral tibolone or placebo for 12 months.\n Frequency and severity of hot flushes (diary cards); intensity of hot flushes and sweats (Landgren scale); interference of hot flushes and sweats with normal life; frequency and intensity of other climacteric symptoms; endometrial thickness and histology; vaginal bleeding; breast cancer recurrence and serum lipid/lipoproteins.\n Daily card data showed no change in the daily number of hot flushes with either tibolone or placebo (P= 0.219) after three months. There was a significant reduction in the severity of flushes with tibolone compared with placebo (-0.4 vs 0.2, P= 0.031). The Landgren scale showed a mean change in the number of hot flushes of -0.6 with tibolone and +1.1 with placebo after 12 months (P= 0.022). Endometrial biopsies were normal and vaginal bleeding was similar in both groups. A significant decrease in triglycerides (-23% vs 1.4%) and HDL (-12% vs 19%) was seen with tibolone compared with placebo after 12 months.\n Tibolone prevented an increase in hot flushes in postmenopausal women given tamoxifen following surgery for breast cancer without untoward effects on the endometrium. Beneficial effects on serum lipid profile were noted.", "The objective of this study was to evaluate the efficacy of fluoxetine and black cohosh in the treatment of women with postmenopausal symptoms. A total of 120 healthy women with menopausal symptoms were recruited to this prospective study with a follow-up period of 6 mo. They were randomly assigned to 1 of 2 groups and were treated with fluoxetine or black cohosh. After entry into the study, patients were examined at the first, second, third, and sixth months of the treatment period. The women kept diaries in which they reported the daily number and intensity of hot flushes and night sweats. In addition, at the beginning and end of the third month, they completed questionnaires consisting of a modified Kupperman Index, Beck's Depression Scale, and a RAND-36 Quality-of-Life Questionnaire. Statistically significant differences were noted in the Kupperman Index and Beck's Depression Scale at the end of the third month in both groups compared with baseline values. In the black cohosh group, the Kupperman Index decreased significantly compared with that in the fluoxetine group by the end of the third month. On the other hand, in the fluoxetine group, Beck's Depression Scale decreased significantly compared with that in the black cohosh group. Monthly scores for hot flushes and night sweats decreased significantly in both groups; however, black cohosh reduced monthly scores for hot flushes and night sweats to a greater extent than did fluoxetine. At the end of the sixth month of treatment, black cohosh reduced the hot flush score by 85%, compared with a 62% result for fluoxetine. By the sixth month of the study, 40 women had discontinued the study--20 (33%) in the fluoxetine group and 20 (33%) in the black cohosh group. Compared with fluoxetine, black cohosh is more effective for treating hot flushes and night sweats. On the other hand, fluoxetine is more effective in improvements shown on Beck's Depression Scale.", "Climacteric symptoms such as hot flushes and vaginal dryness are very common in breast cancer patients, resulting either from age or adjuvant therapy. Tibolone, a synthetic steroid, is effective in reducing these symptoms in healthy post-menopausal women, but this has never been studied in a large breast cancer population.\n The primary objective of LIBERATE trial was to study safety of tibolone 2.5mg daily versus placebo as primary, in symptomatic breast cancer survivors. The aim of this present paper was to report effects of tibolone on climacteric symptoms, vaginal dryness and health-related quality of life in the study population. This trial is registered with ClinicalTrials.gov, n. NCT00408863.\n The trial was conducted between June 2002 and July 2007. Concerning quality of life variables, a daily Diary Cards during the first three months and the Climacteric Symptoms Form and at each visit were used to register frequency and intensity of hot flushes. Mean vaginal dryness scores were calculated on the basis of individual ratings at baseline and at week 104. A subset of patients assessed their quality of life filling in the Women's Health Questionnaire (WHQ).\n Of the 3148 women recruited, 3133 received trial medication (1575 in the tibolone group and 1558 in the placebo group). The median duration of treatment was 2.75 years. In total 3098 women (1556 on tibolone, 1542 on placebo) were included in the intention-to-treat (ITT) population for efficacy analysis. Data on vaginal dryness are available for 2144 patients and 883 women (438 on tibolone, 445 on placebo) answered to WHQ. The mean change in number of hot flushes per day was 2.74 (43.1%) in the tibolone group and -1.77 (-27.5%) in the placebo group (p<0.0001) at week 12 and -4.62 (-65.6%) on tibolone as compared to -3.73 (-52.5%) on placebo (p<0.0001) at week 104. For the composite score the mean changes at week 12 were -0.19 (-10.6%) and -0.14 (-7.7%), respectively (p=0.0006). Vaginal dryness score improved at week 104 in the tibolone group as compared to placebo (-0.46 versus -0.29, respectively; p<0.0001). Across the assessments up to two years with WHQ, tibolone was more effective than placebo in improving sexual health, sleep quality and mood domains. Women using tamoxifen showed less improvement in climacteric symptoms with tibolone, than women only receiving tibolone without any adjuvant therapy.\n The results of the LIBERATE trial show that tibolone is effective in symptomatic breast cancer patients and improves their quality of life. However, this finding should be judged within the context of the main outcome of the trial, showing that tibolone increases the risk of recurrence. The use of tibolone in women with breast cancer will remain contraindicated and any off-label use incurs a now proven risk.\n Copyright Â© 2011 Elsevier Ireland Ltd. All rights reserved.", "A double blind crossover study was planned in order to compare the effects of oestrogen, progestogen and placebo on hot flushes. The 49 women studied had previously undergone hysterectomy and bilateral oophorectomy. The drug regimen consisted of three months each of ethinyl oestradiol 50 microgram/day, d norgestrel 250 microgram/day, a combination of these two substance (\"Nordiol\") and a placebo. The predominant reason for requesting a change of medication was intolerable hot flushes associated with placebo use. All hormonal preparations were found to be significantly more effective than placebo in reducing hot flush frequency and intensity. Oestrogen containing medications were more effective than the progestogen (norgestrel).", "We observed the relief of hot flashes in breast cancer survivors taking tamoxifen and treated with sertraline for depression. Our objective was to assess the effect of sertraline on the frequency and severity of hot flashes, mood status, and health-related quality of life. We used a randomized, double-blind, placebo-controlled, crossover study using 6 weeks of sertraline (50 mg each morning) versus placebo. Study participants were 62 breast cancer survivors from an oncology clinic in a tertiary care center on adjuvant tamoxifen reporting bothersome hot flashes. Patients were asked to keep a daily hot flash diary to record hot flash frequency and severity, from which hot flash scores (frequency x severity) were calculated. The Center for Epidemiologic Studies depression scale and Functional Assessment of Cancer Therapy--Breast (FACT-B) (at baseline, 6 weeks, and 12 weeks) were used to assess mood and quality of life. Sixty-two women were accrued. Forty-seven women (median age 53.9 years, range 36.6-77.1 years; 89% postmenopausal; 85.5% Caucasian) completed the first 6 weeks and 39 completed 12 weeks. The baseline daily hot flash frequency and score were 5.8 (standard deviation 4.1) and 11.5 (14.0), respectively. At the end of the first 6 weeks, hot flash frequency decreased by 50% in 36% of those taking sertraline compared to 27% taking placebo. In the crossover analysis, sertraline was significantly more effective than placebo: women crossing from placebo to sertraline had a decrease (-0.9 and -1.7) in hot flash frequency and score, whereas those crossing from sertraline to placebo had an increase (1.5 and 3.4) in hot flash frequency and score (p = 0.03 and 0.03). Forty-eight percent preferred the sertraline period, 11% preferred the placebo period, and 41% had no preference (p = 0.006). Measures of depression and quality of life were within normal range and did not change significantly within treatment groups. Sertraline decreases hot flashes in breast cancer survivors taking tamoxifen and women prefer sertraline to placebo. Further study of sertraline for the management of hot flashes is warranted.", "Hot flashes can be troublesome, especially when hormonal therapy is contraindicated. Preliminary data have suggested that newer antidepressants, such as venlafaxine, can diminish hot flashes. We undertook a double-blind, placebo-controlled, randomised trial to assess the efficacy of venlafaxine in women with a history of breast cancer or reluctance to take hormonal treatment because of fear of breast cancer.\n Participants were assigned placebo (n=56) or venlafaxine 37.5 mg daily (n=56), 75 mg daily (n=55), or 150 mg daily (n=54). After a baseline assessment week, patients took the study medication for 4 weeks. All venlafaxine treatment started at 37.5 mg daily and gradually increased in the 75 mg and 150 mg groups. Patients completed daily hot-flash questionnaire diaries. The primary endpoint was average daily hot-flash activity (number of flashes and a score combining number and severity). Analyses were based on the women who provided data throughout the baseline and study weeks.\n 191 patients had evaluable data for the whole study period (50 placebo, 49 venlafaxine 37.5 mg, 43 venlafaxine 75 mg, 49 venlafaxine 150 mg). After week 4 of treatment, median hot flash scores were reduced from baseline by 27% (95% CI 11-34), 37% (26-54), 61% (50-68), and 61% (48-75) in the four groups. Frequencies of some side-effects (mouth dryness, decreased appetite, nausea, and constipation) were significantly higher in the venlafaxine 75 mg and 150 mg groups than in the placebo group.\n Venlafaxine is an effective non-hormonal treatment for hot flashes, though the efficacy must be balanced against the drug's side-effects. Confirmation of the results of this 4-week study awaits the completion of three ongoing randomised studies to assess the effects of other related antidepressants for the treatment of hot flashes.", "In an open-label trial we have previously demonstrated that paroxetine reduces hot flashes. We initiated a stratified, randomized, double-blind, cross-over, placebo-controlled trial to investigate the efficacy of paroxetine 10 mg and 20 mg compared to placebo in reducing hot flash frequency and composite score. A secondary objective was to evaluate quality of life (QOL) parameters.\n Women who suffered at least two hot flashes a day for 1 month or longer were eligible. Women were randomly assigned to 4 weeks of paroxetine 10 mg or 20 mg followed by placebo for 4 weeks, or placebo for 4 weeks followed by paroxetine 10 mg or 20 mg for 4 weeks. Participants completed baseline daily hot flash diaries for one week prior to the start of the study and throughout the study, and QOL questionnaires at baseline, week 5 and week 9.\n 279 women were screened, and 151 were randomly assigned. Paroxetine 10 mg reduced hot flash frequency and composite score by 40.6% and 45.6%, respectively, compared to 13.7% and 13.7% for placebo (P = .0006 and P = .0008, respectively). Paroxetine 20 mg reduced hot flash frequency and composite score by 51.7% and 56.1%, respectively, compared with 26.6% and 28.8% for placebo (P = .002 and P = .004, respectively). Efficacy was similar between the two doses, but women were less likely to discontinue low-dose paroxetine. Paroxetine 10 mg was associated with a significant improvement in sleep compared with placebo (P = .01).\n Paroxetine is an effective treatment for hot flashes in women with or without a prior breast cancer." ]	Clonidine, SSRIs and SNRIs, gabapentin and relaxation therapy showed a mild to moderate effect on reducing hot flushes in women with a history of breast cancer.
CD000560	[ "10473306", "9328501", "14702229", "17924246", "20181120", "9803707", "12611847", "12765500", "2571625", "18519824" ]	[ "A randomized controlled trial of individual psychological debriefing for victims of violent crime.", "Randomised controlled trial of psychological debriefing for victims of acute burn trauma.", "Early cognitive-behavioural therapy for post-traumatic stress symptoms after physical injury. Randomised controlled trial.", "Trial of interpersonal counselling after major physical trauma.", "Effectiveness of a single-session early psychological intervention for children after road traffic accidents: a randomised controlled trial.", "Treatment of acute stress disorder: a comparison of cognitive-behavioral therapy and supportive counseling.", "Treating acute stress disorder following mild traumatic brain injury.", "Stress debriefing after childbirth: a randomised controlled trial.", "Brief psychotherapy for posttraumatic stress disorders.", "Treatment of acute stress disorder: a randomized controlled trial." ]	[ "It has been suggested that giving people the opportunity talk about a traumatic experience may prevent the development of later disorder. We tested the efficacy of two brief interventions, education and psychological debriefing, designed to prevent adverse psychological reactions to criminal victimization.\n Individuals who had been the victims of a violent crime within the past month were written to and invited to take part in a study of their attitudes to crime and punishment: 2161 were contacted and 243 replied, of whom 157 were eligible and were randomly assigned either to an education condition, to a psychological debriefing plus education condition, or to an assessment only condition. Education involved providing information about normal post-traumatic reactions. Debriefing involved in-depth probing about events, thoughts and feelings experienced during the crime. Subjects were recruited from police and hospital sources and interviewed in their own homes: 138 were followed up at 6 months, and 92 at 11 months.\n Outcome was assessed using a DSM-III-R diagnosis of PTSD, the Post-traumatic Symptom Scale, the Impact of Event Scale and the Beck Depression Inventory. All groups improved over time but there were no between-group differences.\n No evidence was found to support the efficacy of brief one-session interventions for preventing post-traumatic symptoms in individual victims of violent crime.", "Psychological debriefing (PD) is widely used following major traumatic events in an attempt to reduce psychological sequelae.\n One hundred and thirty-three adult burn trauma victims entered the study. After initial questionnaire completion, participants were randomly allocated to an individual/couple PD group or a control group who received no intervention; 110 (83%) were interviewed by an assessor blind to PD status three and 13 months later.\n Sixteen (26%) of the PD group had PTSD at 13-month follow-up, compared with four (9%) of the control group. The PD group had higher initial questionnaire scores and more severe dimensions of burn trauma than the control group, both of which were associated with a poorer outcome.\n This study seriously questions the wisdom of advocating one-off interventions post-trauma, and should stimulate research into more effective initiatives.", "Early single-session psychological interventions, including psychological debriefing following trauma, have not been shown to reduce psychological distress. Longer early psychological interventions have shown some promise.\n To examine the efficacy of a four-session cognitive-behavioural intervention following physical injury.\n A total of 152 patients attending an accident and emergency department displaying psychological distress following physical injury were randomised 1-3 weeks post-injury to a four-session cognitive-behavioural intervention that started 5-10 weeks after the injury or to no intervention and then followed up for 13 months.\n At 13 months, the total Impact of Event Scale score was significantly more reduced in the intervention group (adjusted mean difference=8.4,95% CI 2.4-14.36). Other differences were not statistically significant.\n A brief cognitive-behavioural intervention reduces symptoms of post-traumatic stress disorder in individuals with physical injury who display initial distress.", "The purpose of the present study was to determine if interpersonal counselling (IPC) was effective in reducing psychological morbidity after major physical trauma.\n One hundred and seventeen subjects were recruited from two major trauma centres and randomized to treatment as usual or IPC in the first 3 months following trauma. Measures of depressive, anxiety and post-traumatic symptoms were taken at baseline, 3 months and 6 months. The Structured Clinical Interview for DSM IV diagnoses was conducted at baseline and at 6 months to assess for psychiatric disorder.\n Fifty-eight patients completed the study. Only half the patients randomized to IPC completed the therapy. At 6 months the level of depressive, anxiety and post-traumatic symptoms and the prevalence of psychiatric disorder did not differ significantly between the intervention and treatment-as-usual groups. Subjects with a past history of major depression who received IPC had significantly higher levels of depressive symptoms at 6 months.\n IPC was not effective as a universal intervention to reduce psychiatric morbidity after major physical trauma and may increase morbidity in vulnerable individuals. Patient dropout is likely to be a major problem in universal multi-session preventative interventions.", "Road traffic accidents (RTAs) are the leading health threat to children in Europe, resulting in 355,000 injuries annually. Because children can suffer significant and long-term mental health problems following RTAs, there is considerable interest in the development of early psychological interventions. To date, the research in this field is scarce, and currently no evidence-based recommendations can be made.\n To evaluate the effectiveness of a single-session early psychological intervention, 99 children age 7-16 were randomly assigned to an intervention or control group. The manualised intervention was provided to the child and at least one parent around 10 days after the child's involvement in an RTA. It included reconstruction of the accident using drawings and accident-related toys, and psychoeducation. All of the children were interviewed at 10 days, 2 months and 6 months after the accident. Parents filled in questionnaires. Standardised instruments were used to assess acute stress disorder (ASD), posttraumatic stress disorder (PTSD), depressive symptoms and behavioural problems.\n The children of the two study groups showed no significant differences concerning posttraumatic symptoms and other outcome variables at 2 or at 6 months. Interestingly, analyses showed a significant intervention x age-group effect, indicating that for preadolescent children the intervention was effective in decreasing depressive symptoms and behavioural problems.\n This study is the first to show a beneficial effect of a single-session early psychological intervention after RTA in preadolescent children. Therefore, an age-specific approach in an early stage after RTAs may be a promising way for further research. Younger children can benefit from the intervention evaluated here. However, these results have to be interpreted with caution, because of small subgroup sizes. Future studies are needed to examine specific approaches for children and adolescents. Also, the intervention evaluated here needs to be studied in other groups of traumatised children.\n Clinical Trial Registry: ClinicalTrials.gov: NCT00296842.", "Acute stress disorder (ASD) is a precursor of chronic posttraumatic stress disorder (PTSD). Twenty-four participants with ASD following civilian trauma were given 5 sessions of either cognitive-behavioral therapy (CBT) or supportive counseling (SC) within 2 weeks of their trauma. Fewer participants in CBT (8%) than in SC (83%) met criteria for PTSD at posttreatment. There were also fewer cases of PTSD in the CBT condition (17%) than in the SC condition (67%) 6 months posttrauma. There were greater statistically and clinically significant reductions in intrusive, avoidance, and depressive symptomatology among the CBT participants than among the SC participants. This study represents the 1st demonstration of successful treatment of ASD with CBT and its efficacy in preventing chronic PTSD.", "Acute stress disorder permits early identification of trauma survivors who are at risk of developing chronic posttraumatic stress disorder (PTSD). This study aimed to prevent PTSD in people who developed acute stress disorder after a mild brain injury by early provision of cognitive behavior therapy.\n Twenty-four civilian trauma survivors with acute stress disorder were given five individually administered sessions of either cognitive behavior therapy or supportive counseling within 2 weeks of their trauma.\n Fewer patients receiving cognitive behavior therapy than supportive counseling met criteria for PTSD at a posttreatment evaluation (8% versus 58%, respectively). There were also fewer cases of PTSD at a 6-month follow-up evaluation among those receiving cognitive behavior therapy (17%) than among those receiving supportive counseling (58%). Patients in the cognitive behavior therapy condition displayed less reexperiencing and avoidance symptoms at the follow-up evaluation than patients receiving supportive counseling.\n These findings suggest that PTSD following mild brain injury can be effectively prevented with early provision of cognitive behavior therapy.", "To test whether critical incident stress debriefing after childbirth reduces the incidence of postnatal psychological disorders.\n Randomised single-blind controlled trial stratified for parity and delivery mode.\n Two large maternity hospitals in Perth.\n 1745 women who delivered healthy term infants between April 1996 and December 1997 (875 allocated to intervention and 870 to control group).\n An individual, standardised debriefing session based on the principles of critical incident stress debriefing carried out within 72 hours of delivery.\n Diagnosis of stress disorders or depression in the 12 months postpartum, using structured psychological interview and criteria of the Diagnostic and statistical manual of mental disorders, 4th edition.\n Follow-up information was available for 1730 women (99.1%), 482 of whom underwent psychological interview. There were no significant differences between control and intervention groups in scores on Impact of Events or Edinburgh Postnatal Depression Scales at 2, 6 or 12 months postpartum, or in proportions of women who met diagnostic criteria for a stress disorder (intervention, 0.6% v control, 0.8%; P = 0.58) or major or minor depression (intervention, 17.8% v control, 18.2%; relative risk [95% CI], 0.99 [0.87-1.11]) during the postpartum year. Nor were there differences in median time to onset of depression (intervention, 6 [interquartile range, 4-9] weeks v control, 4 [3-8] weeks; P = 0.84), or duration of depression (intervention, 24 [12-46] weeks v control, 22 [10-52] weeks; P = 0.98).\n There is a high prevalence of depression in women during the first year after childbirth. A session of midwife-led, critical incident stress debriefing was not effective in preventing postnatal psychological disorders, but had no adverse effects.", "A large-scale study of the effectiveness of psychotherapeutic methods for the treatment of posttraumatic stress disorders was conducted. The sample consisted of 112 persons suffering from serious disorders resulting from traumatic events (bereavement, acts of violence, and traffic accidents) that had taken place not more than 5 years before. Trauma desensitization, hypnotherapy, and psychodynamic therapy were tested for their effectiveness in comparison with a waiting-list control group. The results indicated that treated cases were significantly lower in trauma-related symptoms than the control group.", "Recent trauma survivors with acute stress disorder (ASD) are likely to subsequently develop chronic posttraumatic stress disorder (PTSD). Cognitive behavioral therapy for ASD may prevent PTSD, but trauma survivors may not tolerate exposure-based therapy in the acute phase. There is a need to compare nonexposure therapy techniques with prolonged exposure for ASD.\n To determine the efficacy of exposure therapy or trauma-focused cognitive restructuring in preventing chronic PTSD relative to a wait-list control group.\n A randomized controlled trial of civilians who experienced trauma and who met the diagnostic criteria for ASD (N = 90) seen at an outpatient clinic between March 1, 2002, and June 30, 2006.\n Patients were randomly assigned to receive 5 weekly 90-minute sessions of either imaginal and in vivo exposure (n = 30) or cognitive restructuring (n = 30), or assessment at baseline and after 6 weeks (wait-list group; n = 30).\n Measures of PTSD at the 6-month follow-up visit by clinical interview and self-report assessments of PTSD, depression, anxiety, and trauma-related cognition.\n Intent-to-treat analyses indicated that at posttreatment, fewer patients in the exposure group had PTSD than those in the cognitive restructuring or wait-list groups (33% vs 63% vs 77%; P = .002). At follow-up, patients who underwent exposure therapy were more likely to not meet diagnostic criteria for PTSD than those who underwent cognitive restructuring (37% vs 63%; odds ratio, 2.10; 95% confidence interval, 1.12-3.94; P = .05) and to achieve full remission (47% vs 13%; odds ratio, 2.78; 95% confidence interval, 1.14-6.83; P = .005). On assessments of PTSD, depression, and anxiety, exposure resulted in markedly larger effect sizes at posttreatment and follow-up than cognitive restructuring.\n Exposure-based therapy leads to greater reduction in subsequent PTSD symptoms in patients with ASD when compared with cognitive restructuring. Exposure should be used in early intervention for people who are at high risk for developing PTSD." ]	There is no evidence that single session individual psychological debriefing is a useful treatment for the prevention of post traumatic stress disorder after traumatic incidents. Compulsory debriefing of victims of trauma should cease. A more appropriate response could involve a 'screen and treat' model (NICE 2005).
CD006396	[ "21059594", "7113926", "2392973", "14501543", "10665215", "1165499", "10772609", "9800180", "17228988", "1800294", "21193566", "7395724", "19800914", "18726988", "21091403", "17450706", "14726777", "7987019", "12486782", "8936577", "8284053", "17162478", "7113925" ]	[ "Use of historical data and a novel metric in the evaluation of the effectiveness of hearing conservation program components.", "Efficacy of enforcement in an industrial hearing conservation program.", "Hearing conservation programs (HCPs): the effectiveness of one company's HCP in a 12-hr work shift environment.", "Effectiveness of a tailored intervention to increase factory workers' use of hearing protection.", "Effectiveness of an intervention to increase construction workers' use of hearing protection.", "The effectiveness of hearing protective devices.", "Use of comparison populations for evaluating the effectiveness of hearing loss prevention programs.", "A hearing conservation program for Wisconsin youth working in agriculture.", "Efficacy of a computer-based hearing test and tailored hearing protection intervention.", "A controlled investigation of in-field attenuation performance of selected insert, earmuff, and canal cap hearing protectors.", "Effect of daily noise exposure monitoring on annual rates of hearing loss in industrial workers.", "An evaluation of the effectiveness of two different insert types of ear protection in preventing TTS in an industrial environment.", "Hearing conservation program for agricultural students: short-term outcomes from a cluster-randomized trial with planned long-term follow-up.", "The impact of hearing conservation programs on incidence of noise-induced hearing loss in Canadian workers.", "A multi-component intervention to promote hearing protector use among construction workers.", "Effectiveness of computer-based tailoring versus targeting to promote use of hearing protection.", "Effects of booster interventions on factory workers' use of hearing protection.", "Early indicators of hearing conservation program performance.", "Changes over time in audiometric thresholds in a group of automobile stamping and assembly workers with a hearing conservation program.", "Does a 3-day workshop for family medicine trainees improve preventive care? A randomized control trial.", "An epidemiologic method for assessing the effectiveness of hearing conservation programs using audiometric data.", "Noise exposure and hearing conservation in U.S. coal mines--a surveillance report.", "The application of positive practice overcorrection to the use of hearing protection." ]	[ "To evaluate the effectiveness of hearing conservation programs (HCP) and their specific components in reducing noise-induced hearing loss (NIHL).\n This retrospective cohort study was conducted at one food-processing plant and two automotive plants. Audiometric and work-history databases were combined with historical noise monitoring data to develop a time-dependent exposure matrix for each plant. Historical changes in production and HCP implementation were collected from company records, employee interviews and focus groups. These data were used to develop time-dependent quality assessments for various HCP components. 5478 male (30,427 observations) and 1005 female (5816 observations) subjects were included in the analysis.\n Analyses were conducted separately for males and females. Females tended to have less NIHL at given exposure levels than males. Duration of noise exposure stratified by intensity (dBA) was a better predictor of NIHL than the standard equivalent continuous noise level (L(eq)) based upon a 3-dBA exchange. Within this cohort, efficient dBA strata for males were <95 versus ≥ 95, and for females <90 versus ≥ 90. The reported enforced use of hearing protection devices (HPDs) significantly reduced NIHL. The data did not have sufficient within-plant variation to determine the effectiveness of noise monitoring or worker training. An association between increased audiometric testing and NIHL was believed to be an artifact of increased participation in screening.\n Historical audiometric data combined with noise monitoring data can be used to better understand the effectiveness of HCPs. Regular collection and maintenance of quality data should be encouraged and used to monitor the effectiveness of these interventions.", "Relative efficacy of various levels of enforcement in the use of personal hearing protective devices was investigated among employees of a large industrial plant. The main variable was that each of four groups of employees worked during a different period of enforcement policy on the use of personal hearing protection. Analysis of variance of mean hearing levels using three different audiometric grading schemes with different levels of sensitivity, namely, the 0.5, 1, 2 kHz Hearing Level Index, the 1, 2, 3 kHz Hearing Level Index, and the 4000 Hz single puretone test indicate that the enforcement policy did have a dramatic effect on the efficacy of the hearing conservation program and should give similar results in other industrial settings. When and where the use of personal hearing protection was left to the employee it was found that hearing loss among the noise-exposed was very much in excess of that among a non-noise-exposed group. Mandatory use of personal protective devices was found to be much more effective in conserving hearing that the voluntary approach. Mandatory use of earmuffs exclusively proved to be less effective than mandatory use of personal hearing protection when the employee was given a choice of earmuffs or earplugs. Enactment of the Occupational Safety and Health Act did not result in greater hearing conservation over the existing company mandatory hearing conservation program which is quite effective.", "An existing hearing conservation program (HCP), originally designed when an 8-hr work shift schedule was in effect, was evaluated at a plant site where a 12-hr work shift schedule is now utilized. The study included the following phases: a noise analysis of the work environment, HCP evaluation through the use of audiometric data base analysis (ADBA), applying ADBA procedures and a comparison of the shift in hearing threshold levels (HTLs) for the 8-hr and 12-hr work shifts, and an evaluation of the hearing protection devices (HPDs) being used at the facility over the 12-hr work shift by measuring temporary threshold shift (TTS). The mean measured employee time-weighted average (TWA) in the process area where the TTS study was conducted was 92 dBA. It was found that the existing HCP is at best marginal. The most likely causes of this less-than-desirable rating are inadequate audiometric testing procedures and inadequate HPD utilization. Furthermore, it was concluded that, at this time, the introduction of the 12-hr work shift has had no impact on the level of effectiveness of the HCP. In evaluating the three HPDs in use at the facility (3-M foam earplug, E-A-R foam earplug, and Bilsom Soft earplug), it was found that they all offered effective protection from noise at all audiometric test frequencies (0.5 to 6 kHz) except 0.5 kHz. All three HPDs exhibited TTS at 0.5 kHz with the TTS measured significant at the p less than 0.05 level for the E-A-R and 3-M wearer groups.", "In the United States it is estimated that more than 30 million workers are exposed to harmful levels of noise on the job. When engineering or administrative controls cannot be used to reduce noise, workers should always use hearing protection devices (HPDs) when exposed to loud noise to prevent noise-induced hearing loss (NIHL). Previous research has shown that workers do not always use HPDs when required; therefore, it is essential that workers assume personal responsibility for preventing NIHL by increasing their use of HPDs.\n This study tested the effectiveness of an individually tailored multimedia intervention to increase use of HPDs by factory workers.\n A randomized controlled design was used to compare the effects of a tailored intervention (n= 446) with two other interventions (a nontailored predictor-based intervention (n= 447) and a control intervention (n= 432)) on workers' self-reported use of HPDs 6 to 18 months following the intervention.\n Only those workers receiving the tailored intervention significantly increased their use of HPDs from pretest to posttest. However, this increase significantly differed from the nontailored group but not from the control group.\n Individually-tailored interventions offer promise for changing behavior. In light of the similarity between the results for the tailored intervention and the control intervention groups, further research is needed to understand barriers to HPD use and how to maximize the benefits of individually tailored interventions in this setting.", "In this project we tested the effectiveness of a theory-based intervention (video, pamphlets, and guided practice session) to increase the use of hearing protection devices (HPDs) among Midwestern construction workers and a national group of plumber/pipefitter trainers. Posttest measures were collected 10-12 months following this intervention. Pender's Health Promotion Model (1987) provided the conceptual basis for development of the training program. A total of 837 high-noise-exposed workers were included in the analysis: 652 regional Midwestern construction workers and 185 national plumber/pipefitter trainers. Effectiveness of the intervention was determined through the sequence of analyses recommended by Braver and Braver (1988) for the Solomon Four-Group Design. Analysis of variance and covariance of postintervention use and intention to use HPDs and a meta-analytic test were done. These analyses indicated that the intervention significantly increased use of HPDs but had no effect on intention to use HPDs in the future. Pretesting had no effect on use. Actual or potential applications of this research include guidance in the development of successful theory-based interventions to increase use of HPDs.", "The effectiveness of a hearing conservation program, and specifically the effectiveness of hearing protection devices (muffs in this case), was investigated over a five-year period, since the inception of the program at a major plant of the Ingersoll-Rand Company. The study concentrated on three groups (Class I, II, and III) of 213 employees whose noise level exposure did not change during the five-year study period. A hearing conservation criterion of 90dBA was utilized. One group consisted of office workers in which the level was well below this, a second group from a machine shop in which the level was slightly below the criterion, and a third group from foundry areas in which the levels were considerably above the 90dBA level. Personal ear protection was worn during the study period only by the last group. The mean differences in hearing levels were insignificant and were essentially the same in the three groups, at each frequency, and regardless of the baseline hearing thresholds. It is apparent that there were no significant changes in hearing threshodls during the study period among a non-noise exposed group; a mild to moderate noise-exposed group; and a group exposed to high levels of steady state noise, but wearing ear protectors. These results indicate that a hearing conservation program which includes audiometric testing and personal ear protection, utilizing a hearing conservation criterion of approximately 90dBA, does adequately protect the hearing of noise-exposed workers.", "One approach for evaluating the effectiveness of Hearing loss prevention programs (HLPPs) is to compare the rate of hearing loss in a study population with that in a reference population. This approach was used to evaluate the HLPP of a population of 14,900 employees of an industrial company with branches across the United States. Three reference populations were selected from a database of 22 industrial companies compiled under the sponsorship of the National Institute for Occupational Safety and Health. The risk of hearing loss in the study population was estimated relative to each of the three reference populations using the Cox proportional hazards model after adjustment for race, age at baseline, and hearing threshold at time of enrollment in the HLPP. In comparison with the three reference populations, hearing loss was 2.1 to 3.9 times more likely to occur in study population males and 1.8 to 5.1 times more likely in study population females. The 95% confidence interval around each risk estimate precluded unity, indicating that each risk estimate was statistically significant. These results indicate that the performance of the subject HLPP needs improvement. This study demonstrated the use of comparison populations for evaluating the effectiveness of HLPPs.", "Adolescents working in agricultural settings may be exposed to noise levels that result in hearing loss. The article describes the design, implementation, and results of a four-year, hearing conservation program (HCP) conducted at school. Thirty-four schools (753 students) were randomly assigned to either an intervention or control group. The intervention included multicomponent educational strategies and employed features of an industrial HCP. Final compliance surveys indicated 87.5% of intervention students reported using hearing protection devices (HPD) at least some of the time, compared to 45% of control students. The HCP components with the greatest reported influence were distribution of HPDs for use on the farm and yearly hearing tests. Eighty percent of intervention students reported intention to use HPDs in the future. It is feasible to conduct a hearing conservation program with junior high school and senior high school students, and it appears possible to persuade teen-agers to protect themselves from exposure to loud noise while working on a farm.", "Advances in computer technology and accessibility enable researchers to provide individually tailored interventions for behavioral change. Using multimedia technology, this study developed and tested a computer-based hearing test and a tailored intervention. The purpose of this study was to evaluate, using a randomized experimental design, the efficacy of the intervention to increase workers' use of hearing protection. The tailored intervention developed by the research team showed more significant short-term effect measured immediately after the intervention than the control intervention. For the long-term effect measured 1 year after the intervention, both tailored and control groups showed significant increase in their reported use (7% vs. 6%) from preintervention to postintervention, but no significant difference between the two groups. The change accomplished in this study was small progress toward the desired level of 100% use of hearing protection to prevent noise-induced hearing loss. This finding showed that changing workers' hearing protection behavior is difficult.", "A field study assessed the actual spectral noise attenuation achieved by 40 industrial workers wearing four different hearing protection devices (HPDs) while on the job. The effect of two different HPD fitting procedures (subject fit vs. trained fit) on attenuation performance over two three-week periods of protector use was determined. Subjects were retrieved from their workplaces without prior knowledge of when they were to be tested and were not permitted to readjust the fit of their HPDs. Attenuation data were then collected using psychophysical procedures testing real ear attenuation at threshold. Statistical analyses indicated that the earplugs' attenuation significantly improved when training for proper fitting was used, whereas the earmuff and the ear canal cap were relatively insensitive to the training effect. The training was most effective for a slow-recovery foam plug over the three-week period. Results confirmed that laboratory protocols designed to simulate workplace influences on attenuation may not be relied on to yield reasonable estimates of field protection performance of HPDs, particularly for earplugs; however, the laboratory results were much better predictors of field protection for the earmuff. This study also demonstrated that the labeled manufacturers' noise reduction ratings (NRRs) substantially overestimated the actual field attenuation performance.", "Occupational noise-induced hearing loss (NIHL) is prevalent, yet evidence on the effectiveness of preventive interventions is lacking. The effectiveness of a new technology allowing workers to monitor daily at-ear noise exposure was analysed.\n Workers in the hearing conservation program of an aluminium smelter were recruited because of accelerated rates of hearing loss. The intervention consisted of daily monitoring of at-ear noise exposure and regular feedback on exposures from supervisors. The annual rate of change in high frequency hearing average at 2, 3 and 4 KHz before intervention (2000-2004) and 4 years after intervention (2006-2009) was determined. Annual rates of loss were compared between 78 intervention subjects and 234 controls in other company smelters matched for age, gender and high frequency hearing threshold level in 2005.\n Individuals monitoring daily noise exposure experienced on average no further worsening of high frequency hearing (average rate of hearing change at 2, 3 and 4 KHz = -0.5 dB/year). Matched controls also showed decelerating hearing loss, the difference in rates between the two groups being significant (p < 0.0001). Analysis of a subset of intervention subjects matched to controls for initial rate of hearing loss showed a similar trend but the difference was not statistically significant (p = 0.06).\n Monitoring daily occupational noise exposure inside hearing protection with ongoing administrative feedback apparently reduces the risk of occupational NIHL in industrial workers. Longer follow-up of these workers will help determine the significance of the intervention effect. Intervention studies for the prevention of NIHL need to include appropriate control groups.", "The effectiveness of a V-51R insert hearing protector in preventing daily temporary threshold shifts in one industrial environment where the employees were exposed to an A-weighted energy average noise level of 95.6 dB was investigated. For comparison purposes the E-A-R Plug Insert hearing protector was also evaluated. The results indicated that the employees who wore the V-51R design incurred significant daily shifts in their hearing levels as compared to their initial hearing exam and significantly greater shifts than the employees who wore the E-A-R Plugs. The greater than expected measured shifts in hearing levels over the past six years in the two departments investigated is attributed at least partially to the use of the V-51R design.", "(1) To conduct a contemporary analysis of historical data on short-term efficacy of a 3-year hearing conservation program conducted from 1992 to 1996 in Wisconsin, USA, with 753 high school students actively involved in farm work; (2) to establish procedures for assessment of hearing loss for use in a recently funded follow-up of this same hearing conservation program cohort.\n We analyzed a pragmatic cluster-randomized controlled trial, with schools as the unit of randomization. Thirty-four rural schools were recruited and randomized to intervention or control. The intervention included classroom instruction, distribution of hearing protection devices, direct mailings, noise level assessments, and yearly audiometric testing. The control group received the audiometric testing.\n Students exposed to the hearing conservation program reported more frequent use of hearing protection devices, but there was no evidence of reduced levels of noise-induced hearing loss (NIHL).\n Our analysis suggests that, since NIHL is cumulative, a 3-year study was likely not long enough to evaluate the efficacy of this intervention. While improvements in reported use of hearing protection devices were noted, the lasting impact of these behaviors is unknown and the finding merits corroboration by longer term objective hearing tests. A follow-up study of the cohort has recently been started.", "Noise exposure remains one of the most ubiquitous of occupational hazards. Hearing conservation program legislation and the programs themselves were designed to lower risk of resulting occupational noise-induced hearing loss, but there has been no broad-based effort to assess the effectiveness of this policy.\n The incidence of a 10-dB standard threshold shift was examined in a group of Canadian lumber mill workers, using annual audiogram series obtained from the Workers' Compensation Board of British Columbia for the period 1979-1996 and using Cox proportional hazard models.\n Mean cumulative noise exposure was 98.1 dB-years. The audiograms from 22,376 individuals, among whom there were 2,839 threshold shifts of 10 dB or greater (i.e., a \"standard threshold shift\"), were retained in multivariable analyses. After adjusting for potential confounders, continuous use of hearing protection, and initial hearing tests later in the study period, the risk for standard threshold shift was reduced by 30%. Risk increased sixfold, however, in those with the highest noise exposure.\n Hearing conservation programs may be effective in reducing overall incidence of hearing loss. In the absence of noise control at source, however, highly exposed workers remain at unnecessary risk.\n Copyright 2008 Wiley-Liss, Inc.", "Hearing protection devices (HPD) remain a primary method of prevention of noise-induced hearing loss despite their well-known limitations. A three-pronged intervention to increase HPD use was conducted among construction workers and included a baseline hearing loss prevention training, follow-up 'toolbox' (TB) reinforcement trainings, and use of a personal noise level indicator (NLI). A total of 176 subjects on eight sites completed three assessments. Prior to intervention, HPDs were used an average of 34.5% of the time and increased significantly, up about 12.1% after intervention and 7.5% two months after interventions were completed. The increase in HPD use was greatest among the group receiving both TB and NLI interventions; up about 25% from baseline, and this group was about two times more likely to use HPDs than the BL (baseline) training only group. This study demonstrates the mild impact of a well-constructed HPD use training and provides support for the additional use of a personal NLI to increase use of HPDs among construction workers. The most effective procedures for using such instruments require further exploration.", "The purpose of this study was to evaluate the effectiveness of 2 computer-based interventions and booster messages on construction workers' use of hearing protection. Construction workers (n = 343) were randomly assigned to receive tailored (addressing individual characteristics) or targeted (addressing shared characteristics) education, with or without booster messages, in an experimental 4-group pretest-post-test design. Post hoc message matching compared the value of tailored and targeted approaches. Participants improved use of hearing protection from 42% to 50% of the time they were exposed to noise 1 year post-intervention. Differences between intervention groups were not significant. The significant improvement in use of hearing protection demonstrates that interventions can have an impact on preventing noise-induced hearing loss. Since targeted and tailored intervention groups did not significantly differ in use of hearing protection, and since targeted interventions are less costly to develop, targeted interventions offer greater value.", "The provision of reinforcements or boosters to interventions is seen as a logical approach to enhancing or maintaining desired behavior. Empirical studies, however, have not confirmed the effectiveness of boosters nor assessed the optimum number of boosters or the timing for their delivery.\n This randomized controlled trial contrasted the effect of four booster conditions (a). 30 days; (b). 90 days; (c). 30 and at 90 days; and (d). no boosters of the intervention to increase the use of hearing protection devices (HPDs).\n A total of 1325 factory workers completed a computerized questionnaire and were randomly assigned to one of three computer-based (tailored, nontailored predictor-based, or control) multimedia interventions designed to increase the use of hearing protection devices. After the intervention, colorful boosters specific to the type of training received were mailed to workers' homes. Posttest measures of use were administered at the time of their next annual audiogram 6 to 18 months after the intervention. RESULTS Repeated measures of analysis of variance (ANOVA) showed a significant main effect for the booster (after 30 days) in the group that received tailored training (F[3442] = 2.722; p =.04). However, in the assessment of the interaction between time (pretest and posttest) and boosters (four groups), the ANOVA did not find significant differences in hearing protection device use for any of the training groups. To assess for significant differences between groups, post hoc comparisons were conducted at the pretest and posttest for the total sample and for the subsample of workers who reported using hearing protection devices less than 100% of the time needed. Sheffé contrasts by intervention group, gender, ethnicity, and hearing ability found no significant changes in the mean use of hearing protection devices for the booster groups.\n Although the provision of boosters represented a considerable commitment of resources, their use was not effective in this study. However, it would be premature to eliminate boosters of interventions. Further study is needed to explore the effects of different booster types for increasing the use of hearing protection devices, and to assess carefully the effects of boosters on other health behaviors in studies with controlled designs.", "Retrospective analysis of initial audiograms from 21 hearing conservation programs (HCPs) revealed several statistical protocols capable of identifying HCPs of known performance. American National Standards Institute (ANSI) and Occupational Safety and Health Administration (OSHA) protocols clearly identified 3 HCPs known to have demonstrated excellent overall programs. ANSI and OSHA outcomes appeared equivalent in ability to provide early warnings of potentially unacceptable HCP practices.", "Noise induced hearing loss (NIHL) is among the 10 leading occupational diseases, afflicting between 7.4 and 10.2 million people who work in noise above 85 dBA. Although mandatory hearing conservation programs (HCPs) have been in effect since 1972, this problem persists, as hearing protectors are not consistently used by workers, or may not attenuate to manufacturer's estimates in real world conditions. In this study, information from noise and hearing protection use measurements taken at an automobile assembly plant were used to construct average lifetime noise exposure and hearing protection compliance estimates for use in modeling to predict both total hearing loss and onset of two accepted definitions of hearing loss. There were 301 males and females in this cohort; their mean age was 42.6 (7.2) years, and mean tenure was 14.3 (3.5) years. Average length of follow-up was 14.0 years. There were 16 members of this cohort who had hearing loss at the speech frequencies (defined as an average hearing level > or = 25 dB at 500, 1000, and 2000 Hz). In cross-sectional multivariate analyses, years of employment, male gender, and proportion of time wearing hearing protection were the factors most associated with hearing loss at the average of 2000, 3000, and 4000 Hz (p < 0.0001) controlling for age, transfer status (as a surrogate for previous noise exposure), race, and lifetime average noise exposure. The most consistent predictor of hearing loss in both univariate and multivariate analyses was percentage of time having used hearing protection during the workers' tenure.", "To evaluate the impact on clinical behavior of a 3-day workshop designed to increase trainees' rates of smoking cessation counseling and reminders about Pap smears in routine consultations.\n Randomized control trial.\n Accredited teaching practices of the Royal Australian College of General Practitioners' Training Program.\n Thirty-four trainees and 1,500 consecutive adult patients ages 16-65 years.\n Trainees randomly allocated to the experimental group participated in a 3-day interactive workshop on disease prevention during their 13-week family medicine term. Audiotapes of consultations with adults conducted by trainees at the beginning and end of the rotation were analyzed blind to compare assessment of patients' smoking status and, for women, date of last Pap smear. A questionnaire mailed to each patient after the consultation also allowed identification of smokers and women overdue for a smear. Consultations with these patients at risk were analyzed for preventive counseling. Inter- and intrarater reliability was calculated for audiotape analysis.\n Preworkshop rates of questions about smoking were low, occurring in 22% of consultations. While trainees allocated to the experimental workshop were more likely to ask a routine question about smoking at the end of the term than those in the control group (P = 0.01), two-thirds of smokers remained undetected irrespective of trainee group and fewer than one in five were advised to stop smoking. Reminders about Pap smears did not change as a result of training and remained low in fewer than 20% of consultations. kappa values demonstrated high reliability of audiotape analysis.\n This direct measurement of clinical behavior revealed that low levels of preventive care provided by trainees are resistant to skills training without reinforcement in clinical practice. In view of the importance of prevention in routine consultations, we recommend continued evaluation of more intensive educational programs. Those withstanding rigorous evaluation could be considered for implementation in similar training contexts seeking to improve the frequency and quality of disease prevention in primary medical care.", "A hearing conservation program (HCP) must include audiometric monitoring. In keeping with this requirement, enormous bodies of audiometric data have been accumulated. However, only a limited number of methods are available for using audiometric data to assess HCP effectiveness. This study illustrates an epidemiologic method. The risk of developing hearing loss (measured by the standard threshold shift) was compared between study and reference populations using the risk ratio. The study population had an increased risk of nearly 3-fold. Epidemiologic risk comparison methods, using reference populations, offer an alternative to current methods for HCP evaluation using audiometric data.", "This study examines the patterns and trends in noise exposure documented in data collected by Mine Safety and Health Administration inspectors at U.S. coal mines from 1987 through 2004. During this period, MSHA issued a new regulation on occupational noise exposure that changed the regulatory requirements and enforcement policies. The data were examined to identify potential impacts from these changes. The overall annual median noise dose declined 67% for surface coal mining and 24% for underground coal mining, and the reduction in each group accelerated after promulgation of the new noise rule. However, not all mining occupations experienced a decrease. The exposure reduction was accompanied by an increase of shift length as represented by dosimeter sample duration. For coal miners exposed above the permissible exposure level, use of hearing protection devices increased from 61% to 89% during this period. Participation of miners exposed at or above the action level in hearing conservation programs rapidly reached 86% following the effective date of the noise rule. Based on inspection data, the occupational noise regulation appears to be having a strong positive impact on hearing conservation by reducing exposures and increasing the use of hearing protection devices and medical surveillance. However, the increase in shift duration and resulting reduction in recovery time may mitigate the gains somewhat.", "A successful habit-building technique, overcorrection, was extended into an industrial type military setting to increase hearing protection usage among airplane mechanics in a high intensity noise environment. Three natural groups were assigned randomly to three conditions: a standard daily safety lecture group (S) for an attention-Placebo control; a leader-directed overcorrection group (A); and a leader-participative overcorrection group (P). Unobtrusive pre-test baseline observations of hearing protection usage established no significant difference among groups. Overcorrection requires persons not using hearing protection to practice repeatedly putting on protection after their failure is discovered by leaders or coworkers. During the application phase, the overcorrection groups successfully increased hearing protection usage over pre-test usage and in comparison to the Standard group which remained unchanged throughout the study. One of the overcorrection groups approached perfect usage. Members of the P group gave higher preference ratings than A group members. There was a decline toward original usage levels once the test was called off." ]	There is low quality evidence that implementation of stricter legislation can reduce noise levels in workplaces. Even though case studies show that substantial reductions in noise levels in the workplace can be achieved, there are no controlled studies of the effectiveness of such measures. The effectiveness of hearing protection devices depends on training and their proper use. There is very low quality evidence that the better use of hearing protection devices as part of HLPPs reduces the risk of hearing loss, whereas for other programme components of HLPPs we did not find such an effect. Better implementation and reinforcement of HLPPs is needed. Better evaluations of technical interventions and long-term effects are needed.
CD007476	[ "16818273", "16352812", "17233848", "12064916" ]	[ "Randomized phase II trial of deferasirox (Exjade, ICL670), a once-daily, orally-administered iron chelator, in comparison to deferoxamine in thalassemia patients with transfusional iron overload.", "A phase 3 study of deferasirox (ICL670), a once-daily oral iron chelator, in patients with beta-thalassemia.", "A randomised comparison of deferasirox versus deferoxamine for the treatment of transfusional iron overload in sickle cell disease.", "Deferiprone versus deferoxamine in patients with thalassemia major: a randomized clinical trial." ]	[ "Iron accumulation is an inevitable consequence of chronic blood transfusions and results in serious complications in the absence of chelation treatment to remove excess iron. Deferoxamine (Desferal, DFO) reduces morbidity and mortality although the administration schedule of slow, parenteral infusions several days each week limits compliance and negatively affects long-term outcome. Deferasirox (Exjade, ICL670) is an oral chelator with high iron-binding potency and selectivity. In a phase II study, the tolerability and efficacy of deferasirox were compared with those of DFO in 71 adults with transfusional hemosiderosis.\n Patients were randomized to receive once-daily deferasirox (10 or 20 mg/kg; n=24 in both groups) or DFO (40 mg/kg, 5 days/week; n=23) for 48 weeks. Results. Both treatments were well tolerated and no patient discontinued deferasirox due to drug-related adverse events. The reported frequency of transient, mild to moderate gastrointestinal disturbances was higher in the deferasirox group than in the DFO group, but these disturbances settled spontaneously without dose interruption in all patients. Decreases in liver iron concentration (LIC) were comparable in the deferasirox 20 mg/kg/day and DFO groups; baseline values of 8.5 and 7.9 mg Fe/g dw fell to 6.6 and 5.9 mg Fe/g dw, respectively, by week 48. Deferasirox showed a plasma elimination half-life of 8-16 hours, supporting its once-daily administration.\n Deferasirox at daily doses of 10 or 20 mg/kg was well tolerated and, at 20 mg/kg, showed similar efficacy to DFO 40 mg/kg in terms of decreases in LIC.", "Deferasirox (ICL670) is a once-daily oral iron chelator developed for the treatment of chronic iron overload from blood transfusions. A comparative phase 3 trial was conducted to demonstrate the efficacy of deferasirox in regularly transfused patients with beta-thalassemia aged 2 years or older. Patients were randomized and received treatment with deferasirox (n = 296) or deferoxamine (n = 290), with dosing of each according to baseline liver iron concentration (LIC). The primary endpoint was maintenance or reduction of LIC; secondary endpoints included safety and tolerability, change in serum ferritin level, and net body iron balance. In both arms, patients with LIC values of 7 mg Fe/g dry weight (dw) or higher had significant and similar dose-dependent reductions in LIC and serum ferritin, and effects on net body iron balance. However, the primary endpoint was not met in the overall population, possibly due to the fact that proportionally lower doses of deferasirox relative to deferoxamine were administered to patients with LIC values less than 7 mg Fe/g dw. The most common adverse events included rash, gastrointestinal disturbances, and mild nonprogressive increases in serum creatinine. No agranulocytosis, arthropathy, or growth failure was associated with deferasirox administration. Deferasirox is a promising once-daily oral therapy for the treatment of transfusional iron overload.", "Deferasirox is a once-daily, oral iron chelator developed for treating transfusional iron overload. Preclinical studies indicated that the kidney was a potential target organ of toxicity. As patients with sickle cell disease often have abnormal baseline renal function, the primary objective of this randomised, open-label, phase II trial was to evaluate the safety and tolerability of deferasirox in comparison with deferoxamine in this population. Assessment of efficacy, as measured by change in liver iron concentration (LIC) using biosusceptometry, was a secondary objective. A total of 195 adult and paediatric patients received deferasirox (n = 132) or deferoxamine (n = 63). Adverse events most commonly associated with deferasirox were mild, including transient nausea, vomiting, diarrhoea, abdominal pain and skin rash. Abnormal laboratory studies with deferasirox were occasionally associated with mild non-progressive increases in serum creatinine and reversible elevations in liver function tests. Discontinuation rates from deferasirox (11.4%) and deferoxamine (11.1%) were similar. Over 1 year, similar dose-dependent LIC reductions were observed with deferasirox and deferoxamine. Once-daily oral deferasirox has acceptable tolerability and appears to have similar efficacy to deferoxamine in reducing iron burden in transfused patients with sickle cell disease.", "Deferiprone has been suggested as an effective oral chelation therapy for thalassemia major. To assess its clinical efficacy, we compared deferiprone with deferoxamine in a large multicenter randomized clinical trial. One-hundred forty-four consecutive patients with thalassemia major and serum ferritin between 1500 and 3000 ng/ml were randomly assigned to deferiprone (75 mg/kg/day) (n = 71) or deferoxamine (50 mg/kg/day) (n = 73) for 1 year. The main measure of efficacy was the reduction of serum ferritin. Liver and heart iron contents were assessed by magnetic resonance. Liver iron content and fibrosis stage variations were assessed on liver biopsy by the Ishak score in all patients willing to undergo liver biopsy before and after treatment. The mean serum ferritin reduction was 222 +/- 783 ng/ml in the deferiprone and 232 +/- 619 ng/ml in the deferoxamine group (P = 0.81). No difference in the reduction of liver and heart iron content was found by magnetic resonance between the two groups. Thirty-six patients accepted to undergo repeat liver biopsy: 21 in the deferiprone and 15 in the deferoxamine group. Their mean reduction of liver iron content was 1022 +/- 3511 microg/g of dry liver and 350 +/- 524, respectively (P = 0.4). No difference in variation of the Ishak fibrosis stage was observed between the two groups. Treatment was discontinued because of reversible side effects in 5 patients in the deferiprone group (3 hypertransamin/asemia and 2 leukocytopenia) and in none in the deferoxamine group. These findings suggest that deferiprone may be as effective as deferoxamine in the treatment of thalassemia major with few mild and reversible side effects." ]	Deferasirox offers an important alternative line of treatment for people with thalassaemia and secondary iron overload. Based on the available data, deferasirox does not seem to be superior to deferoxamine at the usually recommended ratio of 1 mg of deferasirox to 2 mg of deferoxamine. However, similar efficacy seems to be achievable depending on the dose and ratio of deferasirox compared to deferoxamine. Whether this will result in similar efficacy in the long run and will translate to similar benefits as has been shown for deferoxamine, needs to be confirmed. Data on safety, particularly on rare toxicities and long-term safety, are still limited. Therefore, we think that deferasirox should be offered as an alternative to all patients with thalassaemia who either show intolerance to deferoxamine or poor compliance with deferoxamine. In our opinion, data are still too limited to support the general recommendation of deferasirox as first-line treatment instead of deferoxamine. If a strong preference for deferasirox is expressed, it could be offered as first-line option to individual patients after a detailed discussion of the potential benefits and risks.
CD003343	[ "10696421", "12971668", "15527158", "12631309", "11247549", "15117299", "9802271", "15868015", "16546538", "19858174", "11165450" ]	[ "Randomized controlled trial of directly observed treatment (DOT) for patients with pulmonary tuberculosis in Thailand.", "A randomised controlled clinical trial of the efficacy of family-based direct observation of anti-tuberculosis treatment in an urban, developed-country setting.", "Effectiveness of community-based directly observed treatment for tuberculosis in an urban setting in Tanzania: a randomised controlled trial.", "Evaluation of efficacy of community-based vs. institutional-based direct observed short-course treatment for the control of tuberculosis in Kilombero district, Tanzania.", "Effectiveness of the direct observation component of DOTS for tuberculosis: a randomised controlled trial in Pakistan.", "Direct observation of treatment for tuberculosis: a randomized controlled trial of community health workers versus family members.", "Randomised controlled trial of self-supervised and directly observed treatment of tuberculosis.", "Staff training and ambulatory tuberculosis treatment outcomes: a cluster randomized controlled trial in South Africa.", "Family-member DOTS and community DOTS for tuberculosis control in Nepal: cluster-randomised controlled trial.", "Food incentives to improve completion of tuberculosis treatment: randomised controlled trial in Dili, Timor-Leste.", "Incentives vs outreach workers for latent tuberculosis treatment in drug users." ]	[ "While directly observed treatment (DOT) has been recommended as the standard approach to tuberculosis control, empirical data on its feasibility and efficiency are still scarce. We conducted a controlled trial of DOT at 15 health care facilities at various levels of the government health care system in Thailand. A total of 836 patients diagnosed between August 1996 and October 1997 were randomly assigned to be treated either under DOT or self-supervised using monthly drug supplies (SS). Options for treatment supervisors were health staff, community members or members of the patients' families. Treatment outcomes were compared on the basis of cure, treatment-completion, default and death rates. In both study arms, treatment outcomes were improved compared to pre-study conditions. Cure and treatment-completion rates were significantly higher in the DOT cohort (76% and 84%) than in the SS group (67% and 76%). The benefits of DOT were more pronounced at district and provincial hospitals (DOT cure rate 81% vs. 69% in the SS group), while differences for patients treated at referral centres were non-significant (DOT cure rate 72% vs. 66% in the SS group). No significant differences in outcomes could be observed between patient groups receiving DOT under the various options for treatment supervisors. DOT appears especially suited for treatment at decentralized facilities. While a general focus on programme performance can improve outcomes, DOT provides significant additional benefits. If basic conditions are met, a DOT strategy can be tailored to country-specific conditions by exploring multiple observation options, without decreasing its effectiveness.", "A randomised, controlled clinical trial of the effectiveness of a family-based programme of directly observed treatment (DOT) for tuberculosis.\n TB patients seen in Victoria, Australia, were randomly allocated to DOT observed by a family member (FDOT), or to standard supervised but non-observed therapy (ST). The outcome measure was compliance, measured by blinded testing of isoniazid levels in urine. An intention-to-treat analysis was used.\n Of 173 patients, 87 were allocated to FDOT and 86 to ST. Only 58% in the FDOT group were able to receive FDOT, the major reason being living alone and not having a family member to observe treatment. The rate of non-compliance was 24% (41/173), with no significant difference between FDOT (22/87) and ST (19/86). No clinical or socio-demographic variable predicted compliance.\n We were unable to demonstrate a benefit of FDOT in an urban, industrialised country setting. FDOT may be more appropriate in developing countries, where extended family support is often available and the burden of TB is much higher. Poor compliance and the difficulty in predicting non-compliance shown in this study highlights the need for DOT for all TB patients.", "An urban district in Dar es Salaam city with a high tuberculosis (TB) caseload.\n To evaluate the effectiveness of community-based direct observation of treatment (DOT) using guardians and former TB patients compared to hospital-based DOT in an urban setting in Tanzania.\n Unblinded randomised control trial conducted in five sites under operational conditions in Temeke district. No changes to existing treatment delivery were made other than randomisation. The main outcome measure was treatment success. Analysis was by intention to treat.\n A total of 587 new tuberculosis patients were enrolled. Among enrolled patients, 260 were assigned to community-based DOT using guardians and former TB patients and 327 to health facility-based DOT. Both DOT options gave similar treatment outcomes. Treatment success rate among patients under community and health facility-based DOT were 85% and 83%, respectively (OR 1.17, 95%CI 0.75-1.83).\n Community-based DOT is as effective as health facility-based DOT and can achieve good treatment outcomes, even in countries with well functioning National Tuberculosis Programmes.", "Tuberculosis (TB) has reappeared as a serious public health problem. Non-compliance to antituber-culous drug treatment is cited as one of the major obstacles to the containment of the epidemic. Compliance may be optimized by Directly Observed Treatment (DOT) and short-course treatment regimens. Since 1986, Tanzanian TB patients have received daily DOT at health facilities for the first 2 months of the treatment course. However, adherence and cure rates have been falling as the number of TB cases continues to increase and the burden on already stretched health facilities threatens to become unmanageable. We used an open cluster randomized controlled trial to compare community-based DOT (CBDOT) using a short-course drug regimen with institutional-based DOT (IBDOT). A total of 522 (301 IBDOT and 221 CBDOT) patients with sputum-positive TB were recruited. Overall, there was no significant difference in conversion and cure rates between the two strategies [M-H pooled odds ratio (OR) 0.62; 95% confidence interval (CI) 0.23, 1.71 and OR = 1.58; 95% CI 0.32, 7.88, respectively] suggesting that CBDOT may be a viable alternative to IBDOT. CBDOT may be particularly useful in parts of the country where people live far from health facilities.", "DOTS is the control strategy for tuberculosis promoted by WHO. Pakistan is currently developing its National Tuberculosis Programme, and requires guidance on types of direct observation of treatment appropriate for the local conditions. We did a randomised trial to assess the effectiveness of different packages for tuberculosis treatment under operational conditions in Pakistan.\n We enrolled 497 adults with new sputum-positive tuberculosis. 170 were assigned DOTS with direct observation of treatment by health workers; 165 were assigned DOTS with direct observation of treatment by family members; and 162 were assigned self-administered treatment. The trial was done at three sites that provide tuberculosis services strengthened according to WHO guidelines for the purposes of the research, with a standard daily short-course drugs regimen (2 months of isoniazid, rifampicin, pyrazinamide, and ethambutol, followed by 6 months of isoniazid and ethambutol). The main outcome measures were cure, and cure or treatment completion. Analysis was by intention to treat.\n Within the strengthened tuberculosis services, the health-worker DOTS, family-member DOTS, and self-administered treatment strategies gave very similar outcomes, with cure rates of 64%, 55%, and 62%, respectively, and cure or treatment-completed rates of 67%, 62%, and 65%, respectively.\n None of the three strategies tested was shown to be superior to the others, and direct observation of treatment did not give any additional improvement in cure rates. The effectiveness of direct observation of treatment remains unclear, and further operational research is needed.", "We implemented community-based direct observation of treatment, short course (DOTS), including a randomized controlled trial of direct observation either by community health workers (CHWs) or family members, under operational conditions in a region of Swaziland. There was a high death rate of 15%, due to the high HIV rates in the region. There was no significant difference in the cure and completion rate between direct observation of treatment by CHWs and family members [2% difference (95% CI -3% to 7%), exact P = 0.52]. A before-and-after comparison of outcomes demonstrated that the cure and treatment completion rate improved from a baseline of 27-67% following implementation of community-based DOTS. We conclude that community-based tuberculosis DOTS can improve successful outcomes of treatment. However, direct observation can be undertaken effectively using either daily family or CHW supervision. The choice of treatment supporter should be based on access, patient preference and availability of CHW resource.", "Tuberculosis is a major public-health problem in South Africa, made worse by poor adherence to and frequent interruption of treatment. Direct observation (DO) of tuberculosis patients taking their drugs is supposed to improve treatment completion and outcome. We compared DO with self-supervision, in which patients on the same drug regimen are not observed taking their pills, to assess the effect of each on the success of tuberculosis treatment.\n We undertook an unblinded randomised controlled trial in two communities with large tuberculosis caseloads. The trial included 216 adults who started pulmonary tuberculosis treatment for the first time, or who had a second course of treatment (retreatment patients). No changes to existing treatment delivery were made other than randomisation. Analysis was by intention to treat. Individual patient data from the two communities were combined.\n Treatment for tuberculosis was more successful among self-supervised patients (60% of patients) than among those on DO (54% of patients, difference between groups 6% [90% CI -5.1 to 17.0]). Retreatment patients had significantly more successful treatment outcomes if self-supervised (74% of patients) than on DO (42% of patients, difference between groups 32% [11%-52%]).\n At high rates of treatment interruption, self-supervision achieved equivalent outcomes to clinic DO at lower cost. Self-supervision achieved better outcomes for retreatment patients. Supportive patient-carer relations, rather than the authoritarian surveillance implicit in DO, may improve treatment outcomes and help to control tuberculosis.", "To assess whether adding a training intervention for clinic staff to the usual DOTS strategy (the internationally recommended control strategy for tuberculosis (TB)) would affect the outcomes of TB treatment in primary care clinics with treatment success rates below 70%.\n A cluster randomized controlled trial was conducted from July 1996 to July 2000 in nurse-managed ambulatory primary care clinics in Cape Town, South Africa. Clinics with successful TB treatment completion rates of less than 70% and annual adult pulmonary TB loads of more than 40 patients per year were randomly assigned to either the intervention (n = 12) or control (n = 12) groups. All clinics completed follow-up. Treatment outcomes were measured in cohorts of adult, pulmonary TB patients before the intervention (n = 1200) and 9 months following the training (n = 1177). The intervention comprised an 18-hour experiential, participatory in-service training programme for clinic staff delivered by nurse facilitators and focusing on patient centredness, critical reflection on practice, and quality improvement. The main outcome measure was successful treatment, defined as patients who were cured and those who had completed tuberculosis treatment.\n The estimated effect of the intervention was an increase in successful treatment rates of 4.8% (95% confidence interval (CI): -5.5% to 15.2%) and in bacteriological cure rates of 10.4% (CI: -1.2% to 22%). A treatment effect of 10% was envisaged, based on the views of policy-makers on the minimum effect size for large-scale implementation.\n This is the first evidence from a randomized controlled trial on the effects of experiential, participatory training on TB outcomes in primary care facilities in a developing country. Such training did not appear to improve TB outcomes. However, the results were inconclusive and further studies are required.", "A key component of the DOTS strategy for tuberculosis control (short-course chemotherapy following WHO guidelines) is direct observation of treatment. WHO technical guidelines recommend that health workers should undertake this part of the strategy, but will also accept direct observation of treatment in the community; WHO does not think that a family member should undertake this role. Supporting evidence for these recommendations is not available. The Nepal national tuberculosis programme asked us to develop and test a strategy of direct observation of treatment for the hill districts of Nepal, where direct observation of treatment by health workers is not feasible. We aimed to assess the success rates of two DOTS strategies developed for such areas.\n Between mid-July, 2002, and mid-July, 2003, we undertook a cluster-randomised controlled trial to compare two strategies-community DOTS and family-member DOTS--in ten hill and mountain districts of Nepal. Districts were used as the unit of randomisation. Primary outcome was success rate (proportion of registered patients who achieved cure or completed treatment), and analysis was by intention to treat.\n Five districts (549 patients) were allocated to community DOTS and five (358 patients) were allocated family-member DOTS. Community DOTS and family-member DOTS achieved success rates of 85% and 89%, respectively (odds ratio of success for community DOTS relative to family-member DOTS, 0.67 [95% CI 0.41-1.10]; p=0.09). Estimated case-finding rates were 63% with the community strategy and 44% with family-member DOTS.\n The family-member DOTS and community DOTS strategies can both attain international targets for treatment success under programme conditions, and thus are appropriate for the hill and mountain districts of Nepal. Both strategies might also be appropriate in other parts of the world where directly observed treatment by health workers is not feasible. Our findings lend support to adoption of this patient-responsive approach to direct observation of treatment within global tuberculosis control policy.", "To determine the effectiveness of the provision of whole food to enhance completion of treatment for tuberculosis.\n Parallel group randomised controlled trial.\n Three primary care clinics in Dili, Timor-Leste.\n 270 adults aged >or=18 with previously untreated newly diagnosed pulmonary tuberculosis.\n Completion of treatment (including cure). Secondary outcomes included adherence to treatment, weight gain, and clearance of sputum smears. Outcomes were assessed remotely, blinded to allocation status. Interventions Participants started standard tuberculosis treatment and were randomly assigned to intervention (nutritious, culturally appropriate daily meal (weeks 1-8) and food package (weeks 9-32) (n=137) or control (nutritional advice, n=133) groups. Randomisation sequence was computer generated with allocation concealment by sequentially numbered, opaque, sealed envelopes.\n Most patients with tuberculosis were poor, malnourished men living close to the clinics; 265/270 (98%) contributed to the analysis. The intervention had no significant beneficial or harmful impact on the outcome of treatment (76% v 78% completion, P=0.7) or adherence (93% for both groups, P=0.7) but did lead to improved weight gain at the end of treatment (10.1% v 7.5% improvement, P=0.04). Itch was more common in the intervention group (21% v 9%, P<0.01). In a subgroup analysis of patients with positive results on sputum smears, there were clinically important improvements in one month sputum clearance (85% v 67%, P=0.13) and completion of treatment (78% v 68%, P=0.3).\n Provision of food did not improve outcomes with tuberculosis treatment in these patients in Timor-Leste. Further studies in different settings and measuring different outcomes are required.\n Clinical Trials NCT0019256.", "Drug users are at increased risk for latent tuberculosis infection (LTBI) and also at increased risk for noncompletion of medication regimens for treatment of LTBI or tuberculosis disease. Directly observed therapy (DOT) provided by outreach workers, the use of incentives, or both have been suggested as a means to increase adherence.\n To compare the independent and combined effects of monetary incentives and outreach worker provision of DOT for LTBI treatment in a sample of active drug users.\n The research design was a randomized controlled trial in a community outreach program setting. Participants consisted of a volunteer sample of 163 active injection drug and crack cocaine users placed on twice weekly DOT. Condition 1 of the interventions consisted of provision of DOT by an outreach worker at a location chosen by the participant (active outreach) and a $5 per visit incentive. Condition 2 was comprised of active outreach with no monetary incentive, and Condition 3, provision of DOT at the study community site and a $5 per visit incentive. The main outcome measures were percentage of medication taken as prescribed and completion of medication regimen.\n The percentage of prescribed medication taken was higher for those who received incentives, either with (71%) or without (68%) active outreach, compared to those who received active outreach alone (13%). Only 4% of participants assigned to Condition 2 completed treatment, compared to 53% of Condition 1 participants, and 60% of Condition 3 participants.\n Monetary incentives were clearly superior to active outreach. Active outreach in combination with monetary incentives did not increase adherence over incentives alone." ]	The results of randomized controlled trials conducted in low-, middle-, and high-income countries provide no assurance that DOT compared with self administration of treatment has any quantitatively important effect on cure or treatment completion in people receiving treatment for tuberculosis.
CD005285	[ "2197001", "8818089", "1567037", "8431336", "2321772", "7702152", "8279255", "7476741", "1997058", "1785235", "3565725", "1867580", "8865709", "8467543", "2205129", "2271192", "2782569", "1781536", "9420391" ]	[ "Clear fluids three hours before surgery do not affect the gastric fluid contents of children.", "[Possibility of rice porridge for preoperative feeding in children].", "Shortened preanesthetic fasting interval in pediatric cardiac surgical patients.", "Preoperative drinking does not affect gastric contents.", "Ingestion of liquids compared with preoperative fasting in pediatric outpatients.", "The effect of pre-operative oral fluids on morbidity following anaesthesia for minor surgery.", "Effects of 2-, 4- and 12-hour fasting intervals on preoperative gastric fluid pH and volume, and plasma glucose and lipid homeostasis in children.", "Effect of preoperative oral fluids on gastric volume and pH in postpartum patients.", "Ingestion of clear fluids is safe for adolescents up to 3 h before anaesthesia.", "Allowing pre-operative patients to drink: effects on patients' safety and comfort of unlimited oral water until 2 hours before anaesthesia.", "The effect of different pre-operative feeding regimens on plasma glucose and gastric volume and pH in infancy.", "Immediate postoperative oral hydration after caesarean section.", "[The volume and pH of gastric fluid in elective surgical patients after preoperative oral fluid intake].", "Gastric pH and volume after oral fluids in the postpartum patient.", "Effects of duration of fasting on gastric fluid pH and volume in healthy children.", "Gastric residual volume in infants and children following a 3-hour fast.", "Fluid deprivation before operation. The effect of a small drink.", "Oral fluids prior to day surgery. The effect of shortening the pre-operative fluid fast on postoperative morbidity.", "The effect of pre-operative intake of oral water and ranitidine on gastric fluid volume and pH in children undergoing elective surgery." ]	[ "This prospective, randomized, single-blind study of 121 healthy children aged 2 to 12 yr investigated the effect of clear fluids on gastric contents. Gastric fluid volume and pH were measured immediately following the induction of general anaesthesia and were not significantly affected by the ingestion of unlimited clear fluids up to three hours preoperatively. After a prolonged fast (mean fast 14 hr), gastric fluid volume was 0.39 +/- 0.37 ml.kg-1 and gastric pH was 1.7 +/- 0.4; after unlimited clear fluids (203 +/- 109 ml) up to three hours before surgery gastric fluid volume was 0.34 +/- 0.28 ml.kg-1 and gastric pH was 1.8 +/- 0.7 (mean +/- SD). Gastric fluid volume (ml.kg-1) increased in both the control and study groups as age increased, P less than 0.005. It is concluded that drinking clear fluid up to three hours before scheduled surgery does not have a measurable effect on gastric volume and pH of healthy children of ages 2 to 12 yr.", "To determine the effect of rice porridge feeding before elective surgery on preoperative gastric fluid pH, volume and starvation, a prospective study was undertaken in pediatric patients. Twenty healthy children ranged in age from 5 to 12 years were allocated randomly to either a fasted or rice porridge group. The children of fasted group (control group) were allowed to take solid food until midnight before the operation. The rice porridge group (study group) patients received a small amount of rice porridge 5 hours 30 minutes before the induction of anesthesia. The patients of both groups were permitted to take clear fluid until 5 hours before the induction of anesthesia. After the induction of anesthesia, gastric fluid was aspirated through an orogastric tube. The mean gastric fluid volume was 0.43 +/- 0.32 ml.kg-1 in the control group and 0.5 +/- 0.6 ml.kg-1 in the study group. The mean gastric fluid pH was 1.43 +/- 0.27 ml.kg-1 in the control group and 1.89 +/- 0.75 ml.kg-1 in the study group. There were no significant differences between the two groups concerning the gastric fluid volume and pH. The patient of the study group complained of less hunger. Preoperative rice porridge feeding is a possible preoperative feeding for pediatric patients.", "The recent liberalization of preoperative feeding orders in healthy pediatric outpatients prompts the question of whether this applies to children about to have cardiac surgery. The authors compared gastric fluid volume and pH in two groups of children undergoing elective cardiac surgery, one of which was not only permitted ad libitum clear liquids but was mandated to drink clear liquids 2-3 h before induction of anesthesia (study group). The other group followed routine inpatient preoperative fasting orders (control group). The study group (n = 44) averaged 3.1 +/- 4.1 yr and weighed 15.3 +/- 16.3 kg; the control group averaged 3.3 +/- 3.9 yr and weighed 14.3 +/- 12.1 kg (P = 0.82, 0.73, respectively). Aspiration of residual gastric fluid volume was attempted in all patients after induction of anesthesia. Gastric fluid volume averaged 0.6 +/- 0.9 mL/kg in the study group and 0.4 +/- 0.6 mL/kg in the control group (P = 0.13). Of the study patients, 41% had a measured gastric volume greater than or equal to 0.4 mL/kg compared with 32% of the control patients (P = 0.50). Of the 42 patients who had residual gastric fluid aspirated, pH determinations were completed on 37 aspirates; of these 19 of 20 (95%) in the study group and 14 of 17 (82%) in the control group had a gastric pH less than or equal to 2.5. Using a linear analogue scale, parents rated children in the study group to be more comfortable, less hungry, and less thirsty compared with the control patients (P = 0.004, 0.002, 0.0001, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)", "We have compared the effect of allowing free clear fluids until the time of oral premedication with conventional preoperative fasting. In a prospective, randomized trial, the residual volume and pH of gastric contents after induction of anaesthesia were measured in 100 elective surgical patients allocated randomly to a group in whom the intake of free clear fluids up to the time of premedication was measured (mean 388 ml in 6 h before surgery) or a control group who were fasted for 6 h. Preoperative drinking did not affect either mean (SD) residual gastric volume (22 (21) ml in the study group vs 19 (16) ml in the control group) or pH (study group 2.64 (1.57) vs control group 2.26 (1.45)). The study group experienced less preoperative thirst. Problems with aspiration or regurgitation were not encountered. We believe that allowing elective surgical patients to drink clear fluids until 2 h before anaesthesia may enhance patient comfort without compromising safety.", "The preoperative fast is often an unpleasant preoperative experience that might be alleviated by allowing children to drink clear liquids. The authors compared gastric fluid volume and pH in two groups of children, one of whom was permitted clear liquids until 2 h before surgery (study group) and the other followed routine preoperative fasting orders (control group). The study group was not limited in the quantity of clear liquid allowed with the exception that the last intake prior to surgery was limited to 8 ounces. The study group (n = 53) averaged 5.9 +/- 5 yr and weighed 23.6 +/- 17 kg, while the control group averaged 7.3 +/- 4.6 yr and weighed 29 +/- 17.7 kg (P = NS). Gastric contents were aspirated following induction of anesthesia. Gastric fluid volume averaged 0.44 +/- 0.51 ml/kg for study group and 0.57 +/- 0.51 ml/kg in the control group (P = 0.12). Of the study patients, 48% had a measured gastric fluid volume greater than or equal to 0.4 ml/kg compared with 58% of the control patients (P = 0.77). Eighty three patients had sufficient gastric fluid for pH determination; of these 34/35 (97%) in the study group and 44/48 (92%) in the control group had a gastric fluid pH less than or equal to 2.5. Using a linear analog scale parents rated the children in the study group to be less irritable (P less than 0.001) and to have had a better overall preoperative experience (P less than 0.01) compared with the control patients.(ABSTRACT TRUNCATED AT 250 WORDS)", "Postoperative morbidity and serum osmolality were studied in 46 patients who were encouraged to drink water until 3 h pre-operatively and 49 receiving the normal fasting regimen prior to minor surgery. There was significantly less thirst in the postoperative period in those patients allowed to drink and subjectively better recovery than after previous anaesthesia. There was no morbidity from ingestion of up to 11 of water 2.5 h pre-operatively. Although there was only a moderate improvement in postoperative recovery we feel that allowing patients to drink water pre-operatively improves patient comfort, especially since patients may have to fast for much longer than guidelines recommend, simply because of the traditional organisation of operating lists.", "We evaluated 105 randomly-selected unpremedicated children aged 1-14 years to determine the effects of a 2-, 4- and 12-h preoperative fasting interval on the preoperative gastric fluid pH and volume, and plasma glucose and lipid homeostasis. Each child undergoing elective surgery ingested a large volume (approximately 10 ml/kg b.w.) of apple juice and then fasted for 2, 4 or 12 h before the estimated induction of anaesthesia. After induction of anaesthesia, gastric fluid was aspirated through a large-bore, multiorifice orogastric tube. Plasma concentrations of glucose, total ketone bodies, non-esterified fatty acid (NEFA), triglycerides, and cortisol were measured at the time of induction to evaluate the fasting interval effects on preoperative plasma glucose and lipid homeostasis. There were no significant differences between the three groups in either gastric fluid volume or pH. In addition, there were no significant differences between the groups with respect to the proportion with a pH < 2.5 and volume > 0.4 ml/kg b.w. Neither plasma concentrations of glucose, triglycerides, nor cortisol at the time of anaesthetic induction differed between the three groups. Both 4 and 12 h nil per os (NPO) caused an increase in lipolysis, which was presumably a compensatory mechanism to maintain normoglycaemia. The plasma NEFA and total ketone bodies concentrations were therefore significantly higher in these two fasting intervals than in 2 h NPO. These data suggest that a 2-h NPO, after a large volume of ingested apple juice, may offer additional benefits by preventing an increase in lipolysis during the fasting interval without either increasing the volume of gastric fluid or decreasing the gastric pH.(ABSTRACT TRUNCATED AT 250 WORDS)", "The effect of preoperative oral fluids to postpartum patients on the gastric volume and pH was compared with normally fasting postpartum and non-pregnant patients undergoing sterilisation. Forty consecutive postpartum patients and twenty non-pregnant patients scheduled for sterilisation procedure were selected for the study. All patients were fasted overnight. Twenty postpartum patients were randomly allocated to receive 150 ml of plain water two and half hours before surgery (Group 1), while the remaining postpartum patients (Group 2) and non-pregnant patients (Group 3) continued their overnight fast as usual. After induction of anesthesia, gastric volume and pH was measured in all the patients. The mean gastric volume was found to be 21.9 +/- 8.49 ml in Group 1, 22.55 +/- 8.30 ml in Group 2 and 22.65 +/- 8.17 ml in Group 3. The mean pH was found to be 2.21 +/- 0.98 in Group 1, 2.18 +/- 0.88 in Group 2 and 2.12 +/- 1.02 in Group 3. The difference in the volume and pH in all the three groups was statistically insignificant. The difference in the incidence of patients with combined high risk factors of acid aspiration syndrome (gastric fluid volume > 25 ml and pH < 2.5) among the three groups was also insignificant. The authors conclude that ingestion of 150 ml of plain water approximately two and half hours before scheduled time of surgery in overnight fasted postpartum patients does not increase the risk of aspiration syndrome.", "We have studied the effect of ingestion of unlimited clear fluids by adolescents up to 3 h before anaesthesia to determine the effect this fluid ingestion would have on thirst, hunger and gastric contents at induction of anaesthesia. We studied prospectively 152 adolescents (ages 13-19 yr) undergoing elective surgery. Fifty percent of the patients had nothing by mouth after midnight. The other 50% were instructed to ingest unlimited clear fluids up to 3 h before surgery. On arrival in the operating room, subjects were asked to assess thirst and hunger with a linear analogue scale of 0-10 (0 corresponding to no thirst or no hunger). After induction of anaesthesia, gastric contents were aspirated via a 16-French gauge orogastric tube. Gastric fluid volume (GV) was measured with a syringe and gastric pH (GpH) was assessed with Merck pH strips. GV, GpH and subject hunger were unaffected by ingestion of clear fluids. Subject thirst was reduced by clear fluids. It is concluded that unlimited clear fluid ingestion by healthy adolescents up to 3 h before operation decreases thirst and does not affect gastric contents.", "The effect of allowing patients unlimited access to oral water in the time up until 2 h pre-operatively was the subject of a randomised, blind, controlled trial. No effect was seen on gastric volume or pH, or on plasma osmolality, and allowing water pre-operatively was associated with a reduction in anxiety in the anaesthetic room.", "The effects of four different pre-operative feeding regimens were studied in 123 children below the age of one year presenting for surgery. Plasma glucose concentrations, blood acid-base values, gastric volume and gastric pH were measured before and after induction of anaesthesia. No patient was found to be hypoglycaemic and there were no significant differences in plasma glucose concentration and acid-base values between the groups. No correlation was demonstrated between the age and weight of the patients and the duration of fasting and the plasma glucose concentration. There was a significant elevation of plasma glucose concentration in all four groups after induction of anaesthesia (P less than 0.001) compared with the pre-induction level which is a reflection of the stress of blood sampling and induction of anaesthesia. Infants less than three months of age in the milk-feed group had a significantly higher gastric volume with low pH (P less than 0.05) signifying a potentially greater risk of pulmonary acid aspiration. The practice of timing the last pre-operative feed in infancy according to the infant's normal feeding pattern does not appear to increase the risk factors for pulmonary aspiration, if milk is avoided.", "A study was carried out to assess the effects of immediate postoperative oral rehydration in 51 unpremedicated women undergoing caesarean section under epidural anesthesia. The patients were randomly assigned to 2 groups: group 1 (n = 22)--fasting at least until 24 hours after the end of the operation, and group 2 (n = 29)--receiving immediate oral intake of fluids (water, tea or coffee with sugar) without limitation of quantity. The 2 groups were compared for the occurrence of postoperative nausea and vomiting, onset of peristalsis, rectal gas emission, first bowel movement, and possible complications. The results demonstrate no significant differences between the parturients who drank immediately postoperatively as compared to those in whom oral fluid intake was delayed for 24 hours or more. It is concluded that immediate postoperative oral rehydration had no harmful effect upon peristalsis post-caesarean section.", "The effect of preoperative oral fluid intake on the volume and pH of gastric fluid was examined in 45 elective surgical patients ranged in ages from 18 to 70 years. Two hours preoperatively they all received oral roxatidine 75 mg with 10 ml water, immediately followed by 150 ml oral water or 150 ml refreshing drink or no fluid as control. Just after the induction of anesthesia, a Salem-sump tube was put down to the stomach to collect gastric fluid in each patient. The volume and pH of gastric fluid taken were 10.9 +/- 7.9 ml, 16.3 +/- 2.3 in control group, 8.0 +/- 6.0 ml, 6.2 +/- 2.4 in the water group and 6.3 +/- 6.0 ml, 7.1 +/- 1.7 in the refreshing drink group. As there were no significant differences in gastric pH values in the three groups, the highest value was found in the refreshing drink group. No significant difference in VAS of hungry and thirsty feeling was found among the three groups. We conclude that preoperative oral water or refreshing drink with roxatidine 75 mg 2 hours before the start of anesthesia may not increase the risk of aspiration during the induction of anesthesia.", "The aim of this study was to investigate the relationship between preoperative oral fluids and gastric pH and volume in women undergoing sterilization between one and five days postpartum. Fifty postpartum patients received 150 ml water approximately two to three hours before surgery while 50 postpartum and 50 non-pregnant women were fasted from midnight. After induction of anaesthesia, gastric contents were aspirated using a Salem sump tube and the gastric pH and volume were measured. There were no differences in intragastric pH and volume, median (range), among the postpartum fasted group, 1.19 (0.74-4.57), 22 (1-78) ml, postpartum water group 1.18 (0.70-6.4), 25.5 (3-66) ml and the non-pregnant group 1.27 (0.51-6.63), 25 (3-69) ml. There was no correlation between postpartum interval, 60 (12-120) hr, and intragastric pH or volume. It is concluded that oral water may be given safely two to three hours preoperatively to patients more than one day postpartum. Intragastric volume and acidity were not increased and the findings in postpartum patients were similar to those found in non-pregnant patients.", "To determine the effects of duration of fasting before elective surgery on gastric fluid pH and volume in children, a prospective, randomized, blinded study of 100 unpremedicated children, aged 1-14 yr, was undertaken. Each child was given 2 mL/kg of water orally and then fasted 2, 4, or 6 h preoperatively. After induction of anesthesia and tracheal intubation, gastric fluid was aspirated through a large-bore, multiorifice orogastric tube. Gastric fluid pH was measured using a calibrated PHM62 radiometer. Gastric fluid volume was the total volume of fluid aspirated from the stomach. The duration of fasting was between 2.0 and 8.5 h. We found that neither gastric fluid pH nor gastric fluid volume correlated with the duration of fasting. The mean (+/- SD) gastric fluid pH was 1.80 +/- 0.79 and the mean (+/- SD) gastric fluid volume was 0.56 +/- 0.39 mL/kg. Gastric fluid pH was less than 2.5 and volume greater than 0.4 mL/kg in 53% of children. We conclude that healthy children may receive 2 mL/kg of water up to 2 h before elective surgery without decreasing gastric fluid pH or increasing gastric fluid volume beyond values obtained after fasting for 6 h.", "The effect of a 3-hour versus a 10-hour preoperative fasting interval on the gastric residual volume and gastric pH of pediatric patients was evaluated. Forty-four healthy infants, 1 month to 5 years of age, were randomly assigned to one of two groups. The 3-hour nil per os (NPO) group consisted of 19 infants kept NPO for 3 hours following ingestion of up to 4 ounces of 5% dextrose in water (D5W). The control group consisted of 25 infants who remained NPO an average of 10 hours prior to surgery. Gastric residual volume was calculated using the dye-dilution technique. After the dye marker was injected into the stomach, complete aspiration of the stomach (including the volume of dye marker plus residual gastric contents) was attempted as another method to measure gastric residual volume. There were no significant differences in gastric residual volume between the 3-hour and the 10-hour NPO groups using either the dye-dilution or aspiration methods. However, there were significant differences between the two measuring techniques. Gastric residual volume was significantly greater in volume when measured by the dye-dilution technique than it was when measured by the aspiration technique in both the 10-hour (p less than 0.009) and the 3-hour (p less than 0.0009) NPO groups. Complete aspiration of a known volume of fluid injected through the orogastric tube was not possible in 23 of the 44 (52.4%) infants. Mean gastric pH was less than 2.0 in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)", "The effect of oral fluids before operation, followed by intramuscular morphine, on gastric volume and pH was examined in 150 elective surgical patients, ASA physical status 1 and 2, who were randomly assigned to one of the three groups of 50 each. Group 1 (control) continued their overnight fast; patients in Groups 2 and 3 received 150 ml water 2 hours before the scheduled time of surgery. Patients in Group 3 received intramuscular morphine 0.15 mg/kg and promethazine 0.5 mg/kg one hour before operation. The residual gastric volume was obtained by suction and its volume and pH measured immediately after induction of anaesthesia. Statistically significant (p less than 0.05) decrease in residual gastric volume was observed in Groups 2 and 3 as compared to Group 1. However, the difference between these two groups was not statistically significant. There was no statistically significant difference in pH among the three groups. Overnight fluid fasting is not justified in elective surgical patients. Morphine can be safely given one hour before surgery in patients who have received water (150 ml) 2 hours before operation.", "One hundred day surgical patients undergoing first trimester termination of pregnancy were randomly allocated to receive either 150 ml of clear fluid 1.5-2 hours before anaesthesia or to remain fasted from midnight the night before. Patients were anaesthetised using a total intravenous technique which consisted of propofol and alfentanil. No adverse intra-operative events were noted in either group. There were no significant differences in immediate recovery time, or pain, nausea and headache scores at 30 or 120 minutes following recovery. The fasted group had less pain (p less than 0.05) at 60 minutes after recovery than the fluid group, although the mean pain scores in both groups were low. Eighty two per cent of the patients returned questionnaires about pain, nausea and headache scores on arriving home, and at 12 and 24 hours after surgery. There were no significant differences between the two groups. In conclusion, pain, nausea and headache scores are low following total intravenous anaesthesia with propofol and alfentanil for termination of pregnancy and these were unaffected by the administration of 150 ml of clear fluid given approximately 1.5 hours pre-operatively.", "The effect of pre-operative intake of oral water and ranitidine on gastric fluid volume and pH was studied in 75 children of American Society of Anesthetists (ASA) grade I and grade II undergoing elective surgery. Group I patients fasted from midnight and acted as control. Group II patients received 5 ml/kg plain water orally 3 hours before surgery. Group III children received 5 ml/kg of plain water and 2 mg/kg of ranitidine orally 3 hours before surgery. Mean volume of gastric aspirate was comparable in all 3 groups (p > 0.05). Mean pH was significantly higher in ranitidine treated patients (5.12 +/- 1.73) as compared to non-ranitidine treated patients (2.26 +/- 0.57 and 2.53 +/ 0.79 in group I and group II respectively). Number of patients at risk (pH < or = 2.5 and volume > or = 0.4 ml/kg) was not significantly different in group I and group II. Mean thirst and behaviour scores were significantly higher in fluid treated patients (groups II and III) as compared to control (p < 0.01). To conclude, administration of pre-operative water (5 ml/kg) along with ranitidine (2 mg/kg) favourably modifies gastric fluid volume and pH, improves patient behaviour and minimises the number of patients at risk of aspiration pneumonitis, should the child aspirate." ]	There is no evidence that children who are denied oral fluids for more than six hours preoperatively benefit in terms of intraoperative gastric volume and pH compared with children permitted unlimited fluids up to two hours preoperatively. Children permitted fluids have a more comfortable preoperative experience in terms of thirst and hunger. This evidence applies only to children who are considered to be at normal risk of aspiration/regurgitation during anaesthesia.
CD003486	[ "20947097", "12042546", "19057612" ]	[ "Randomized controlled trial of lung lavage with dilute surfactant for meconium aspiration syndrome.", "A multicenter, randomized, controlled trial comparing Surfaxin (Lucinactant) lavage with standard care for treatment of meconium aspiration syndrome.", "Treatment of MAS with PPHN using combined therapy: SLL, bolus surfactant and iNO." ]	[ "To evaluate whether lung lavage with surfactant changes the duration of mechanical respiratory support or other outcomes in meconium aspiration syndrome (MAS).\n We conducted a randomized controlled trial that enrolled ventilated infants with MAS. Infants randomized to lavage received two 15-mL/kg aliquots of dilute bovine surfactant instilled into, and recovered from, the lung. Control subjects received standard care, which in both groups included high frequency ventilation, nitric oxide, and, where available, extracorporeal membrane oxygenation (ECMO).\n Sixty-six infants were randomized, with one ineligible infant excluded from analysis. Median duration of respiratory support was similar in infants who underwent lavage and control subjects (5.5 versus 6.0 days, P = .77). Requirement for high frequency ventilation and nitric oxide did not differ between the groups. Fewer infants who underwent lavage died or required ECMO: 10% (3/30) compared with 31% (11/35) in the control group (odds ratio, 0.24; 95% confidence interval, 0.060-0.97). Lavage transiently reduced oxygen saturation without substantial heart rate or blood pressure alterations. Mean airway pressure was more rapidly weaned in the lavage group after randomization.\n Lung lavage with dilute surfactant does not alter duration of respiratory support, but may reduce mortality, especially in units not offering ECMO.\n Copyright © 2011 Mosby, Inc. All rights reserved.", "Infants with meconium aspiration syndrome (MAS) have marked surfactant dysfunction. Airways and alveoli of affected neonates contain meconium, inflammatory cells, inflammatory mediators, edema fluid, protein, and other debris. The objective of this study was to compare treatment with bronchoalveolar lavage using dilute Surfaxin with standard therapy in a population of newborn infants with MAS.\n Inclusion criteria were 1) gestational age > or =35 weeks, 2) enrollment within 72 hours of birth, 3) diagnosis of MAS, 4) need for mechanical ventilation, and 5) an oxygenation index > or =8 and < or =25. Subjects were randomized to either lavage with Surfaxin or standard care (2:1 proportion). In lavaged infants, a volume of 8 mL/kg dilute Surfaxin (2.5 mg/mL) was instilled into each lung over approximately 20 seconds followed by suctioning after 5 ventilator breaths. The procedure was repeated twice. The third and final lavage was with a more concentrated solution (10 mg/mL) of Surfaxin.\n Twenty-two infants were enrolled (15 Surfaxin and 7 control). Demographic characteristics were similar. There were trends (not significant) for Surfaxin-lavaged infants to be weaned from mechanical ventilation earlier (mean of 6.3 vs 9.9 days, respectively), as well as to have a more rapid decline in their oxygenation indexes compared with control infants, the latter difference persisting for the 96-hour-long study period. The therapy was safe and generally well tolerated by the infants.\n Dilute Surfaxin lavage seems to be a safe and potentially effective therapy in the treatment of MAS. Data from this investigation support future prospective, controlled clinical trials of bronchoalveolar lavage with Surfaxin in neonates with MAS.", "The objective of the study was to compare the effectiveness of surfactant treatment either by bolus or surfactant lung lavage followed by inhaled nitric oxide (iNO) therapy in infants with meconium aspiration syndrome (MAS) complicated by persistent pulmonary hypertension (PPHN). In this study, thirteen infants with diagnosis of MAS and PPHN were first treated with conventional respiratory support. Then between 2 and 22h of life they were randomized either to bolus surfactant treatment (n=6) or surfactant lung lavage (SLL, n=7) treatment. Then all infants were treated with iNO therapy. The groups were compared with regard to their clinical course: changes in PaO(2), FiO(2), MAP, OI, A-a oxygen gradient, duration of iNO therapy, length of ventilation and hospitalization. Complications and mortality were also compared. The results showed that infants treated with SLL had significant improvements in oxygenation, decreases in MAP and A-a gradients. But there were no significant differences in duration of ventilation, iNO treatment, length of hospitalization or complications. In conclusion these data show no advantage of SLL therapy over bolus surfactant treatment in infants with MAS complicated by PPHN." ]	In infants with meconium aspiration syndrome, lung lavage with diluted surfactant may be beneficial, but additional controlled clinical trials of lavage therapy should be conducted to confirm the treatment effect, to refine the method of lavage treatment, and to compare lavage treatment with other approaches, including surfactant bolus therapy. Long-term outcomes should be evaluated in further clinical trials.
CD008420	[ "15118469" ]	[ "A prospective, comparative study between endoscopic cyclophotocoagulation and the Ahmed drainage implant in refractory glaucoma." ]	[ "To compare endoscopic cyclophotocoagulation (ECP) and the Ahmed drainage implant in the treatment of refractory glaucoma.\n Sixty-eight eyes of 68 patients with refractory glaucoma were prospectively assigned to either ECP or Ahmed tube shunt implantation. All procedures were performed by a single surgeon. Eyes that were included were pseudophakic with a history of at least one trabeculectomy with antimetabolite, an intraocular pressure (IOP) equal to or above 35 mm Hg on maximum tolerated medical therapy, and a visual acuity better than light perception. Exclusion criteria included eyes that had had previous glaucoma drainage device implantation or a cyclodestructive procedure. Success was defined as an IOP more than 6 mm Hg and less than 21 mm Hg, with or without topical anti-hypertensive therapy.\n The mean follow-up was 19.82 +/- 8.35 months and 21.29 +/- 6.42 months, for the Ahmed and ECP groups, respectively (P = 0.4). The preoperative IOP, 41.32 +/- 3.03 mm Hg (Ahmed) and 41.61 +/- 3.42 mm Hg (ECP) (P = 0.5), and the mean postoperative IOP, at 24 months follow-up, 14.73 +/- 6.44 mm Hg (Ahmed) and 14.07 +/- 7.21 mm Hg (ECP) (P = 0.7), were significantly different from baseline in both groups (P < 0.001). Kaplan-Meier survival curve analysis showed a probability of success at 24 months of 70.59% and 73.53% for the Ahmed and ECP groups, respectively (P = 0.7). Complications included choroidal detachment (Ahmed 17.64%, ECP 2.94%), shallow anterior chamber (Ahmed 17.64%, ECP 0.0%), and hyphema (Ahmed 14.7%, ECP 17.64%).\n There was no difference in the success rate between the Ahmed Glaucoma Valve and ECP in refractory glaucoma. The eyes that underwent Ahmed tube shunt implantation had more complications than those treated with ECP." ]	There is no high quality evidence that EK is superior to PKP in the treatment of FED considering the studies that satisfied our primary and secondary outcome measures. One RCT demonstrated that HOAs are lower following EK and some lower quality evidence suggests that endothelial rejection episodes may be less with EK. These findings should be interpreted with caution as they are based on data with risk of biases. Further RCTs of visual and refractive outcomes needs to be performed in this field, comparing EK to PKP, with a larger sample size and at least five years of follow up. To avoid bias due to a surgeon's learning curve, procedures should be performed by experienced surgeons only. Quality of life and vision should also be evaluated. The risk of endothelial rejection will be difficult to address in the context of a RCT because of power considerations but large non-randomised comparative case series and corneal graft registry outcome data will be useful in this regard.
CD004270	[ "15379121", "20194844", "15071604", "21231927" ]	[ "[Preliminary results of a multicenter randomized study on the treatment of acute promyelocytic leukemias].", "Rituximab plus fludarabine and cyclophosphamide prolongs progression-free survival compared with fludarabine and cyclophosphamide alone in previously treated chronic lymphocytic leukemia.", "Consolidation with alemtuzumab in patients with chronic lymphocytic leukemia (CLL) in first remission--experience on safety and efficacy within a randomized multicenter phase III trial of the German CLL Study Group (GCLLSG).", "A randomized phase II trial of fludarabine, cyclophosphamide and mitoxantrone (FCM) with or without rituximab in previously treated chronic lymphocytic leukaemia." ]	[ "To study efficacy of maintenance therapy of patients with acute promyelocytic leukemia (APL) in the APL treatment Russian multicenter trial.\n The trial was made with participation of 18 hematological departments of clinics in Russia. A total of 68 APL patients entered the trial. The maintenance therapy consisted of 5-day courses of cytostatic drugs which alternated or did not alternate with 5-day courses of ATRA. Cytogenetic tests were made in 31 patients, t(15;17) was detected in 26 of them. Molecular examination conducted in 28 patients discovered chimeric transcript PML/RARa in 26 of them. Of 20 patients examined in Hematological Research Center, 7 (35%) had a bcr 1/2 variant of the transcript PML/RARa, 13 (65%)--bcr 3 variant.\n 65 patients were eligible for assessment. A complete remission was achieved in 90% cases. No resistance was observed. In follow-up within 30 months the recurrence rate was similar on both treatments. The results of the induction therapy and survival in patients with different variants of the transcripts were also similar. Overall 2.5 year survival for all the patients was 77%, recurrence-free--80%. The survival analysis in patients with leukocytosis higher and lower 10 x 10(9)/l found no statistical differences by the survival. Patients with hyperleukocytosis had higher early lethality than patients with leukocytes under 10 x 10(9)/l (25% vs 5.3%, p = 0.03).\n The APL 06.01 protocol showed high efficacy of the relevant maintenance which provides a complete molecular remission in the majority of patients with probable recurrence-free 2.5 year survival 80%.", "Rituximab, a monoclonal antibody that targets the CD20 cell surface antigen, has clinical activity in patients with non-Hodgkin's lymphoma and other B-lymphocyte disorders when administered alone or in combination with chemotherapy. Promising results have previously been reported in nonrandomized studies in patients with chronic lymphocytic leukemia (CLL). This trial was designed to compare chemoimmunotherapy with chemotherapy alone in patients with previously treated CLL.\n This international, multicenter, randomized trial compared six cycles of rituximab plus fludarabine and cyclophosphamide (R-FC) with six cycles of fludarabine and cyclophosphamide alone (FC) in patients with previously treated CLL. A total of 552 patients with Binet stage A (1%), B (59%), or C (31%) disease entered the study and were randomly assigned to receive R-FC (n = 276) or FC (n = 276).\n After a median follow-up time of 25 months, rituximab significantly improved progression-free survival in patients with previously treated CLL (hazard ratio = 0.65; P < .001; median, 30.6 months for R-FC v 20.6 months for FC). Event-free survival, response rate, complete response rate, duration of response, and time to new CLL treatment or death were also significantly improved. Although the rates of adverse events, grade 3 or 4 events, and serious adverse events were slightly higher in the R-FC arm, R-FC was generally well tolerated, with no new safety findings and no detrimental effect on quality of life.\n R-FC significantly improved the outcome of patients with previously treated CLL.", "Patients with CLL responding to initial chemotherapy with fludarabine alone (F) or in combination with cyclophosphamide (FC) were randomized for treatment with alemtuzumab (30 mg i.v. TIW, 12 weeks) or observation. Of 21 evaluable patients, 11 were randomized to alemtuzumab before the study was stopped due to severe infections in seven of 11 patients. These infections (one life-threatening pulmonary aspergillosis IV; four CMV reactivations III requiring i.v. ganciclovir; one pulmonary tuberculosis III; one herpes zoster III) were successfully treated and not associated with cumulative dose of alemtuzumab. In the observation arm, one herpes zoster infection II and one sinusitis I were documented. At 6 months after randomization, two patients in the alemtuzumab arm converted to CR, while three patients in the observation arm progressed. After alemtuzumab treatment, five of six patients achieved a molecular remission in peripheral blood while all patients in the observation arm remained MRD-positive (P=0.048). At 21.4 months median follow-up, patients receiving alemtuzumab showed a significant longer progression-free survival (no progression vs mean 24.7 months; P=0.036). In conclusion, a consolidation therapy with alemtuzumab is able to achieve molecular remissions and longer survival in CLL, but a safe treatment regimen needs to be determined.", "Combination fludarabine (F), cyclophosphamide (C) and rituximab (R) is the standard front-line therapy in chronic lymphocytic leukaemia (CLL), but appropriate treatment of relapsed/refractory CLL is less clear. Combined FC and mitoxantrone (M) has been reported to be effective in a single arm study, and rituximab when added to chemotherapy in CLL is synergistic. A randomized, two-stage, Phase II trial of FCM and FCM-R was conducted in relapsed CLL. The primary endpoint was response rate 2 months after therapy, assessed according to the 2008 International Workshop CLL criteria. In addition, minimal residual disease (MRD) in the marrow was studied 2 months after therapy, with MRD negativity defined as <0·01% CLL cells. Fifty-two patients were entered, 26 in each arm. The overall response rates to FCM and FCM-R were 58% and 65% respectively. Combined complete response (CR) and CR with incomplete marrow recovery [CR(i)] was 15% (95% confidence interval [CI]:4-35%) for FCM and 42% (95%CI:23-63%) for FCM-R, with eight patients achieving MRD negativity (3 FCM; 5 FCM-R). The toxicity of both regimens was acceptable. In conclusion, the addition of rituximab to FCM improves the response rates in relapsed CLL, resulting in more complete remissions and without additional safety concerns. Efficacy and safety should be fully tested in a randomized Phase III trial.\n © 2011 Blackwell Publishing Ltd." ]	Despite significantly increased overall response and complete remission rates and longer progression-free survival with first-line treatment of B-CLL patients with single-agent purine antagonists, we were not able to detect a statistically significant improvement of overall survival compared to alkylator-based regimens. Furthermore, the use of purine antagonists also augments the risk for grade III/IV infections and haemolytic anaemia.
CD006885	[ "8348504", "20034729", "9119635", "8692531", "8727805" ]	[ "Intravesical 4'-epi-doxorubicin (epirubicin) versus bacillus Calmette-Guérin. A controlled prospective study on the prophylaxis of superficial bladder cancer.", "Long-term efficacy results of EORTC genito-urinary group randomized phase 3 study 30911 comparing intravesical instillations of epirubicin, bacillus Calmette-Guérin, and bacillus Calmette-Guérin plus isoniazid in patients with intermediate- and high-risk stage Ta T1 urothelial carcinoma of the bladder.", "BCG versus epirubicin in the prophylaxis of multiple superficial bladder tumours: results of a prospective randomized study using modified treatment schemes.", "Intravesical bacillus Calmette-Guérin versus epirubicin in the prophylaxis of recurrent and/or multiple superficial bladder tumours.", "Update on the Dutch Cooperative Trial: mitomycin versus bacillus Calmette-Guérin-Tice versus bacillus Calmette-Guérin RIVM in the treatment of patients with pTA-pT1 papillary carcinoma and carcinoma in situ of the urinary bladder. Dutch South East Cooperative Urological Group." ]	[ "The selection of the most appropriate antineoplastic agent and optimal treatment schedule for the prophylaxis of superficial bladder cancer against tumor recurrences is the subject of continual investigations.\n A controlled prospective trial involving 161 patients evaluated and compared the efficacy of intravesical epirubicin and bacillus Calmette-Guérin (BCG) administration as prophylaxis against recurrences after complete transurethral resection of superficial bladder cancer. The treatment schedule, consisting of one 6- or 8-week course of instillations (50 mg epirubicin or 150 mg BCG per instillation) followed by single maintenance doses to the responders at follow-up examinations, was modified for those of the initial responders who were at high risk for recurrence and who received an additional separate 4-week course of treatment 6 months after the start of therapy.\n Sixty percent of the patients treated with epirubicin, 68% of the patients treated with BCG, and 41% of the control subjects, who underwent resection only, remained free of recurrences for a mean follow-up of 32.9 months. The only significant difference was found between patients treated with BCG and control subjects, in favor of the former. Conversely, recurrence rate per 100 patient-months and mean interval to recurrence showed both drugs to be superior to resection alone regarding several tumor characteristics. However, a significant benefit in favor of BCG when compared with epirubicin was shown in those patients who had Stage T1 and Grade 3 tumors at presentation.\n Intravesical epirubicin and BCG were superior to transurethral resection alone in the prophylaxis of superficial bladder cancer, but with respect to superficially invasive and high-grade tumors, BCG demonstrated a remarkable advantage.", "Intravesical chemotherapy and bacillus Calmette-Guérin (BCG) reduce the recurrence rate in patients with stage Ta T1 urothelial bladder cancer; however, the benefit of BCG relative to chemotherapy for long-term end points is controversial, especially in intermediate-risk patients.\n The aim of the study was to compare the long-term efficacy of BCG and epirubicin.\n From January 1992 to February 1997, 957 patients with intermediate- or high-risk stage Ta T1 urothelial bladder cancer were randomized after transurethral resection to one of three treatment groups in the European Organization for Research and Treatment of Cancer Genito-Urinary Group phase 3 trial 30911.\n Patients received six weekly instillations of epirubicin, BCG, or BCG plus isoniazid (INH) followed by three weekly maintenance instillations at months 3, 6, 12, 18, 24, 30, and 36.\n End points were time to recurrence, progression, distant metastases, overall survival, and disease-specific survival.\n With 837 eligible patients and a median follow-up of 9.2 yr, time to first recurrence (p<0.001), distant metastases (p=0.046), overall survival (p=0.023), and disease-specific survival (p=0.026) were significantly longer in the two BCG arms combined as compared with epirubicin; however, there was no difference for progression. Three hundred twenty-three patients with stage T1 or grade 3 tumors were high risk, and the remaining 497 patients were intermediate risk. The observed treatment benefit was at least as large, if not larger, in the intermediate-risk patients compared with the high-risk patients.\n In patients with intermediate- and high-risk stage Ta and T1 urothelial bladder cancer, intravesical BCG with or without INH is superior to intravesical epirubicin not only for time to first recurrence but also for time to distant metastases, overall survival, and disease-specific survival. The benefit of BCG is not limited to just high-risk patients; intermediate-risk patients also benefit from BCG.\n This study was registered with the US National Cancer Institute clinical trials database [protocol ID: EORTC-30911]. http://www.cancer.gov/search/ViewClinicalTrials.aspx?cdrid=77075&version=HealthProfessional&protocolsearchid=6540260.\n Copyright © 2009 European Association of Urology. Published by Elsevier B.V. All rights reserved.", "A prospective randomized trial on 94 eligible patients evaluated and compared the efficacy of adjuvant intravesical epirubicin and bacillus Calmette-Guérin (BCG) after complete resection of multifocal superficial bladder cancer. BCG treatment schedule consisted of an induction 6-week course of instillations (150 mg Pasteur BCG per instillation) and single maintenance doses to patients who remained free of recurrences at follow-up examinations for a total treatment period of 2 years. These initial responders received additionally a separate 4-week course of therapy 6 months after the start of treatment. Chemoprophylaxis included an early (on the second postoperative day) instillation followed by 4 weekly treatments with epirubicin (50 mg per instillation) and then by 10 monthly treatments for the initial responders during the first year of follow-up and at every follow-up examination for a total treatment period of 2 years. The overall treatment results did not differ significantly between the 2 arms (54% of patients of the epirubicin group remained free of recurrences compared to 65% of those treated with BCG) for an identical mean follow-up of 35.1 months. However, a significant benefit in favour of BCG when compared with epirubicin was shown in patients who had stage T1 and grade 3 tumours and in terms of relative risk of recurrences, disease-free interval and recurrence rate per 100 patient-months. Both drugs were proved to be safe with manageable toxicity.", "A prospective, randomized trial was conducted to evaluate and compare the effects of modified adjuvant intravesical bacillus Calmette-Guérin (BCG) and epirubicin regimens in patients with superficial bladder cancer. One hundred thirty-two individuals with recurrent and/or multiple neoplasms, i.e. at high risk for tumour recurrence and progression, were enrolled. After complete transurethral resection of their tumours, the patients received a 6-week course of BCG instillations or an early 4-week course of epirubicin instillations as their initial therapy. Those with stage Ta and grade 1 neoplasms who remained free of recurrences received maintenance therapy consisting of single quarterly instillations. However, for those with stage T1 cancer of any grade or stage Ta of grade 2 or 3 neoplasms who also remained free of recurrences, the treatment schedules were modified: they received, instead of single maintenance doses, 3 weekly instillations of epirubicin at months 3 and 6 of follow-up, or a 3-week course of BCG at month 6 of follow-up. The recurrence-free rates did not differ significantly between the two study groups (44% for epirubicin versus 55% for BCG), for an identical median follow-up of 43 months. However, in terms of relative risk of recurrences, disease-free intervals and recurrence rate per 100 patient-months, a significant benefit in favour of BCG when compared with epirubicin was demonstrated in patients who had stage T1 or grade 3 neoplasms.", "Prophylactic intravesical treatment with chemotherapeutic agents or one of the different strains of the immunomodulator bacillus Calmette-Guérin (BCG) reduces tumor recurrence and may prevent progression after transurethral resection (TUR) of superficial bladder cancer. Clinical and pathological prognostic factors are used to categorize different groups at risk for disease recurrence and progression. Solitary low-grade (G1, 2A), low-stage (pTa) tumors have less than a 5% risk of progression, while pT1 G3 tumors with concomitant carcinoma in situ (CIS) have a considerably higher risk of progression and metastases. Thus, prospective clinical trials should consider the different risks associated with different prognostic groups and stratify patients accordingly. The Dutch Cooperative Trial evaluated mitomycin versus BCG-Tice versus BCG-RIVM in 469 patients with pTA/pT1 carcinoma and CIS of the urinary bladder after TUR. Of 437 evaluable patients, 50 had CIS, 254 had pTA tumors, and 133 had pT1 tumors. No statistical differences were observed in toxicity between the two strains of BCG, but local and systemic side effects were more frequent in the BCG groups versus the mitomycin group. No differences in response rate were observed between the 3 treatment groups in patients with CIS. A statistically significant difference in favor of mitomycin was seen, however, in patients with papillary tumors. Mitomycin and BCG-RIVM were equally effective, and mitomycin proved significantly more effective than BCG-Tice. No significant difference in efficacy was observed between the two strains of BCG. Disease recurrence during the study in patients with papillary tumors was seen in 43% of mitomycin-treated patients, 64% of the BCG-Tice group, and 46% of patients treated with BCG-Rivm. However, a subgroup analysis for time to first recurrence for pTa versus pT1 and for grade 1 and 2 versus grade 3 papillary tumors showed no statistically significant between-group difference. Further studies comparing identical regimens, doses, and patient groups are needed to define more clearly which patient groups and tumors are more likely to respond to intravesical therapy." ]	The data from the present meta-analysis indicate that intravesical BCG treatment is more efficacious than EPI in reducing tumour recurrence for Ta and T1 bladder cancer. However, BCG appears to be associated with a higher incidence of adverse effects, such as drug-induced cystitis, haematuria and systemic toxicity, than EPI. The overall quality of the evidence is rather low. Well-designed, high quality randomised controlled trials with good allocation concealment are required.
CD005032	[ "9811084", "18054445", "10519687", "17364418", "11414349", "16150764", "12127464", "9264626" ]	[ "Matching alcoholism treatments to client heterogeneity: treatment main effects and matching effects on drinking during treatment. Project MATCH Research Group.", "Brief alcohol intervention for general hospital inpatients: a randomized controlled trial.", "A study of minimal interventions for problem drinkers in acute care settings.", "A cognitive behavioral therapy for alcohol-dependent domestic violence offenders: an integrated substance abuse-domestic violence treatment approach (SADV).", "A randomized controlled trial of motivational enhancement therapy (MET) for mild to moderate alcohol dependence.", "Effectiveness of treatment for alcohol problems: findings of the randomised UK alcohol treatment trial (UKATT).", "A trial of \"standard\" outpatient alcoholism treatment vs. a minimal treatment control.", "[Effectiveness of brief medical counseling to reduce drinkers' alcohol consumption]." ]	[ "This article examines client drinking and related psychosocial functioning during the course of alcoholism treatment. It focuses on (1) the main effects of the three Project MATCH treatments, (2) the prognostic value of client attributes employed in the matching hypotheses, and (3) the attribute by treatment interaction effects.\n Clients recruited from outpatient settings (n = 952) or from aftercare settings (n = 774) were randomized to one of the following treatments: Motivational Enhancement Therapy (MET), Cognitive Behavioral Therapy (CBT) and Twelve-Step Facilitation (TSF). Alcohol consumption and psychosocial functioning during treatment were assessed at the end of the 12-week treatment phase.\n During the treatment phase, small but statistically significant differences among treatments were found only in the outpatient arm on measures of alcohol consumption and alcohol-related negative consequences. Forty-one percent (41%) of CBT and TSF clients were abstinent or drank moderately without alcohol-related consequences, compared with 28% of MET clients. Tests of 10 a priori primary client-treatment matching hypotheses failed to find any interaction effects that had an impact on drinking throughout the treatment phase.\n In the outpatient setting there appears to be a temporary advantage to assigning individuals to CBT or TSF rather than MET. When there is a need to quickly reduce heavy drinking and alcohol-related consequences, it appears that CBT or TSF should be the treatment of choice.", "To test the effectiveness of a brief alcohol intervention among non-dependent general hospital inpatients with alcohol problems, delivered by either a specialized liaison service or hospital physicians.\n All inpatients of 29 wards from four general hospitals of one region in Germany were screened for alcohol problems (n=14,332). Of those screening positive, 595 patients were included in a randomized controlled group design using a time-frame. Patients with alcohol dependence were not considered in this study. Patients received Motivational Interviewing based counselling either by a specialized liaison service, by hospital physicians trained under routine conditions or received hospital treatment as usual without additional counselling. One year later, alcohol consumption, motivation and well-being were assessed. Sample survey analyses and generalized estimating equations were conducted.\n At baseline, the three groups differed regarding motivation, with higher motivation among the controls. At follow-up, the groups did not differ regarding alcohol consumption, alcohol-related problems and well-being. All groups decreased their alcohol consumption significantly. Regarding motivation, longitudinal analyses revealed significant interaction effects of time and intervention (p<0.05), indicating a stronger increase of readiness to change drinking and a less profound drop of readiness to seek help among those who received intervention compared to the controls.\n The intervention was not effective in reducing alcohol consumption or in increasing well-being 12 months after hospitalization. It had a positive effect on readiness to change drinking and on readiness to seek formal help for alcohol problems. The intervention groups compensated their lag of motivation.", "This article reports an investigation of three minimal interventions for potential problem drinkers in general hospital wards. The interventions were: (a) brief advice; (b) the provision of health education literature; (c) a combination of both the advice and literature. One year after recruitment the mean levels of alcohol consumption and the number of alcohol-related problems reported by the cohort was significantly reduced. These reductions were supported by reductions in the mean levels of GGT and AST, but not in mean MCV. No statistically significant treatment effects were found. The results are presented and implications for nursing are discussed.", "This pilot study evaluated the efficacy of a twelve-session cognitive behavioral group therapy for alcohol-dependent males with co-occurring interpersonal violence (IPV). Participants were 85 alcohol-dependent males who were arrested for domestic violence within the past year. Seventy-eight male adults were randomized to either a cognitive behavioral Substance Abuse Domestic Violence (SADV) group (N = 40) or a Twelve-Step Facilitation (TSF) Group (N = 38). There was no significant difference between SADV versus TSF in the number of sessions attended. Regarding substance use, the group assigned to SADV reported using alcohol significantly fewer days (eg, 90 days of abstinence across the 12 weeks of treatment) as compared to the TSF group. Regarding physical violence, there was a trend for participants in the SADV condition to achieve a greater reduction in the frequency of violent episodes across time compared to individuals in the TSF group. These data suggest the promise of the SADV group therapy approach for alcohol-dependent males with a history of IPV who present for substance abuse treatment.", "This study was designed to conduct a randomized controlled trial of motivational enhancement therapy (MET) with two control conditions: nondirective reflective listening (NDRL) and no further counseling (NFC); and to conduct this study in a sample of patients with a primary diagnosis of mild to moderate alcohol dependence, in a \"real-life\" clinical setting.\n Patients with mild to moderate alcohol dependence were recruited, assessed and treated at the Community Alcohol and Drug Service of Christchurch, New Zealand. All patients received a feedback/education session before randomization to either four sessions of MET, four sessions of NDRL, or NFC. Outcome data on 122 subjects (57.4% men) were obtained 6 months following the end of treatment, by an interviewer who was blind to the treatment condition. The primary drinking outcome was unequivocal heavy drinking, defined as drinking 10 or more standard drinks six or more times in the follow-up period. Global assessment scale (GAS) measured general personal/social functioning.\n Of patients treated with MET, 42.9% showed unequivocal heavy drinking compared with 62.5% of the NDRL and 65.0% of the NFC groups (p = .04). No significant differences were found for GAS score according to treatment condition.\n In patients with mild to moderate alcohol dependence, MET is more effective for reducing unequivocal heavy drinking than either a feedback/education session alone or four sessions of NDRL. MET can be considered an effective \"value added\" counseling intervention in a real-life clinical setting. In patients with mild to moderate alcohol dependence, nondirective reflective listening provides no additional advantage over a feedback/education session alone.", "To compare the effectiveness of social behaviour and network therapy, a new treatment for alcohol problems, with that of the proved motivational enhancement therapy.\n Pragmatic randomised trial.\n Seven treatment sites around Birmingham, Cardiff, and Leeds.\n 742 clients with alcohol problems; 689 (93.0%) were interviewed at three months and 617 (83.2%) at 12 months.\n Social behaviour and network therapy and motivational enhancement therapy.\n Changes in alcohol consumption, alcohol dependence, and alcohol related problems over 12 months.\n Both groups reported substantial reductions in alcohol consumption, dependence, and problems, and better mental health related quality of life over 12 months. Between groups we found only one significant difference in outcome, probably due to chance: the social network group showed significantly better physical health at three months. Non-significant differences at 12 months in the motivational group relative to the social network group included: the number of drinks consumed per drinking day had decreased by an extra 1.1 (95% confidence interval -1.0 to 3.2); scores on the Leeds dependence questionnaire had improved by an extra 0.6 (-0.7 to 2.0); scores on the alcohol problems questionnaire had improved by an extra 0.5 (-0.4 to 1.4); but the number of days abstinent from drinking had increased by 1.2% less (-4.5% to 6.9%).\n The novel social behaviour and network therapy for alcohol problems did not differ significantly in effectiveness from the proved motivational enhancement therapy.", "This study sought to examine the effectiveness of a \"standard\" outpatient alcoholism treatment (ST) program. An outpatient alcoholism treatment as it is commonly practiced in the US (with group and individual therapy, and an emphasis on Alcoholics Anonymous [AA]), was compared with a minimal treatment (MT) approach (weekly alcohol education movies). At 6 months, ST patients surpassed those in MT in terms of complete abstinence, reduction in amount of alcohol consumed, length of sobriety at follow-up, improvement in employment status, number of AA meetings attended, and lower initial drop-out. It is concluded that a ST approach is more helpful than MT in treating severely alcohol-dependent individuals who have not been able to cut down drinking on their own. Those already drinking less appeared to be helped by MT.", "To evaluate the effectiveness of medical counselling in reducing alcohol consumption in male heavy drinkers.\n A controlled, randomised, simple-blind intervention study.\n Four Primary Care teams in Area 10, Madrid.\n 152 men who attended for on-demand treatment from the four teams and whose alcohol consumption was over 21 International Units (IU) a week.\n Brief medical counselling backed up by didactic material. Two questionnaires on alcohol consumption in IU, consumption habits and problems related to alcohol were administered, separated by an interval of between 6 and 18 months. Non-parametric tests for paired samples (McNemar) were applied.\n 60% answered the second questionnaire. Neither sociodemographic nor health habit differences were found between those who responded and those who did not, except for social class. There were no appreciable differences between the intervention and control groups. The percentage of drinkers above 35 IU decreased significantly in the intervention group.\n The intervention was clearly effective in reducing the percentage of drinkers whose weekly consumption was over 35 IU." ]	No experimental studies unequivocally demonstrated the effectiveness of AA or TSF approaches for reducing alcohol dependence or problems. One large study focused on the prognostic factors associated with interventions that were assumed to be successful rather than on the effectiveness of interventions themselves, so more efficacy studies are needed.
CD008880	[ "21303529", "15770171", "18775942", "8976475", "16426449", "14965404", "15507794", "19539115", "15967762", "17250965", "17621203", "9431627", "9106321", "14521638", "12809196", "11353937" ]	[ "A randomised controlled trial of preventive spinal manipulation with and without a home exercise program for patients with chronic neck pain.", "Implementation of the Dutch low back pain guideline for general practitioners: a cluster randomized controlled trial.", "A randomised controlled trial of spinal manipulative therapy in acute low back pain.", "Trunk exercise combined with spinal manipulative or NSAID therapy for chronic low back pain: a randomized, observer-blinded clinical trial.", "Active rehabilitation for chronic low back pain: cognitive-behavioral, physical, or both? First direct post-treatment results from a randomized controlled trial [ISRCTN22714229].", "Implementation of RCGP guidelines for acute low back pain: a cluster randomised controlled trial.", "Early intervention for the management of acute low back pain: a single-blind randomized controlled trial of biopsychosocial education, manual therapy, and exercise.", "A randomized controlled trial comparing 2 types of spinal manipulation and minimal conservative medical care for adults 55 years and older with subacute or chronic low back pain.", "Should treatment of (sub)acute low back pain be aimed at psychosocial prognostic factors? Cluster randomised clinical trial in general practice.", "Comparison of general exercise, motor control exercise and spinal manipulative therapy for chronic low back pain: A randomized trial.", "Active exercise, education, and cognitive behavioral therapy for persistent disabling low back pain: a randomized controlled trial.", "A population-based, randomized clinical trial on back pain management.", "Local and remote sustained trigger point therapy for exacerbations of chronic low back pain. A randomized, double-blind, controlled, multicenter trial.", "Randomized controlled trial of education and feedback for implementation of guidelines for acute low back pain.", "Intensive group training versus cognitive intervention in sub-acute low back pain: short-term results of a single-blind randomized controlled trial.", "A pilot randomized clinical trial on the relative effect of instrumental (MFMA) versus manual (HVLA) manipulation in the treatment of cervical spine dysfunction." ]	[ "Evidence indicates that supervised home exercises, combined or not with manual therapy, can be beneficial for patients with non-specific chronic neck pain (NCNP). The objective of the study is to investigate the efficacy of preventive spinal manipulative therapy (SMT) compared to a no treatment group in NCNP patients. Another objective is to assess the efficacy of SMT with and without a home exercise program.\n Ninety-eight patients underwent a short symptomatic phase of treatment before being randomly allocated to either an attention-group (n = 29), a SMT group (n = 36) or a SMT + exercise group (n = 33). The preventive phase of treatment, which lasted for 10 months, consisted of meeting with a chiropractor every two months to evaluate and discuss symptoms (attention-control group), 1 monthly SMT session (SMT group) or 1 monthly SMT session combined with a home exercise program (SMT + exercise group). The primary and secondary outcome measures were represented by scores on a 10-cm visual analog scale (VAS), active cervical ranges of motion (cROM), the neck disability index (NDI) and the Bournemouth questionnaire (BQ). Exploratory outcome measures were scored on the Fear-avoidance Behaviour Questionnaire (FABQ) and the SF-12 Questionnaire.\n Our results show that, in the preventive phase of the trial, all 3 groups showed primary and secondary outcomes scores similar to those obtain following the non-randomised, symptomatic phase. No group difference was observed for the primary, secondary and exploratory variables. Significant improvements in FABQ scores were noted in all groups during the preventive phase of the trial. However, no significant change in health related quality of life (HRQL) was associated with the preventive phase.\n This study hypothesised that participants in the combined intervention group would have less pain and disability and better function than participants from the 2 other groups during the preventive phase of the trial. This hypothesis was not supported by the study results. Lack of a treatment specific effect is discussed in relation to the placebo and patient provider interactions in manual therapies. Further research is needed to delineate the specific and non-specific effects of treatment modalities to prevent unnecessary disability and to minimise morbidity related to NCNP. Additional investigation is also required to identify the best strategies for secondary and tertiary prevention of NCNP.\n ClinicalTrials.gov: NCT00566930.", "Cluster randomized controlled trial for a multifaceted implementation strategy.\n To assess the effectiveness of tailored interventions (multifaceted implementation strategy) to implement the Dutch low back pain guideline for general practitioners with regard to adherence to guideline recommendations.\n Guidelines for the management of low back pain in primary care have been developed in various countries, but little is known about the optimal implementation strategy. A multifaceted implementation strategy was developed to overcome identified barriers to the implementation of the Dutch low back pain guideline for general practitioners.\n General practitioners were randomized to an intervention or a control group. The general practitioners in the intervention group (n = 21) received tailored interventions consisting of the Dutch low back pain guideline for general practitioners, a 2-hour educational and clinical practice workshop; two scientific articles on low back pain management; the guideline for occupational physicians; a tool for patient education; and a tool for reaching agreement on low back care with physical, exercise, and manual therapists. The control group (n = 20) received no intervention. The participating general practitioners were asked to recruit consecutive patients with a new episode of low back pain as the main reason for consultation. General practitioners completed registration forms of each individual consultation with regard to the main outcome measures: advice and information, referral to other health-care providers, and prescription of medication.\n Forty-one of the 67 randomized general practitioners reported on a total of 616 consultations for 531 patients with nonspecific low back pain. The advice and explanation provided by the general practitioners, the prescription of paracetamol or nonsteroidal anti-inflammatory drugs, and prescription of pain medication on atime contingent or a pain contingent basis showed no statistically significant differences between the intervention and control groups. There were also no differences in overall referral rate. However, in follow-up consultations fewer patients were referred to a physical or exercise therapist by the general practitioners in the intervention group than in the control group.\n The multifaceted intervention strategy modestly improved implementation (for parts of the recommendations in) the Dutch low back pain guideline by general practitioners and produced small concomitant changes in patient management. The implementation strategy produced fewer referrals to therapists during follow-up consultations.", "To determine whether treatment with spinal manipulative therapy (SMT) administered in addition to standard care is associated with clinically relevant early reductions in pain and analgesic consumption.\n 104 patients with acute low back pain were randomly assigned to SMT in addition to standard care (n = 52) or standard care alone (n = 52). Standard care consisted of general advice and paracetamol, diclofenac or dihydrocodeine as required. Other analgesic drugs or non-pharmacological treatments were not allowed. Primary outcomes were pain intensity assessed on the 11-point box scale (BS-11) and analgesic use based on diclofenac equivalence doses during days 1-14. An extended follow-up was performed at 6 months.\n Pain reductions were similar in experimental and control groups, with the lower limit of the 95% CI excluding a relevant benefit of SMT (difference 0.5 on the BS-11, 95% CI -0.2 to 1.2, p = 0.13). Analgesic consumptions were also similar (difference -18 mg diclofenac equivalents, 95% CI -43 mg to 7 mg, p = 0.17), with small initial differences diminishing over time. There were no differences between groups in any of the secondary outcomes and stratified analyses provided no evidence for potential benefits of SMT in specific patient groups. The extended follow-up showed similar patterns.\n SMT is unlikely to result in relevant early pain reduction in patients with acute low back pain.", "To study the relative efficacy of three different treatment for chronic low back pain (CLBP). Two preplanned comparisons were made: (a) Spinal manipulative therapy (SMT) combined with trunk strengthening exercises (TSE) vs. SMT combined with trunk stretching exercises, and (b) SMT combined with TSE vs. nonsteroidal anti-inflammatory drug (NSAID) therapy combined with TSE.\n Interdisciplinary, prospective, observer-blinded, randomized clinical trial with a 1-yr follow-up period. The trial evaluated therapies in combination only and was not designed to test the individual treatment components.\n Primary contact, college out-patient clinic.\n In total, 174 patients aged 20-60 yr were admitted to the study.\n Patient-rated low back pain, disability, and functional health status at 5 and 11 wk.\n Five weeks of SMT or NSAID therapy in combination with supervised trunk exercise, followed by and additional 6 wk of supervised exercise alone.\n Individual group comparisons after 5 and 11 wk of intervention on all three main outcome measures did not reveal any clear clinically important or statistically significant differences. There seemed to be a sustained reduction in medication use at the 1-yr follow-up. in the SMT/TSE group. Continuance of exercise during the follow-up year, regardless of type, was associated with a better outcome.\n Each of the three therapeutic regimens was associated with similar and clinically important improvement over time that was considered superior to the expected natural history of long-standing CLBP. For the management of CLBP, trunk exercise in combination with SMT or NSAID therapy seemed to be beneficial and worthwhile. The magnitude of nonspecific therapeutic (placebo) effects, cost-effectiveness and relative risks of side effects associated with these types of therapy need to be addressed in future studies.", "The treatment of non-specific chronic low back pain is often based on three different models regarding the development and maintenance of pain and especially functional limitations: the deconditioning model, the cognitive behavioral model and the biopsychosocial model. There is evidence that rehabilitation of patients with chronic low back pain is more effective than no treatment, but information is lacking about the differential effectiveness of different kinds of rehabilitation. A direct comparison of a physical, a cognitive-behavioral treatment and a combination of both has never been carried out so far.\n The effectiveness of active physical, cognitive-behavioral and combined treatment for chronic non-specific low back pain compared with a waiting list control group was determined by performing a randomized controlled trial in three rehabilitation centers. Two hundred and twenty three patients were randomized, using concealed block randomization to one of the following treatments, which they attended three times a week for 10 weeks: Active Physical Treatment (APT), Cognitive-Behavioral Treatment (CBT), Combined Treatment of APT and CBT (CT), or Waiting List (WL). The outcome variables were self-reported functional limitations, patient's main complaints, pain, mood, self-rated treatment effectiveness, treatment satisfaction and physical performance including walking, standing up, reaching forward, stair climbing and lifting. Assessments were carried out by blinded research assistants at baseline and immediately post-treatment. The data were analyzed using the intention-to-treat principle.\n For 212 patients, data were available for analysis. After treatment, significant reductions were observed in functional limitations, patient's main complaints and pain intensity for all three active treatments compared to the WL. Also, the self-rated treatment effectiveness and satisfaction appeared to be higher in the three active treatments. Several physical performance tasks improved in APT and CT but not in CBT. No clinically relevant differences were found between the CT and APT, or between CT and CBT.\n All three active treatments were effective in comparison to no treatment, but no clinically relevant differences between the combined and the single component treatments were found.", "The Royal College of General Practitioners (RCGP) has produced guidelines for the management of acute low back pain in primary care.\n To investigate the impact on patient management of an educational strategy to promote these guidelines among general practitioners (GPs).\n Group randomised controlled trial, using the health centre as the unit of randomisation.\n Primary care teams in north-west England.\n Twenty-four health centres were randomly allocated to an intervention or control arm. Practices in the intervention arm were offered outreach visits to promote national guidelines on acute low back pain, as well as access to fast-track physiotherapy and to a triage service for patients with persistent symptoms.\n Twenty-four centres were randomised. Two thousand, one hundred and eighty-seven eligible patients presented with acute low back pain during the study period: 1049 in the intervention group and 1138 in the control group. There were no significant differences between study groups in the proportion of patients who were referred for X-ray, issued with a sickness certificate, prescribed opioids or muscle relaxants, or who were referred to secondary care, but significantly more patients in the intervention group were referred to physiotherapy or the back pain unit (difference in proportion = 12.2%, 95% confidence interval [CI] = 2.8% to 21.6%).\n The management of patients presenting with low back pain to primary care was mostly unchanged by an outreach educational strategy to promote greater adherence to RCGP guidelines among GPs. An increase in referral to physiotherapy or educational programmes followed the provision of a triage service.", "A single blind randomized controlled trial comparing two models of care for patients with acute simple low back pain.\n To compare two research-based models of care for acute low back pain and investigate the effect of the timing of physical intervention.\n National guidelines offer conflicting information on the delivery of physical treatment in the management of acute low back pain. The guidelines suggest two different models of care. Direct comparisons between these models are lacking in the literature. The present study aims to compare these approaches to the management of acute low back pain.\n Among 804 referred patients, 102 subjects met the specific admission criteria and were randomly assigned to an \"assess/advise/treat\" group or an \"assess/advise/wait\" group. The intervention consisted of biopsychosocial education, manual therapy, and exercise. Assessment of short-term outcome enables comparison to be made between intervention and advice to stay active. Assessment of long-term outcome enables comparison to be made between early and late intervention. Study outcomes of reported pain (Visual Analogue Scale), functional disability (the Roland and Morris Disability Questionnaire), mood (Modified Zung Self Rated Depression Score, Modified Somatic Perception Questionnaire, State-Trait Anxiety Inventory), general health (Euroqol), and quality of life (Short Form 36) were assessed at baseline, 6 weeks, 3 months, and 6 months.\n At 6 weeks, the assess/advise/treat group demonstrated greater improvements in disability, mood, general health, and quality of life than patients in the assess/advise/wait group (P < 0.05). Disability and pain were not significantly different between the groups at long-term follow up (P > 0.05). However, mood, general health, and quality of life remained significantly better in the assess/advise/treat group (P < 0.05).\n At short-term, intervention is more effective than advice on staying active, leading to more rapid improvement in function, mood, quality of life, and general health. The timing of intervention affects the development of psychosocial features. If treatment is provided later, the same psychosocial benefits are not achieved. Therefore, an assess/advise/treat model of care seems to offer better outcomes than an assess/advise/wait model of care.", "Chiropractic care is used by many older patients for low back pain (LBP), but there are no published results of randomized trials examining spinal manipulation (SM) for older adults. The purpose of this study was to compare the effects of 2 biomechanically distinct forms of SM and minimal conservative medical care (MCMC) for participants at least 55 years old with subacute or chronic nonradicular LBP.\n Randomized controlled trial. The primary outcome variable was low back-related disability assessed with the 24-item Roland Morris Disability questionnaire at 3, 6, 12, and 24 weeks. Participants were randomly allocated to 6 weeks of care including 12 visits of either high-velocity, low-amplitude (HVLA)-SM, low-velocity, variable-amplitude (LVVA)-SM, or 3 visits of MCMC.\n Two hundred forty participants (105 women and 135 men) ages 63.1 +/- 6.7 years without significant comorbidities. Adjusted mean Roland Morris Disability change scores (95% confidence intervals) from baseline to the end of active care were 2.9 (2.2, 3.6) and 2.7 (2.0, 3.3) in the LVVA-SM and HVLA-SM groups, respectively, and 1.6 (0.5, 2.8) in the MCMC group. There were no significant differences between LVVA-SM and HVLA-SM at any of the end points. The LVVA-SM group had significant improvements in mean functional status ranging from 1.3 to 2.2 points over the MCMC group. There were no serious adverse events associated with any of the interventions.\n Biomechanically distinct forms of SM did not lead to different outcomes in older LBP patients and both SM procedures were associated with small yet clinically important changes in functional status by the end of treatment for this relatively healthy older population. Participants who received either form of SM had improvements on average in functional status ranging from 1 to 2.2 over those who received MCMC. From an evidence-based care perspective, patient preference and clinical experience should drive how clinicians and patients make the SM procedure decision for this patient population.", "To compare the effects of a minimal intervention strategy aimed at assessment and modification of psychosocial prognostic factors and usual care for treatment of (sub)acute low back pain in general practice.\n Cluster randomised clinical trial.\n 60 general practitioners in 41 general practices.\n 314 patients with non-specific low back pain of less than 12 weeks' duration, recruited by their general practitioner.\n In the minimal intervention strategy group the general practitioner explored the presence of psychosocial prognostic factors, discussed these factors, set specific goals for reactivation, and provided an educational booklet. The consultation took about 20 minutes. Usual care was not standardised.\n Functional disability (Roland-Morris disability questionnaire), perceived recovery, and sick leave because of low back pain assessed at baseline and after 6, 13, 26, and 52 weeks.\n The dropout rate was 8% in the minimal intervention strategy group and 9% in the usual care group. Multilevel analyses showed no significant differences between the groups on any outcome measure during 12 months of follow-up in the whole group or in relevant subgroups (patients with high scores on psychosocial measures at baseline or a history of frequent or prolonged low back pain).\n This study provides no evidence that (Dutch) general practitioners should adopt our new treatment strategy aimed at psychosocial prognostic factors in patients with (sub)acute low back pain. Further research should examine why our new strategy was not more effective than usual care.", "Practice guidelines recommend various types of exercise and manipulative therapy for chronic back pain but there have been few head-to-head comparisons of these interventions. We conducted a randomized controlled trial to compare effects of general exercise, motor control exercise and manipulative therapy on function and perceived effect of intervention in patients with chronic back pain. Two hundred and forty adults with non-specific low back pain 3months were allocated to groups that received 8weeks of general exercise, motor control exercise or spinal manipulative therapy. General exercise included strengthening, stretching and aerobic exercises. Motor control exercise involved retraining specific trunk muscles using ultrasound feedback. Spinal manipulative therapy included joint mobilization and manipulation. Primary outcomes were patient-specific function (PSFS, 3-30) and global perceived effect (GPE, -5 to 5) at 8weeks. These outcomes were also measured at 6 and 12months. Follow-up was 93% at 8weeks and 88% at 6 and 12months. The motor control exercise group had slightly better outcomes than the general exercise group at 8weeks (between-group difference: PSFS 2.9, 95% CI: 0.9-4.8; GPE 1.7, 95% CI: 0.9-2.4), as did the spinal manipulative therapy group (PSFS 2.3, 95% CI: 0.4-4.2; GPE 1.2, 95% CI: 0.4-2.0). The groups had similar outcomes at 6 and 12months. Motor control exercise and spinal manipulative therapy produce slightly better short-term function and perceptions of effect than general exercise, but not better medium or long-term effects, in patients with chronic non-specific back pain.", "A randomized controlled trial.\n To determine 1) whether, among patients with persistent disabling low back pain (LBP), a group program of exercise and education using a cognitive behavioral therapy (CBT) approach, reduces pain and disability over a subsequent 12-month period; 2) the cost-effectiveness of the intervention; and 3) whether a priori preference for type of treatment influences outcome.\n There is evidence that both exercise and CBT delivered in specialist settings is effective in improving LBP. There is a lack of evidence on whether such interventions, delivered by trained individuals in primary care, result in improved outcomes.\n The study was conducted in nine family medical practices in East Cheshire, UK. Patients 18 to 65 years of age, consulting with LBP, were recruited; those still reporting LBP 3 months after the initial consultation were randomized between the two trial arms. The intervention arm received a program of eight 2-hour group exercise session over 6 weeks comprising active exercise and education delivered by physiotherapists using a CBT approach. Both arms received an educational booklet and audio-cassette. The primary outcome measures were pain (0-100 Visual Analogue Scale) and disability (Roland and Morris Disability Scale; score 0-24).\n A total of 196 subjects (84%) completed follow-up 12 months after the completion of the intervention program. The intervention showed only a small and nonsignificant effect at reducing pain (-3.6 mm; 95% confidence interval, -8.5, 1.2 mm) and disability (-0.6 score; 95% confidence interval, -1.6, 0.4). The cost of the intervention was low with an incremental cost-effectiveness ratio of pound5000 (U.S. $8650) per quality adjusted life year. In addition, patients allocated to the intervention that had expressed a preference for it had clinically important reductions in pain and disability.\n This intervention program produces only modest effects in reducing LBP and disability over a 1-year period. The observation that patient preference for treatment influences outcome warrants further investigation.", "Population-based randomized clinical trial.\n To develop and test a model of management of subacute back pain, to prevent prolonged disability.\n The present management of back pain seems inadequate, and development of innovative models has been urged.\n A model for the treatment of subacute work-related back pain has been developed and evaluated in a population-based randomized clinical trial. Workers (n = 130) from eligible workplaces in the Sherbrooke area (N = 31), who had been absent from work for more than 4 weeks for back pain, were randomized, based on their workplace, in one of four treatment groups: usual care, clinical intervention, occupational intervention, and full intervention (a combination of the last two). The duration of absence from regular work and from any work was evaluated using survival analysis. Functional status and pain were compared at study entry and after 1 year of follow-up.\n The full intervention group returned to regular work 2.41 times faster than the usual care intervention group (95% confidence interval 1.19-4.89; P < 0.01). The specific effect of the occupational intervention accounted for the most important part of this result, with a rate ratio of return to regular work of 1.91 (95% confidence interval = 1.18-3.10; P < 0.01). Pain and disability scales demonstrated either a statistically significant reduction or a trend toward reduction in the three intervention groups, compared with the trend in the usual care intervention group.\n Close association of occupational intervention with clinical care is of primary importance in impeding progression toward chronicity of low back pain.", "A randomized, double-blind, controlled, multicenter trial was conducted.\n To assess the efficacy of neuroreflexotherapy in the management of low back pain.\n Neuroreflexotherapy consists of temporary implantation of epidermal devices in trigger points in the back and referred tender points in the ear.\n The rheumatology and rehabilitation departments of three teaching hospitals in Madrid recruited 78 patients with chronic low back pain. These patients were randomly assigned to the control group (37 patients) or to the treatment group (41 patients). Patients in the treatment group underwent one neuroreflexotherapeutic intervention. The control group received sham treatment consisting of placement of the same number of epidermal devices within a 5-cm radius of the target zones. Patients from both groups were allowed to continue drug treatment as previously prescribed. The use of medications during the trial was recorded.\n Patients underwent clinical evaluations on three occasions: within 5 minutes before intervention, within 5 minutes after intervention, and 45 days later. The preintervention assessment was carried out by the physician from each hospital department who included the patient in the study. Each of the two follow-up assessments were carried out independently by two of three physicians who had no connection with the research team. Patients in the treatment group showed immediate lessening of pain compared with the results in patients in the control group. The pain relief was clinically relevant and statistically significant, and it persisted up to the end of the trial.\n Neuroreflexotherapy intervention seems to be a simple and effective treatment for rapid amelioration of pain episodes in patients with chronic low back pain. At this time, the duration of pain relief beyond 45 days has not been evaluated.", "The effect of clinical guidelines on resource utilization for complex conditions with substantial barriers to clinician behavior change has not been well studied. We report the impact of a multifaceted guideline implementation intervention on primary care clinician utilization of radiologic and specialty services for the care of acute low back pain.\n Physician groups were randomized to receive guideline education and individual feedback, supporting patient education materials, both, or neither. The impact on guideline adherence and resource utilization was evaluated during the 12-month period before and after implementation.\n Fourteen physician groups with 120 primary care physician and associate practitioners from 2 group model HMO practices.\n Guideline implementation utilized an education/audit/feedback model with local peer opinion leaders. The patient education component included written and videotaped materials on the care of low back pain.\n The clinician intervention was associated with an absolute increase in guideline-consistent behavior of 5.4% in the intervention group versus a decline of 2.7% in the control group (P =.04). The patient education intervention produced no significant change in guideline-consistent behavior, but was poorly adopted. Patient characteristics including duration of pain, prior history of low back pain, and number of visits during the illness episode were strong predictors of service utilization and guideline-consistent behavior.\n Implementation of an education and feedback-supported acute low back pain care guideline for primary care clinicians was associated with an increase in guideline-consistent behavior. Patient education materials did not enhance guideline effectiveness. Implementation barriers could limit the utility of this approach in usual care settings.", "To evaluate the short-term effect of physical exercise and a cognitive intervention in low back pain.\n Randomized controlled trial.\n Ninety-three patients sick-listed for 8-12 weeks for sub-acute low back pain were randomized to an exercise regime (n = 30), a cognitive intervention (n = 34) or a control group (n = 29).\n Primary outcome measures were pain, disability, sick-listing and satisfaction with care. Secondary outcome measures were self-efficacy for pain and for function, fear-avoidance beliefs, emotional distress, generic health status and life satisfaction.\n Eighteen percent of subjects dropped out. Drop-out was most frequent in the exercise group. At 18 weeks after inclusion fear-avoidance beliefs were reduced in both intervention groups. The cognitive group demonstrated significant improvement in disability, self-efficacy for pain, emotional distress, general health and life satisfaction. Patients in the exercise group were significantly more satisfied with the treatment, and patients following the exercise protocol reduced pain significantly. No effect on sick-listing was seen.\n Cognitive intervention improved disability and may be feasible for most patients sick-listed in the sub-acute phase. Physical exercise reduced patients' symptoms, but requires high motivation by patients. Despite positive effects in intervention groups on variables considered as negative prognostic factors for long-term disability and sickness absence, interventions had no effect on sick-listing.", "To determine the relative effect of instrument-delivered thrust cervical manipulations in comparison with traditional manual-delivered thrust cervical manipulations in the treatment of cervical spine dysfunction.\n Prospective, randomized, comparative clinical trial.\n Outpatient chiropractic clinic, Technikon Natal, South Africa.\n Thirty patients diagnosed with neck pain and restricted cervical spine range of motion without complicating pathosis for at least 1 month were included in the study.\n The patients were randomized into 2 groups. Those in one group received mechanical force, manually assisted (MFMA) manipulation to the cervical spine, delivered by means of a hand-held instrument (Activator II Adjusting Instrument). Those in the other group received specific contact high-velocity, low-amplitude (HVLA) manipulation consisting of standard Diversified rotary/lateral break techniques to the cervical spine. Each group received only the specific therapeutic intervention, no other treatment modalities or interventions (including medication) being used, until asymptomatic status was achieved or a maximum of 8 treatments had been received. Main Outcome Measures: Both treatment groups were assessed through use of subjective (Numerical Pain Rating Scale 101, McGill Short-Form Pain Questionnaire, and Neck Disability Index) and objective (goniometer cervical range of motion) measurement parameters at specific intervals during the treatment period and at 1-month follow-up. The data were assessed through use of 2-tailed nonparametric paired and unpaired analysis, descriptive statistics, and power analysis of the data.\n The results indicate that both treatment methods had a positive effect on the subjective and objective clinical outcome measures, no significant difference being observed between the 2 groups (P < .025). The subjective data from all 3 questionnaires showed statistically significant changes from initial to final consultations as well as from initial consultation to 1-month follow-up (P < .025). The objective range of motion measures showed statistically significant changes in the MFMA group for left and right rotation and left and right lateral flexion from initial consultation to final consultations and for right rotation and right lateral flexion from initial consultation to 1-month follow-up. The HVLA group showed only the change in left rotation from initial to final consultations and from initial consultation to 1-month follow-up to be statistically significant.\n The results of this clinical trial indicate that both instrumental (MFMA) manipulation and manual (HVLA) manipulation have beneficial effects associated with reducing pain and disability and improving cervical range of motion in this patient population. A randomized, controlled clinical trial in a similar patient base with a larger sample size is necessary to verify the clinical relevance of these findings." ]	SMT is no more effective in participants with acute low-back pain than inert interventions, sham SMT, or when added to another intervention. SMT also appears to be no better than other recommended therapies. Our evaluation is limited by the small number of studies per comparison, outcome, and time interval. Therefore, future research is likely to have an important impact on these estimates. The decision to refer patients for SMT should be based upon costs, preferences of the patients and providers, and relative safety of SMT compared to other treatment options. Future RCTs should examine specific subgroups and include an economic evaluation.
CD006503	[ "14711910", "9163613" ]	[ "Efficacy and safety of low-dose aspirin in polycythemia vera.", "Low-dose aspirin in polycythaemia vera: a pilot study. Gruppo Italiano Studio Policitemia (GISP)." ]	[ "The use of aspirin for the prevention of thrombotic complications in polycythemia vera is controversial.\n We enrolled 518 patients with polycythemia vera, no clear indication for aspirin treatment, and no contraindication to such treatment in a double-blind, placebo-controlled, randomized trial to assess the safety and efficacy of prophylaxis with low-dose aspirin (100 mg daily). The two primary end points were the cumulative rate of nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes and the cumulative rate of nonfatal myocardial infarction, nonfatal stroke, pulmonary embolism, major venous thrombosis, or death from cardiovascular causes. The mean duration of follow-up was about three years.\n Treatment with aspirin, as compared with placebo, reduced the risk of the combined end point of nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes (relative risk, 0.41; 95 percent confidence interval, 0.15 to 1.15; P=0.09) and the risk of the combined end point of nonfatal myocardial infarction, nonfatal stroke, pulmonary embolism, major venous thrombosis, or death from cardiovascular causes (relative risk, 0.40; 95 percent confidence interval, 0.18 to 0.91; P=0.03). Overall mortality and cardiovascular mortality were not reduced significantly. The incidence of major bleeding episodes was not significantly increased in the aspirin group (relative risk, 1.62; 95 percent confidence interval, 0.27 to 9.71).\n Low-dose aspirin can safely prevent thrombotic complications in patients with polycythemia vera who have no contraindications to such treatment.\n Copyright 2004 Massachusetts Medical Society", "In this pilot study, aimed at exploring the feasibility of a large-scale trial of low-dose aspirin in polycythaemia vera (PV), 112 PV patients (42 females, 70 males. aged 17-80 years) were selected for not having a clear indication for, or contraindication to, aspirin treatment and randomized to receive oral aspirin (40 mg/d) or placebo. Follow-up duration was 16 +/- 6 months. Measurements of thromboxane A2 production during whole blood clotting demonstrated complete inhibition of platelet cyclooxygenase activity in patients receiving aspirin. Aspirin administration was not associated with any bleeding complication. Within the limitations of the small sample size, this study indicates that a biochemically effective regimen of antiplatelet therapy is well tolerated in patients with polycythaemia vera and that a large-scale placebo-controlled trial is feasible." ]	For patients with polycythaemia vera who have no clear indication or contraindication to aspirin therapy, available evidence suggests that the use of low-dose aspirin, when compared with no treatment, is associated with a statistically non-significant reduction in the risk of fatal thrombotic events and all-cause mortality, without an increased risk of major bleeding.
CD008195	[ "16970163", "16418103", "11313839" ]	[ "[Interventional effect of behaviour psychotherapy on patients with premature ejaculation].", "Effects of a new functional-sexological treatment for premature ejaculation.", "Assessment of as needed use of pharmacotherapy and the pause-squeeze technique in premature ejaculation." ]	[ "To investigate the interventional effect of comprehensive behaviour psychotherapy on the ejaculatory latency of premature ejaculation (PE) patients, sexual satisfaction of sexual partners, as well as its influence on the results of clinical treatment.\n Ninety PE patients were randomly divided into a psychological intervention group (n = 45) and a control group (n = 45). Both groups were given medicine therapy, and the former also received comprehensive behaviour psychotherapy for 6 weeks. All the patients were assessed with the Chinese index of sexual function for PE and ejaculatory latency in the vagina, and the clinical efficacy was compared between the two groups.\n Before treatment, the ejaculatory latency in the vagina was (0.69 +/- 0.25) min and (0.71 +/- 0.19) min respectively in the intervention and the control groups, as compared with (5.87 +/- 0.59) min and (4.76 +/- 0.54) min before treatment, with significant difference (P < 0.01). In the intervention group, the scores in the control of ejaculatory reflex, the sexual satisfaction of the patients and their sexual partners and anxiety or depress in sexual activity in CIPE were higher than in the control group, with significant difference between the two groups (t = 2.12, 2.31, 2.01, 2.24, P < 0.05). The difference in the SAS score after therapy was of significance (P < 0.01). A month after treatment, the effectivity rates of the two groups were 82.9% and 30% respectively, and the difference was significant (P < .01).\n Comprehensive behaviour psychotherapy obviously adds to the clinical efficacy of drugs in the treatment of PE.", "Premature ejaculation is the most-prevalent sexual problem in men. Various treatments have been developed to increase control over the moment of ejaculation, with two of the most frequent techniques used in behavior therapy being the squeeze method developed by Masters and Johnson (1970) and the \"stop-and-start\" technique described by Semans (1956). These treatments are effective and improve matters in most cases. However, couples can be averse to using them, with some women reluctant to squeeze their partner's penis and some couples unwilling to interrupt sexual interaction once initiated. Under a new functional-sexological treatment intended to improve control over the moment of ejaculation, men learn how to control their arousal without having to interrupt sexual activity. In this study, we compared three groups of couples in which the man suffered from premature ejaculation. One followed the new functional-sexological treatment, another followed a behavioral treatment--including the squeeze and stop-and-start techniques--and a control group was placed on a waiting list. We used several questionnaires to assess the effects of the various treatments. Moreover, subjects provided an objective measure of duration of intercourse from penetration to ejaculation. These measures were taken pre- and posttreatment and at three-month follow-up. We ran analyses of variance to assess the effects of the treatments. Results indicate that the new treatment is very effective. We observed significant improvements in duration of intercourse, sexual satisfaction, and sexual functioning. The subjects in the behavioral treatment group obtained similar results. Furthermore, subjects from both groups were satisfied with their respective treatment.", "The objective was to compare the efficacy and safety of the as needed use of clomipramine, sertraline, paroxetine, sildenafil and the pause-squeeze technique in treatment of primary premature ejaculation. A prospective double blind randomized crossover study involving 31 patients was performed. Treatment phases comprised five 4-week consecutive treatment periods, each separated by a two-week washout period. Patients were randomly assigned to receive each of the 4 drugs and use pause-squeeze on an as needed basis. Drugs were administered 3 to 5 hours before anticipated coitus. Anxiety score and ejaculation latency time were measured before treatment, after each treatment, and during washout periods. Sexual satisfaction score was measured after each treatment. The median ejaculation latency time was significantly increased from the pretreatment median of 1 minute to 4 minutes, 3 minutes, 4 minutes, 15 minutes and 3 minutes during treatment with clomipramine, sertraline, paroxetine, sildenafil and pause-squeeze technique, respectively (all P 0.0001). Sildenafil was superior to other modalities in terms of ejaculation latency and satisfaction (P = 0.0001). The three antidepressants were comparable to each other in terms of efficacy (P > 0.05). Paroxetine was superior to the pause-squeeze technique in terms of efficacy (P < 0.05). In conclusion, sildenafil appears to be superior to other modalities and a valid alternative in treatment of premature ejaculation. The 3 antidepressants were equivalent to each other in terms of efficacy and safety. Paroxetine was superior to pause-squeeze technique in terms of efficacy." ]	Overall, there is weak and inconsistent evidence regarding the effectiveness of psychological interventions for the treatment of premature ejaculation. Three of the four included randomised controlled studies of psychotherapy for PE reported our primary outcome (Improvement in IELT), and the majority have a small sample size. The early success reports (97.8%) of Masters and Johnson could not be replicated. One study found a significant improvement from baseline in the duration of intercourse, sexual satisfaction and sexual function with a new functional-sexological treatment and behavior therapy compared to waiting list. One study showed that the combination of chlorpromazine and BT was superior to chlorpromazine alone. Randomised trials with larger group samples are still needed to further confirm or deny the current available evidence for psychological interventions for treating PE.
CD008205	[ "2029465", "3859744", "10407809", "7796018", "8665186", "1653063", "2957943", "7954233", "16505413", "6576846", "19052125", "3460683", "9345068", "9484732", "2970744", "2200559", "15636619", "11896097", "8852910", "8792690" ]	[ "Delta virus and childhood leukemia.", "Acute and chronic hepatitis in childhood leukemia: a multicentric study from the Italian Pediatric Cooperative Group for Therapy of Acute Leukemia (AIL-AIEOP).", "[Chronic liver disease after treatment of malignancies in children].", "Improved outcome for children with hepatoblastoma.", "Adjuvant oral chemotherapy to prevent recurrence after curative resection for hepatocellular carcinoma.", "Hepatitis C virus infection and chronic liver disease in children with leukemia in long-term remission.", "Intrahepatic or systemic infusion of fluorodeoxyuridine in patients with liver metastases from colorectal carcinoma. A randomized trial.", "Treatment of liver metastases from colorectal cancer with hepatic artery occlusion, intraportal 5-fluorouracil infusion, and oral allopurinol. A randomized clinical trial.", "Hepatic arterial infusion versus systemic therapy for hepatic metastases from colorectal cancer: a randomized trial of efficacy, quality of life, and molecular markers (CALGB 9481).", "Chronic liver disease in children with leukemia in long-term remission.", "Prolonged therapy of advanced chronic hepatitis C with low-dose peginterferon.", "Adverse prognostic influence of hepatitis B virus infection in acute lymphoblastic leukemia.", "Morbidity and mortality due to liver disease in children undergoing allogeneic bone marrow transplantation: a 10-year prospective study.", "Postoperative adjuvant chemotherapy after curative resection of hepatocellular carcinoma: a randomized controlled trial.", "[Prophylactic efficacy of reaferon in viral hepatitis A and acute respiratory infections in children].", "Prospective randomized controlled trial of hepatic arterial embolization or infusion chemotherapy with 5-fluorouracil and degradable starch microspheres for colorectal liver metastases.", "Applicability, tolerability and efficacy of preemptive antiviral therapy in hepatitis C-infected patients undergoing liver transplantation.", "Combined-modality treatment for resectable metastatic colorectal carcinoma to the liver: surgical resection of hepatic metastases in combination with continuous infusion of chemotherapy--an intergroup study.", "Prolonged and high dose recombinant interferon alpha-2b alone or after prednisone priming accelerates termination of active viral replication in children with chronic hepatitis B infection.", "Comparative efficacy of a high or low dose of interferon alpha 2b in chronic hepatitis C: a randomized controlled trial." ]	[ "We studied 145 children with acute lymphocytic leukemia (ALL) in remission who had been off chemotherapy for at least 2 years, to assess the prevalence of hepatitis delta virus (HDV) infection, and to determine whether HDV infection was associated with more severe chronic liver disease. The prevalence of chronic HBV infection was 41.5% (60/145). The prevalence of HDV infection among these patients with chronic HBV infection was 50% (30/60). Eighty-five patients were HBsAg-negative. There was evidence that HDV-infected children had more severe chronic liver disease than did HBsAg-positive, anti-HDV-negative patients: (1) their serum ALT levels were significantly more likely to be elevated at long-term follow-up (27/30 vs. 10/26, p = 0.0001); (2) their mean ALT levels were significantly higher 3 years after the cessation of chemotherapy (128 vs. 84 IU/L, p = 0.001); and (3) they were more likely to have either chronic acute hepatitis or cirrhosis when liver biopsy was done (18/23 vs. 6/18, p = 0.0038). Children who were HBsAg-negative had the lowest alanine aminotransferase (ALT) levels and were least likely to have chronic active hepatitis or cirrhosis (3/31). We conclude that infection with HDV in children with ALL is associated with serious chronic liver disease. In long-term survivors, HDV infection is a major cause of morbidity and an adverse prognostic factor in terms of leukemia-free survival.", "The incidence of acute and chronic liver damage and its relation to hepatitis B virus (HBV) infection was evaluated in 164 consecutive children with acute leukemia seen in ten Italian hemato-pediatric units. Thirteen out of 164 children (7.9%) had acute hepatitis (AH) during treatment, while 8/90 (8.8%) showed an acute exacerbation of liver damage within 6 months after therapy withdrawal. Seven of the 13 children with AH while on therapy were HBsAg positive. In 12/13 cases, liver disease progressed to chronicity. Five of eight children who developed AH after completion of treatment were HBsAg positive. Eighty-nine patients (54.2%) developed biochemical evidence of chronic hepatitis during therapy; 48/89 were followed after cessation of treatment and 33 of them showed persisting evidence of liver cell necrosis. Thirty-three out of 133 children (24.8%) tested for serum HBsAg were found positive: 26 (78.7%) of them developed chronic hepatitis. Sixty-four out of 133 patients were evaluated after cessation of treatment: Chronic hepatitis persisted in 16/22 HBsAg-positive (72.7%) and in 17/42 HBsAg-negative (40.4%) children during follow-up. The outcome of these liver diseases after treatment withdrawal did not differ significantly in relation to HBV serology, suggesting that viral rather than toxic agents were responsible for liver damage also in most HBsAg-negative patients. The high incidence of chronic HBV infection in children with leukemia found in this multicentric study could suggest a need for active immunization with HBV vaccine, but the efficacy of such approach in this clinical setting is still to be validated.", "Chemotherapy, which has greatly improved the prognosis of children with malignant diseases, is potentially hepatotoxic. Furthermore, there is a risk for viral hepatitis acquired by blood products. In this study we looked for hepatotoxicity and for chronic viral hepatitis during and after chemotherapy in 50 unselected children with malignant diseases. 29 children had been treated for leukemia or lymphoma, 19 for solid tumors, 2 for histiocytosis. All patients had been treated before 1991 and had received blood products not screened for hepatitis C-antibodies. In 18 girls and 32 boys aged 12.3 years (range 6.7-24.5 years) hepatitis B- and hepatitis C-serology and liver function tests were measured during a routine check-up 3.6 years (range 0.5-11.8 years) after the last chemotherapy. Liver function tests during chemotherapy were reviewed retrospectively. During chemotherapy 86% of children showed increased ALT and AST levels, 10% had levels above 500 U/l. At follow up 16 children (32%) had pathological liver function tests, especially slightly increased AST and ALT, 13 of these 16 patients had chronic hepatitis C. In contrast only 2 of 34 patients with normal liver function tests had a viral hepatitis (p = 0.001). Patients with elevation of AST and ALT above 100 U/l during chemotherapy had significantly more often a viral hepatitis than those with normal or slightly elevated aminotransferases. Our study shows that hepatocellular damage is a frequent complication following chemotherapy. However this progresses to chronic liver disease very rarely unless the patient acquired a viral hepatitis. The prevalence of chronic hepatitis C was very high in our patients. As screening of blood products for hepatitis C-antibodies is routinely performed since 1991 this problem is likely to have decreased.", "Between 1981 and 1993, 41 children were treated for hepatoblastoma. Clinical, radiological and pathological data were reviewed retrospectively, focusing on surgical aspects of treatment and outcome. Fourteen children underwent primary resection of the hepatic tumour. One infant with severe congenital anomalies received only palliative treatment. Of 26 with irresectable disease, pulsed cytotoxic chemotherapy (cisplatin and doxorubicin) enabled subsequent surgical excision in 22 and one child with persistent extensive intrahepatic disease was successfully treated by liver transplantation. Thus, with a policy of selective preoperative chemotherapy, 90 per cent of hepatoblastomas were resectable. There were no perioperative deaths from haemorrhage but one child died from an intraoperative tumour embolus. A total of 28 survivors, 27 of whom are disease-free, were followed for a median of 5 years. The cumulative probability of survival in patients treated with intent to cure was 67 per cent. Analysis of survival data suggested a favourable outcome for those with a pure fetal histological tumour subtype. These results demonstrate significant progress in the treatment of hepatoblastoma.", "Adjuvant oral chemotherapy was studied in 67 patients with stage II hepatocellular carcinoma who underwent curative resection between May 1988 and December 1990. Patients were stratified into two groups according to preoperative liver dysfunction: 55 had stage I disease (mild dysfunction) and 12 had stage II (moderate dysfunction). A randomized controlled study of postoperative oral administration of 1-hexylcarbamoyl-5-fluorouracil (HCFU) was conducted in each group. From October 1994 HCFU administration was suspended because of side-effects in nine patients with stage I liver dysfunction and in three with stage II dysfunction who had received the drug for more than 4 weeks. Cumulative survival and recurrence-free survival rates of patients with stage I disease in the treatment group were higher (P = 0.08 and P = 0.04 respectively) than those in the control group. However, in patients with stage II disease no significant difference was observed (P = 0.77 and P = 1.0 respectively). This study suggests that the potential benefits of HCFU on tumour recurrence should be weighed against the risk of adverse reactions in patients with mild liver dysfunction.", "Antibody to the recently identified hepatitis C virus (HCV) was investigated in sera of 50 leukemic children who had chronic liver disease (CLD), observed for 1 to 12.6 years after therapy withdrawal. All patients were tested for anti-HCV at regular intervals: Ortho-enzyme-linked immunosorbent assay (ELISA) test was performed in all cases. Reactive sera were also tested by recombinant immunoblotting assay to define the specificity of the results obtained by ELISA. Twelve cases (24%) were persistently positive (group A), 11 (22%) were transiently anti-HCV+ positive (group B), and 27 (54%) were negative. Mean SGPT peak during follow-up was significantly higher in group A (P = .014, A v B and P less than .00001, A v C). SGPT normalized off-therapy in 1 of 12 cases (group A), 10 of 11 (group B), and 19 of 27 (group C) (P = .0004, A v B and P = .012, A v C). Accordingly, liver histology, available in 37 patients, showed signs of chronic hepatitis in all patients in group A while most patients in group B and C had less severe liver lesions. These results indicate that HCV plays a significant role in the etiology of chronic hepatitis in leukemic patients and that persistent anti-HCV activity correlates with a more severe CLD, which could jeopardize the final prognosis of children cured of leukemia.", "Objective: To compare the efficacy of direct hepatic arterial chemotherapy with systemic chemotherapy in patients with liver metastases from colorectal carcinoma. Design: Randomized trial with crossover allowed from systemic to intrahepatic therapy if tumor progression occurred on systemic therapy. Setting: Academic medical center, referral-based clinic. Patients: One hundred sixty-two patients with hepatic metastases from colorectal carcinoma agreed to be randomly assigned to treatment groups. At laparotomy, 63 were excluded from the study: 25 had hepatic resection; 33, extrahepatic disease; 1, infection; and 4, no tumor. Intervention: Fourteen-day continuous infusion of fluorodeoxyuridine each month using an infusaid pump (0.3 and 0.15 mg/kg body weight X d in the intrahepatic and systemic arms, respectively). Main Results: Intrahepatic therapy produced a significantly higher complete and partial response rate, 50%, compared with 20% for systemic therapy (p = 0.001). After tumor progression, 60% of the systemic patients crossed over to intrahepatic therapy; 25% then had a partial response, and 33% a minor response or stabilization of disease on intrahepatic therapy. Toxicity included ulcer disease (17%) and biliary sclerosis (8%) in patients receiving intrahepatic therapy and diarrhea (70%) in patients receiving systemic therapy. Extrahepatic disease occurred in 56% and 37% of the patients in the intrahepatic and systemic groups, respectively (p = 0.092). The median survivals were 17 and 12 months, for the intrahepatic and systemic groups, respectively. Conclusion: When compared with systemic therapy, hepatic arterial chemotherapy significantly increases response rate for hepatic metastases from colorectal carcinoma and appears to be a more effective treatment.", "Regional therapy for colorectal liver metastases aimed at prolonging survival has not been tested fully in a randomized trial with untreated control subjects. This study explored the efficacy of temporary hepatic artery occlusion followed by intraportal infusion of 5-fluorouracil (5-FU) and oral allopurinol as biochemical modulators in prolonging the survival of patients with nonresectable liver metastases and no extrahepatic cancer.\n Eighty-four patients were considered for randomization, of whom 24 were excluded at laparotomy because of extrahepatic cancer (n = 17) or resectable lesions (n = 5). In two patients, no cancer was identified in the liver. Thirty-two patients were allocated to receive treatment, and 28 were allocated to receive no regional or systemic treatment. Six patients were excluded after randomization because of major protocol violations.\n The median survival time for patients was 17 months (range, 0-66), and for control subjects, the median was 8 months (range, 0-31). Log rank analysis demonstrated a significant survival benefit for treatment versus no treatment (P = 0.0039). (In two patients, early death was due to toxicity from the wrong dose of 5-FU and the wrong route of administration, respectively; the mean and median survival were reduced by 1 month).\n This study identified a treatment modality that prolongs survival in patients with nonresectable liver metastases and no extrahepatic metastases from colorectal cancer, suggesting that control subjects receiving no therapy may not be necessary in future randomized trials.", "Hepatic metastases derive most of their blood supply from the hepatic artery; therefore, for patients with hepatic metastases from colorectal cancer, hepatic arterial infusion (HAI) of chemotherapy may improve outcome.\n In a multi-institutional trial, 135 patients were randomly assigned to receive HAI versus systemic bolus fluorouracil and leucovorin. The primary end point was survival; secondary end points were response, recurrence, toxicity, quality of life, cost, and the influence of molecular markers.\n Overall survival was significantly longer for HAI versus systemic treatment (median, 24.4 v 20 months; P = .0034), as were response rates (47% and 24%; P = .012) and time to hepatic progression (THP; 9.8 v 7.3 months; P = .034). Time to extrahepatic progression (7.7 v 14.8 months; P = .029) was significantly shorter in the HAI group. Quality-of-life measurements showed improved physical functioning in the HAI group at the 3- and 6-month follow-up assessments. Toxicity included grade > or = 3 neutropenia (2% and 45%; P < .01), stomatitis (0% and 24%; P < .01), and bilirubin elevation (18.6% and 0; P < .01) in the HAI and systemic treatment groups, respectively. A greater proportion of men versus women receiving HAI experienced biliary toxicity (37% and 15%, respectively; P = .05). For HAI patients with thymidylate synthase levels in tumor less than or > or = 4, the median survival was 24 and 14 months, respectively (P = .17).\n HAI therapy increased overall survival, response rate, THP, and was associated with better physical functioning compared with systemic therapy. Additional studies need to address the overall benefit and cost of new chemotherapy agents versus HAI alone or the combination of HAI with new agents.", "Liver disease during chemotherapy and after its completion was studied in 103 leukemic children in long-term remission. Seventy developed chronic liver disease during therapy; 22 out of 56 with adequate follow-up showed persisting abnormality or deterioration of liver function after stopping therapy. In 38 studied prospectively, biopsies were obtained at treatment withdrawal. Five showed chronic lobular, 17 chronic persistent, 9 chronic active hepatitis whereas 7 had minimal changes. These children had transiently detectable serum hepatitis-B virus (HBV) markers during (44.4%), at completion of (7.8%) and subsequent to (48.3%) chemotherapy. Serum HBV markers correlated significantly with both severity of histologic changes (P less than 0.05) and persistent biochemical abnormalities for over 6 months after treatment suspension (P less than 0.001). No direct relationship was found between drug administration and liver damage. The data from the study suggest that in leukemic children viral infections contribute to chronic liver damage, which can jeopardize the long-term prognosis of acute leukemia.", "In patients with chronic hepatitis C who do not have a response to antiviral treatment, the disease may progress to cirrhosis, liver failure, hepatocellular carcinoma, and death. Whether long-term antiviral therapy can prevent progressive liver disease in such patients remains uncertain.\n We conducted a randomized, controlled trial of peginterferon alfa-2a at a dosage of 90 microg per week for 3.5 years, as compared with no treatment, in 1050 patients with chronic hepatitis C and advanced fibrosis who had not had a response to previous therapy with peginterferon and ribavirin. The patients, who were stratified according to stage of fibrosis (622 with noncirrhotic fibrosis and 428 with cirrhosis), were seen at 3-month intervals and underwent liver biopsy at 1.5 and 3.5 years after randomization. The primary end point was progression of liver disease, as indicated by death, hepatocellular carcinoma, hepatic decompensation, or, for those with bridging fibrosis at baseline, an increase in the Ishak fibrosis score of 2 or more points.\n We randomly assigned the patients to receive peginterferon (517 patients) or no therapy (533 patients) for 3.5 years. The level of serum aminotransferases, the level of serum hepatitis C virus RNA, and histologic necroinflammatory scores all decreased significantly (P<0.001) with treatment, but there was no significant difference between the groups in the rate of any primary outcome (34.1% in the treatment group and 33.8% in the control group; hazard ratio, 1.01; 95% confidence interval, 0.81 to 1.27; P=0.90). The percentage of patients with at least one serious adverse event was 38.6% in the treatment group and 31.8% in the control group (P=0.07).\n Long-term therapy with peginterferon did not reduce the rate of disease progression in patients with chronic hepatitis C and advanced fibrosis, with or without cirrhosis, who had not had a response to initial treatment with peginterferon and ribavirin. (ClinicalTrials.gov number, NCT00006164.)\n 2008 Massachusetts Medical Society", "Liver function test abnormalities were examined in a retrospective survey in a population of 90 children with acute lymphoblastic leukemia (ALL) treated in a similar fashion with therapy, using primarily methotrexate, mercaptopurine, vincristine, and prednisone. A twofold or greater elevation of serum glutamyl pyruvic transaminase (SGPT) was found in 80% of the patients during induction therapy, in 63% of the patients during maintenance therapy, and 31% of the patients who completed therapy. Circulating hepatitis B virus surface antigen (HBsAg) was noted in 26% of patients with liver function test abnormalities during maintenance therapy, and 45% of patients with liver function test abnormalities after the completion of therapy. Hepatitis B virus infection was therefore, the most important single cause of abnormal liver function during remission in our patient population. Though others have asserted that hepatitis B virus infection is relatively benign in immunosuppressed individuals, in our population, this agent often caused severe pathological and clinical sequelae. This may be related to the high frequency (50%) of co-infection with the delta agent in our HBsAg-positive patients. Furthermore, hepatitis B virus surface antigenemia conferred an adverse prognostic influence for these children in terms of their leukemia-free survival.", "We have conducted a long-term prospective study of children undergoing bone marrow transplantation (BMT) to assess morbidity and mortality for liver disease. One hundred eleven consecutive children were enrolled between June 1985 and June 1995 and were followed-up for a median of 5.5 years after BMT. Before transplant 48/111 children (43%) had abnormal alanine aminotransferase (ALT), none were HBsAg+ and 4/111 were anti-HCV+. After BMT 4/111 patients (3. 6%) died of liver failure. No relationship was found between pretransplant hepatitis B (HBV) or C (HCV) infection or elevated transaminases and development of severe liver damage. Eighty-two out of one hundred and eleven patients (74%) had abnormalities of ALT after BMT, transient (n = 54) or persistent (n = 28). None developed clinical signs or symptoms of end stage liver disease or of cirrhosis during follow-up. No significant difference in prevalence of liver disease, was found between children with normal or abnormal ALT at BMT (relative risk [RR] = 1.04). HCV infection could be implicated in the etiology of chronic liver disease in 14/28 patients; 2 other patients were found infected by HBV alone (1 case) or combined with HCV (1 case). In the remaining 12 the etiology of chronic liver disease could not be defined. Posttransplant hepatitis B occurred in 4/111 children (3.6%), including a recipient from a donor who had been previously vaccinated against HBV, while no patient who had been vaccinated developed hepatitis B. The rate of posttransplant seroconversion to anti-HCV was 15%.", "To study the effect of adjuvant chemotherapy after curative hepatic resection in patients with hepatocellular carcinoma.\n A randomized controlled trial.\n A tertiary referral center.\n During a 54-month period, 142 patients with hepatocellular carcinoma underwent hepatic resection at 1 institution. Sixty-six patients who survived the operation and had no demonstrable evidence of residual disease on ultrasonographic examination and hepatic angiographic testing at 1 month after surgery agreed to participate in the study. The median follow-up time was 28.3 months.\n Thirty patients received a combination of intravenous epirubicin hydrochloride (8 doses of 40 mg/m2 each at 6-week intervals) and transarterial chemotherapy using an emulsion of iodized oil and cisplatin (3 courses with a maximum dose of 20 mL each at 2-month intervals). Thirty-six patients had no adjuvant treatment.\n Recurrence rate and disease-free survival.\n A total of 138 courses of intravenous epirubicin was given to the 30 patients. Sixty-one courses of transarterial chemotherapy were given to only 29 of the 30 patients assigned to the treatment group, because the hepatic artery in 1 patient was thrombosed. Six patients (20%) had chemotherapy-related complications with no mortality. Twenty-three of 30 patients in the treatment group and 17 of 36 patients in the control group had recurrences (P=.01). Patients who received adjuvant chemotherapy had a higher incidence of extrahepatic metastases (11 patients vs 5 patients; P=.03). The respective disease-free survival rates at 1, 2, and 3 years were 50%,36%, and 18% for the treatment group and 69%, 53%, and 48% for the control group (P=.04).\n In a group of patients who underwent curative resection of hepatocellular carcinoma, postoperative adjuvant chemotherapy using the present regimen was associated with more frequent extrahepatic recurrences and a worse outcome.", "Reaferon, the analog of human alpha 2-interferon obtained by gene engineering techniques, was studied with a view to its use for the prevention of hepatitis A. The study involved children of preschool age in Tashkent. In a strictly controlled trial children aged 2-6 years received the preparation orally in a dose of 1 X 10(6) I. U. or the diluent alone used as placebo. The preparation was administered to 1,100 children and the placebo to 1,078 children. The preparation and placebo were administered twice a week for two months. On the whole, during that period hepatitis A morbidity in both test and control groups of children was the same (5.1% and 4.9% respectively), but among children of nursery age receiving Reaferon the incidence of hepatitis A and acute respiratory viral infections was lower than among those receiving the placebo, though this difference was statistically significant only for cases of acute respiratory infections.", "Survival benefit from hepatic artery embolization (HAE) or hepatic arterial infusion chemotherapy (HAI) in patients with unresectable colorectal liver metastases has not previously been assessed in a randomized controlled trial. Sixty-one patients were randomized, 20 to receive no treatment, 22 to receive HAE, and 19 to receive HAI with 5-fluorouracil and degradable starch microspheres. Both treatments were acceptable to the patients in terms of low treatment morbidity rate. Median survival from diagnosis of metastases was 9.6 months for controls, 8.7 months for the HAE group and 13.0 months in the HAI group. There was no apparent survival benefit for the HAE group. The increased survival in the HAI group was observed in all the subgroups analysed but failed to reach statistical significance. The greatest observed benefit was achieved in the subgroup with less than 50 per cent hepatic replacement with tumour at presentation (median survival from diagnosis 10.0 months for controls, 10.2 months for HAE and 23.6 months for HAI); 36 per cent of patients developed extrahepatic disease recurrence. No significant benefit has been shown from either HAE or HAI, but a more carefully selected group of patients with only low volume hepatic disease may benefit from HAI therapy.", "Preliminary studies suggest preemptive anti-HCV therapy in liver transplant recipients may enhance the rates of viral clearance, but the applicability and tolerability of preemptive therapy has not been evaluated in a contemporary cohort. In this randomized study, the safety and tolerability of preemptive standard (IFN) or pegylated (peg-IFN) interferon alfa-2b (3 MU thrice weekly or 1.5 microg/kg weekly), or IFN/peg-IFN plus ribavirin (600 mg increased to 1.0-1.2 g daily) was initiated 2-6 weeks post-transplantation and continued for a total of 48 weeks. Only 51 (41%) of 124 transplant recipients were eligible for preemptive treatment; eligible patients had lower model for end-stage liver disease (MELD) and Childs-Pugh scores pre-transplantation and were more frequently live donor transplant recipients than ineligible patients. Dose reductions and discontinuations were required in 85% and 37% of patients, respectively, and 27% experienced serious adverse events. Growth factor (GF) use (erythropoietin and GCSF) in the latter half of the study did not significantly affect the frequency of dose reductions. Only 15% of patients were able to achieve full-dose treatment during treatment. End-of-treatment and sustained virological responses were 13.6% and 9.1%, respectively, with most responders in the combination therapy group. We conclude that preemptive antiviral therapy is applicable to only a portion of transplant recipients, with 'sicker' patients less likely to be managed by this approach. Living donor liver transplant recipients were more frequently eligible for treatment than deceased donor recipients. Virological response rates are low, likely related to the poor tolerability of therapy and the lack of achievement of target drug doses. Future studies should focus on alternative dosing schedules with more aggressive use of adjuvant therapies, including GFs.", "Despite technical improvements that have minimized the morbidity and mortality of hepatic surgery, the long-term outcome of resection of hepatic metastases of colorectal cancer remains poor, with the majority of patients experiencing treatment failure in the liver. Because arterial chemotherapy regimens targeted to the liver have demonstrated high response rates, an intergroup trial of adjuvant therapy for patients undergoing hepatic resection of liver metastases from colorectal cancer was initiated.\n Patients with one to three potentially resectable metastases were randomized preoperatively to receive no further therapy (control arm, 56 patients) or postoperative hepatic arterial floxuridine combined with intravenous continuous-infusion fluorouracil (chemotherapy arm, 53 patients). After exclusion of patients identified as ineligible for the planned treatment at the time of surgery, there were 45 control patients and 30 on the chemotherapy arm. The study was powered to evaluate improvement in time to recurrence and hepatic disease-free survival, not overall survival.\n The 4-year recurrence-free rate was 25% for the control arm and 46% for the chemotherapy group (P =.04). The 4-year liver recurrence-free rate was 43% in the control group and 67% in the chemotherapy group (P =.03). The median survival of the 75 assessable patients was 49 months for the control arm and 63.7 months for the chemotherapy arm (P =.60). The median survival of all 109 patients was 47 months for the control arm compared with 34 months for the chemotherapy arm (P =.19)\n These data demonstrate that adjuvant intra-arterial and intravenous chemotherapy was beneficial in prolonging time to recurrence and pre-venting hepatic recurrence after hepatic resection of colorectal cancer.", "There is no generally accepted treatment for chronic hepatitis B (HB) infection in children.\n To evaluate the efficacy of a prolonged course of high dose interferon alone or after prednisone priming in children with chronic HB infection.\n The outcome of 31 children with HB e antigen (HBeAg)-positive chronic hepatitis who randomly received either no treatment (n = 9) or 10 million units of interferon alpha-2b/m2, alone (n = 13) or after prednisone priming (n = 9), three times weekly for 1 year was studied.\n One patient withdrew from treatment. By the end of the first year treatment induced a loss of HB virus DNA and HBeAg from serum in 10 of 21 patients (48%), and a loss of HB surface antigen (HBsAg) in 4 (19%). Alanine aminotransferase values became normal in one patient (4.8%). Response rates in the two groups of treated patients were similar. In controls only one patient lost HBeAg and HBV DNA (11%; P = 0.05), and none lost HBsAg or showed alanine aminotransferase normalization (P = 0.21 and 0.70, respectively). After a posttreatment 2-year follow-up there were still no differences in the response rates of the two treatments; of the 21 pooled treated patients, 61% lost HBeAg and DNA and 67% normalized alanine aminotransferase (vs. 33 and 44% of controls, respectively; P = 0.32 and 0.40). Reversion to HBeAg and HBV DNA negativity in treated patients occurred significantly earlier (P = 0.02 and 0.006, respectively) than in controls. No further patient lost HBsAg, but one reacquired HBsAg. Treated patients had posttreatment histologic scores better than controls (P = 0.03).\n Our medium term follow-up results indicate that a prolonged course of high dose interferon in children with chronic HB infection, regardless of prednisone priming, poorly affects response rates but significantly speeds termination of active viral replication.", "Our objective was to determine the relative efficacy of 6 months of treatment with 10 MU versus 3 MU of interferon-alpha 2b (IFN-alpha), three times weekly, in chronic hepatitis C (HCV) in a randomized trial.\n Ten megaunits of IFN-alpha were given to 28 patients (group A), and 3 MU were given to 30 patients (group B). After treatment ended, follow-up was continued for 26 wk.\n Overall, the sustained response rate was higher in group A than in group B (16/26 or 61.5% vs. 12/28 or 42.9%, p = 0.17), but the difference did not reach statistical significance. However, it was higher in group A than in group B among patients with minimal or mild chronic hepatitis (15/20 or 75% vs. 9/24 or 37.5%, p = 0.013) and among those with mild or moderate fibrosis (15/17 or 88.2% vs. 11/19 or 57.9%, p = 0.042). IFN-alpha treatment significantly reduced histological activity index (HAI) scoring and all its parameters, except fibrosis, but the decrease was similar in the two groups. Sex, age, stage, and HCV genotype were statistically significant predictors of sustained response in univariate analysis. However, multiple logistic regression analysis revealed that advanced histological stage (severe fibrosis and cirrhosis) was the only significant prognostic factor of poor sustained response (RR = 31.0, 95% CI 2-460, p = 0.01), whereas the presence of genotype 1 had marginal statistical significance (RR = 5.0, 95% CI 0.9-28, p = 0.07).\n 1) A larger dose of IFN-alpha does not improve the sustained response rate; however, it may be of benefit in early stages of chronic hepatitis C. 2) Pretreatment, histological stage, and possibly HCV genotype appear to be the main prognostic factors of sustained response." ]	The prevalence of hepatic late adverse effects ranged from 7.9% to 52.8% when selecting studies with an adequate outcome definition. It has not been established which childhood cancer treatments result in hepatic late adverse effects. There is a suggestion that chronic viral hepatitis increases the risk of hepatic late adverse effects. More well-designed studies are needed to reliably evaluate the prevalence of, and risk factors for, hepatic late adverse effects after antineoplastic treatment for childhood cancer.
CD004910	[ "15113492", "14760042", "7748631", "11116772", "11939381", "10480824", "15120768", "1483075", "18237352", "12534758", "16899964", "15883143", "17267931", "21041350", "15514186", "16084925", "22032247", "15066200" ]	[ "Exploratory cluster randomised controlled trial of shared care development for long-term mental illness.", "The North Dublin randomized controlled trial of structured diabetes shared care.", "Coordinating and standardizing long-term care: evaluation of the west of Scotland shared-care scheme for hypertension.", "Patient-held shared care records for individuals with mental illness. Randomised controlled evaluation.", "Randomized controlled trial to assess the effectiveness of a primary health care liaison worker in promoting shared care for opiate users.", "Multifaceted shared care intervention for late life depression in residential care: randomised controlled trial.", "Evaluation of a short-term group intervention for informal carers of patients attending a home palliative care service.", "Randomised controlled trial of effects of coordinating care for terminally ill cancer patients.", "Strategies for improving the quality of health care in maternal and child health in low- and middle-income countries: an overview of systematic reviews.", "Effectiveness of collaborative care depression treatment in Veterans' Affairs primary care.", "Randomised controlled trial of a collaborative care model with psychiatric consultation for persistent medically unexplained symptoms in general practice.", "Can collaborative care address the needs of low-income Latinas with comorbid depression and cancer? Results from a randomized pilot study.", "Reducing emotional distress in people caring for patients receiving specialist palliative care. Randomised trial.", "Effectiveness of collaborative care in addressing depression treatment preferences among low-income Latinos.", "Multicenter randomized controlled trial of an outreach nursing support program for recently discharged stroke patients.", "Can a facilitated programme promote effective multidisciplinary audit in secondary care teams? An exploratory trial.", "Implementing collaborative care for depression treatment in primary care: a cluster randomized evaluation of a quality improvement practice redesign.", "An outreach intervention to implement evidence based practice in residential care: a randomized controlled trial [ISRCTN67855475]." ]	[ "Primary care clinicians have a considerable amount of contact with patients suffering from long-term mental illness. The United Kingdom's National Health Service now requires general practices to contribute more systematically to care for this group of patients.\n To determine the effects of Mental Health Link, a facilitation-based quality improvement programme designed to improve communication between the teams and systems of care within general practice. Design of study: Exploratory cluster randomised controlled trial.\n Twenty-three urban general practices and associated community mental health teams.\n Practices were randomised to service development as usual or to the Mental Health Link programme. Questionnaires and an audit of notes assessed 335 patients' satisfaction, unmet need, mental health status, processes of mental and physical care, and general practitioners' satisfaction with services and beliefs about service development. Service use and intervention costs were also measured.\n There were no significant differences in patients' perception of their unmet need, satisfaction or general health. Intervention patients had fewer psychiatric relapses than control patients (mean = 0.39 versus 0.71, respectively, P = 0.02) but there were no differences in documented processes of care. Intervention practitioners were more satisfied and services improved significantly for intervention practices. There was an additional mean direct cost of pound 63 per patient with long-term mental illness for the intervention compared with the control.\n Significant differences were seen in relapse rates and practitioner satisfaction. Improvements in service development did not translate into documented improvements in care. This could be explained by the intervention working via the improvements in informal shared care developed through better link working. This type of facilitated intervention tailored to context has the potential to improve care and interface working.", "A new diabetes shared care service was introduced in North Dublin. It was designed as a randomized controlled trial with a complex intervention comprising education of participating practitioners, the introduction of a community-based diabetes nurse specialist, local agreement on clinical protocols and structured communication across the primary-secondary care interface.\n Our aim was to assess the feasibility and effectiveness of a structured diabetes shared care service in a mixed health care system and to analyse the impact on total patient care.\n A Cluster randomized controlled trial lasting 18 months was carried out in 183 patients with type 2 diabetes from 30 general practices in North Dublin. Biophysical outcomes (HbA1c, blood pressure, body mass index), psychosocial measures (smoking status and Diabetes Clinic Treatment Satisfaction and Diabetes Well-being scores) and process outcomes were collected.\n There were significant improvements in diabetes care delivery and in psychosocial outcomes, but no significant improvements in biomedical outcomes. Process data collection revealed a significant increase in diabetes care-related activity for participating patients with an increase in structured annual reviews and fewer patients defaulting from care. There were also significant improvements in information exchange between primary and secondary care.\n Structured diabetes shared care, in a mixed health care system, can produce significant improvements in diabetes care delivery and in psychosocial outcomes for patients, with improved information exchange across the primary-secondary care interface.", "The long-term management of patients with chronic conditions such as hypertension presents problems for the health services. Shared care addresses these by coordinating care and defining responsibilities.\n This study set out to investigate the feasibility, acceptability and cost effectiveness of shared general practitioner-hospital care for well-controlled hypertensive patients in an urban area by comparing three matched groups of patients.\n A total of 554 outpatient clinic attenders, considered suitable for shared care by their consultant, were randomly allocated to shared care or follow up in the outpatient clinic; a third group of 277 patients was selected from a nurse practitioner clinic. Main outcome measures were the proportion of patients in the second year of follow up who had undergone a complete review (blood pressure measurement, serum creatinine level result and electrocardiograph report), acceptability to patients and general practitioners as assessed by questionnaire, and cost per complete review in year two (National Health Service and patient costs).\n After two years 220 (82%) shared care patients had had a complete review compared with 146 (54%) outpatient clinic attenders and 202 (75%) nurse practitioner clinic attenders. Blood pressure control was similar in each group. Of 297 general practitioners invited, 85% wished to participate in the study; 61% of questionnaire respondents subsequently wanted shared care to continue while 25% were unsure. Half of the patients receiving shared care preferred this method of follow up. The rank order of cost-effectiveness ratios was shared care, nurse practitioner care and conventional outpatient care, relative differences being most marked when only patient costs were considered.\n Shared care for hypertension is feasible in an urban setting, acceptable to the majority of participants and is a cost-effective method of long-term follow up.", "Few formalized shared care schemes exist within psychiatry and the evidence base for sharing psychiatric care is weak.\n To evaluate the utility of patient-held shared care records for individuals with long-term mental illness.\n Cluster-randomised controlled parallel-group 12-month trial involving 90 patients with long-term mental illness drawn from 28 general practices.\n Carrying a shared care record had no significant effect on mental state or satisfaction with psychiatric services. Compared with controls, patients in the shared care group were no more likely to be admitted (relative risk 1.2, 95% CI 0.86-1.67) and attend clinic (relative risk 0.96, 95% CI 0.67-1.36) over the study period. Uptake of the shared care scheme was low by patients and professionals alike. Subjects with psychotic illness were significantly less likely to use their records (relative risk 0.51, 95% CI 0.27-0.99).\n Patient-held records may not be helpful for patients with long-term mental illness.", "Recent national guidelines emphasize the requirement for all general practitioners to manage drug users within a shared care scheme and suggest that a primary health care liaison worker (PHCLW) may facilitate these arrangements. We undertook a group-randomized, randomized controlled trial to determine the effectiveness of a PHCLW in promoting shared care.\n Primary health care teams in Stockport Health Authority, North West England, were randomly allocated to either an intervention arm, who were offered the services of a PHCLW, or to a control arm, who were offered standard support from the community drug team (CDT). The proportion of CDT clients with a history of regular opiate misuse who were in shared care 12 months after randomization was compared across study arms.\n Eighteen (24.0 per cent) of the 75 CDT clients in the intervention arm but none of the 80 CDT clients in the control arm were in shared care at 12 months (chi2 = 9.37, df = 1, p < 0.01; 95 per cent confidence interval 8.6-39.4 per cent).\n A PHCLW can significantly increase the number of CDT clients in shared care arrangements.", "To evaluate the effectiveness of a population based, multifaceted shared care intervention for late life depression in residential care.\n Randomised controlled trial, with control and intervention groups studied one after the other and blind follow up after 9.5 months.\n Population of residential facility in Sydney living in self care units and hostels.\n 220 depressed residents aged >/=65 without severe cognitive impairment.\n The shared care intervention included: (a) multidisciplinary consultation and collaboration, (b) training of general practitioners and carers in detection and management of depression, and (c) depression related health education and activity programmes for residents. The control group received routine care.\n Geriatric depression scale.\n Intention to treat analysis was used. There was significantly more movement to \"less depressed\" levels of depression at follow up in the intervention than control group (Mantel-Haenszel stratification test, P=0.0125). Multiple linear regression analysis found a significant intervention effect after controlling for possible confounders, with the intervention group showing an average improvement of 1.87 points on the geriatric depression scale compared with the control group (95% confidence interval 0.76 to 2.97, P=0.0011).\n The outcome of depression among elderly people in residential care can be improved by multidisciplinary collaboration, by enhancing the clinical skills of general practitioners and care staff, and by providing depression related health education and activity programmes for residents.", "Despite evidence of high psychological distress and unmet needs, evaluated interventions for informal caregivers in palliative care are few. This study involved an observational outcome evaluation of attendees, and a comparison group, in specialist home palliative care. The measures included carer psychological status and patient physical status at baseline, 8 weeks, and 20 weeks. Qualitative data were collected regarding content, satisfaction with, and impact of intervention. Process data described the uptake, resources, and group activity. The intervention combined informal multiprofessional teaching with facilitated peer exchange and support, and was delivered over 6 sessions of 90 minutes per week. The uptake rate was 25%; carers were less likely to accept if they were in paid employment (OR=0.26, P=0.06), and more likely to accept if they utilized avoidance coping (OR=1.13, P=0.04) or their patient had worse physical status (OR=2.1, P=0.03). Attendees described significant support and knowledge gains from the multiprofessional input and peer group. Most relied on social comparison processes to appraise their situation. Potential detection of significant effects on global psychological scores (i.e. anxiety, depression, and burden) using multivariate analysis was disallowed due to attrition. This acceptable and accessible intervention provided information and support; further outcome studies are needed for a range of interventions. Short-term interventions are unlikely to affect global psychological scores, and future evaluations should include additional time points of data collection to demonstrate support during attendance.", "To measure effects on terminally ill cancer patients and their families of coordinating the services available within the NHS and from local authorities and the voluntary sector.\n Randomised controlled trial.\n Inner London health district.\n Cancer patients were routinely notified from 1987 to 1990. 554 patients expected to survive less than one year entered the trial and were randomly allocated to a coordination or a control group.\n All patients received routinely available services. Coordination group patients received the assistance of two nurse coordinators, whose role was to ensure that patients received appropriate and well coordinated services, tailored to their individual needs and circumstances.\n Patients and carers were interviewed at home on entry to the trial and at intervals until death. Interviews after bereavement were also conducted. Outcome measures included the presence and severity of physical symptoms, psychiatric morbidity, use of and satisfaction with services, and carers' problems. Results from the baseline interview, the interview closest to death, and the interview after bereavement were analysed.\n Few differences between groups were significant. Coordination group patients were less likely to suffer from vomiting, were more likely to report effective treatment for it, and less likely to be concerned about having an itchy skin. Their carers were more likely to report that in the last week of life the patient had had a cough and had had effective treatment for constipation, and they were less likely to rate the patient's difficulty swallowing as severe or to report effective treatment for anxiety. Coordination group patients were more likely to have seen a chiropodist and their carers were more likely to contact a specialist nurse in a night time emergency. These carers were less likely to feel angry about the death of the patient.\n This coordinating service made little difference to patient or family outcomes, perhaps because the service did not have a budget with which it could obtain services or because the professional skills of the nurse-coordinators may have conflicted with the requirements of the coordinating role.", "There are many systematic reviews of continuing education programmes and educational strategies for quality improvement in health care. Most of the reviewed studies are one-off evaluations rather than impact evaluations with long-term follow-up. There are few systematic reviews of organisational, financial and regulatory interventions, and few high-quality studies. These interventions are probably as or more important than educational strategies, although they are less well evaluated. Few studies have been undertaken in low- and middle-income countries (LMIC) or that address maternal and child health (MCH). Thus, the results of the available studies and reviews need to be interpreted cautiously when applied to LMIC. Interactive workshops, reminders and multifaceted interventions can improve professional practice, and they generally have moderate effects. Educational outreach visits consistently improve prescribing but have variable effects on other behaviours. Audit and feedback interventions have variable effects on professional practice, but most often these are small to moderate effects. Mass-media and patient-mediated interventions may change professional practice. Multifaceted interventions that combine several quality-improvement strategies are also effective but may not be more so than single interventions. While all of these strategies are applicable to MCH in LMIC, the applicability of the results to rural settings, in particular, may be limited. Use of these strategies could exacerbate inequalities, and this should be taken into consideration when planning implementation. Scaling up and sustainability may be difficult to achieve in LMIC contexts and need careful consideration. The use of financial interventions has not been well studied; financial incentives and disincentives may be difficult to use effectively and efficiently, although their impact on practice needs to be considered. Organisational interventions are likely to be important, given that there are often underlying organisational or system problems. Regulatory interventions have not been well evaluated, but may sometimes be both inexpensive and effective. There are no 'magic bullets' or simple solutions for ensuring the quality of health care services. Interventions should be selected or tailored to address the underlying reasons for a failure to deliver effective services. Decision-makers should select the most appropriate interventions for specific problems. This requires a governance structure that clearly assigns responsibility for quality-improvement activities, priority setting, selection and design of interventions, and evaluation.", "To compare collaborative care for treatment of depression in primary care with consult-liaison (CL) care. In collaborative care, a mental health team provided a treatment plan to the primary care provider, telephoned patients to support adherence to the plan, reviewed treatment results, and suggested modifications to the provider. In CL care, study clinicians informed the primary care provider of the diagnosis and facilitated referrals to psychiatry residents practicing in the primary care clinic.\n Patients were randomly assigned to treatment model by clinic firm.\n VA primary care clinic.\n One hundred sixty-eight collaborative care and 186 CL patients who met criteria for major depression and/or dysthymia.\n Hopkins Symptom Checklist (SCL-20), Short Form (SF)-36, Sheehan Disability Scale.\n Collaborative care produced greater improvement than CL in depressive symptomatology from baseline to 3 months (SCL-20 change scores), but at 9 months there was no significant difference. The intervention increased the proportion of patients receiving prescriptions and cognitive behavioral therapy. Collaborative care produced significantly greater improvement on the Sheehan at 3 months. A greater proportion of collaborative care patients exhibited an improvement in SF-36 Mental Component Score of 5 points or more from baseline to 9 months.\n Collaborative care resulted in more rapid improvement in depression symptomatology, and a more rapid and sustained improvement in mental health status compared to the more standard model. Mounting evidence indicates that collaboration between primary care providers and mental health specialists can improve depression treatment and supports the necessary changes in clinic structure and incentives.", "Patients with persistent medically unexplained symptoms often exhibit general dysfunction and psychiatric comorbidity and frequently resist psychiatric referral. The aim of this study was to evaluate the efficacy of a collaborative care model including training for general practitioners (GPs) and a psychiatric consultation model for patients with persistent medically unexplained symptoms in general practice.\n Randomised controlled trial. Cluster randomisation at GP practices and multilevel analysis were performed. A total of 81 patients from 36 general practices completed the study. A collaborative care model of training and psychiatric consultation in general practice in the presence of the GP was compared with training plus care as usual by the GP. Outcome assessment on the patients' well-being, functioning and utilisation of health care services was performed 6 weeks and 6 months later.\n All the patients had somatoform disorders (Whitely Index 7.46), and 86% had comorbid psychiatric disorders. In the intervention group, the severity of the main medically unexplained symptoms decreased by 58%. The patients' social functioning improved. The utilization of health care was lower than in the care as usual group.\n A collaborative care model combining training with psychiatric consultation in the general practice setting is an effective intervention in the treatment of persistent medically unexplained symptoms. Anxiety and depressive disorders are highly comorbid in this group. The findings warrant a larger study.", "In a pilot study, 55 low-income Latina patients with breast or cervical cancer and comorbid depression were randomly assigned to receive collaborative care as part of the Multifaceted Oncology Depression Program or usual care. Relative to patients in the usual care condition, patients receiving collaborative care were more likely to show>or=50% improvement in depressive symptoms as measured by the Personal Health Questionnaire (OR=4.51, 95% CI=1.07-18.93). Patients in the collaborative care program were also more likely to show improvement in emotional well-being (increase of 2.15) as measured by the Functional Assessment of Cancer Therapy Scale than were those receiving usual care (decrease of 0.50) (group difference=2.65, 95% CI: 0.18-5.12). Despite health system, provider, and patient barriers to care, these initial results suggest that patients in public sector oncology clinics can benefit from onsite depression treatment.", "Caring for relatives with advanced cancer may cause psychological and physical ill health.\n To evaluate the effectiveness of increased support for distressed, informal carers of patients receiving palliative care.\n The sample was composed of 271 informal carers who scored over 5 on the 28-item General Health Questionnaire (GHQ-28). The intervention comprised six weekly visits by a trained advisor. Primary outcome was carer distress (GHQ-28) at 4-week, 9-week and 12-week follow-up. Secondary outcomes were carer strain and quality of life, satisfaction with care, and bereavement outcome.\n Scores on the GHQ-28 fell below the threshold of 5/6 in a third of participants in each trial arm at any follow-up point. Mean scores in the intervention group were lower at all time points but these differences were not significant. No difference was observed in secondary outcomes. Carers receiving the intervention reported qualitative benefit.\n The intervention might have been too brief, and ongoing help might have had accruing benefits. Alternatively, informal carers of patients with cancer may already receive considerable input and the advisor's help gave little additional advantage; or caring for a dying relative is extremely stressful and no amount of support is going to make it much better.", "This study assessed treatment preferences among low-income Latino patients in public-sector primary care clinics and examined whether a collaborative care intervention that included patient education and allowed patients to choose between medication, therapy, or both would increase the likelihood that patients received preferred treatment.\n A total of 339 Latino patients with probable depressive disorders were recruited; participants completed a baseline conjoint analysis preference survey and were randomly assigned to receive the intervention or enhanced usual care. At 16 weeks, a patient survey assessed depression treatment received during the study period. Logistic regression models were constructed to estimate treatment preferences, examine patient characteristics associated with treatment preferences, and examine patient characteristics associated with a match between stated preference and actual treatment received.\n The conjoint analysis preference survey showed that patients preferred counseling or counseling plus medication over antidepressant medication alone and that they preferred treatment in primary care over specialty mental health care, but they showed no significant preference for individual versus group treatment. Patients also indicated that individual education sessions, telephone sessions, transportation assistance, and family involvement were barrier reduction strategies that would enhance their likelihood of accepting treatment. Compared with patients assigned to usual care, those in the intervention group were 21 times as likely to receive preferred treatment. Among all participants, women, unemployed persons, those who spoke English, and those referred by providers were more likely to receive preferred treatment.\n Collaborative care interventions that include psychotherapy can increase the likelihood that Latino patients receive preferred care; however, special efforts may be needed to address preferences of working persons, men, and Spanish-speaking patients.", "Many stroke patients and informal carers experience a decreased quality of life after discharge home and are dissatisfied with the care received. We assessed the effectiveness of an outreach nursing care program.\n In a multicenter trial, 536 stroke patients were randomized at discharge to standard care (n=273) or standard care plus outreach care (n=263). The outreach care consisted of 3 telephone calls and 1 home visit within 5 months after discharge by 1 of 13 stroke nurses. Patients were masked for the trial objectives. Six months after discharge, they assessed the 2 primary outcomes: quality of life (Short Form 36 [SF-36]) and dissatisfaction with care. Secondary measures of outcome were disability, handicap, depression, anxiety, and use of health care services and secondary prevention drugs. Informal carers assessed strain, and social support. Analysis was by intention to treat.\n Twelve patients died before follow-up, 38 declined outcome assessment, and 486 completed the primary outcome assessments. Outreach care patients had better scores on the SF-36 domain \"Role Emotional\" than controls (mean difference 7.9 [95% confidence limit, 0.1 to 15.7]). No statistically significant differences were found on the other primary outcome measures. For secondary outcomes, no statistically significant differences were found, except that intervention patients used fewer rehabilitation services (relative risk, 0.66 [0.44 to 1.00]) and had lower anxiety scores (median difference 1 [0.19 to 2.79]).\n This outreach nursing stroke care was not effective in improving quality of life and dissatisfaction with care of recently discharged patients.", "This 24-month exploratory study evaluated whether a 6-month programme supported by a trained external facilitator was feasible, acceptable and led to the adoption of a multidisciplinary approach to audit by secondary care staff. Undertaken in five acute hospital sites in the East Midlands UK, 22 multidisciplinary teams were randomised to either an intervention or control arm. Employing mixed methods, a range of outcomes, including collaborative behaviour, was measured. The intervention was feasible and acceptable to staff. Involvement in the facilitated programme had a positive impact on self-reported knowledge (P=0.000 post-intervention and at 4-months follow-up), skills (P=0.000 post-intervention and P=0.02 at 4-months follow-up) and attitudes (P<0.01 post-intervention), appeared to have some influence on improving self-reported (P<0.05 post-intervention) and observed collaborative behaviour (P=0.01) and led to better quality audit resulting in measurable improvements to care. Improved collaborative behaviour may have resulted from an increase in assertive behaviour by nurses. Research to test approaches to support teams to work effectively together is currently hampered by a lack of suitable research instruments and needs addressing before main (phase 111) trials are undertaken.", "Meta-analyses show collaborative care models (CCMs) with nurse care management are effective for improving primary care for depression. This study aimed to develop CCM approaches that could be sustained and spread within Veterans Affairs (VA). Evidence-based quality improvement (EBQI) uses QI approaches within a research/clinical partnership to redesign care. The study used EBQI methods for CCM redesign, tested the effectiveness of the locally adapted model as implemented, and assessed the contextual factors shaping intervention effectiveness.\n The study intervention is EBQI as applied to CCM implementation. The study uses a cluster randomized design as a formative evaluation tool to test and improve the effectiveness of the redesign process, with seven intervention and three non-intervention VA primary care practices in five different states. The primary study outcome is patient antidepressant use. The context evaluation is descriptive and uses subgroup analysis. The primary context evaluation measure is naturalistic primary care clinician (PCC) predilection to adopt CCM.For the randomized evaluation, trained telephone research interviewers enrolled consecutive primary care patients with major depression in the evaluation, referred enrolled patients in intervention practices to the implemented CCM, and re-surveyed at seven months.\n Interviewers enrolled 288 CCM site and 258 non-CCM site patients. Enrolled intervention site patients were more likely to receive appropriate antidepressant care (66% versus 43%, p = 0.01), but showed no significant difference in symptom improvement compared to usual care. In terms of context, only 40% of enrolled patients received complete care management per protocol. PCC predilection to adopt CCM had substantial effects on patient participation, with patients belonging to early adopter clinicians completing adequate care manager follow-up significantly more often than patients of clinicians with low predilection to adopt CCM (74% versus 48%%, p = 0.003).\n Depression CCM designed and implemented by primary care practices using EBQI improved antidepressant initiation. Combining QI methods with a randomized evaluation proved challenging, but enabled new insights into the process of translating research-based CCM into practice. Future research on the effects of PCC attitudes and skills on CCM results, as well as on enhancing the link between improved antidepressant use and symptom outcomes, is needed.\n ClinicalTrials.gov: NCT00105820.", "The aim of this project was to assess whether outreach visits would improve the implementation of evidence based clinical practice in the area of falls reduction and stroke prevention in a residential care setting.\n Twenty facilities took part in a randomized controlled trial with a seven month follow-up period. Two outreach visits were delivered by a pharmacist. At the first a summary of the relevant evidence was provided and at the second detailed audit information was provided about fall rates, psychotropic drug prescribing and stroke risk reduction practices (BP monitoring, aspirin and warfarin use) for the facility relevant to the physician. The effect of the interventions was determined via pre- and post-intervention case note audit. Outcomes included change in percentage patients at risk of falling who fell in a three month period prior to follow-up and changes in use of psychotropic medications. Chi-square tests, independent samples t-test, and logistic regression were used in the analysis.\n Data were available from case notes at baseline (n = 897) and seven months follow-up (n = 902), 452 residential care staff were surveyed and 121 physicians were involved with 61 receiving outreach visits. Pre-and post-intervention data were available for 715 participants. There were no differences between the intervention and control groups for the three month fall rate. We were unable to detect statistically significant differences between groups for the psychotropic drug use of the patients before or after the intervention. The exception was significantly greater use of \"as required\" antipsychotics in the intervention group compared with the control group after the pharmacy intervention (RR = 4.95; 95%CI 1.69-14.50). There was no statistically significant difference between groups for the numbers of patients \"at risk of stroke\" on aspirin at follow-up.\n While the strategy was well received by the physicians involved, there was no change in prescribing patterns. Patient care in residential settings is complex and involves contributions from the patient's physician, family and residential care staff. The project highlights challenges of delivering evidence based care in a setting in which there is a paucity of well controlled trial evidence but where significant health outcomes can be attained." ]	This review indicates that there is, at present, insufficient evidence to demonstrate significant benefits from shared care apart from improved prescribing. Methodological shortcomings, particularly inadequate length of follow-up, may partially account for this lack of evidence. This review indicates that there is no evidence to support the widespread introduction of shared care services at present. Future shared-care interventions should only be developed within research settings and with account taken of the complexity of such interventions and the need to carry out longer studies to test the effectiveness and sustainability of shared care over time.
CD001750	[ "20008886", "17854523", "15608037", "18335226", "19357861", "15925049", "15533377", "15755044", "15979994", "19165664", "20379731", "17462639", "18802744", "17347165", "15672958", "16168215", "19834718", "18345521", "19909586", "16926261", "19523618", "15567879", "19225876", "14688156", "18572861", "16084881", "17428479", "15760966", "19340626", "16253978", "16603428", "8974615", "18192671", "15705369" ]	[ "Flexible GnRH antagonist protocol versus GnRH agonist long protocol in patients with polycystic ovary syndrome treated for IVF: a prospective randomised controlled trial (RCT).", "A prospective randomized study comparing coasting with GnRH antagonist administration in patients at risk for severe OHSS.", "GnRH antagonist versus long GnRH agonist protocol in poor responders undergoing IVF: a randomized controlled trial.", "Comparison of multiple dose GnRH antagonist and minidose long agonist protocols in poor responders undergoing in vitro fertilization: a randomized controlled trial.", "Comparing GnRH agonist long protocol and GnRH antagonist protocol in outcome the first cycle of ART.", "A randomised study of GnRH antagonist (cetrorelix) versus agonist (busereline) for controlled ovarian stimulation: effect on safety and efficacy.", "A modified gonadotropin-releasing hormone (GnRH) antagonist protocol failed to increase clinical pregnancy rates in comparison with the long GnRH protocol.", "Use of a GnRH antagonist in controlled ovarian hyperstimulation for assisted conception in women with polycystic ovary disease: a randomized, prospective, pilot study.", "A lower ongoing pregnancy rate can be expected when GnRH agonist is used for triggering final oocyte maturation instead of HCG in patients undergoing IVF with GnRH antagonists.", "Triggering with HCG or GnRH agonist in GnRH antagonist treated oocyte donation cycles: a randomised clinical trial.", "Comparison of GnRH antagonist with long GnRH agonist protocol after OCP pretreatment in PCOs patients.", "The use of gonadotropin-releasing hormone (GnRH) agonist to induce oocyte maturation after cotreatment with GnRH antagonist in high-risk patients undergoing in vitro fertilization prevents the risk of ovarian hyperstimulation syndrome: a prospective randomized controlled study.", "Comparison of embryological and clinical outcome in GnRH antagonist vs. GnRH agonist protocols for in vitro fertilization in PCOS non-obese patients. A prospective randomized study.", "Initiation of GnRH antagonist on Day 1 of stimulation as compared to the long agonist protocol in PCOS patients. A randomized controlled trial: effect on hormonal levels and follicular development.", "Effect of antagonists vs agonists on in vitro fertilization outcome.", "GnRH antagonist in IVF poor-responder patients: results of a randomized trial.", "Comparison of mild stimulation and conventional stimulation in ART outcome.", "Comparison of GnRH agonists and antagonists in normoresponder IVF/ICSI in Turkish female patients.", "Single-dose GnRH agonist administration in the luteal phase of GnRH antagonist cycles: a prospective randomized study.", "Beneficial effect of luteal-phase GnRH agonist administration on embryo implantation after ICSI in both GnRH agonist- and antagonist-treated ovarian stimulation cycles.", "Comparison of GnRH antagonist protocol with or without oral contraceptive pill pretreatment and GnRH agonist low-dose long protocol in low responders undergoing IVF/intracytoplasmic sperm injection.", "Timing ovulation for intrauterine insemination with a GnRH antagonist.", "IVF/ICSI outcomes between cycles with luteal estradiol (E2) pre-treatment before GnRH antagonist protocol and standard long GnRH agonist protocol: a prospective and randomized study.", "GnRH antagonists and mild ovarian stimulation for intrauterine insemination: a randomized study comparing different gonadotrophin dosages.", "[Application of GnRH-antagonist to IVF-ET for patients with poor ovarian response].", "Comparison of a gonadotropin-releasing hormone (GnRH) antagonist and GnRH agonist flare-up regimen in poor responders undergoing ovarian stimulation.", "GnRH agonist and antagonist protocols for stage I-II endometriosis and endometrioma in in vitro fertilization/intracytoplasmic sperm injection cycles.", "GnRH agonist (buserelin) or hCG for ovulation induction in GnRH antagonist IVF/ICSI cycles: a prospective randomized study.", "Follicular growth and oocyte maturation in GnRH agonist and antagonist protocols for in vitro fertilisation and embryo transfer.", "A comparative randomized trial to assess the impact of oral contraceptive pretreatment on follicular growth and hormone profiles in GnRH antagonist-treated patients.", "Effect of gonadotropin-releasing hormone agonist and antagonist on steroidogenesis of low responders undergoing in vitro fertilization.", "[Can the type of GnRH used during long in vitro fertilization protocols influence the pregnancy rate?].", "GnRH agonist protocol administration in the luteal phase in ICSI-ET cycles stimulated with the long GnRH agonist protocol: a randomized, controlled double blind study.", "A randomized prospective trial comparing gonadotropin-releasing hormone (GnRH) antagonist/recombinant follicle-stimulating hormone (rFSH) versus GnRH-agonist/rFSH in women pretreated with oral contraceptives before in vitro fertilization." ]	[ "Women with polycystic ovary syndrome (PCOS) are at risk of developing ovarian hyperstimulation syndrome (OHSS) during ovarian stimulation. Use of GnRH antagonist in the general subfertile population is associated with lower incidence of OHSS than agonists and similar probability of live birth but it is unclear if this is true for patients with PCOS. Our aim was to compare the flexible GnRH antagonist and GnRH agonist long protocols in patients with PCOS undergoing IVF (primary end-point: ongoing pregnancy rate per patient randomized).\n In this randomised controlled trial (RCT), 220 patients with PCOS were randomly allocated in two groups: long GnRH agonist down-regulation protocol (n = 110) and flexible GnRH antagonist protocol (n = 110).\n No differences were observed in ongoing pregnancy rates [50.9 versus 47.3%, difference 3.6%, 95% confidence interval (CI): -9.6 to +16.8%] in the agonist and antagonist protocols, respectively. Incidence of OHSS Grade II was lower in the antagonist compared with agonist group (40.0 versus 60.0%, difference -20.0%, 95% CI: -7.1 to -32.9%, P < 0.01). Duration of stimulation (10 versus 12 days, difference 2 days, 95% CI: +1 to +2, P < 0.001) and total gonadotrophin required (1575 versus 1850 IU, difference -275 IU, 95% CI: -25 to -400, P < 0.05) were also lower in the antagonist compared with agonist protocol.\n The current RCT suggests that the flexible GnRH antagonist protocol is associated with a similar ongoing pregnancy rate, lower incidence of OHSS grade II, lower gonadotrophin requirement and shorter duration of stimulation, compared with GnRH agonist. The GnRH antagonist might be the treatment choice for patients with PCOS undergoing IVF. The study was registered at clinicaltrials.gov. ID: NCT00417144.", "This work evaluated possible advantages of gonadotrophin-releasing hormone (GnRH) antagonist administration as an alternative to coasting in prevention of severe ovarian hyperstimulation syndrome (OHSS) in women undergoing IVF/ intracytoplasmic sperm injection. A prospective randomized study comparing coasting (group A) (n = 96) and GnRH antagonist administration (group B) (n = 94) in patients at risk of OHSS was performed. The primary outcome measure was high quality embryos. The secondary outcome measures were days of intervention, number of oocytes, pregnancy rate, number of cryopreserved embryos and incidence of severe OHSS. There were significantly more high quality embryos (2.87 +/- 1.2 versus 2.21 +/- 1.1; P < 0.0001), and more oocytes (16.5 +/- 7.6 versus 14.06 +/- 5.2; P = 0.02), in group B as compared with group A. There were more days of coasting as compared with days of antagonist administration (2.82 +/- 0.97 versus 1.74 +/- 0.91; P < 0.0001). In conclusion, GnRH antagonist was superior to coasting in producing significantly more high quality embryos and more oocytes as well as reducing the time until HCG administration. There was no significant difference in pregnancy rate between the two groups. No OHSS developed in either group.", "This is the first published report of a prospective, randomized, controlled trial comparing a fixed, multi-dose GnRH antagonist protocol with a long GnRH agonist protocol in poor responders undergoing IVF.\n Sixty-six poor responders were randomized into two groups: the study group received 0.25 mg of cetrorelix daily starting on day 6 of stimulation; the control group received 600 microg of buserelin acetate daily starting in the mid-luteal phase of the preceding cycle. Both groups were given a fixed dose of recombinant FSH (300 IU daily) for stimulation.\n There were no significant differences in the cycle cancellation rates, duration of stimulation, consumption of gonadotrophins, and mean numbers of mature follicles, oocytes and embryos obtained. The implantation rates were similar, but the number of embryos transferred was significantly higher for the antagonist group (2.32 +/- 0.58 versus 1.50 +/- 0.83; P = 0.01). The pregnancy rates were also higher in the antagonist group, but the difference was not statistically significant.\n A fixed multi-dose GnRH antagonist protocol is feasible for patients who are poor responders on a long agonist protocol; however, our study failed to demonstrate an overall improvement in ovarian responsiveness. Clinical outcomes may be improved by developing more flexible antagonist regimens, an approach that requires further evaluation.", "To investigate the efficacy of gonadotropin releasing hormone antagonist (GnRH) in poor responders undergoing in vitro fertilization.\n Ninety-six patients with poor ovarian response in previous treatment cycles were prospectively randomized into two groups. Forty-four patients were stimulated with GnRH antagonist multidose protocol and 45 patients received a standard long agonist protocol. Ovarian response was evaluated by transvaginal ultrasound and hormonal parameters. Cycle characteristics and treatment outcomes were statistically compared between groups.\n There was significantly reduced duration of stimulation and consumption of gonadotrophins in the antagonist group when compared to the agonist group. The estradiol concentrations on the day of human chorionic gonadotropin (hCG) injection, the number of oocytes retrieved, and the number of embryos transferred were similar for both groups. In the antagonist group, eight (18.1%) ongoing pregnancies were achieved and in the agonist group, ten (22.2%) clinical pregnancies were achieved but the difference was not statistically significant.\n The present study was not powered to detect clinically relevant differences between two protocols in outcomes such as pregnancy rate, with confidence.", "This prospective study evaluated the efficacy of gonadotropin-releasing hormone (GnRH) antagonist protocol in comparison with the GnRH agonist protocol in the first cycle of assisted reproductive technique (ART).\n We randomized 235 patients undergoing ART for the first time. The first group was stimulated with a standard long protocol and the second group stimulated with GnRH antagonis.\n There was no statistically significant difference in the age, infertility cause, basal FSH, BMI, the number of oocytes retrieved, number of M2 oocytes, embryo obtained and endometrial thickness between the two groups. But Serum estradiol, consumption of gonadotropins and ovarian hyperstimulation syndrome were significantly lower in the antagonist protocol. Cancellation rate of embryo transfer due to poor-quality embryo in the antagonist protocol was higher, but it was not significant. There was no significant difference in the clinical pregnancy and ongoing pregnancy between the two groups.\n GnRH-antagonist is an effective, safe, and well-tolerated alternative to agonist in the first cycle of ART.", "To assess safety and efficacy of cetrorelix utilisation in controlled ovarian stimulation (COS).\n Phase III, randomized, single center study of 131 patients undergoing COS and IVF with or without ICSI, in a University affiliated Hospital. Sixty-six patients were allocated to the protocol with antagonist and 65 to the agonist protocol arm. The Student's t-test, the Mann-Whitney test and the chi-square test were applied as required, using SPSS for Windows with a two-sided 5% significance level.\n The mean (+/-S.D.) duration of stimulation was 9.5+/-1.7 days in the antagonist group and 10.6+/-2.1 days in the agonist group (P=0.02). The mean (+/-S.D.) duration of suppression was 4.6+/-1.3 days in the antagonist group and 27.3+/-5.2 days in the agonist group (P<0.0001). No significant differences were noted in other outcome measures: amount of rFSH required, estradiol level on hCG day, number of follicles>or=15 mm and endometrial thickness on oocyte retrieval day, number of oocytes retrieved, fertilization rate and number of OHS cases. Clinical pregnancy rates per-attempt and per-transfer were 15.1% and 17.0% in the antagonist group and 16.9% and 20.0% in the agonist group (P=0.79 and 0.71, respectively).\n GnRH antagonists are an effective, safe and well tolerated alternative to agonists for COS.", "The purpose of this prospective randomized study was to compare stimulation characteristics and IVF outcomes of the standard long GnRH agonist protocol for ovarian stimulation with a modified GnRH antagonist protocol. Starting GnRH antagonist in a flexible protocol according to the size of the leading follicle, with simultaneous augmentation of 75 IU recombinant FSH, failed to increase clinical pregnancy rates.", "To compare the outcome of using gonadotropin-releasing hormone (GnRH) antagonists versus agonists in women with polycystic ovary disease (PCOD) who underwent controlled ovarian hyperstimulation (COH) for assisted reproductive techniques (ART).\n A total of 129 patients with PCOD were randomly allocated to undergo COH with a GnRH antagonist (59 patients) and GnRH agonist (leuprolide acetate) (70 patients) to prevent a premature luteinizing hormone (LH) surge. Assisted fertilization following oocyte retrieval and embryo transfer was performed.\n None of the cycles were cancelled due to a premature LH surge. There was no significant difference between the antagonist and agonist arms in the number of gonadotropin ampules consumed per cycle. However, in the antagonist arm a shorter duration of ovarian stimulation was recorded as compared to the agonist arm. Although similar numbers of oocytes was retrieved from both groups of patients, the quality of the oocytes, as measured by metaphase 2/total oocyte ratio, was lower in the antagonist arm as compared to the agonist arm. Pregnancy rates were 57.6% and 58.5% in the antagonist and agonist arms, respectively (p > 0.05). Implantation rates were not different (34.0% and 34.6%, respectively). The frequency of ovarian hyperstimulation syndrome also did not differ between the treatment groups (5% and 7.1%, respectively).\n The size of our study, on a specific subgroup of patients, does not allow a reliable conclusion regarding ART outcomefollowing the use of a GnRH antagonist versus agonist. Nevertheless, the protocol with the antagonist gave results that were as good as those of the protocol with the agonist in this PCOD patient population.", "Eliciting an endogenous LH surge by GnRH-agonist for the induction of final oocyte maturation may be more physiological compared with the administration of HCG. However, the efficacy of this intervention in patients treated for IVF with GnRH antagonists remains to be assessed.\n 106 patients were randomized to receive either 10 000 IU urinary HCG or 0.2 mg Triptorelin for triggering final oocyte maturation. Ovarian stimulation for IVF was performed with a fixed dose of 200 IU recombinant FSH and GnRH antagonist was started on stimulation day 6. Luteal phase was supported with micronized vaginal progesterone and oral estradiol. The study was monitored continuously for safety and stopping rules were established.\n No significant differences were present in the number of cumulus-oocyte complexes retrieved, in the proportion of metaphase II oocytes, in fertilization rates or in the number and quality of the embryos transferred between the two groups. However, a significantly lower probability of ongoing pregnancy in the GnRH agonist arm prompted discontinuation of the trial, according to the stopping rules established (odds ratio 0.11; 95% confidence interval 0.02-0.52).\n Lower probability of ongoing pregnancy can be expected when GnRH agonist is used for triggering final oocyte maturation instead of HCG in patients undergoing ovarian stimulation for IVF with GnRH antagonists.", "To compare donor and recipient outcome after inducing the final oocyte maturation with hCG or GnRH agonist in GnRH-antagonist treated oocyte donation (OD) cycles.\n Two-hundred fifty-seven oocyte donors were enrolled to participate in a clinical trial in a private fertility centre. After stimulation with 225 IU rFSH and Cetrorelix 0.25 mg/day, 212 oocyte donors were randomised with sealed envelopes for triggering with recombinant hCG (Ovitrelle 250 microgr, n = 106) or a GnRH agonist (triptorelin 0.2 mg, n = 106).\n The number of retrieved COCs (12 +/- 6.3 vs 11.4 +/- 6.4), mature oocytes (8 +/- 4.6 vs 7.5 +/- 4.1), the proportion of mature oocytes (67.2 +/- 20.4% vs 67.1 +/- 20.9%) and fertilisation rates (67.8 +/- 23.5% vs 71.1 +/- 22.1%) were comparable. Clinical, ongoing pregnancy and live birth rates were not statistically different in the corresponding recipient groups. Nine cases of mild and one case of severe OHSS occurred in hCG group, whereas no cases were detected in GnRH agonist group.\n The findings of our RCT suggest that donor and recipient outcome are comparable in OD cycles triggered with hCG or a GnRH agonist. Furthermore, the risk of OHSS seems to be reduced considerably, therefore the combination of a GnRH antagonist protocol with GnRH agonist triggering constitutes a safe treatment option for egg-donors.", "To evaluate the efficacy of GnRH antagonist in comparison with the GnRH agonist protocol in OCP pretreated polycystic ovary syndrome (PCOs) patients undergoing their first ART cycle.\n Prospective randomized controlled trial. University-based tertiary fertility center. Ninety-five PCOs patients under 35 years of age, with primary infertility were randomized to an ovarian stimulation protocol consisting of either. GnRh antagonist (study group) or GnRH agonist (control group) after pretreatment with OCP. Coasting or GnRH agonist Trigger was used when estradiol level > or =3,000 pgr/ml in the control and study group, respectively. Both groups received 800 mg vaginal progesterone and 4 mg oral estradiol valerate for luteal phase support.\n There was no statistically significant difference in the age, body mass index, basal FSH, duration of infertility, the number of oocytes retrieved, the number of embryos transferred, Serum E2 levels on day of trigger, fertilization rate, chemical and clinical pregnancy rates between the two groups. None of the patients in the study group developed ovarian hyperstimulation syndrome (OHSS) compared with 22.2% of patients in the control group. Total duration of treatment and the number of HMG ampoules used were lower in the study group.\n Antagonist protocol and GnRH agonist trigger for ovulation whenever necessary has a similar cycle outcome to the GnRH-agonist protocol in OCP pretreated PCOs patients, with significantly reduced risk of OHSS.", "To determine whether there are any differences in the incidence of ovarian hyperstimulation syndrome (OHSS) and implantation rates in high-risk patients undergoing IVF using a protocol consisting of GnRH agonist trigger after cotreatment with GnRH antagonist or hCG trigger after dual pituitary suppression protocol.\n Prospective randomized controlled trial.\n University-based tertiary fertility center.\n Sixty-six patients under 40 years of age with polycystic ovarian syndrome, polycystic ovarian morphology, or previous high response undergoing IVF.\n Patients were randomized to an ovarian stimulation protocol consisting of either GnRH agonist trigger after cotreatment with GnRH antagonist (study group) or hCG trigger after dual pituitary suppression with a GnRH agonist (control group). Both groups received luteal phase and early pregnancy supplementation with IM progesterone (P), and patients in the study group also received E(2) patches and their doses were adjusted according to the serum levels.\n Incidence of OHSS and implantation rate.\n None of the patients in the study group developed any form of OHSS compared with 31% (10/32) of the patients in the control group. There were no significant differences in the implantation (22/61 [36.0%] vs. 20/64 [31.0%]), clinical pregnancy (17/30 [56.7%] vs. 15/29 [51.7%]), and ongoing pregnancy rates (16/30 [53.3%] vs. 14/29 [48.3%]) between the study and control groups, respectively.\n The use of a protocol consisting of GnRH agonist trigger after GnRH antagonist cotreatment combined with adequate luteal phase and early pregnancy E(2) and P supplementation reduces the risk of OHSS in high-risk patients undergoing IVF without affecting implantation rate.", "Embryological and clinical efficacy of gonadotropin-releasing hormone (GnRH) antagonist and agonist stimulation protocols in non-obese women with polycystic ovarian syndrome (PCOS) were compared.\n A prospective randomized study. Setting: Medical University Hospital. Patients: 70 infertile PCOS patients; 33 in GnRH antagonist and 37 in GnRH agonist group.\n Similar mature metaphase II oocyte rate (76% vs. 76%) was observed in both protocols. Optimal pronuclear morphology zygotes dominated in both groups (64% vs. 66%). Transferred embryo quality did not differ in both protocols. No significant differences between both protocols were found in delivery rate (p = 0.481), pregnancy rate (p = 0.810), multiple pregnancy rate (p = 0.501), miscarriage rate (p = 0.154), fertilization rate (p = 0.388) and implantation rate (p = 1.000). Duration of stimulation and total follicle-stimulating hormone (FSH) dose were significantly lower in GnRH antagonist protocol (p = 0.0005).\n GnRH antagonist and agonist protocols in non-obese PCOS patients yield similar embryological and clinical outcomes. Shorter duration of treatment and lower FSH requirement in GnRH antagonist group may be financially beneficial and therefore attractive for patients.", "BACKGROUND The optimal time for GnRH antagonist initiation is still debatable. The purpose of the current randomized controlled trial is to provide endocrine and follicular data during ovarian stimulation for IVF in patients with polycystic ovarian syndrome (PCOS) treated either with a long GnRH agonist scheme or a fixed day-1 GnRH antagonist protocol. METHODS Randomized patients in both groups (antagonist: n = 26; long agonist: n = 52) received oral contraceptive pill treatment for three weeks and a starting dose of 150 IU of follitropin beta. The primary outcome was E(2) level on Day 5 of stimulation, while secondary outcomes were follicular development, LH during ovarian stimulation and progesterone levels. RESULTS Significantly more follicles on days 5, 7 and 8 of stimulation, significantly higher estradiol (E(2)) levels on days 1, 3, 5, 7 and 8 and significantly higher progesterone levels on days 1, 5 and 8 of stimulation were observed in the antagonist when compared with the agonist group. E(2) was approximately twice as high in the antagonist when compared with the agonist group on day 5 of stimulation (432 versus 204 pg ml(-1), P lt; 0.001). These differences were accompanied by significantly lower LH levels on days 3 and 5 and significantly higher LH levels on days 1, 7 and 8 of stimulation in the antagonist when compared with the agonist group. CONCLUSIONS In PCOS patients undergoing IVF, initiation of GnRH antagonist concomitantly with recombinant FSH is associated with an earlier follicular growth and a different hormonal environment during the follicular phase when compared with the long agonist protocol.", "To compare outcome following in vitro fertilization-embryo transfer (IVF-ET) using controlled ovarian hyperstimulation (COH) regimens using either the gonadotropin-releasing hormone (GnRH) agonist leuprolide acetate vs the GnRH antagonist ganirelix.\n Women needing IVF for conception were randomly assigned to 300 IU of gonadotropins with ganirelix used in the follicular phase when a follicle with a 14 mm average diameter was attained vs a regimen using leuprolide acetate from the mid-luteal phase of the previous cycle.\n There were no differences found in clinical, ongoing, delivered pregnancy rates or implantation rates between groups.\n The use of GnRH antagonists do not seem to reduce IVF outcome compared to using GnRH agonists in COH regimens.", "The aim of this prospective study was to evaluate the efficacy of gonadotrophin-releasing hormone antagonist (GnRH) in comparison with the standard long protocol in poor-responder patients. Sixty patients with poor ovarian response in previous treatment cycles were randomized into two groups: group A (n = 30) was stimulated with a standard long protocol, and group B (n = 30) received GnRH antagonist. Vaginal ultrasound was performed to evaluate ovarian response. There was a significantly reduced duration of ovarian stimulation (9.8 +/- 0.8 versus 14.6 +/- 1.2, P = 0.001) in group B in comparison with group A, and a reduced number of ampoules was used in group B (49.3 +/- 4.3 versus 72.6 +/- 6.8, P = 0.0001). In group B, the number of oocytes retrieved was significantly higher than in group A (5.6 +/- 1.6 versus 4.3 +/- 2.2, P = 0.02) and there was an increased number of follicles with a diameter >15 mm at human chorionic gonadotrophin administration in group B (P = 0.0001). Fewer cycles were cancelled with the use of an antagonist protocol. Five pregnancies (17% for embryo transfer) were obtained with GnRH antagonist protocol and two (7% for embryo transfer) with GnRH agonist protocol.", "To provide a treatment for particular condition that is the most effective treatment with the least risk and cost for the patient we compared the efficacy of using clomiphene 100 mg + delayed low dose gonadotropin + flexible GnRH antagonist administration for ovarian stimulation protocol and GnRH agonist + gonadotropin for stimulation protocol in IVF outcome.\n Clinical outcome of 243 women with regularly menstruation who were candidate for IVF. They had undergone stimulation with GnRH agonist and gonadotropin (group A) or clomiphene citrate, gonadotropin and GnRH antagonist (group B). Main outcome was ongoing pregnancy.\n There were no significant difference in mean age, cause of infertility, basal FSH, BMI, duration of infertility, endometrial thickness on the day HCG administration in two groups. The number of recovered oocytes, obtained embryos, transferred embryos, peak of estradiol on the day HCG administration and OHSS were significantly higher in group A. Significantly more patients in control group had embryos for cryopreservation. There were no significant difference in clinical pregnancy rate and ongoing pregnancy rate between two groups.\n Clomiphene + delayed low dose gonadotropin + flexible GnRH - antagonist stimulation is an acceptable alternative protocol for IVF in patients with regularly menstruation.", "To evaluate the results of gonadotropin-releasing hormone agonist (GnRHa) and gonadotropin-releasing hormone antagonist (GnRHant) use in two demographically matched groups of normoresponder in-vitro fertilisation or intracytoplasmic sperm injection (IVF/ICSI) patients in a prospective study.\n We randomised 93 patients undergoing IVF/ICSI between May 2005 and August 2006. Patients with IVF indications were included except for those with polycystic ovary syndrome or azoospermia, women older than 38 years and those with follicle-stimulating hormone (FSH) > or =10 IU/ml. Patients were stimulated with standard 225 IU recombinant FSH. In Group I (n=45) a daily dose of GnRHant cetrorelix acetate 0.25 mg was administered when follicles reached a diameter of > or =14 mm. Group II (n=48) patients were desensitised with the GnRHa, leuprolide acetate, in a long protocol. Human chorionic gonadotropin (hCG) was administered when at least three follicles of 18 mm in diameter were observed. Oocyte retrieval was scheduled 36 hours following hCG administration and embryos were transferred on day 3 after oocyte retrieval.\n The two groups were homogenous for age, infertility duration, basal FSH and serum oestradiol (E2) (P=0.537, P=0.911, P=0.103 and P=0.733, respectively). In Group II (the GnRHa group) more antral follicles (P<0.001), a longer induction duration (P=0.017) and higher peak E2 levels (P<0.001) were observed. No differences were observed in the number of oocytes retrieved (P=0.749), embryos achieved and transferred (P=0.677), or fertilisation rates (P=0.839) between the two groups. There was no statistically significant difference between groups in clinical pregnancy rates, cycle cancellation and ovarian hyperstimulation (P=0.437, P=0.109 and P=0.415, respectively).\n GnRHant and GnRHa provide comparable results in normoresponder patients, while GnRHant allows a greater flexibility in their treatment.", "This study was designed to evaluate the effect of luteal-phase administration of single-dose gonadotrophin-releasing hormone (GnRH) agonist on pregnancy, implantation and live birth rates in patients who received GnRH antagonist for pituitary suppression. The study population consisted of 164 patients who underwent intracytoplasmic sperm injection (ICSI) after ovulation induction by gonadotrophins and GnRH antagonist for the prevention of a premature LH surge. For luteal-phase support, all the cases received intravaginal 600 mg micronized progesterone. In this prospective study, patients were randomly assigned to two groups. In one group, patients received an additional single dose of GnRH agonist (0.5 mg leuprolide acetate) subcutaneously on day 6 after ICSI, whereas the patients in the other group did not. Although the number of embryos transferred and the grade of the embryos were similar in the two groups, the patients in the luteal-phase agonist group had significantly higher rates of implantation and clinical pregnancy rates ( P < 0.05). When the two groups were compared, there were also statistically significant differences in multiple pregnancy and live birth rates ( P < 0.05). Administration of single-dose GnRH agonist as a luteal-phase support in ovarian stimulation-GnRH antagonist cycles in addition to standard luteal support seems to be effective in all cycle outcome parameters.", "GnRH agonist was recently suggested as a novel luteal-phase support that may act at different levels, including the pituitary gonadotrophs, the endometrium and the embryo itself. This prospective randomized study evaluates the effect of GnRH agonist administered in the luteal phase on ICSI outcomes in both GnRH agonist- and GnRH antagonist-treated ovarian stimulation protocols.\n Six hundred women about to undergo ovarian stimulation for ICSI (300 using a long GnRH agonist protocol and 300 using a GnRH antagonist protocol) were enrolled in this study. Patients treated with each of these two protocols were randomly assigned to receive a single injection of GnRH agonist or placebo 6 days after ICSI. Implantation and live birth rates were the primary outcomes.\n Administration of 0.1 mg of GnRH agonist triptorelin on day 6 after ICSI led to a significant improvement of implantation and live birth rates after ICSI as compared with placebo. In GnRH antagonist-treated ovarian stimulation cycles, luteal-phase GnRH agonist also increased ongoing pregnancy rate. Moreover, luteal-phase GnRH agonist administration increased luteal-phase serum HCG, estradiol and progesterone concentrations in both ovarian stimulation regimens.\n Luteal-phase GnRH agonist administration enhances ICSI clinical outcomes after GnRH agonist- and GnRH antagonist-treated ovarian stimulation cycles, possibly by a combination of effects on the embryo and the corpus luteum.", "This prospective randomized study was performed to compare the efficacy of GnRH antagonist multiple-dose protocol (MDP) with or without oral contraceptive pill (OCP) pretreatment and GnRH agonist low-dose long protocol (LP) in 82 patients undergoing IVF/intracytoplasmic sperm injection (ICSI). GnRH antagonist MDP with OCP pretreatment was at least as effective as GnRH agonist low-dose LP in low responders, and can benefit the low responders by reducing the amount of FSH and the number of days of stimulation required for follicular maturation.", "We aimed to assess the efficacy of a GnRH antagonist in intrauterine insemination (IUI) cycles to increase number of mature ovulatory follicles and pregnancy rates.\n Prospective randomized study. Women (18-38 years old) with primary/secondary infertility were included. Eighty-two patients were randomly assigned to controlled ovarian stimulation (COS) consisting of rFSH + GnRH antagonist or rFSH alone.\n A non-significant increase in the total amount of rFSH was seen in the GnRH antagonist group (707+/-240 IU) with respect to the control group (657+/-194 IU). The number of mature follicles (> or =16 mm) was significantly higher in the GnRH antagonist group than in the control group (2.4+/-1.4 versus 1.7+/-1.2, P<0.05). Pregnancy rates were significantly increased in the group of patients receiving the GnRH antagonist (38%) compared to the control group (14%). The only non-single pregnancy (triplets) occurred in the antagonist group.\n In this preliminary study, adding the GnRH antagonist to the COS protocol for IUI cycles significantly increased pregnancy rates. Nevertheless, these results may not be associated directly with the antagonist itself but with the fact that more mature ovulatory follicles are present by the day of the hCG. Finally, the risk for multiple gestations needs to be carefully evaluated.", "To study if luteal E(2) pre-treatment before GnRH antagonist protocol improves IVF/ICSI outcomes compared with standard long GnRH agonist protocol.\n A prospective, randomized and controlled study.\n ART center of a state public hospital\n Two hundred twenty infertile women underwent IVF/ICSI treatments.\n Participants received oral Estradiol Valerate 4 mg/day preceding the IVF cycle from day 21 until day 2 of next cycle before GnRH antagonist protocol (E(2) pre-treatment group n=109) or received standard long GnRH agonist protocol as control group (n=111).\n Number of oocytes collected, MII oocytes, fertilization, implantation, live birth and early pregnancy rate, and hormone profiles.\n E(2) pre-treatment exerted a significant suppressive effect on FSH but not LH secretion compared with basal FSH and LH levels. In E(2) pre-treatment group serum LH level was significantly higher during COH and serum P was also significantly higher on the day of HCG injection compared with control group. Five patients from E(2) pre-treatment group had elevated LH at all time (>or= 10 IU/L) and also a concomitantly high P (>1 ng/mL). Two of the five women achieved pregnancy but had early pregnancy loss. Overall, IVF/ICSI outcomes such as implantation, clinical pregnancy and live birth rates were similar between E(2) pre-treatment and control groups.\n Luteal E(2) pre-treatment before GnRH antagonist protocol significantly increases serum LH level and incidence rate of premature LH but no significant effect is observed on implantation, clinical pregnancy, live birth and early pregnancy loss rates compared with long GnRH agonist protocol. However, more studies in large numbers of cycles are needed to confirm that increased serum LH level by E(2) pre-treatment during COH has no negative effect on the IVF/ICSI outcomes.", "The precise role of GnRH antagonists in the armamentarium of drugs for stimulation of ovulation associated with intrauterine insemination remains to be clarified. In this study, we have compared two different protocols employing GnRH antagonists in order to determine the lower effective dose of gonadotrophins to use.\n Sixty-six couples with unexplained infertility or moderate male subfertility were recruited. Starting on day 3 of the cycle, 32 patients were randomized to receive 50 IU of recombinant FSH per day, whereas 34 were treated with 50 IU of recombinant FSH on alternate days. Women received the GnRH antagonist Ganirelix at a dose of 0.25 mg per day starting on the day in which a leading follicle > or =14 mm in mean diameter was visualized, until HCG administration. Insemination was performed 34 h after HCG injection.\n The regimen with daily recombinant FSH was associated with a lower rate of mono-ovulation (53.3% versus 78.8%, P=0.06) but also with a higher clinical pregnancy rate per initiated cycle (34.4% versus 5.9%, P=0.005).\n A protocol of recombinant FSH 50 IU daily and GnRH antagonist may represent an effective and safe regimen for ovulation induction associated with intrauterine insemination.", "To compare the outcomes achieved by GnRH-antagonist and GnRH-agonist in IVF-ET for patients with poor ovarian responses, and to find out a better protocol for ovulation stimulation.\n (1) Patients with poor ovarian responses were assigned to an experimental (n = 63) and a control group (n = 58), treated respectively with GnRH-Ant and oral contraceptive plus micro-dose GnRH-a (OC + GnRH-a), and comparisons were made of the medication doses, laboratory results and pregnancy outcomes between the two groups. (2) Twenty of the patients were treated first with GnRH-Ant and then with OC + GnRH-a, and the same comparisons were made between the two protocols.\n Between the experimental and the control groups, there were no significant differences in the dose of Gn and number of retrieved oocytes and transplanted embryos (P > 0.05), nor in the pregnancy rate of transplantation cycles (37.29% vs 35.29%). The cycle cancellation rate was lower in the experimental than in the control group (6.35% vs 12.07%), with no statistical difference (P > 0.05). The cycle duration was significantly different between the two groups ([9.65 +/- 1.60] d vs [19.05 +/- 3.94] d) (P < 0.05). As for the comparison of GnRH-Ant with GnRH-a, no significant differences were observed in the dose of Gn and the numbers of retrieved oocytes and transplanted embryos (P > 0.05). GnRH-Ant achieved a higher pregnancy rate of transplantation cycles but a significantly lower cancellation rate than GnRH-a (38.09% vs 17.64% and 0% vs 15%) (P > 0.05 and P < 0.01), respectively. The cycle duration of the former was statistically shorter than that of the latter ([9.91 +/- 2.49] d vs [27.74 +/- 25.39] d) (P < 0.05).\n Compared with micro-dose GnRH-a, GnRH-Ant can shorten the cycle duration and reduce the cancellation rate in IVF-ET for patients with poor response. And for those who have failed to respond to GnRH-a, GnRH-Ant may be tried in another attempt at IVF-ET.", "To compare the efficacy of flare-up and GnRH-antagonist treatment in poor-responder patients.\n Randomized prospective study.\n Assisted reproduction center.\n Fifty-five poor-responder patients undergoing intracytoplasmic sperm injection (ICSI).\n Thirty patients received GnRH agonist on the 1st day of menstruation, followed by exogenous gonadotropins from the 2nd day. Twenty-five patients received exogenous gonadotropins starting on the second day of menstruation, followed by GnRH antagonist when the leading follicle reached 14 mm in diameter.\n The total dose of FSH administered during the ovarian stimulation, as well as the number of mature oocytes retrieved, embryo quality, fertilization, implantation, and pregnancy rates were evaluated.\n The number of ampules and units of FSH administered were significantly less in the flare-up than in the antagonistic group. The numbers of mature oocytes retrieved and of top-quality embryos transferred were significantly greater in the flare-up than in the GnRH-antagonist group. The fertilization rate (84% vs. 63%) was significantly higher in the flare-up than in the GnRH-antagonist group. The implantation and pregnancy rate were similar in the two groups.\n The flare-up protocol appears to be more effective than the GnRH-antagonist protocol in terms of mature oocytes retrieved, fertilization rate, and top-quality embryos transferred in poor-responder patients.", "To investigate the outcomes of intracytoplasmic sperm injection (ICSI) cycles after controlled ovarian hyperstimulation (COH) with GnRH antagonist or GnRH agonist (GnRH-a) in mild-to-moderate endometriosis and endometrioma.\n Prospective randomize trial.\n A private IVF center.\n A total of 246 ICSI cycles in 246 patients were divided into three groups: women with mild-to-moderate endometriosis (n = 98); women who had ovarian surgery for endometrioma (n = 81); women with endometrioma and no history of previous surgery (n = 67).\n Patients in each group were randomized to COH with either triptrolein or cetrorelix.\n Clinical parameters, characteristics of COH, and ICSI results were analyzed.\n Outcomes of COH with both GnRH antagonist and GnRH-a were similar in patients with mild-to-moderate endometriosis. Implantation rates were 15.9% vs. 22.6% and clinical pregnancy rates were 27.5% vs. 39% with GnRH antagonist and GnRH-a protocols, respectively, in patients who had ovarian surgery for endometrioma. Implantation rates were 12.5% vs. 14.8% and clinical pregnancy rates were 20.5% vs. 24.2% with GnRH antagonist and GnRH-a protocols, respectively, in patients with endometrioma and no history of ovarian surgery.\n Considering the implantation and clinical pregnancy rates, COH with both GnRH antagonist and GnRH-a protocols may be equally effective in patients with mild-to-moderate endometriosis and endometrioma who did and did not undergo ovarian surgery.", "We aimed to determine the efficacy of ovarian hyperstimulation protocols employing a GnRH antagonist to prevent a premature LH rise allowing final oocyte maturation and ovulation to be induced by a single bolus of either a GnRH agonist or hCG.\n A total of 122 normogonadotrophic patients following a flexible antagonist protocol was stimulated with recombinant human FSH and prospectively randomized (sealed envelopes) to ovulation induction with a single bolus of either 0.5 mg buserelin s.c. (n = 55) or 10,000 IU of hCG (n = 67). A maximum of two embryos was transferred. Luteal support consisted of micronized progesterone vaginally, 90 mg a day, and estradiol, 4 mg a day per os.\n Ovulation was induced with GnRH agonist in 55 patients and hCG in 67 patients. Significantly more metaphase II (MII) oocytes were retrieved in the GnRH agonist group (P < 0.02). Significantly higher levels of LH and FSH (P < 0.001) and significantly lower levels of progesterone and estradiol (P < 0.001) were seen in the GnRH agonist group during the luteal phase. The implantation rate, 33/97 versus 3/89 (P < 0.001), clinical pregnancy rate, 36 versus 6% (P = 0.002), and rate of early pregnancy loss, 4% versus 79% (P = 0.005), were significantly in favour of hCG.\n Ovulation induction with a GnRH agonist resulted in significantly more MII oocytes. However, a significantly lower implantation rate and clinical pregnancy rate in addition to a significantly higher rate of early pregnancy loss was seen in the GnRH agonist group, most probably due to a luteal phase deficiency.", "The aim of this study was to evaluate the response to treatment in a group of patients undergoing IVF and randomised to receive GnRH-antagonist or the GnRH-agonist. The endpoints were the pattern of follicular growth, the maturity of the oocytes collected, the embryo quality and the pregnancy outcome.\n A total of 136 patients undergoing IVF were included. Sixty-seven patients were allocated to the GnRH antagonist and 69 patients to the GnRH agonist. GnRH antagonist was administered when the leading follicle reached a diameter of 12-14 mm. GnRH agonist was administered in a long luteal protocol.\n The mean numbers of oocytes retrieved and mature oocytes were significantly higher in the agonist than in the antagonist group (p < 0.02 and p < 0.01, respectively). Embryo quality, implantation rate, clinical pregnancy rates, ongoing pregnancy rate and miscarriage rate were similar in both groups.\n Better follicular growth and oocyte maturation are achieved with GnRH agonist treatment. However, both regimens seem to have similar efficacy in terms of implantation and pregnancy rates. Further studies clarifying the effect of the GnRH antagonist on ovarian function are needed, as well as a clear definition of the best period of the follicular phase for the GnRH antagonist administration.", "This randomized controlled trial was designed to assess the impact of oral contraceptive (OC) scheduling with a GnRH antagonist (ganirelix) regimen on the ovarian response of women undergoing recombinant FSH (rFSH) stimulation for IVF, compared with a non-scheduled ganirelix regimen and a long GnRH agonist (nafarelin) protocol.\n A total of 110 women was treated with an OC and ganirelix, 111 with ganirelix alone and 111 with nafarelin. The OC (containing 30 microg ethinylestradiol/150 microg desogestrel) was taken for 14-28 days and stopped 2 days prior to the start of rFSH treatment. Primary efficiency parameters were the number of cumulus-oocyte complexes (per attempt) and the number of grade 1 or 2 embryos (per attempt).\n In terms of follicular growth and hormone profiles, the OC-scheduled antagonist regimen mimicked the agonist regimen rather than the (non-scheduled) GnRH antagonist regimen. In the OC-scheduled GnRH antagonist group and the nafarelin group (versus the non-scheduled antagonist group), pituitary suppression was more profound at the start of stimulation (P < or = 0.001), there was a slower start of follicular growth (P < or = 0.001), longer stimulation was required (11.7 and 10.3 days respectively versus 9.4; P < or = 0.001), and more rFSH was used (2667 and 2222 IU versus 1966 IU; P < or = 0.001). In the three groups, the number of oocytes was similar (13.1, 12.9 and 11.5 respectively; not significant) as well as the number of good quality embryos (5.1, 5.7 and 5.0 respectively; not significant).\n OC treatment prior to the rFSH/ganirelix regimen can be successfully applied to schedule patients, although more days of stimulation and more rFSH are required than with a non-scheduled GnRH antagonist regimen.", "The aim of the study was to investigate the cause of the lower estradiol (E(2)) concentration in women treated with gonadotropin-releasing hormone (GnRH) antagonist compared with those treated with agonist protocol in in vitro fertilization (IVF). Thirty patients who were known low responders were prospectively randomized into two equal groups for IVF treatment. Group 1 used GnRH agonist (flare-up) protocol and group 2 used antagonist protocol. The results showed that serum luteinizing hormone (LH) levels were significantly higher in the agonist group during the folliculogenesis stage. Despite this higher LH, serum E(2) levels were significantly higher in the agonist group on cycle day 2 only, not on day 5 or day 9. The significantly higher E(2) level in the agonist group reappeared on the day of administration of human chorionic gonadotropin (hCG). The rate of folliculogenesis in the antagonist group was faster than in the agonist group; therefore their E(2) production should have been higher on hCG day. Furthermore, the rate of decline in E(2) after hCG administration was significantly higher in the antagonist group. These findings, along with the fact that both groups received exogenous LH (human menopausal gonadotropin) that should optimize steroidogenesis and make the difference in E(2) insignificant, enable us to conclude that GnRH antagonists have a suppressive effect on the production of E(2).", "Luteal defect is common during IVF cycles using GnRH agonist. It could be interesting to make up for this problem by using short acting GnRH agonist (effective for 24 hours), more handy at the end of the stimulation. 160 patients included in a long IVF protocol at the Bordeaux CHRU FIV center have been randomized, from September 1993 to August 1994, for the analog's choice (long or short) at the beginning of the stimulation. The stimulation's parameters, the hormonal dosages and the pregnancy rate are independent of the galenic form used. In close, the use of long-acting GnRH analog (sympler to use) sems preferable.", "GnRH agonist administration in the luteal phase was reported to beneficially affect the clinical outcome of intracytoplasmic sperm injection (ICSI) and embryo transfer (ET) cycles. This double blind, randomized, placebo controlled trial evaluates whether a single dose GnRH agonist administered 6 days after ICSI increases ongoing pregnancy rates following ET in cycles stimulated with the long GnRH agonist protocol.\n Five hundred and seventy women undergoing ET following controlled ovarian stimulation with a long GnRH agonist protocol were included. In addition to routine luteal phase support with progesterone, women were randomized to receive a single 0.1 mg dose of triptorelin or placebo 6 days after ICSI. Randomization was done on the day of ET according to a computer generated randomization table. Ongoing pregnancy rate beyond 20th week of gestation was the primary outcome measure. The trial was powered to detect a 12% absolute increase from an assumed 38% ongoing pregnancy rate in the placebo group, with an alpha error level of 0.05 and a beta error level of 0.2.\n There were 89 (31.2%) ongoing pregnancies in the GnRH agonist group, and 84 (29.5%) in the control group (absolute difference +1.7%, 95% confidence interval -5.8% to +9.2%). Implantation, clinical pregnancy and multiple pregnancy rates were likewise similar in the GnRH agonist and placebo groups.\n Single 0.1 mg triptorelin administration 6 days after ICSI following ovarian stimulation with the long GnRH agonist protocol does not seem to result in an increase >or=12% in ongoing pregnancy rates.", "To compare the effects of oral contraceptive (OC) pill pretreatment in recombinant FSH/GnRH-antagonist versus recombinant FSH/GnRH-agonist stimulation in in vitro fertilization (IVF) patients, and to evaluate optimization of retrieval day.\n Prospective, randomized, multicenter study.\n Private practice and university centers.\n Eighty patients undergoing IVF who met the appropriate inclusion criteria.\n Four study centers recruited 80 patients. The OC regimen began on cycle days 2 to 4 and was discontinued on a Sunday after 14 to 28 days. The recombinant FSH regimen was begun on the following Friday. The GnRH-agonist group was treated with a long protocol; the GnRH-antagonist was initiated when the lead follicle reached 12 to 14 mm. When two follicles had reached 16 to 18 mm, hCG was administered.\n The primary outcome measures were the number of cumulus-oocyte complexes, day of the week for oocyte retrieval, and total dose and days of stimulation of recombinant FSH. Secondary efficacy variables included pregnancy and implantation rate; serum E(2) levels on stimulation day 1; serum E(2), P, and LH levels on the day of hCG administration; follicle size on day 6 and day of hCG administration; the total days of GnRH-analogue treatment; total days on OC; total days from end of OC to oocyte retrieval; and the cycle cancellation rate.\n Patient outcomes were similar for the days of stimulation, total dose of gonadotropin used, two-pronuclei embryos, pregnancy (44.4% GnRH-antagonist vs. 45.0% GnRH-agonist, P=.86) and implantation rates (22.2% GnRH-antagonist vs. 26.4% GnRH-agonist, P=.71). Oral contraceptive cycle scheduling resulted in 78% and 90% of retrievals performed Monday through Friday for GnRH-antagonist and GnRH-agonist. A one day delay in OC discontinuation and recombinant FSH start would result in over 90% of oocyte retrievals occurring Monday through Friday in both groups.\n The OC pretreatment in recombinant FSH/GnRH-antagonist protocols provides a patient-friendly regimen and can be optimized for weekday retrievals. No difference was seen in number of 2PN embryos, cryopreserved embryos, embryos transferred, implantation and pregnancy rates between the two stimulation protocols." ]	The use of antagonist compared with long GnRH agonist protocols was associated with a large reduction in OHSS and there was no evidence of a difference in live-birth rates.
CD002960	[ "7980301" ]	[ "A safer and more effective treatment regimen for eclampsia." ]	[ "In a prospective controlled trial 91 consecutive women with eclampsia were randomly allocated either to a magnesium sulphate and nifedipine regime or to a lytic cocktail and nifedipine group. The type and severity of disease, details of labour and delivery, and the maternal and perinatal outcomes and complications related to the 2 treatment regimens were compared. Recurrence of fits, aspiration pneumonia and sudden hypotension were significantly reduced when patients were treated with the new magnesium sulphate and nifedipine regimen compared with the lytic cocktail plus nifedipine regimen. No patient treated with the new regimen died or had respiratory depression; in the other group there were 2 maternal deaths plus 1 case of severe hypoxic brain damage. No difference was observed in duration of labour or mode of delivery. Perinatal mortality was significantly lower in the magnesium sulphate plus nifedipine treated group. The synergistic action of magnesium sulphate and nifedipine in the dosage employed in this study may be used to reduce maternal and perinatal mortality and morbidity in women with eclampsia." ]	Magnesium sulphate, rather than lytic cocktail, for women with eclampsia reduces the RR of maternal death, of further seizures and of serious maternal morbidity (respiratory depression, coma, pneumonia). Magnesium sulphate is the anticonvulsant of choice for women with eclampsia; the use of lytic cocktail should be abandoned.
CD007170	[ "16549460", "16634838", "17392542", "14633804", "17718288", "20854384", "19734396", "17563345" ]	[ "Cinnamon supplementation does not improve glycemic control in postmenopausal type 2 diabetes patients.", "Effects of a cinnamon extract on plasma glucose, HbA, and serum lipids in diabetes mellitus type 2.", "The effect of cinnamon on A1C among adolescents with type 1 diabetes.", "Cinnamon improves glucose and lipids of people with type 2 diabetes.", "The effect of cinnamon cassia powder in type 2 diabetes mellitus.", "Glycated haemoglobin and blood pressure-lowering effect of cinnamon in multi-ethnic Type 2 diabetic patients in the UK: a randomized, placebo-controlled, double-blind clinical trial.", "Effectiveness of cinnamon for lowering hemoglobin A1C in patients with type 2 diabetes: a randomized, controlled trial.", "Effect of cinnamon on glucose and lipid levels in non insulin-dependent type 2 diabetes." ]	[ "In vitro and in vivo animal studies have reported strong insulin-like or insulin-potentiating effects after cinnamon administration. Recently, a human intervention study showed that cinnamon supplementation (1 g/d) strongly reduced fasting blood glucose concentration (30%) and improved the blood lipid profile in patients with type 2 diabetes. The objective of this study was to investigate the effects of cinnamon supplementation on insulin sensitivity and/or glucose tolerance and blood lipid profile in patients with type 2 diabetes. Therefore, a total of 25 postmenopausal patients with type 2 diabetes (aged 62.9 +/- 1.5 y, BMI 30.4 +/- 0.9 kg/m2) participated in a 6-wk intervention during which they were supplemented with either cinnamon (Cinnamomum cassia, 1.5 g/d) or a placebo. Before and after 2 and 6 wk of supplementation, arterialized blood samples were obtained and oral glucose tolerance tests were performed. Blood lipid profiles and multiple indices of whole-body insulin sensitivity were determined. There were no time x treatment interactions for whole-body insulin sensitivity or oral glucose tolerance. The blood lipid profile of fasting subjects did not change after cinnamon supplementation. We conclude that cinnamon supplementation (1.5 g/d) does not improve whole-body insulin sensitivity or oral glucose tolerance and does not modulate blood lipid profile in postmenopausal patients with type 2 diabetes. More research on the proposed health benefits of cinnamon supplementation is warranted before health claims should be made.", "According to previous studies, cinnamon may have a positive effect on the glycaemic control and the lipid profile in patients with diabetes mellitus type 2. The aim of this trial was to determine whether an aqueous cinnamon purified extract improves glycated haemoglobin A1c (HbA1c), fasting plasma glucose, total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL) and triacylglycerol concentrations in patients with type 2 diabetes.\n A total of 79 patients with diagnosed diabetes mellitus type 2 not on insulin therapy but treated with oral antidiabetics or diet were randomly assigned to take either a cinnamon extract or a placebo capsule three times a day for 4 months in a double-blind study. The amount of aqueous cinnamon extract corresponded to 3 g of cinnamon powder per day.\n The mean absolute and percentage differences between the pre- and post-intervention fasting plasma glucose level of the cinnamon and placebo groups were significantly different. There was a significantly higher reduction in the cinnamon group (10.3%) than in the placebo group (3.4%). No significant intragroup or intergroup differences were observed regarding HbA1c, lipid profiles or differences between the pre- and postintervention levels of these variables. The decrease in plasma glucose correlated significantly with the baseline concentrations, indicating that subjects with a higher initial plasma glucose level may benefit more from cinnamon intake. No adverse effects were observed.\n The cinnamon extract seems to have a moderate effect in reducing fasting plasma glucose concentrations in diabetic patients with poor glycaemic control.", "The purpose of this study was to determine the effect of cinnamon on glycemic control in adolescents with type 1 diabetes.\n Using a prospective, double-blind, placebo-controlled design, 72 adolescent type 1 diabetic subjects were treated in an outpatient setting with cinnamon (1 g/day) or an equivalent-appearing placebo for 90 days. A1C, total daily insulin intake, and adverse events were recorded and compared between groups.\n There were no significant differences in final A1C (8.8 vs. 8.7, P = 0.88), change in A1C (0.3 vs. 0.0, P = 0.13), total daily insulin intake, or number of hypoglycemic episodes between the cinnamon and placebo arms.\n Cinnamon is not effective for improving glycemic control in adolescents with type 1 diabetes.", "The objective of this study was to determine whether cinnamon improves blood glucose, triglyceride, total cholesterol, HDL cholesterol, and LDL cholesterol levels in people with type 2 diabetes.\n A total of 60 people with type 2 diabetes, 30 men and 30 women aged 52.2 +/- 6.32 years, were divided randomly into six groups. Groups 1, 2, and 3 consumed 1, 3, or 6 g of cinnamon daily, respectively, and groups 4, 5, and 6 were given placebo capsules corresponding to the number of capsules consumed for the three levels of cinnamon. The cinnamon was consumed for 40 days followed by a 20-day washout period.\n After 40 days, all three levels of cinnamon reduced the mean fasting serum glucose (18-29%), triglyceride (23-30%), LDL cholesterol (7-27%), and total cholesterol (12-26%) levels; no significant changes were noted in the placebo groups. Changes in HDL cholesterol were not significant.\n The results of this study demonstrate that intake of 1, 3, or 6 g of cinnamon per day reduces serum glucose, triglyceride, LDL cholesterol, and total cholesterol in people with type 2 diabetes and suggest that the inclusion of cinnamon in the diet of people with type 2 diabetes will reduce risk factors associated with diabetes and cardiovascular diseases.", "Type 2 diabetes is a chronic metabolic disorder and the incidence of cardiovascular is increased two- to fourfold in its complications. Cinnamon is expected to have some degree of anti-diabetic efficacy without troublesome side effects. The objective of the present study was to investigate the anti-diabetic effect of cinnamon cassia powder in type 2 diabetic patients\n Sixty type 2 diabetic patients were randomized either 1.5 g/d of cinnamon cassia powder or placebo. Both groups were in combination with their current treatment (metformin or sulfonylurea) according to single blind randomized, placebo-control trial in a 12-week period. Efficacy was evaluated by HbA1c fasting plasma glucose, Lipid profile, BUN, creatinine, liver function test and adverse effects were recorded.\n After a 12-week period, HbA1c was decreased similarly in both groups from 8.14% to 7.76% in the cinnamon group and from 8.06% to 7.87% in the placebo group. This was not found statistically significantly different. However the proportion of patients achieving HbA1c < or = 7% was also greater in patients receiving cinnamon compared with patients receiving placebo, nevertheless, it was not found statistically significantly different (35% vs 15%, x2 = 3.14, p > 0.05). No significant intergroup differences were observed in lipid profile, fasting plasma glucose except in SGOT 27.1 (8.75) to 22.1 (5) in cinnamon group and 24.08 (8.5) to 23.63 (8.88) in the placebo group (p = 0.001).\n The cinnamon cassia powder 1.5 g/d did not have any significant difference in reducing fasting plasma glucose, HbA1c and serum lipid profile in type 2 diabetes patients who had mean fasting plasma glucose 154.40 +/- 24.72 mg/dl.", "To determine the blood glucose lowering effect of cinnamon on HbA1c, blood pressure and lipid profiles in people with type 2 diabetes.\n 58 type 2 diabetic patients (25 males and 33 females), aged 54.9 ± 9.8, treated only with hypoglycemic agents and with an HbA1c more than 7% were randomly assigned to receive either 2g of cinnamon or placebo daily for 12 weeks.\n After intervention, the mean HbA1c was significantly decreased (P<0.005) in the cinnamon group (8.22% to 7.86%) compared with placebo group (8.55% to 8.68%). Mean systolic and diastolic blood pressures (SBP and DBP) were also significantly reduced (P<0.001) after 12 weeks in the cinnamon group (SBP: 132.6 to 129.2 mmHg and DBP: 85.2 to 80.2 mmHg) compared with the placebo group (SBP: 134.5 to 134.9 mmHg and DBP: 86.8 to 86.1 mmHg). A significant reduction in fasting plasma glucose (FPG), waist circumference and body mass index (BMI) was observed at week 12 compared to baseline in the cinnamon group, however, the changes were not significant when compared to placebo group. There were no significant differences in serum lipid profiles of total cholesterol, triglycerides, HDL and LDL cholesterols neither between nor within the groups.\n Intake of 2g of cinnamon for 12 weeks significantly reduces the HbA1c, SBP and DBP among poorly controlled type 2 diabetes patients. Cinnamon supplementation could be considered as an additional dietary supplement option to regulate blood glucose and blood pressure levels along with conventional medications to treat type 2 diabetes mellitus.\n © 2010 The Authors. Diabetic Medicine © 2010 Diabetes UK.", "Multiple trials in the past have shown conflicting results of whether cinnamon lowers glucose or hemoglobin A1C (HbA1C). The purpose of this study was to determine whether cinnamon lowers HbA1C in patients with type 2 diabetes. I performed a randomized, controlled trial to evaluate whether daily cinnamon plus usual care versus usual care alone lowers HbA1c.\n I randomized 109 type 2 diabetics (HbA1C >7.0) from 3 primary care clinics caring for pediatric, adult, and geriatric patients at a United States military base. Participants were randomly allocated to either usual care with management changes by their primary care physician or usual care with management changes plus cinnamon capsules, 1g daily for 90 days. HbA1c was drawn at baseline and 90 days and compared with intention-to-treat analysis. This study was approved by an institutional review board.\n Cinnamon lowered HbA1C 0.83% (95% CI, 0.46-1.20) compared with usual care alone lowering HbA1C 0.37% (95% CI, 0.15-0.59).\n Taking cinnamon could be useful for lowering serum HbA1C in type 2 diabetics with HbA1C >7.0 in addition to usual care.", "nan" ]	There is insufficient evidence to support the use of cinnamon for type 1 or type 2 diabetes mellitus. Further trials, which address the issues of allocation concealment and blinding, are now required. The inclusion of other important endpoints, such as health-related quality of life, diabetes complications and costs, is also needed.
CD006742	[ "2046107" ]	[ "Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension. Final results of the Systolic Hypertension in the Elderly Program (SHEP). SHEP Cooperative Research Group." ]	[ "To assess the ability of antihypertensive drug treatment to reduce the risk of nonfatal and fatal (total) stroke in isolated systolic hypertension.\n Multicenter, randomized, double-blind, placebo-controlled.\n Community-based ambulatory population in tertiary care centers.\n 4736 persons (1.06%) from 447,921 screenees aged 60 years and above were randomized (2365 to active treatment, 2371 to placebo). Systolic blood pressure ranged from 160 to 219 mm Hg and diastolic blood pressure was less than 90 mm Hg. Of the participants, 3161 were not receiving antihypertensive medication at initial contact, and 1575 were. The average systolic blood pressure was 170 mm Hg; average diastolic blood pressure, 77 mm Hg. The mean age was 72 years, 57% were women, and 14% were black.\n --Participants were stratified by clinical center and by antihypertensive medication status at initial contact. For step 1 of the trial, dose 1 was chlorthalidone, 12.5 mg/d, or matching placebo; dose 2 was 25 mg/d. For step 2, dose 1 was atenolol, 25 mg/d, or matching placebo; dose 2 was 50 mg/d.\n Primary. Nonfatal and fatal (total) stroke. Secondary. Cardiovascular and coronary morbidity and mortality, all-cause mortality, and quality of life measures.\n Average follow-up was 4.5 years. The 5-year average systolic blood pressure was 155 mm Hg for the placebo group and 143 mm Hg for the active treatment group, and the 5-year average diastolic blood pressure was 72 and 68 mm Hg, respectively. The 5-year incidence of total stroke was 5.2 per 100 participants for active treatment and 8.2 per 100 for placebo. The relative risk by proportional hazards regression analysis was 0.64 (P = .0003). For the secondary end point of clinical nonfatal myocardial infarction plus coronary death, the relative risk was 0.73. Major cardiovascular events were reduced (relative risk, 0.68). For deaths from all causes, the relative risk was 0.87.\n In persons aged 60 years and over with isolated systolic hypertension, antihypertensive stepped-care drug treatment with low-dose chlorthalidone as step 1 medication reduced the incidence of total stroke by 36%, with 5-year absolute benefit of 30 events per 1000 participants. Major cardiovascular events were reduced, with 5-year absolute benefit of 55 events per 1000." ]	Antihypertensive drugs used in the treatment of adults (primary prevention) with mild hypertension (systolic BP 140-159 mmHg and/or diastolic BP 90-99 mmHg) have not been shown to reduce mortality or morbidity in RCTs. Treatment caused 9% of patients to discontinue treatment due to adverse effects. More RCTs are needed in this prevalent population to know whether the benefits of treatment exceed the harms.
CD004772	[ "18580613", "20823434", "18977721", "19549342" ]	[ "Early virological suppression with three-class antiretroviral therapy in HIV-infected African infants.", "Reuse of nevirapine in exposed HIV-infected children after protease inhibitor-based viral suppression: a randomized controlled trial.", "Virologic, immunologic, clinical, safety, and resistance outcomes from a long-term comparison of efavirenz-based versus nevirapine-based antiretroviral regimens as initial therapy in HIV-1-infected persons.", "Medication diaries do not improve outcomes with highly active antiretroviral therapy in Kenyan children: a randomized clinical trial." ]	[ "Infants infected with HIV-1 perinatally despite single-dose nevirapine progress rapidly. Data on treatment outcome in sub-Saharan African infants exposed to single-dose nevirapine are urgently required. This feasibility study addresses efficacy of infant antiretroviral therapy in this setting.\n HIV-infected infants in Durban, South Africa, received randomized immediate or deferred (when CD4 cell count reached <20%) four-drug antiretroviral therapy (zidovudine/lamivudine/nelfinavir/nevirapine). Genotyping for non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance was undertaken pre-antiretroviral therapy. Monthly follow-up to 1-year post-antiretroviral therapy included viral load, CD4 cell count and verbal/measured adherence monitoring.\n All 63 infants were exposed to single-dose nevirapine. Twenty-one out of 51 (39%) infants with baseline genotyping results had NNRTI resistance (most frequently Y181C; 20%). Forty-three infants were randomized to immediate antiretroviral therapy (ART): three withdrew pre-antiretroviral therapy; 36 out of 40 completed 1-year of ART. Twenty infants received deferred ART: 17 reached CD4 cell counts less than 20% (median d99) and 13 out of 17 started antiretroviral therapy in year 1. Verbal and measured adherence was 99% and 95%, respectively. One-year post-ART, 49 out of 49 (100%) infants had a viral load less than 400 copies/ml; 46 out of 49 (94%) had viral load less than 50 copies/ml. Ten infants (20%) required second-line ART due to virological failure or tuberculosis treatment, therefore 39 out of 49 (80%) achieved viral load less than 400 copies/ml by intention-to-treat. Time to viral load less than 50 copies/ml correlated with maternal CD4 cell count (r = -0.42; P = 0.005) and infant pre-ART viral load (r = 0.64; P < 0.001). NNRTI mutations had no significant effect on virological suppression. Infants starting immediate compared with deferred ART had fewer illness episodes (P = 0.003), but no significant difference in virological suppression.\n Excellent adherence and virological suppression are achievable in infants, despite high-frequency NNRTI mutations and rapid disease progression. Infants remain relatively neglected in roll-out programmes and ART provision must be expanded.", "Protease inhibitor (PI)-based therapy is recommended for infants infected with human immunodeficiency virus (HIV) who were exposed to nevirapine for prevention of mother-to-child HIV transmission. However, there are limitations of continuing PI-based therapy indefinitely and reuse of nevirapine has many advantages.\n To test whether nevirapine-exposed infants who initially achieve viral suppression with PI-based therapy can maintain viral suppression when switched to nevirapine-based therapy.\n Randomized trial conducted between April 2005 and May 2009 at a hospital in Johannesburg, South Africa, among 195 children who achieved viral suppression less than 400 copies/mL for 3 or more months from a cohort of 323 nevirapine-exposed children who initiated PI-based therapy before 24 months of age.\n Control group children continued to receive ritonavir-boosted lopinavir, stavudine, and lamivudine (n = 99). Switch group children substituted nevirapine for ritonavir-boosted lopinavir (n = 96).\n Children were followed up for 52 weeks after randomization. Plasma HIV-1 RNA of greater than 50 copies/mL was the primary end point. Confirmed viremia greater than 1000 copies/mL was used as a criterion to consider regimen changes for children in either group (safety end point).\n Plasma viremia greater than 50 copies/mL occurred less frequently in the switch group (Kaplan-Meier probability, 0.438; 95% CI, 0.334-0.537) than in the control group (0.576; 95% CI, 0.470-0.668) (P = .02). Confirmed viremia greater than 1000 copies/mL occurred more frequently in the switch group (0.201; 95% CI, 0.125-0.289) than in the control group (0.022; 95% CI, 0.004-0.069) (P < .001). CD4 cell response was better in the switch group (median CD4 percentage at 52 weeks, 34.7) vs the control group (CD4 percentage, 31.3) (P = .004). Older age (relative hazard [RH], 1.71; 95% CI, 1.08-2.72) was associated with viremia greater than 50 copies/mL in the control group. Inadequate adherence (RH, 4.14; 95% CI, 1.18-14.57) and drug resistance (RH, 4.04; 95% CI, 1.40-11.65) before treatment were associated with confirmed viremia greater than 1000 copies/mL in the switch group.\n Among HIV-infected children previously exposed to nevirapine, switching to nevirapine-based therapy after achieving viral suppression with a ritonavir-boosted lopinavir regimen resulted in lower rates of viremia greater than 50 copies/mL than maintaining the primary ritonavir-boosted lopinavir regimen.\n clinicaltrials.gov Identifier: NCT00117728.", "To compare long-term virologic, immunologic, and clinical outcomes in antiretroviral-naïve persons starting efavirenz (EFV)- versus nevirapine (NVP)-based regimens.\n The FIRST study randomized patients into three strategy arms: PI+NRTI, NNRTI+NRTI, and PI+NNRTI+NRTI. NNRTI was determined by optional randomization (NVP or EFV) or by choice. For this randomized substudy, the primary endpoint was HIV RNA >50 copies/mL after 8 months or death. Genotypic resistance testing was done at virologic failure (VF; HIV RNA >1,000 copies/mL at or after 4 months).\n 228 persons (111 randomized to EFV, 117 to NVP) were followed for median 5 years. Rates per 100 person years for the primary endpoint were 41.2 (EFV) and 42.8 (NVP; p = .59). The percent of persons with HIV RNA <50 copies/mL was similar throughout follow-up (p = .24), as were average increases in CD4+ cells (p = .30). 423 persons declining the substudy chose EFV; 264 chose NVP. There were 915 persons in the combined cohort (randomized and choice). In the combined cohort, the risk of VF and VF with any NNRTI or NRTI resistance or resistance of any class was significantly less for EFV compared to NVP.\n EFV-based regimens as initial therapy resulted in a lower risk of VF and VF with resistance than did NVP-based regimens, although immunologic and clinical outcomes were similar.", "As highly active antiretroviral therapy (HAART) becomes increasingly available to African children, it is important to evaluate simple and feasible methods of improving adherence in order to maximize benefits of therapy.\n HIV-1-infected children initiating World Health Organization non-nucleoside reverse transcriptase-inhibitor-containing first-line HAART regimens were randomized to use medication diaries plus counselling, or counselling only (the control arm of the study). The diaries were completed daily by caregivers of children randomized to the diary and counselling arm for nine months. HIV-1 RNA, CD4+ T cell count, and z-scores for weight-for-age, height-for-age and weight-for-height were measured at a baseline and every three to six months. Self-reported adherence was assessed by questionnaires for nine months.\n Ninety HIV-1-infected children initiated HAART, and were followed for a median of 15 months (interquartile range: 2-21). Mean CD4 percentage was 17.2% in the diary arm versus 16.3% in the control arm at six months (p = 0.92), and 17.6% versus 18.9% at 15 months (p = 0.36). Virologic response with HIV-1 RNA of <100 copies/ml at nine months was similar between the two arms (50% for the diary arm and 36% for the control, p = 0.83). The weight-for-age, height-for-age and weight-for-height at three, nine and 15 months after HAART initiation were similar between arms. A trend towards lower self-reported adherence was observed in the diary versus the control arm (85% versus 92%, p = 0.08).\n Medication diaries did not improve clinical and virologic response to HAART over a 15-month period. Children had good adherence and clinical response without additional interventions. This suggests that paediatric HAART with conventional counselling can be a successful approach. Further studies on targeted approaches for non-adherent children will be important." ]	Immediate ART reduces morbidity and mortality among infants and may improve neurodevelopmental outcome. However It remains unclear whether all children diagnosed with HIV infection between 1-2 years of age should start ART, as has been recommended by the World Health Organization on practical grounds. The available evidence suggests that a LPV/r-based first-line regimen is more potent than NVP, regardless of PMTCT exposure status. However, this finding provides a dilemma to policy-makers because higher cost, poor palatability, inconvenient formulation and cold chain requirements make LPV/r a more costly and challenging first-line regimen. An alternative approach to long-term LPV/r is switching to NVP (maintaining the NRTI backbone) once virological suppression is achieved. This strategy looked promising in the one trial undertaken, but may be difficult to implement in the absence of VL testing. Ongoing trials are exploring the possibility of starting early ART and interrupting treatment beyond the critical period of rapid disease progression and neurological development. Further evidence is urgently required to better inform policy on first-line treatment recommendations in young children and more robust data addressing non-virological outcomes are also needed.
CD006880	[ "15746784", "17318804", "16327491", "16034832", "11485528", "15798459", "16491462" ]	[ "Sharp liver transection versus clamp crushing technique in liver resections: a prospective study.", "Randomized clinical trial of radiofrequency-assisted versus clamp-crushing liver resection.", "How should transection of the liver be performed?: a prospective randomized study in 100 consecutive patients: comparing four different transection strategies.", "Randomized clinical trial of the effect of a saline-linked radiofrequency coagulator on blood loss during hepatic resection.", "Randomized comparison of ultrasonic vs clamp transection of the liver.", "Complete versus selective portal triad clamping for minor liver resections: a prospective randomized trial.", "Randomized clinical trial of the effects of abdominal drainage after elective hepatectomy using the crushing clamp method." ]	[ "Parenchymal liver transection constitutes an important phase of liver resection. Serious intraoperative bleeding, together with injuries to vital structures of the liver remnant, can occur during this stage. A method of sharp liver parenchymal transection with scalpel is compared in a prospective randomized manner with the widely used clamp crushing technique.\n Patients scheduled for hepatectomy under selective hepatic vascular exclusion (N = 82) were allocated randomly to either the sharp transection group (n = 41) or the clamp crushing group (n = 41). Warm ischemic time, blood loss and transfusions, postoperative morbidity and mortality, and tumor-free margins were recorded in both groups and analyzed.\n When the sharp transection group was compared with the clamp crushing group, the two groups were similar in warm ischemic time (median 36 vs 34 minutes), total operative time (median 205 vs 211 minutes), intraoperative blood loss (median 500 vs 460 mL), blood transfusion requirements (median value 0 in both groups), and overall complication rate (44% vs 39%). However, sharp transection yielded better tumor-free margins compared with the clamp crushing technique (12 +/- 1.4 mm vs 8 +/- 1.5 mm, mean +/- SD, P < .05).\n Sharp liver parenchymal transection with a scalpel is equally safe in terms of blood loss and mortality compared with the clamp crushing method. Although it is a technically demanding method, requiring selective hepatic vascular occlusion, it may be recommended when the tumor-free margins are anticipated to be narrow.", "Surgical resection remains the treatment of choice for primary and secondary liver cancer. Complications are mainly related to blood loss. Radiofrequency-assisted liver resection (RF-R) has been proposed for parenchymal division as an alternative to clamp crushing in order to reduce blood loss.\n Fifty patients (median age 62 (range 30-82) years) undergoing hepatectomy were randomized to RF-R (24 patients) or the clamp-crushing method (26). In the RF-R group the resection plane was precoagulated by multiple insertion of a planar triple-cooled radiofrequency ablation needle, and then the parenchyma was sectioned using a scalpel.\n The two groups were well matched in terms of age, sex, liver disease and type of resection. There were no deaths. Eight in the RF-R group developed complications (abscess in six, biliary fistula in three and biliary stenosis in one) compared with none of those who had resection by the crush method (P < 0.001). Two patients with cirrhosis in each group developed decompensation. Blood transfusion was required in eight of 24 patients in the RF-R group and 13 of 26 in the clamp-crushing group (P = 0.079).\n RF-R allows parenchymal resection in a clean surgical field but is associated with a higher rate of postoperative complications than the clamp-crushing technique.\n (c) 2007 British Journal of Surgery Society Ltd.", "To identify the most efficient parenchyma transection technique for liver resection using a prospective randomized protocol.\n Liver resection can be performed by different transection devices with or without inflow occlusion (Pringle maneuver). Only limited data are currently available on the best transection technique.\n A randomized controlled trial was performed in noncirrhotic and noncholestatic patients undergoing liver resection comparing the clamp crushing technique with Pringle maneuver versus CUSA versus Hydrojet versus dissecting sealer without Pringle maneuver (25 patients each group). Primary endpoints were intraoperative blood loss, resection time, and postoperative liver injury. Secondary end points included the use of inflow occlusion, postoperative complications, and costs.\n The clamp crushing technique had the highest transection velocity (3.9 +/- 0.3 cm/min) and lowest blood loss (1.5 +/- 0.3 mL/cm) compared with CUSA (2.3 +/- 0.2 cm/min and 4 +/- 0.7 mL/cm), Hydrojet (2.4 +/- 0.3 cm/min and 3.5 +/- 0.5 mL/cm), and dissecting sealer (2.5 +/- 0.3 cm/min and 3.4 +/- 0.4 mL/cm) (velocity: P = 0.001; blood loss: P = 0.003). Clamp crushing technique was associated with the lowest need for postoperative blood transfusions. The degree of postoperative reperfusion injury and complications were not significantly different among the groups. The clamp crushing technique proved to be most cost-efficient device and had a cost-saving potential of 600 to 2400 per case.\n The clamp crushing technique was the most efficient device in terms of resection time, blood loss, and blood transfusion frequency compared with CUSA, Hydrojet, and dissecting sealer, and proved to be also the most cost-efficient device.", "Use of a saline-linked radiofrequency coagulator (dissecting sealer) has been suggested to reduce blood loss during hepatic resection. A randomized clinical trial was conducted to assess the effects of using the device on the amount of blood loss.\n Patients scheduled to undergo hepatic resection were randomly assigned to either use of the dissecting sealer or the clamp crushing method. The primary outcome measure was blood loss during liver parenchymal division. Multivariate analysis was also performed.\n Ninety-four consecutive patients underwent hepatic resection and 40 patients were assigned to each group. There were no significant differences between the dissecting sealer and clamp crushing groups in blood loss during liver parenchymal division (median 373 versus 535 ml; P = 0.252) or total intraoperative blood loss (665 versus 733 ml; P = 0.450). Multivariate analysis revealed that use of the dissecting sealer offered no protection against blood loss compared with the clamp crushing method (odds ratio 1.17 (95 per cent confidence interval 0.39 to 3.53); P = 0.777), whereas number of resections, thoracotomy and type of resection had a significant effect.\n Use of a dissecting sealer offered no substantial benefit over the clamp crushing method in reducing blood loss during hepatic resection.", "Hepatic parenchymal transection is a technical priority in liver surgery. The use of an ultrasonic dissector for hepatectomy may result in less blood loss than conventional clamp crushing.\n Randomized controlled trial.\n University teaching hospital.\n The 132 patients scheduled to undergo partial hepatectomies were randomly assigned to receive hepatic transection by ultrasonic dissector or by clamp crushing (66 patients by each method).\n All resections were performed with inflow occlusion and were guided ultrasonographically. Hepatectomies were graded according to a predefined system based on 6 criteria (blood loss, transection time, technical error, surgical margin, landmark appearance, and postoperative morbidity), each with 3 scores (lower scores indicating higher quality).\n Blood loss and hepatectomy grade.\n No difference was found between the ultrasonic and clamp groups in median blood loss (515 mL [range, 15-2527 mL] vs 452 mL [range, 17-1912 mL]; P =.63), transection time (61 minutes [range, 16-177 minutes] vs 54 minutes [range, 7-205 minutes]; P =.58), or transection speed (1.1 cm(2)/min [range, 0.4-4.0 cm(2)/min] vs 1.0 cm(2)/min [range, 0.4-3.0 cm(2)/min]; P =.90). Ultrasonic dissection caused more frequent histologically proven tumor exposure at the surgical margin (9 vs 3 patients; P =.09), incomplete appearance of landmark hepatic veins on the cut surface after anatomical resection (12 vs 4 patients; P =.03), and postoperative morbidity (20 vs 14 patients; P =.32) than did clamp crushing. The hepatectomies with clamp crushing had significantly higher grades than those with ultrasonic dissection (P =.05), as indicated by the lower median sum score (4.0 [range, 0-12] vs 5.0 [range, 0-19]; 95% confidence interval for difference, -2.0 to 0; P =.03). The transection method independently influenced hepatectomy grade (adjusted odds ratio = 3.06; 95% confidence interval, 1.35-6.92; P =.01).\n Ultrasonic dissection offers no reduction in blood loss compared with clamp crushing for transection of the liver. Clamp crushing results in a higher quality of hepatectomy and is therefore the option of choice.", "To evaluate the feasibility, safety, efficacy, amount of hemorrhage, postoperative complications, and ischemic injury of selective clamping in patients undergoing minor liver resections.\n Inflow occlusion can reduce blood loss during hepatectomy. However, Pringle maneuver produces ischemic injury to the remaining liver. Selective hemihepatic vascular occlusion technique can reduce the severity of visceral congestion and total liver ischemia.\n Eighty patients undergoing minor hepatic resection were randomly assigned to complete clamping (CC) or selective clamping (SC). Hemodynamic parameters, including portal pressure and the hepatic venous pressure gradient (HVPG), were evaluated. The amount of blood loss, measurements of liver enzymes alanine aminotransferase (ALT), aspartate aminotransferase (AST), and postoperative evolution were also recorded.\n No differences were observed in the amount of hemorrhage (671 +/- 533 mL versus 735 +/- 397 mL; P = 0.54) or the patients that required transfusion (10% versus 15%; P = 0.55). There were no differences on postoperative morbidity between groups (38% versus 29%; P = 0.38). Cirrhotic patients with CC had significantly higher ALT (7.7 +/- 4.6 versus 4.5 +/- 2.7 mukat/L, P = 0.01) and AST (10.2 +/- 8.7 versus 4.9 +/- 2.1 mukat/L; P = 0.03) values on the first postoperative day than SC. The multivariate analysis demonstrated that high central venous pressure, HVPG >10 mm Hg, and intraoperative blood loss were independent factors related to morbidity.\n Both techniques of clamping are equally effective and feasible for patients with normal liver and undergoing minor hepatectomies. However, in cirrhotic patients selective clamping induces less ischemic injury and should be recommended. Finally, even for minor hepatic resections, central venous pressure, HVPG, and intraoperative blood loss are factors related to morbidity and should be considered.", "Abdominal drainage is a standard procedure after hepatectomy, but this practice has been challenged recently.\n Between September 2004 and March 2005, 120 consecutive patients who had undergone hepatic resection by the same surgical team were randomly allocated into drainage and no drainage groups (60 in each group). Patient characteristics, preoperative liver function, presence of cirrhosis, resection-related factors and postoperative complications were compared between the two groups.\n The groups were comparable in terms of demographics, indications for surgery, preoperative liver function test results, presence of cirrhosis, extent of hepatectomy, intraoperative blood loss and requirement for blood transfusion. Symptomatic subphrenic collection and pleural effusion occurred in four patients (7 per cent) who had abdominal drainage and three (5 per cent) who did not. Local wound complications occurred in 17 (28 per cent) and two (3 per cent) patients respectively (P < 0.001). The postoperative hospital stay was similar in the two groups. Multivariate analysis indicated that the presence of cirrhosis and abdominal drainage were independently related to the development of postoperative wound complications.\n Routine abdominal drainage is unnecessary after elective hepatectomy using the crushing clamp method." ]	Clamp-crush technique is advocated as the method of choice in liver parenchymal transection because it avoids special equipment, whereas the newer methods do not seem to offer any benefit in decreasing the morbidity or transfusion requirement.
CD008829	[ "18672987", "17240933", "8267871", "8941832", "19161059", "10530095", "16881807", "12699051", "8144738", "8144734", "2083478", "18277739" ]	[ "Comparison of the use of different modes of mechanical oral hygiene in prevention of plaque and gingivitis.", "A clinical investigation of the efficacy of three different treatment regimens for the control of plaque and gingivitis.", "A comparison of the Braun Oral-B Plaque Remover (D5) electric and a manual toothbrush in affecting gingivitis.", "Clinical evaluation of an ionic toothbrush in the removal of established plaque and reduction of gingivitis.", "Evaluation of an educational program for children with high risk of caries.", "A 3-month clinical investigation comparing the safety and efficacy of a novel electric toothbrush (Braun Oral-B 3D Plaque Remover) with a manual toothbrush.", "Clinical efficacy of flossing versus use of antimicrobial rinses.", "The efficacy of an essential oil antiseptic mouthrinse vs. dental floss in controlling interproximal gingivitis: a comparative study.", "Comparison of a manual and a new electric toothbrush for controlling plaque and gingivitis.", "The long-term effect of an oscillating/rotating electric toothbrush on gingivitis. An 8-month clinical study.", "Mechanical devices versus antimicrobial rinses in plaque and gingivitis reduction.", "Oral hygiene regimens, plaque control, and gingival health: a two-month clinical trial with antimicrobial agents." ]	[ "The objective of this study was to evaluate the effect of an oscillating/rotating/pulsating powered toothbrush on plaque and gingivitis prevention over a 9-month period.\n The study had an examiner-masked, randomized, three-group parallel design. A total of 122 subjects >or= 18 years of age in good general health and with at least five teeth per quadrant and no pockets >or= 5 mm were included. A 3-week preexperimental period of extensive oral home care, including rinses, was started to improve gingival health. Professional oral hygiene instruction with a manual brush was provided. At baseline, subjects were assigned to one of three regimens: twice daily brushing with a manual toothbrush, a manual toothbrush and the use of floss, or a powered toothbrush. Subjects were professionally instructed in their regimen and given a prophylaxis. Two weeks later, oral hygiene reinforcement was provided. Gingival bleeding, plaque, staining, and gingival abrasion were assessed during the preexperimental period and at baseline, 10 weeks, and 6 and 9 months.\n There was a significant reduction in plaque and gingivitis from the preexperimental period to baseline. At 10 weeks and 6 and 9 months, the level of plaque was statistically significantly lower with the powered toothbrush versus the other two regimens (P <or= 0.002). At 10 weeks and 6 months, the level of bleeding in the powered toothbrush group was statistically significantly lower versus manual brushing alone (P <or= 0.024).\n The powered toothbrush maintained lower plaque levels for 9 months following the 3-week treatment phase better than the manual toothbrush with or without floss. The powered toothbrush showed significant benefits in preventing gingival bleeding versus manual brushing alone. All regimens were safe for oral tissues.", "The objective of this examiner-blind clinical study was to investigate the efficacy of three oral hygiene regimens for the control of gingivitis and supragingival plaque.\n Following a baseline examination for gingivitis and supragingival plaque, qualifying adult male and female subjects from the San Francisco, California area were stratified into three treatment groups, which were balanced for plaque. The groups were then randomly assigned to one of three oral hygiene regimens: 1) twice-daily tooth brushing with Colgate Total Toothpaste, accompanied by once-daily flossing after brushing; 2) twice-daily tooth brushing with Colgate Total Toothpaste without flossing; and 3) twice-daily tooth brushing with a sodium fluoride toothpaste, accompanied by once-daily flossing after brushing. All subjects were given a complete oral prophylaxis, and dispensed their assigned treatment product(s), along with a soft-bristled adult toothbrush for home use. All dentifrice products were supplied in the original packaging to which overwrapping had been applied. Subjects were instructed to brush their teeth for one minute twice daily (morning and evening) using only the dentifrice provided, and to refrain from using anything other than their assigned oral hygiene products for the duration of the study. In addition, subjects were instructed to refrain from any routine dental treatment (except emergency) during the course of the study. There were no restrictions regarding diet or smoking habits over the course of the study. Examinations for gingivitis and supragingival plaque, and oral soft tissue assessments were repeated after three months, and again after six months of product use.\n One-hundred fourteen (114) subjects complied with the protocol and completed the six-month examinations. Statistical analyses showed similar results for both whole-mouth and interproximal scoring sites after six months of product use. Although not statistically significant, subjects using Colgate Total Toothpaste accompanied by the use of dental floss had numerically lower six-month scores for gingivitis and supragingival plaque formation when compared to the scores of subjects using Colgate Total Toothpaste without the use of dental floss. Relative to the sodium fluoride toothpaste accompanied by the use of dental floss, subjects using Colgate Total Toothpaste, both with and without the use of dental floss, exhibited statistically significant reductions in gingivitis and supragingival plaque formation after six months of product use.\n The results of this clinical study support the conclusion that the use of Colgate Total Toothpaste, both with and without the use of dental floss, provided statistically significant improvements over the sodium fluoride toothpaste plus flossing regimen with respect to the control of gingivitis and supragingival plaque formation. Although not statistically significant, numerically lower six-month scores for gingivitis and supragingival plaque were associated with Colgate Total Toothpaste accompanied by the use of dental floss, when compared with Colgate Total Toothpaste without the use of dental floss.", "This three-month clinical trial was designed to compare the effect of an electric and a manual toothbrush on reducing primarily gingivitis and secondarily, plaque, in a cohort of 70 healthy adults. After baseline evaluation of gingivitis, soft tissue trauma, and plaque, patients were randomly assigned to one of the two experimental groups, shown an instructional tooth brushing videotape, and had their teeth cleaned. Soft tissue trauma was again scored at 2 weeks. At 12 weeks all three clinical parameters were again evaluated. The results showed statistically significant reductions (baseline vs. 3-month) in both whole mouth (p = 0.003) and interproximal (p = 0.008) gingivitis scores for the electric toothbrush group. No significant reduction at three months compared to baseline was seen for the manual brush group. When gingivitis reductions were compared over the three-month test period, the electric brush was significantly better than the manual toothbrush in both whole mouth (p = 0.0007) and interproximal (p = 0.002) gingivitis reduction. No increase in soft tissue trauma and no significant differences in plaque reductions were seen for either toothbrush.", "The clinical effectiveness of a manual ionic toothbrush in the removal of dental plaque and the reduction of gingivitis was evaluated. A double-blind study evaluated the effect of a small, imperceptible electric current on established dental plaque and gingivitis during toothbrushing. Sixty-four adults completed the study. Gingivitis and plaque scores were determined at baseline and after 3 and 6 months. The baseline indices of the two groups were well balanced. At each examination, the participants were instructed how to hold the toothbrush properly and reminded to change brush heads every 4 weeks. Statistically significant improvements in Löe Gingival Index scores were observed from baseline to 6 months between the control and test groups and within the test group. The Quigley-Hein Plaque Index scores also showed a significant improvement from baseline to 6 months between the control and test groups and within the test group.", "The goal of this study was to evaluate a 15-month educational program designed to children. The sample consisted of 60 six-year olds, randomly assigned into control and experimental group. The control consisted of tooth brushing training, once a year. The experimental group received intensive individual tooth brushing training every three months and guidance on oral health. Initially, both groups were assessed using plaque, gingival, dmfs and DMF-S indexes every three months. In the control, no statistically significant difference was observed for plaque and gingival indexes. The experimental group showed a statistically significant reduction in mean values for two indexes. The caries indexes showed no statistically significant difference. The proposed educational program developed was efficient in reducing gingival and plaque indexes as well caries incidence.", "To compare the efficacy and safety of a novel electric toothbrush (Braun Oral-B 3D Plaque Remover) with a standard reference ADA manual toothbrush.\n 114 subjects were included in a 3-month randomized, parallel group, examiner-blind study and divided into two groups: 3D users and manual toothbrush users. Subjects were instructed to brush twice daily for 2 minutes. Evaluation of oral soft and hard tissue for safety, plaque, gingivitis and bleeding was conducted prior to the start of product use (at baseline), at days 14 and 35, and at 3 months.\n 105 subjects (55 3D users and 50 manual toothbrush users) completed the study. At days 14, 35 and at 3 months both groups showed reductions from baseline in whole mouth plaque, gingivitis and bleeding that were statistically significant (P < 0.005), except in the case of plaque at day 35 in manual toothbrush users. At 3 months, reductions for whole mouth plaque, gingivitis and bleeding were 15%, 16% and 65%, for 3D users and 8%, 12% and 56%, for manual toothbrush users, respectively. Group differences were significant (P < 0.05) in favor of the 3D with respect to plaque reduction for the whole mouth and for interproximal and anterior lingual sites at all three time periods. With respect to gingivitis, reductions for the whole mouth and interproximal and posterior lingual sites at 3 months were significantly greater in the 3D group. There was no clinically significant soft or hard tissue abrasion in either group. In conclusion, the 3D electric toothbrush was found to be safe and had increased efficacy with respect to reduction of plaque and gingivitis compared to a manual toothbrush.", "Dental floss is only used by a small part of the population on a daily basis. Therefore, an easy, applicable alternative is needed. This alternative could be a mouthrinse with antimicrobial activity for daily use. The aim of the present study was to evaluate the efficacy of two mouthrinses in reducing interdental plaque and gingivitis compared to dental floss.\n A total of 156 healthy volunteers were randomly assigned to the following groups: 1) toothbrushing and rinsing (0.06% chlorhexidine and 0.025% fluoride); 2) toothbrushing and rinsing (0.1% cetylpyridiniumchloride and 0.025% fluoride); 3) toothbrushing and flossing; and 4) toothbrushing only (N = 39 subjects in each group). At baseline, the modified proximal plaque index (MPPI) and papillary bleeding index (PBI) were recorded. Thereafter, subjects had to brush in the usual manner during 8 weeks. Additionally, test groups had to rinse once a day (groups 1 and 2: 30 seconds) or to floss (group 3). Eight weeks after baseline, indices were recorded again and improvements were calculated. Analysis of variance (ANOVA) and the Bonferroni test served for statistical analysis.\n After 8 weeks, reductions for all indices were found in all groups (P <0.05). With respect to the MPPI, mouthrinse groups performed better than the control and floss groups: 1) 0.73; 2) 0.82; 3) 0.40; and 4) 0.32 (P <0.05). The PBI showed no statistically significant difference between groups: 1) 0.46; 2); 0.50; 3); 0.42; and 4) 0.37.\n The results suggest that, in combination with toothbrushing, daily use of the tested mouthrinses may result in a higher interproximal plaque reduction than daily flossing.", "The use of dental floss has long been considered to be effective in controlling interproximal plaque and gingivitis. The authors compared this method with that of use of a mouthrinse.\n Subjects with mild-to-moderate gingivitis enrolled in a long-term, six-month study. They received a dental prophylaxis and were randomized into one of the three following treatment groups: brushing and rinsing with an essential oil-containing mouthrinse (the BEO group), brushing and flossing (the BF group) and brushing and rinsing with a control rinse (the B group).\n A total of 326 subjects were evaluated. The BEO and BF had significantly lower (P < .001) mean interproximal Modified Gingival Index, or MGI, scores than did the B group at six months. The BEO group had lower mean interproximal Plaque Index, or PI, scores than the other two groups at both three and six months. The BF group's mean PI score was significantly lower than the B group's mean score at six months only. The magnitude of reductions for the BEO and the BF groups (vs. the B group) in MGI were 11.1 percent and 4.3 percent and for PI were 20.0 percent and 3.4 percent, respectively.\n In conjunction with professional care (prophylaxis) and toothbrushing over six months, rinsing twice daily with an essential oil-containing mouthrinse was at least as good as flossing daily in reducing interproximal plaque and gingivitis. Clinical Implications. When weighing recommendations for oral hygiene home care, clinicians should consider that an essential oil-containing mouthrinse may be a useful adjunct in patients with gingival inflammation.", "In the present clinical trial, the effect on existing plaque and gingivitis of a new electric toothbrush (ET) was compared to that of a manual toothbrush (MT). 40 medical students, age 18-30 years, participated. Plaque index (PlI) and gingival index (GI) were recorded at 6 sites at all teeth. At baseline, a PlI and GI > 1 were required. The participants were at random allocated to a group using either ET or MT and were instructed only to use the assigned toothbrush, brushing each morning and evening for 2 min. No oral hygiene instruction was given. Re-examination was done after 1, 2 and 6 weeks. In the MT group, a minor decrease in mean PlI was found after 6 weeks (all sites: from 1.2 to 1.1, approximal sites: from 1.4 to 1.2). The corresponding figures in the ET group were: 1.2 to 0.6 and 1.4 to 0.8. After 6 weeks, the % of sites with visible plaque with MT was: 24% (all sites) and 30% (approximal sites) and with ET 8% and 9%, respectively. With MT, mean GI was unchanged after 6 weeks compared to baseline, whereas with ET, the changes were from 1.1 to 0.9 (all sites) and from 1.1 to 1.0 (approximal sites). The % of sites with GI score > or = 2 had not changed after 6 weeks with MT (all sites: 11%, approximal sites: 13%). With ET, these results were 3% and 4%, respectively.", "The purpose of this study was to evaluate the safety and efficacy of the Braun Plak Control for the removal of supragingival plaque and improving gingival health in a long-term clinical trial, and to compare it to regular manual toothbrush. Assessed were plaque accumulation, amount of gingival inflammation, gingival bleeding on probing, and calculus. In total, 77 young individuals were selected on the basis of having 'moderate gingivitis'. They were monitored over 8 months and divided among 2 groups; a control group that used a manual toothbrush and a test group that used the Braun Plak Control. The clinical assessments were repeated after 1, 2, 5, and 8 months. At baseline, subjects were handed their assigned toothbrushes together with written oral hygiene instructions. They were instructed to brush for at least 2 min. 1 month after baseline examinations, all subjects received a professional prophylaxis and oral hygiene instruction from an experienced dental hygienist. Plaque removal was reinforced at the 2-and 5-month examination. In conclusion, results indicate that the Braun Plak Control is a safe and efficient home care device. At the end of this trial, this electric toothbrush proved to be more effective than a regular manual toothbrush.", "The effectiveness of mechanical oral cleaning and oral antimicrobial rinses was compared for gingivitis and bacterial plaque control in 158 subjects. Teeth were brushed ad lib throughout; four of the five groups used either an interdental cleaner, dental floss, an essential oil mouthwash or a cetypyridinium mouthwash. Gingival bleeding (EIBI), visual inflammation (VGI), and tooth plaque coverage were evaluated at zero, six and 12 weeks of product use. After six weeks, bleeding reduction was 42% greater for the interdental cleaner and 21% greater for the dental floss than for the control. All groups showed a further decrease after 12 weeks, but only the 49% reduction of the interdental cleaner was significantly greater than the control. The rinses showed no more reduction in bleeding sites than the control throughout the study. VGI scores were no different from the control for any of the groups. However, the EIBI proved much more sensitive than the visual method finding three times as many inflamed sites. Plaque was reduced by both antimicrobial rinses 27% more than the control over 12 weeks; the interdental cleaner and dental floss groups showed no significant incremental plaque reductions. The results suggest antimicrobial rinses reduce plaque on visible tooth surfaces, but do not penetrate sufficiently between teeth to affect interdental plaque and thus interdental inflammation. However, by disturbing interdental plaque, both dental floss and the interdental cleaner have little effect on visible tooth surface plaque accumulation, yet produce a significant reduction in gingival inflammation.", "The purpose of this study was to examine the effects of various product combinations involving brush, paste, rinse, and floss on the prevention of plaque regrowth and gingivitis.\n In this randomized, parallel-group, examiner-blind, eight-week study, 179 subjects with gingivitis had a dental prophylaxis and were randomly assigned to one of six product combinations: 1) Colgate Wave manual toothbrush + Colgate Total dentifrice (0.3% triclosan/copolymer dentifrice); 2) Wave + Total + Listerine (essential oils rinse); 3) Oral-B CrossAction manual toothbrush + Crest Pro-Health dentifrice (0.454% stannous fluoride/sodium hexametaphosphate); 4) CrossAction + Pro-Health dentifrice + Crest Pro-Health Rinse (0.07% cetylpyridinium chloride rinse); 5) Oral-B ProfessionalCare Series 8000 power toothbrush + Pro-Health dentifrice; or 6) ProfessionalCare power brush + Pro-Health dentifrice + Oral-B Hummingbird power flosser. Subjects used their test products for the duration of the study. Whole mouth plaque, gingivitis, and product-related adverse events were assessed. Treatments were compared at a 0.05 level of significance.\n One-hundred and seventy-four subjects completed the study and were included in the data analysis. At Week 8, the overnight adjusted whole mouth plaque scores were statistically significantly lower in all other groups relative to the Wave + Total group (p < or = 0.030). Plaque scores were also statistically significantly lower (approximately 20%) in both groups where a therapeutic rinse was added to a manual brush and therapeutic paste relative to scores for the brush plus paste without a rinse (p < or = 0.034). All groups showed a reduction in gingivitis at Week 4, and mean scores remained stable or increased slightly at Week 8. The power toothbrush groups were directionally better at preventing gingivitis than the manual groups at Weeks 4 and 8.\n Reductions in overnight plaque were seen when therapeutic rinses were added to manual brush plus therapeutic dentifrice regimens above that observed with a manual brush and therapeutic dentifrice alone." ]	There is some evidence from twelve studies that flossing in addition to toothbrushing reduces gingivitis compared to toothbrushing alone. There is weak, very unreliable evidence from 10 studies that flossing plus toothbrushing may be associated with a small reduction in plaque at 1 and 3 months. No studies reported the effectiveness of flossing plus toothbrushing for preventing dental caries.
CD005948	[ "10952698", "6366725", "9212042", "11076326" ]	[ "Randomised trial of iodine intake and thyroid status in preterm infants.", "Results of controlled double-blind study of thyroid replacement in very low-birth-weight premature infants with hypothyroxinemia.", "L-thyroxine treatment of preterm newborns: clinical and endocrine effects.", "Postnatal thyroxine supplementation in infants less than 32 weeks' gestation: effects on pulmonary morbidity." ]	[ "Low levels of circulating thyroid hormones have been associated with poorer general and neurodevelopmental outcome in preterm babies and it has been speculated that the association is causal. Low levels of circulating thyroid hormone have been reported after inadequate intake of iodine in preterm infants being fed milk formula.\n To investigate whether increased iodine intake from supplemented preterm formula would improve thyroid hormone levels in preterm babies (this study) and hence improve neurodevelopmental status (planned subsequent study).\n A total of 121 preterm infants were entered into a randomised controlled trial of standard (68 microg/l) versus increased (272 microg/l) iodine in preterm formula.\n The two groups were comparable at recruitment. No evidence of an effect of the intervention on thyroid hormone levels was seen up to 41 weeks after conception.\n Calls for increased iodine content of preterm infant formulas are not justified by this study.", "The nature of hypothyroxinemia in sick very low-birth-weight (VLBW) infants was evaluated by assessment of the hypothalamic-pituitary axis and by the clinical response to thyroxine (T4) therapy. Twenty-three very low-birth-weight infants of gestational age 26 to 28 weeks, whose serum T4 concentrations were 4 micrograms/dL on two occasions, and thyrotropin less than 20 microU/mL, were included in a double-blind study. Following a thyrotropin-releasing hormone stimulation test, babies were given either T4 or placebo. Nine babies were thyrotropin-releasing hormone tested prior to therapy; four babies, two from each group, were tested 1 to 2 weeks after therapy. In 11 untreated babies, mean base line serum thyrotropin of 7.0 +/- 1.4 rose to 23.7 +/- 4.1 microU/mL in 30 minutes. This response was not significantly greater than the observed response in full-term babies, 23.7 +/- 4.1 v 16.6 +/- 0.97 microU/mL, respectively, P greater than .05. In two babies treated with T4 the thyrotropin response to thyrotropin-releasing hormone was completely suppressed. Serial serum T4 determinations showed normalization in both groups after a similar time interval. There was no beneficial effect of T4 therapy on growth of head circumference, length, or weight. Developmental data revealed no significant differences in the mental, motor, or gross neurologic outcome in the treated and nontreated infants after 1 year of follow-up. These observations imply that hypothyroxinemia in sick preterm infants is not a direct consequence of hypothyroidism. Despite the lack of demonstrable short-term beneficial effects of T4 therapy, follow-up studies are necessary to resolve the question of long-term benefits.", "Preterm newborns have low serum thyroxine (T4) levels compared with late-gestational fetuses. Low thyroid hormone levels are associated with increased severity of neonatal illness and neurodevelopmental dysfunction. We assessed the endocrine and clinical effects of increasing serum T4 levels in preterm newborns with a gestational age <31 wk. Forty newborns were randomized in a double blind protocol: 20 infants received a daily dose of 20 microg/kg L-T4 for 2 wk, whereas 20 control infants received saline. Serum concentrations of T4, triiodothyronine (T3), reverse T3 (rT3), thyroglobulin (TG), and TSH were measured weekly as well as serum levels of GH, prolactin, and IGF-I. After 2 wk, a TSH-releasing hormone (TRH) test was performed. Neonatal illness and outcome was evaluated by noting heart rate, oxygen requirement, duration of ventilation, development of chronic lung disease, oral fluid intake, and weight gain; a Bayley score was done at the corrected age of 7 mo. L-T4 administration induced a marked increase in serum T4 without apparent change in T3 levels, whereas the postnatal decline in serum rT3 was more gradual. L-T4 treatment was associated with a decrease in serum TG and TSH levels. TRH injection induced a definite rise in serum TSH and T3 in controls, but not in L-T4 treated newborns. Neither L-T4 treatment, nor TRH administration appeared to alter circulating levels of prolactin, GH, or IGF-I. In contrast to the pronounced endocrine effects, no clinical effects of L-T4 administration were detected.", "Transient hypothyroxinemia in premature newborns has been linked with poor neonatal outcomes. We designed this study to evaluate the effects of early thyroxine (T4) administration in the premature infant.\n A total of 49 newborns less than 32 weeks' gestation, were randomized in a double-blind, placebo-controlled trial. Within the first 48 hours of life, T4 (10 or 20 micrograms/kg; intravenous or through nasogastric tube, respectively) was administered for a total of 21 days. Chronic lung disease, the primary outcome variable, was defined by oxygen dependency at 28 days of life.\n The incidence of chronic lung disease, death, grade III or IV intraventricular hemorrhage, periventricular leukomalacia, and sepsis was not different in the placebo and treated groups.\n Early T4 supplementation in preterm newborns less than 32 weeks' gestation does not decrease the incidence of chronic lung disease or other complications of prematurity." ]	This review does not support the use of prophylactic thyroid hormones in preterm infants to reduce neonatal mortality, neonatal morbidity or improve neurodevelopmental outcomes. An adequately powered clinical trial of thyroid hormone supplementation with the goal of preventing the postnatal nadir of thyroid hormone levels seen in very preterm infants is required.
CD001277	[ "12554890", "1642520", "10557684", "9476870", "12195271" ]	[ "Breathing retraining for dysfunctional breathing in asthma: a randomised controlled trial.", "Deep diaphragmatic breathing: rehabilitation exercises for the asthmatic patient.", "Can small group education and peer review improve care for patients with asthma/chronic obstructive pulmonary disease?", "A randomized trial comparing peak expiratory flow and symptom self-management plans for patients with asthma attending a primary care clinic.", "Asthma in adolescents: a randomized, controlled trial of an asthma program for adolescents and young adults with severe asthma." ]	[ "Functional breathing disorders may complicate asthma and impair quality of life. This study aimed to determine the effectiveness of physiotherapy based breathing retraining for patients treated for asthma in the community who have symptoms suggestive of dysfunctional breathing.\n 33 adult patients aged 17-65 with diagnosed and currently treated asthma and Nijmegen questionnaire scores > or =23 were recruited to a randomised controlled trial comparing short physiotherapy breathing retraining and an asthma nurse education control. The main outcome measures were asthma specific health status (Asthma Quality of Life questionnaire) and Nijmegen questionnaire scores\n Of the 33 who entered the study, data were available on 31 after 1 month and 28 at 6 months. The median (interquartile range) changes in overall asthma quality of life score at 1 month were 0.6 (0.05-1.12) and 0.09 (-0.25-0.26) for the breathing retraining and education groups, respectively (p=0.018), 0.42 (0.11-1.17) and 0.09 (-0.58-0.5) for the symptoms domain (p=0.042), 0.52 (0.09-1.25) and 0 (-0.45-0.45) for the activities domain (p=0.007), and 0.50 (0-1.50) and -0.25 (-0.75-0.75) for the environment domain (p=0.018). Only the change in the activities domain remained significant at 6 months (0.83 (-0.10-1.71) and -0.05 (-0.74-0.34), p=0.018), although trends to improvement were seen in the overall score (p=0.065), the symptoms domain (p=0.059), and the environment domain (p=0.065). There was a correlation between changes in quality of life scores and Nijmegen questionnaire scores at 1 month and at 6 months. The number needed to treat to produce a clinically important improvement in health status was 1.96 and 3.57 at 1 and 6 months.\n Over half the patients treated for asthma in the community who have symptoms suggestive of dysfunctional breathing show a clinically relevant improvement in quality of life following a brief physiotherapy intervention. This improvement is maintained in over 25% 6 months after the intervention.", "A new diaphragmatic breathing technique practiced without the aid of a physical corset is outlined, and the findings from a study of its application in the respiratory rehabilitation of asthmatic patients are presented. Sixty-seven asthmatic adults randomly assigned to either deep diaphragmatic breathing training, physical exercise training, or a waiting list control group participated in a 16-week program. Deep diaphragmatic training resulted in significant reductions in medication use and in the intensity of asthmatic symptoms. Importantly, a nearly 300% increase in time spent in physical activities also resulted from deep diaphragmatic training. A follow-up at two months found many patients had returned to earlier medication levels and sedentary habits. A strengthened musculature can replace the need for a physical aid in this respiratory habilitation; adherence to its use may require individually-tailored encouragement.", "To study the effectiveness of an intensive small group education and peer review programme aimed at implementing national guidelines on asthma/chronic obstructive pulmonary disease (COPD) on care provision by general practitioners (GPs) and on patient outcomes.\n A randomised experimental study with pre-measurement and post-measurement (after one year) in an experimental group and a control group in Dutch general practice.\n Two groups of GPs were formed and randomised. The education and peer review group (17 GPs with 210 patients) had an intervention consisting of an interactive group education and peer review programme (four sessions each lasting two hours). The control group consisted of 17 GPs with 223 patients (no intervention).\n Knowledge, skills, opinion about asthma and COPD care, presence of equipment in practice; actual performance about peakflow measurement, non-pharmacological and pharmacological treatment; asthma symptoms (Dutch Medical Research Council), smoking habits, exacerbation ratio, and disease specific quality of life (QOL-RIQ). Data were collected by a written questionnaire for GPs, by self recording of consultations by GPs, and by a written self administered questionnaire for adult patients with asthma/COPD.\n Data from 34 GP questionnaires, 433 patient questionnaires, and recordings from 934 consultations/visits and 350 repeat prescriptions were available. Compared with the control group there were only significant changes for self estimated skills (+16%, 95% confidence interval 4% to 26%) and presence of peakflow meters in practice (+18%, p < 0.05). No significant changes were found for provided care and patient outcomes compared with the control group. In the subgroup of more severe patients, the group of older patients, and in the group of patients not using anti-inflammatory medication at baseline, no significant changes compared with the control group were seen in patient outcomes.\n Except for two aspects, intensive small group education and peer review in asthma and COPD care do not seem to be effective in changing relevant aspects of the provided care by GPs in accordance with guidelines, nor in changing patients' health status.", "Great emphasis is placed on educating asthmatics to use action plans to achieve better control of symptoms. The use of peak flow meters (PFM) has been recommended as an important part of self-management plans. We studied 92 (47 F) adult patients with asthma in a primary care setting to compare the effectiveness of action plans using either peak flow monitoring or symptoms to guide self-management. Each patient was instructed in the use of the action plan in the context of a 6-mo asthma education program taught by a nurse. Patients were already using inhaled corticosteroids or were newly prescribed corticosteroids by their family physician. Forty-four patients were randomized to the PFM group and 48 to the symptoms group. Spirometry, symptom scores, quality of life, medication use, and measures of health care utilization and morbidity (emergency department visits, hospitalizations, unscheduled doctor visits, and days lost from work or school) were recorded at baseline and throughout the study period. PC20 methacholine was measured at the first and at the final visits. There were significant improvements within groups for FEV1, symptoms score, PC20 methacholine, and quality of life, but no between-group differences. A significant shift from higher to lower daily use of beta-agonists (p < 0.008 for both groups) and significant shifts to higher daily doses of inhaled steroids (p < 0.001) occurred in each group. Adherence to the self-management plans was only 65% in the PFM group and 52% in the symptoms group. Outcomes for health care utilization were similar except for fewer patients making unscheduled doctor visits within the PFM group. Our findings show that education, regular follow-up, and an action plan are effective in improving asthma control and quality of life, but the routine use of PFM to guide interventions is not the only way to accomplish these objectives.", "Asthma is common and is often poorly controlled in adolescent subjects.\n To determine the impact of an age-specific asthma program on asthma control, particularly on exacerbations of asthma requiring emergency department treatment, and on the quality of life of adolescents with asthma.\n The present randomized, controlled trial included patients who were 15 to 20 years of age and had visited emergency departments for management of their asthma. The interventional group attended an age-specific asthma program that included assessment, education and management by a team of asthma educators, respiratory therapists and respiratory physicians. In the control group, spirometry was performed, and the patients continued to receive usual care from their regular physicians. The outcomes were assessed by a questionnaire six months after entry into the study.\n Ninety-three subjects entered the study and were randomly assigned to the intervention or control group. Of these, only 62 patients were available for review after six months. Subjects in both the control and the intervention groups showed a marked improvement in their level of asthma control, reflected primarily by a 73% reduction in the rate of emergency department attendance for asthma. Other indexes of disease control, including disease-specific quality of life, as assessed by questionnaires, were improved. There was, however, no discernible difference between the subjects in the two groups, with the exception of an improvement in favour of the intervention group in the symptom (actual difference 0.7, P=0.048) and emotional (actual difference 0.8, P=0.028) domains of the asthma quality of life questionnaire. The overall quality of life score favoured the intervention group by a clinically relevant difference of 0.6, but this difference did not reach statistical significance (P=0.06).\n Although all subjects demonstrated a significant improvement in asthma control and quality of life, the improvement attributable to this intervention was limited to two domains in disease-specific quality of life." ]	Comparisons and conclusions were difficult to evaluate as treatment interventions and outcome measurements from the seven trials varied considerably. At present therefore no reliable conclusions can be drawn concerning the use of breathing exercises for asthma in clinical practice. However trends for improvement, notably in quality of life measurements, are encouraging and further studies including full descriptions of treatment methods and outcome measurements are required.
CD003997	[ "10520389", "8630203", "15573192", "11956540", "12670818", "7598849", "9661546", "8895262", "8233511", "11226091", "15979735", "9296405", "2036187", "10736082", "8961683" ]	[ "The effect of single dose intravenous dexamethasone in tonsillectomy in children.", "The effect of intravenous dexamethasone in pediatric adenotonsillectomy.", "Use of dexamethasone to reduce postoperative vomiting and pain after pediatric tonsillectomy procedures.", "Does dexamethasone with preemptive analgesia improve pediatric tonsillectomy pain?", "Dexamethasone reduces postoperative vomiting and pain after pediatric tonsillectomy.", "Use of intraoperative corticosteroids in pediatric tonsillectomy.", "The effect of preoperative dexamethasone on the immediate and delayed postoperative morbidity in children undergoing adenotonsillectomy.", "Dexamethasone decreases vomiting by children after tonsillectomy.", "The effects of preoperative steroids on tonsillectomy patients.", "The effect of dexamethasone on postoperative vomiting after tonsillectomy.", "The effect of preoperative dexamethasone on early oral intake, vomiting and pain after tonsillectomy.", "Prophylaxis for vomiting by children after tonsillectomy: dexamethasone versus perphenazine.", "The effect of steroid therapy on recovery from tonsillectomy in children.", "Tropisetron plus dexamethasone is more effective than tropisetron alone for the prevention of postoperative nausea and vomiting in children undergoing tonsillectomy.", "The efficacy of a single dose antibiotic regimen in adults undergoing tonsillectomy." ]	[ "A prospective, randomized, double-blinded, placebo-controlled clinical trial was conducted in 41 patients evaluating the effect of a single preoperative dose of intravenous dexamethasone on postoperative vomiting and pain in children undergoing elective tonsillectomy. Dexamethasone was found to significantly reduce the incidence of vomiting in the first 24 hours postoperatively (P = 0.02), the time to first intake of solids (P = 0.001), the need to administer a rescue antiemetic (P = 0.005) and intravenous fluid therapy requirements (P = 0.006) in the postoperative period. No significant difference was found between the dexamethasone and placebo groups in the time to first intake of fluids, pain scores or analgesic requirement postoperatively. These results indicate that dexamethasone substantially reduces morbidity after tonsillectomy in children.", "To determine whether the intravenous administration of dexamethasone sodium phosphate before tonsillectomy and adenoidectomy can reduce the morbidity from, and increase the safety of, this procedure.\n Prospective, randomized, double-blind, placebo-controlled clinical trial.\n A university medical center, caring for both ambulatory and hospitalized children.\n Eighty children aged 3 to 15 years undergoing tonsillectomy and adenoidectomy for either chronic tonsillitis or adenotonsillar hypertrophy (obstructive sleep apnea and/or upper airway obstruction).\n Forty-one children received intravenous dexamethasone sodium phosphate (1 mg/kg up to 16 mg) and 39 received placebo before undergoing an electrocautery dissection tonsillectomy and adenoidectomy.\n Postoperative oral intake, pain, vomiting, temperature, and complications.\n Patients who received intravenous dexamethasone had significantly less trismus, vomiting, and elevations of temperature 6 hours after surgery and more oral intake (liquids and soft solids) at 24 hours. Three children, all of whom were in the placebo group, had emergency department visits for pain and dehydration. Each group had one child who had a secondary hemorrhage (no surgery needed), one child who had pneumonia, and one child who had night terrors.\n Treatment with intravenous dexamethasone before electrocautery tonsillectomy and adenoidectomy is safe, increases early postoperative oral intake, and decreases morbidity.", "The purpose of this study is to determine whether a single dose of dexamethasone 0.5mg/kg administered before surgery could decrease post operative vomiting and pain and improves oral intake in the first 24-hours after pediatric tonsillectomy procedures.\n It is a randomized, double blind, placebo controlled study. Sixty children age 2-12-years ASA 1 and 11 were scheduled for tonsillectomy, dexamethasone (n=29) and control group (n=31) were enrolled in the study. Dexamethasone group received 0.5mg/kg intravenous dexamethasone and control group received saline at the time of induction. The anesthetic regimen and surgical procedures were standardized for all patients. All patients were observed in post anesthesia care unit (PACU) and ward for post operative vomiting, pain, need for rescue antiemetic or analgesia and time for first oral intake for 24-hours.\n Data from 60 patients were analyzed. The overall incidence of early as well as late vomiting was significantly less in dexamethasone as compared to control group (37% versus 74% P=0.016), overall incidence of retching was 29% in control and 3.4% in dexamethasone (p=0.008). Vomiting once or more than once was significantly high in control as compared to dexamethasone group. The need for rescue antiemetic, the time to first oral intake and analgesic requirements did not show any significant difference in both groups.\n Dexamethasone is considered safe and there was no adverse effects associated with a single dose of dexamethasone. Although the need for rescue antiemetic, time to oral intake and analgesia requirements in both groups were not significant, however, we found that dexamethasone does have antiemetic properties as overall incidence of retching and vomiting was significantly less in dexamethasone group as compared to control group in children who underwent tonsillectomy.", "The study goal was to determine whether the combination of dexamethasone with preemptive analgesia has an additive effect in further improving recovery.\n We conducted a prospective, randomized, double-blinded trial of 50 children undergoing tonsillectomy at a university ambulatory surgery center. One study group received 1 intravenous dose of dexamethasone, and another group received 1 dose of saline solution. All patients received tonsillar fossa injections of ropivacaine plus clonidine before tonsil excision.\n The 2 study groups were similar in main outcome measurements. Pain intensity and quality of life were not statistically different between the groups. There was a small trend to less trismus and less cumulative codeine use in the steroid group. Overall, there was a very low incidence of nausea and vomiting in both groups, which may have been due to the preemptive analgesia.\n Dexamethasone does not significantly improve the morbidity of pediatric tonsillectomy when preemptive analgesia with ropivacaine and clonidine is used concurrently.", "Previous studies on dexamethasone's antiemetic and analgesic potential in children undergoing tonsillectomy have produced conflicting results. The aim of this study was to evaluate the effects of a single dose of dexamethasone on the incidence and severity of postoperative vomiting and pain in children undergoing electrocautery tonsillectomy under standardized general anesthesia.\n In a double-blinded study, 120 patients were randomly allocated to receive either dexamethasone 0.5 mg.kg(-1) (maximum dose 8 mg) iv or an equivalent volume of saline preoperatively. The incidence of early and late vomiting, need for rescue antiemetics, time to first oral intake, time to first demand of analgesia and analgesic consumption were compared in both groups. Pain scores used included Children's Hospital Eastern Ontario Pain Scale, \"faces\", and a 0-10 visual analogue pain scale.\n Compared with placebo, dexamethasone significantly decreased the incidence of early and late vomiting (P < 0.05, P < 0.001 respectively). Fewer patients in the dexamethasone group needed antiemetic rescue (P < 0.01). The time to first oral intake was shorter, and the time to first dose of analgesic was longer in the dexamethasone group (P < 0.01). Pain scores 30 min after extubation were lower (P < 0.05) in the dexamethasone group. At 12 and 24 hr postoperative swallowing was still significantly less painful in the dexamethasone group than in the control group (P < 0.01).\n Preoperative dexamethasone 0.5 mg.kg(-1) iv reduced both postoperative vomiting and pain in children after electrocautery tonsillectomy.", "To determine the effects of a single dose of dexamethasone sodium phosphate on postoperative morbidity in children undergoing tonsillectomy.\n Randomized, double-blind, placebo-control clinical trial.\n Academic, tertiary care children's hospital.\n Sixty-nine children (35 boys, 34 girls), aged 3 to 18 years, undergoing tonsillectomy with or without adenoidectomy.\n Patients were randomized to receive a single dose of intravenous dexamethasone or saline.\n Pain scores, determined by a Faces Scale, were obtained at 4-hour intervals during the first postoperative day and daily for 7 days thereafter. Total use of an analgesic; type of diet; level of activity; presence of halitosis, nausea, emesis, or fever; and incidence of postoperative bleeding were also compared between the two groups.\n The two groups of children were similar in age, gender, diagnosis, and surgical time. Pain scores in the postoperative period were identical while the patients were in the hospital and for the first 7 days after discharge. No statistically significant differences were noted in pain scores, nausea, emesis, halitosis, analgesic medications required, diet, or activity levels between the two groups of patients.\n A single intraoperative dose of dexamethasone did not appreciably affect postoperative morbidity in children undergoing tonsillectomy.", "In this prospective, randomized, double-blind, placebo-controlled study, we examined the effect of preoperative dexamethasone on postoperative nausea and vomiting (PONV) and 24-h recovery in children undergoing tonsillectomy. One hundred thirty children, 2-12 yr of age, ASA physical status I or II, completed the study. All children received oral midazolam 0.5-0.6 mg/kg preoperatively. Anesthesia was induced with halothane and nitrous oxide in 60% oxygen and maintained with nitrous oxide and isoflurane. Intubation was facilitated by mivacurium 0.2 mg/kg. Each child received fentanyl 1 microgram/kg i.v. before initiation of surgery, as well as dexamethasone 1 mg/kg (maximal dose 25 mg) (steroid group) or an equal volume of saline (control group). Intraoperative fluids were standardized to 25-30 mL/kg lactated Ringer's solution. All tonsillectomies were performed under the supervision of one attending surgeon using an electrodissection technique. Postoperatively, fentanyl and acetaminophen with codeine elixir were administered as needed for pain. Rescue antiemetics were administered when a child experienced two episodes of retching and/or vomiting. Before home discharge, the incidence of PONV, need for rescue antiemetics, quality or oral intake, and analgesic requirements did not differ between groups. However, during the 24 h after discharge, more patients in the control group experienced PONV (62% vs 24% in the steroid group) and complained of poor oral intake. Additionally, more children in the control group (8% vs 0% in the steroid group) returned to the hospital for the management of PONV and/or poor oral intake. The preoperative administration of dexamethasone significantly decreased the incidence of PONV over the 24 h after home discharge in these children. Implications: In this double blind, placebo-controlled study, we examined the efficacy of a single large dose (1 mg/kg; maximal dose 25 mg) of preoperative dexamethasone on posttonsillectomy postoperative nausea and vomiting (PONV) in children 2-12 yr of age undergoing tonsillectomy. Compared with placebo, dexamethasone significantly decreased the incidence of PONV in the 24 h after discharge, improved oral intake, decreased the frequency of parental phone calls, and resulted in no hospital returns for the management of PONV and/or poor oral intake.", "We evaluated the effect of dexamethasone on vomiting after elective tonsillectomy in 133 healthy children aged 2-12 yr in a randomized, stratified, blocked, double-blind, placebo-controlled study. General anesthesia was induced by inhalation of N2O and halothane or intravenously (IV) with propofol. Anesthesia was maintained with N2O and halothane. Dexamethasone 150 micrograms/kg up to a maximum dose of 8 mg, or placebo, was administered IV before surgery. All patients received 1.5 mg/kg codeine intramuscularly (IM) intraoperatively. Perioperative IV fluids, management of emesis, postoperative pain and hospital discharge criteria were all standardized. The groups were similar with respect to number, age, weight, length of surgery, and estimated intraoperative blood loss. Dexamethasone reduced the overall incidence of vomiting from 72% (placebo) to 40% (P < 0.001). Vomiting, both in-hospital and postdischarge, was decreased by the prophylactic administration of dexamethasone. Each episode of in-hospital vomiting prolonged discharge by 13 +/- 2 min, mean +/- SD (P < 0.001). In conclusion, dexamethasone markedly decreased vomiting by healthy children after elective tonsillectomy in an ambulatory hospital setting.", "A prospective, randomized, double-blind study to determine the postoperative efficacy of steroids in tonsillectomy was performed in 49 children. A single dose of intravenous dexamethasone or placebo was administered after each child was anesthetized. Postoperatively each child was examined for objective signs of trismus (measured by interincisor distance), temperature elevation, and weight loss, as well as for subjective signs of mouth odor, oral intake, pain, level of activity, and analgesic usage. There were no statistical differences noted in any of the variables compared in the two groups and the complication rates were also similar.", "In this double-blinded, randomized, placebo-controlled study, we assessed the effect of dexamethasone 0.5 mg/kg IV administered preoperatively in 110 children 2-12 yr old, undergoing electrodissection adenotonsillectomy, using a standardized anesthetic technique. The incidence of early and late vomiting, the time to first oral intake, the quality of oral intake, the satisfaction scores, and the duration of IV hydration were compared in both groups. The overall incidence of vomiting, as well as the incidence of late vomiting, was significantly less in the Dexamethasone group as compared with the Saline group (23% and 19% vs 51% and 34%, respectively). The time to first oral intake and the duration of IV hydration were shorter in the Dexamethasone group compared with the Saline group (P < 0.05). The quality of oral intake and the satisfaction scores were better in the Dexamethasone group than in the Saline group (P < 0.05). This report confirms the beneficial effect of IV dexamethasone on both vomiting and oral intake in children undergoing electrodissection adenotonsillectomy.\n In this double-blinded, placebo-controlled study, we examined the efficacy of a single dose of dexamethasone 0.5 mg/kg IV on posttonsillectomy vomiting and oral intake in children 2-12 yr old. Dexamethasone significantly decreased the incidence of postoperative vomiting during the first 24 h, shortened the time to the first oral intake and the duration of IV hydration, and improved the quality of oral intake and the satisfaction scores of the patients.", "Postoperative morbidity in patients undergoing tonsillectomy with or without adenoidectomy includes inadequate oral intake, pain, nausea, vomiting and bleeding. The purpose of this study is to evaluate the effect of preoperative 0.5 mg/kg i.v. dexamethasone on postoperative early oral intake, pain, vomiting in patients undergoing adenotonsillectomy while performing standard anesthesia technique and sharp dissection tonsillectomy.\n In this prospective, double-blinded, placebo-controlled study 62 children, aged 4-12 years, who underwent tonsillectomy with or without adenoidectomy were randomly assigned to receive single dose of 0.5 mg/kg i.v. dexamethasone preoperatively. Patients started to receive 100 ml of clear fluids 2 h postoperatively, then were offered every hour. When pain score was 3 or above, paracetamol was given for pain control. Tolerating 400 ml of clear fluids, no bleeding and no vomiting were accepted as discharge criteria. The discharge time was also recorded. The incidence of early vomiting, pain scores, amount of oral intake were recorded until the discharge time.\n Compared with placebo, the patients who received preoperative dexamethasone had significantly less pain score during the first 6 h postoperatively (p<0.05), adequate amount of oral intake time was shorter (p<0.05) and the discharge time was earlier (p<0.05). No difference was found in vomiting incidence in both groups.\n Preoperative dexamethasone use significantly reduces early posttonsillectomy pain, improves oral intake and facilitates meeting the discharge criteria while using standard anesthesia technique and sharp dissection tonsillectomy without any significant side effects.", "The effects of dexamethasone and perphenazine on vomiting after tonsillectomy in children were compared in 226 healthy children aged 2-12 yr. The study was randomized, stratified, blocked, and double-blind. Anesthesia was induced intravenously (I.V.) with propofol or by inhalation with halothane and N2O. Dexamethasone 150 microg/kg or perphenazine 70 microg/kg was administered I.V. after the induction of anesthesia in a double-blind fashion. Perioperative management of emesis, pain, fluids, and patient discharge was all standardized. The groups had similar demographic characteristics. Perphenazine significantly reduced the incidence of in-hospital vomiting compared with dexamethasone (13% vs 36%, P < 0.001). The incidence of out-of-hospital vomiting was almost identical. Overall, the incidence was significantly different for perphenazine vs dexamethasone (33% vs 46%, P = 0.04) using logistic regression analysis. Of note, sex and induction technique were significant predictors of postoperative vomiting (P < 0.05) using logistic regression analysis, with male patients and those patients undergoing I.V. induction vomiting less. In conclusion, perphenazine more effectively decreases vomiting by children after tonsillectomy in an ambulatory hospital setting compared with dexamethasone.\n Postoperative vomiting can have many debilitating effects, and children undergoing tonsillectomy are at particular risk. We compared the effects of dexamethasone and perphenazine on vomiting after tonsillectomy in 266 children. We found perphenazine more effective than dexamethasone before discharge from hospital but that the two drugs have similar effects after discharge.", "A prospective, randomized, double-blind study to determine the postoperative effects of steroids in tonsillectomy was performed on 25 children from 4 to 12 years of age. A single intravenous dose of dexamethasone or a placebo was administered at onset of surgery. Other preoperative and postoperative medications, including antibiotics, anesthesia, and surgical techniques were standardized as noted in this article. The ability to return to a full or semifull diet occurred on the third and fourth postoperative days, significantly sooner in the steroid-treated patients than in the control patients. By the fifth and sixth days, the control group were eating as well as those children who received steroids. No significant differences were observed in postoperative pain, nausea, emesis, fever, or in the need for postoperative pain medications. This preliminary article concludes that a single preoperative dose of steroid results in an earlier return to a normal (full) diet in children who had undergone tonsillectomy.", "The 5-HT3 antagonists are effective in reducing postoperative nausea and vomiting (PONV) associated with paediatric tonsillectomy. Although prophylactic tropisetron can reduce the incidence of PONV by half, the resulting level of over 40% is still unacceptably high. The aim of this study was to evaluate the effect of adding dexamethasone to tropisetron. In a blinded study, 59 children (mean age 6.1 years) were administered 0.1 mg.kg-1 up to 2 mg of tropisetron and 66 children (mean age 5.7 years) received the same dose of tropisetron plus 0.5 mg.kg-1 up to 8 mg of dexamethasone. Both drugs were given intravenously during induction of anaesthesia for tonsillectomy. During the inpatient stay of 24 h, the incidence of postoperative vomiting in the tropisetron alone group was 53% compared with 26% in the combination group (P=0.002, chi-squared). A significant reduction in nausea from 53% to 30% was also observed (P=0.02). Parents completed a daily diary for 5 days following discharge. Delayed vomiting occurred in 27% and 11% of the tropisetron and combination therapy groups, respectively (P=0.025) Sixteen percent and 9%, respectively, required medical attention (P=0.27). Tropisetron plus dexamethasone is more effective than tropisetron alone in reducing the incidence of PONV following paediatric tonsillectomy.", "Several studies have indicated that antibiotics given for 5-7 days post-tonsillectomy are beneficial. A prospective double blind randomized study was undertaken to evaluate the efficacy of a long-acting antibiotic (Cefonicid) given prophylactically at the time of tonsillectomy. Dependent variables were percent weight loss, number of doses of pain medications required postoperatively, the number of days required to resume a normal diet, and return to work. The results of all independent tests indicated that there were no statistically significant differences between the Cefonicid group and the placebo group. The results of this study indicate that single dose prophylactic application of Cefonicid is not effective in adults undergoing tonsillectomy." ]	The evidence suggests that a single intravenous dose of dexamethasone is an effective, safe and inexpensive treatment for reducing morbidity from pediatric tonsillectomy.
CD008740	[ "16527165" ]	[ "[Clinical trial comparing efficacy and safety of four highly active antiretroviral therapy (HAART) in antiretroviral-naive treatment with advanced HIV infection]." ]	[ "Comparison of efficacy and safety of four highly active antiretroviral therapy regimens (HAART) including two nucleoside analogues (NA) and a protease inhibitor (PI) in HIV positive patients with advanced infection and antiretroviral naive.\n Multicenter, randomized and open labeled clinical trial in ten community hospitals of Castilla-La Mancha and Madrid. Regimen 1 contains zidovudine (AZT), lamivudine (3TC) and indinavir (IDV) regimen 2 includes AZT, 3TC and ritonavir (RTV), regimen 3 was didanosine (DDI), estavudine (D4T) and IDV, and regimen 4 included DDI, D4T and RTV. Decrease in viral load of HIV (VC) has been assessed as primary endpoint and as secondary one, the increase of the numbers of CD4 lymphocytes, percentage of disease progression, adverse reactions and adherence. Measurements were made at baseline visit and at 6, 12, 24, 36 and 48 weeks.\n A total of 98 patients with a mean baseline CD4 count of 122 x 10(6)/l (range of 5-340) and a baseline viral load of 5.1 log copies/ml were included. At 48 weeks, a mean increase of the CD4 and decrease of the viral load without significant difference between the 4 regimens (103 cells/2.62 log in regimen 1; 169 cells/2.86 log in regimen 2; 171 cells/2.56 log in regimen 3 and 141 cells/1.71 log in regimen 4) were observed in the analysis of the patients in treatment. Treatment was discontinued due to adverse reactions: 24% in regimen 1, 48% in regimen 2, 26% in regimen 3 and 32% in regimen 4, without significant difference. Analyzing by PI groups, 41% of the patients with RTV and 25% of those with IDV discontinued treatment due to adverse effects. There was withdrawal from treatment due to disease progression in 7% of the RTV patients and in 9% of IDV patients.\n In the HIV positive patients with advanced infection, efficacy between the four regimens of HAART is similar, but there is a tendency to require more withdrawal due to adverse effects in the RTV group than in those of IDV, the two used as single PI." ]	We conclude that for the critical outcomes of virologic response and serious adverse events initial ART regimens containing TDF are equivalent to those containing AZT. However, TDF is superior to AZT in terms of immunologic response and adherence and more frequent emergence of resistance. How much the other drugs in the regimens contributed to these findings is unclear, and true head-to-head trials are still warranted. The role of each drug in initial ART will likely be driven by their specific toxicities.
CD008530	[ "14553868", "16708309", "10600085", "2810183" ]	[ "Implementation of an evidence-based guideline to reduce duration of intravenous antibiotic therapy and length of stay for patients hospitalized with community-acquired pneumonia: a randomized controlled trial.", "Communication training and antibiotic use in acute respiratory tract infections. A cluster randomised controlled trial in general practice.", "A randomized, prospective study measuring outcomes after antibiotic therapy intervention by a multidisciplinary consult team.", "Comparison of two prophylactic single-dose intravenous antibiotic regimes in the treatment of patients undergoing elective colorectal surgery in a district general hospital." ]	[ "Patients with pneumonia often remain hospitalized after they are stable clinically, and the duration of intravenous antibiotic therapy is a rate-limiting step for discharge. The purpose of this study was to determine whether implementation of an evidence-based guideline would reduce the duration of intravenous antibiotic therapy and length of stay for patients hospitalized with pneumonia.\n In a seven-site, cluster randomized clinical trial, we enrolled 325 control and 283 intervention patients who were admitted by one of 116 physician groups. Within site, physician groups were assigned randomly to receive a practice guideline alone (control arm) or a practice guideline that was implemented using a multifaceted strategy (intervention arm). The effectiveness of guideline implementation was measured by the duration of intravenous antibiotic therapy and length of stay; differences in the rates of discontinuation and hospital discharge were assessed with proportional hazards models. Medical outcomes were assessed at 30 days.\n Intravenous antibiotic therapy was discontinued somewhat more quickly in the intervention group (hazard ratio [HR] =1.23; 95% confidence interval [CI]: 1.00 to 1.52; P = 0.06) than in the control group. Intervention patients were discharged more quickly, but the difference was not statistically significant (HR = 1.16; 95% CI: 0.97 to 1.38; P = 0.11). Fewer intervention (55% [157/283]) than control (63% [206/325]) patients had medical complications during the index hospitalization (P = 0.04), with no differences in other medical outcomes, including mortality, rehospitalization, and return to usual activities, between treatment arms.\n The multifaceted guideline implementation strategy resulted in a slight reduction in the duration of intravenous antibiotic therapy and a nonsignificant reduction in length of stay, without affecting patient outcomes.", "A cluster-randomised controlled trial in general practice\n Physician-patient communication plays a key role in treatment decisions in primary care. We aimed to reduce the antibiotic prescription rate for acute respiratory tract infections using a short training programme in patient-centred communication.\n We conducted a cluster-randomised controlled trial in 45 general practices in Switzerland. Thirty physicians received evidence-based guidelines for the management of acute respiratory tract infections; 15 physicians randomised to the full intervention additionally received training in patient-centred communication. A further 15 physicians, not randomised, served as a control to blind the physicians in the other two groups to the true comparison. The primary outcome was the antibiotic prescription rate reported by pharmacists. Secondary outcomes were patient satisfaction and enablement, re-consultation rates, days with restrictions, and days off work. 1108 adults with acute respiratory infections were screened between January and May 2004. Outcomes were measured in 837 consultations; 624 patients had follow-up interviews at 7 and 14 days.\n The antibiotic prescription rate reported by pharmacists was low in both full and limited intervention groups (13.5% and 15.7% respectively) but only half of the antibiotics were prescribed according to guidelines (53.8% and 53.1%). No significant differences were seen between the two randomised groups in primary and secondary outcomes. In both groups patient satisfaction was high (median score for both 68 out of 70).\n In this trial, patient-centred communication training did not reduce the rate of antibiotic prescriptions below an already unusually low level. Even with this low prescription rate, patient satisfaction with received care was high.", "Our aim was to identify financial and outcome benefits of therapeutic intervention by a multidisciplinary antimicrobial treatment team composed of pharmacists, a clinical microbiologist, and an infectious disease specialist. Of 252 consecutive inpatients receiving suboptimal intravenous antibiotics identified by the clinical pharmacist, 127 were prospectively randomized to intervention and 125 to a control group. The groups were similar with regard to severity of illness, infection type, and time from admission to randomization. Physicians received timely, detailed reviews of relevant microbiologic and clinical data with recommendations of possible optimal antibiotic choices, dosages, and rationales. Median length of stay after randomization for control and intervention groups was 9.0 days and 5.7 days, respectively (3.3-day difference, p=0.0001). Fifteen (12.0%) and eight patients (6.3%), respectively, died, although the time-specific mortality risk was not significantly different when length of postrandomization follow-up and time to death were taken into account. Physician acceptance of suggestions was 89%. Median patient charges for radiology, laboratory, pharmacy, and room were reduced by $4404/intervention, and median hospital costs were reduced by $2642/intervention. A multidisciplinary antimicrobial therapy team can be a useful information source for physicians, improve outcomes in hospitalized patients receiving intravenous antimicrobials, and result in substantial cost savings.", "Two hundred and twenty-nine patients were entered into a study to compare the effectiveness and safety of two single-shot antibiotic regimes in patients undergoing elective colorectal surgery in two district general hospitals. A single shot of intravenous (IV) latamoxef disodium was as effective as an IV combination of cefuroxime and metronidazole in control of wound infection following elective large bowel surgery when given as a bolus at the time of anaesthetic induction. The incidence of major wound infection was 6% and was evenly distributed in the two treatment groups. Half the major wound infections were associated with faecal fistulae. A single shot of IV antibiotic at the time of anaesthetic induction was safe, simple and an effective prophylaxis against major wound infection. There was a low incidence (1.3%) of serious postoperative bleeding and no serious adverse reactions were noted. The overall mortality was 9%. Death was significantly related to elderly patients, a poor performance status, operative contamination and wound infections." ]	In this meta-analysis, preventive antibiotic therapy seemed to reduce the risk of infection, but did not reduce the number of dependent or deceased patients. However, the included studies were small and heterogeneous. Large randomised trials are urgently needed.
CD006612	[ "16531614", "16531613", "14762035", "18714059", "20571015", "20688574", "18206891", "14535967", "10095804", "10837284" ]	[ "Homocysteine lowering and cardiovascular events after acute myocardial infarction.", "Homocysteine lowering with folic acid and B vitamins in vascular disease.", "Lowering homocysteine in patients with ischemic stroke to prevent recurrent stroke, myocardial infarction, and death: the Vitamin Intervention for Stroke Prevention (VISP) randomized controlled trial.", "Mortality and cardiovascular events in patients treated with homocysteine-lowering B vitamins after coronary angiography: a randomized controlled trial.", "Effects of homocysteine-lowering with folic acid plus vitamin B12 vs placebo on mortality and major morbidity in myocardial infarction survivors: a randomized trial.", "B vitamins in patients with recent transient ischaemic attack or stroke in the VITAmins TO Prevent Stroke (VITATOPS) trial: a randomised, double-blind, parallel, placebo-controlled trial.", "Effect of homocysteine-lowering therapy on arterial elasticity and metabolic parameters in metformin-treated diabetic patients.", "Effects of short-term treatment with metformin on serum concentrations of homocysteine, folate and vitamin B12 in type 2 diabetes mellitus: a randomized, placebo-controlled trial.", "Folate administration reduces circulating homocysteine levels in NIDDM patients on long-term metformin treatment.", "Dietary strategies for lowering homocysteine concentrations." ]	[ "Homocysteine is a risk factor for cardiovascular disease. We evaluated the efficacy of homocysteine-lowering treatment with B vitamins for secondary prevention in patients who had had an acute myocardial infarction.\n The trial included 3749 men and women who had had an acute myocardial infarction within seven days before randomization. Patients were randomly assigned, in a two-by-two factorial design, to receive one of the following four daily treatments: 0.8 mg of folic acid, 0.4 mg of vitamin B12, and 40 mg of vitamin B6; 0.8 mg of folic acid and 0.4 mg of vitamin B12; 40 mg of vitamin B6; or placebo. The primary end point during a median follow-up of 40 months was a composite of recurrent myocardial infarction, stroke, and sudden death attributed to coronary artery disease.\n The mean total homocysteine level was lowered by 27 percent among patients given folic acid plus vitamin B12, but such treatment had no significant effect on the primary end point (risk ratio, 1.08; 95 percent confidence interval, 0.93 to 1.25; P=0.31). Also, treatment with vitamin B6 was not associated with any significant benefit with regard to the primary end point (relative risk of the primary end point, 1.14; 95 percent confidence interval, 0.98 to 1.32; P=0.09). In the group given folic acid, vitamin B12, and vitamin B6, there was a trend toward an increased risk (relative risk, 1.22; 95 percent confidence interval, 1.00 to 1.50; P=0.05).\n Treatment with B vitamins did not lower the risk of recurrent cardiovascular disease after acute myocardial infarction. A harmful effect from combined B vitamin treatment was suggested. Such treatment should therefore not be recommended. (ClinicalTrials.gov number, NCT00266487.).\n Copyright 2006 Massachusetts Medical Society.", "In observational studies, lower homocysteine levels are associated with lower rates of coronary heart disease and stroke. Folic acid and vitamins B6 and B12 lower homocysteine levels. We assessed whether supplementation reduced the risk of major cardiovascular events in patients with vascular disease.\n We randomly assigned 5522 patients 55 years of age or older who had vascular disease or diabetes to daily treatment either with the combination of 2.5 mg of folic acid, 50 mg of vitamin B6, and 1 mg of vitamin B12 or with placebo for an average of five years. The primary outcome was a composite of death from cardiovascular causes, myocardial infarction, and stroke.\n Mean plasma homocysteine levels decreased by 2.4 micromol per liter (0.3 mg per liter) in the active-treatment group and increased by 0.8 micromol per liter (0.1 mg per liter) in the placebo group. Primary outcome events occurred in 519 patients (18.8 percent) assigned to active therapy and 547 (19.8 percent) assigned to placebo (relative risk, 0.95; 95 percent confidence interval, 0.84 to 1.07; P=0.41). As compared with placebo, active treatment did not significantly decrease the risk of death from cardiovascular causes (relative risk, 0.96; 95 percent confidence interval, 0.81 to 1.13), myocardial infarction (relative risk, 0.98; 95 percent confidence interval, 0.85 to 1.14), or any of the secondary outcomes. Fewer patients assigned to active treatment than to placebo had a stroke (relative risk, 0.75; 95 percent confidence interval, 0.59 to 0.97). More patients in the active-treatment group were hospitalized for unstable angina (relative risk, 1.24; 95 percent confidence interval, 1.04 to 1.49).\n Supplements combining folic acid and vitamins B6 and B12 did not reduce the risk of major cardiovascular events in patients with vascular disease. (ClinicalTrials.gov number, NCT00106886; Current Controlled Trials number, ISRCTN14017017.).\n Copyright 2006 Massachusetts Medical Society.", "In observational studies, elevated plasma total homocysteine levels have been positively associated with ischemic stroke risk. However the utility of homocysteine-lowering therapy to reduce that risk has not been confirmed by randomized trials.\n To determine whether high doses of folic acid, pyridoxine (vitamin B6), and cobalamin (vitamin B12), given to lower total homocysteine levels, reduce the risk of recurrent stroke over a 2-year period compared with low doses of these vitamins.\n Double-blind randomized controlled trial (September 1996-May 2003).\n 3680 adults with nondisabling cerebral infarction at 56 university-affiliated hospitals, community hospitals, private neurology practices, and Veterans Affairs medical centers across the United States, Canada, and Scotland.\n All participants received best medical and surgical care plus a daily multivitamin containing the US Food and Drug Administration's reference daily intakes of other vitamins; patients were randomly assigned to receive once-daily doses of the high-dose formulation (n = 1827), containing 25 mg of pyridoxine, 0.4 mg of cobalamin, and 2.5 mg of folic acid; or the low-dose formulation (n = 1853), containing 200 microg of pyridoxine, 6 microg of cobalamin and 20 microg of folic acid.\n Recurrent cerebral infarction (primary outcome); coronary heart disease (CHD) events and death (secondary outcomes).\n Mean reduction of total homocysteine was 2 micromol/L greater in the high-dose group than in the low-dose group, but there was no treatment effect on any end point. The unadjusted risk ratio for any stroke, CHD event, or death was 1.0 (95% confidence interval [CI], 0.8-1.1), with chances of an event within 2 years of 18.0% in the high-dose group and 18.6% in the low-dose group. The risk of ischemic stroke within 2 years was 9.2% for the high-dose and 8.8% for the low-dose groups (risk ratio, 1.0; 95% CI, 0.8-1.3) (P =.80 by log-rank test of the primary hypothesis of difference in ischemic stroke between treatment groups). There was a persistent and graded association between baseline total homocysteine level and outcomes. A 3- micromol/L lower total homocysteine level was associated with a 10% lower risk of stroke (P =.05), a 26% lower risk of CHD events (P<.001), and a 16% lower risk of death (P =.001) in the low-dose group and a nonsignificantly lower risk in the high-dose group by 2% for stroke, 7% for CHD events, and 7% for death.\n In this trial, moderate reduction of total homocysteine after nondisabling cerebral infarction had no effect on vascular outcomes during the 2 years of follow-up. However, the consistent findings of an association of total homocysteine with vascular risk suggests that further exploration of the hypothesis is warranted and longer trials in different populations with elevated total homocysteine may be necessary.", "Observational studies have reported associations between circulating total homocysteine concentration and risk of cardiovascular disease. Oral administration of folic acid and vitamin B(12) can lower plasma total homocysteine levels.\n To assess the effect of treatment with folic acid and vitamin B(12) and the effect of treatment with vitamin B(6) as secondary prevention in patients with coronary artery disease or aortic valve stenosis.\n Randomized, double-blind controlled trial conducted in the 2 university hospitals in western Norway in 1999-2006. A total of 3096 adult participants undergoing coronary angiography (20.5% female; mean age, 61.7 years) were randomized. At baseline, 59.3% had double- or triple-vessel disease, 83.7% had stable angina pectoris, and 14.9% had acute coronary syndromes.\n Using a 2 x 2 factorial design, participants were randomly assigned to 1 of 4 groups receiving daily oral treatment with folic acid, 0.8 mg, plus vitamin B(12), 0.4 mg, plus vitamin B(6), 40 mg (n = 772); folic acid plus vitamin B(12) (n = 772); vitamin B(6) alone (n = 772); or placebo (n = 780).\n The primary end point was a composite of all-cause death, nonfatal acute myocardial infarction, acute hospitalization for unstable angina pectoris, and nonfatal thromboembolic stroke.\n Mean plasma total homocysteine concentration was reduced by 30% after 1 year of treatment in the groups receiving folic acid and vitamin B(12). The trial was terminated early because of concern among participants due to preliminary results from a contemporaneous Norwegian trial suggesting adverse effects from the intervention. During a median 38 months of follow-up, the primary end point was experienced by a total of 422 participants (13.7%): 219 participants (14.2%) receiving folic acid/vitamin B(12) vs 203 (13.1%) not receiving such treatment (hazard ratio, 1.09; 95% confidence interval, 0.90-1.32; P = .36) and 200 participants (13.0%) receiving vitamin B(6) vs 222 (14.3%) not receiving vitamin B(6) (hazard ratio, 0.90; 95% confidence interval, 0.74-1.09; P = .28).\n This trial did not find an effect of treatment with folic acid/vitamin B(12) or vitamin B(6) on total mortality or cardiovascular events. Our findings do not support the use of B vitamins as secondary prevention in patients with coronary artery disease.\n clinicaltrials.gov Identifier: NCT00354081.", "Blood homocysteine levels are positively associated with cardiovascular disease, but it is uncertain whether the association is causal.\n To assess the effects of reducing homocysteine levels with folic acid and vitamin B(12) on vascular and nonvascular outcomes.\n Double-blind randomized controlled trial of 12,064 survivors of myocardial infarction in secondary care hospitals in the United Kingdom between 1998 and 2008.\n 2 mg folic acid plus 1 mg vitamin B(12) daily vs matching placebo.\n First major vascular event, defined as major coronary event (coronary death, myocardial infarction, or coronary revascularization), fatal or nonfatal stroke, or noncoronary revascularization.\n Allocation to the study vitamins reduced homocysteine by a mean of 3.8 micromol/L (28%). During 6.7 years of follow-up, major vascular events occurred in 1537 of 6033 participants (25.5%) allocated folic acid plus vitamin B(12) vs 1493 of 6031 participants (24.8%) allocated placebo (risk ratio [RR], 1.04; 95% confidence interval [CI], 0.97-1.12; P = .28). There were no apparent effects on major coronary events (vitamins, 1229 [20.4%], vs placebo, 1185 [19.6%]; RR, 1.05; 95% CI, 0.97-1.13), stroke (vitamins, 269 [4.5%], vs placebo, 265 [4.4%]; RR, 1.02; 95% CI, 0.86-1.21), or noncoronary revascularizations (vitamins, 178 [3.0%], vs placebo, 152 [2.5%]; RR, 1.18; 95% CI, 0.95-1.46). Nor were there significant differences in the numbers of deaths attributed to vascular causes (vitamins, 578 [9.6%], vs placebo, 559 [9.3%]) or nonvascular causes (vitamins, 405 [6.7%], vs placebo, 392 [6.5%]) or in the incidence of any cancer (vitamins, 678 [11.2%], vs placebo, 639 [10.6%]).\n Substantial long-term reductions in blood homocysteine levels with folic acid and vitamin B(12) supplementation did not have beneficial effects on vascular outcomes but were also not associated with adverse effects on cancer incidence.\n isrctn.org Identifier: ISRCTN74348595.", "Epidemiological studies suggest that raised plasma concentrations of total homocysteine might be a risk factor for major vascular events. Whether lowering total homocysteine with B vitamins prevents major vascular events in patients with previous stroke or transient ischaemic attack is unknown. We aimed to assess whether the addition of once-daily supplements of B vitamins to usual medical care would lower total homocysteine and reduce the combined incidence of non-fatal stroke, non-fatal myocardial infarction, and death attributable to vascular causes in patients with recent stroke or transient ischaemic attack of the brain or eye.\n In this randomised, double-blind, parallel, placebo-controlled trial, we assigned patients with recent stroke or transient ischaemic attack (within the past 7 months) from 123 medical centres in 20 countries to receive one tablet daily of placebo or B vitamins (2 mg folic acid, 25 mg vitamin B6, and 0.5 mg vitamin B12). Patients were randomly allocated by means of a central 24-h telephone service or an interactive website, and allocation was by use of random permuted blocks stratified by hospital. Participants, clinicians, carers, and investigators who assessed outcomes were masked to the assigned intervention. The primary endpoint was the composite of stroke, myocardial infarction, or vascular death. All patients randomly allocated to a group were included in the analysis of the primary endpoint. This trial is registered with ClinicalTrials.gov, NCT00097669, and Current Controlled Trials, ISRCTN74743444.\n Between Nov 19, 1998, and Dec 31, 2008, 8164 patients were randomly assigned to receive B vitamins (n=4089) or placebo (n=4075). Patients were followed up for a median duration of 3.4 years (IQR 2.0-5.5). 616 (15%) patients assigned to B vitamins and 678 (17%) assigned to placebo reached the primary endpoint (risk ratio [RR] 0.91, 95% CI 0.82 to 1.00, p=0.05; absolute risk reduction 1.56%, -0.01 to 3.16). There were no unexpected serious adverse reactions and no significant differences in common adverse effects between the treatment groups.\n Daily administration of folic acid, vitamin B6, and vitamin B12 to patients with recent stroke or transient ischaemic attack was safe but did not seem to be more effective than placebo in reducing the incidence of major vascular events. These results do not support the use of B vitamins to prevent recurrent stroke. The results of ongoing trials and an individual patient data meta-analysis will add statistical power and precision to present estimates of the effect of B vitamins.\n Australia National Health and Medical Research Council, UK Medical Research Council, Singapore Biomedical Research Council, Singapore National Medical Research Council, Australia National Heart Foundation, Royal Perth Hospital Medical Research Foundation, and Health Department of Western Australia.\n Copyright 2010 Elsevier Ltd. All rights reserved.", "Metformin may affect the risk of atherothrombotic disease. However, metformin increases levels of homocysteine (Hcy), considered an independent risk factor for atherosclerosis. We evaluate whether homocysteine-lowering has a beneficial effect on arterial elasticity and metabolic parameters in metformin-treated diabetic patients. In double-blind, placebo-controlled study, 60 diabetic patients treated with high dose of metformin were randomly assigned to receive daily oral supplementation with folate (1000 mcg), vitamins B12 (400 mcg) and B6 (10mg) (group 1) or placebo (group 2). Lipid profile, HbA1C, insulin, C-peptide, hs-CRP, vitamin B12, folic acid, homocysteine, endothelin, homeostasis model assessment-insulin resistance (HOMA-IR) were measured. Arterial elasticity was evaluated using pulse wave contour analysis (HDI CR 2000, Eagan, MN). The two groups were similar at baseline in terms of hemodynamic and arterial elasticity parameters. After a 4-month small artery elasticity index (SAEI) was significantly greater in patients who received Hcy-lowering agents than in the placebo group: 4.3+/-2.04 ml/mm Hg x 100 versus 3.2+/-1.1 ml/mm Hg x 100, p=0.01. Post-treatment vitamin B12 and folic acid levels were greater in group 1 versus group 2: 738.1+/-279.9 pg/ml versus 566.1+/-167.4 pg/ml, p=0.007 and 14.9+/-4.8 ng/ml versus 8.3+/-2.9 ng/ml, p<0.0001, respectively. Hcy level decreased significantly in the treatment group from 10.0+/-4.4 to 7.6+/-2.5 micromol/l, p=0.002 and did not change in placebo group (p=0.9). Hcy-lowering therapy improved small arterial elasticity in diabetic patients treated with high dose of metformin. The improvement was associated with a decrease in Hcy as well as an increase in folic acid and vitamin B12. These findings suggest that Hcy-lowering may have beneficial vascular effect in metformin-treated diabetic patients.", "Metformin is a key treatment option in type 2 diabetes. However, metformin may decrease vitamin B12 levels and increase levels of homocysteine, a cardiovascular risk factor. We investigated whether 16 weeks of treatment with metformin affects serum concentrations of homocysteine, folate and vitamin B12 in subjects with type 2 diabetes treated with insulin.\n Placebo-controlled, randomized trial. Measurements: at baseline and 16 weeks later.\n This trial was conducted in the outpatient clinics of three general hospitals in The Netherlands.\n A total of 745 patients with type 2 diabetes, treated with insulin and not known with a contraindication for the use of metformin, were approached; 390 gave informed consent and entered the study. Thirty-seven subjects dropped out (12 placebo and 25 metformin users).\n Addition of metformin or placebo to insulin therapy. PRIMARY OUTCOME PARAMETERS: Serum homocysteine, folate, vitamin B12, indices of glycaemic control and body weight.\n Amongst those who completed 16 weeks of treatment, metformin use, as compared with placebo, was associated with an increase in homocysteine of 4% (0.2 to 8; P=0.039) and with decreases in folate [-7% (-1.4 to -13); P=0.024] and vitamin B12 [-14% (-4.2 to -24); P<0.0001]. In addition, the increase in homocysteine could be explained by the decreases in folate and vitamin B12.\n In patients with type 2 diabetes, 16 weeks of treatment with metformin reduces levels of folate and vitamin B12, which results in a modest increase in homocysteine. The clinical significance of these findings remains to be investigated.", "Metformin treatment increases circulating homocysteine levels. We studied whether administration of folate reduces serum total homocysteine levels in patients on long-term metformin treatment.\n A prospective, randomized, double-blind, placebo-controlled study lasting for 12 weeks and taking place in a university hospital setting.\n Thirty patients treated with a metformin dose of at least 1000 mg day-1 for a minimum of 1 year were included. At baseline serum total homocysteine levels were within the reference range. One patient who withdrew and one who died were excluded from the statistical evaluation. Twenty-six of the remaining patients suffered from NIDDM, the other two from hyperlipidaemia.\n Patients were randomized into two groups at week 0. The folate group received 0.25 mg day-1 of folate in addition to 60 mg day-1 of Fe2+, while the placebo group received only 60 mg day-1 of Fe2+.\n Fasting homocysteine, cysteine, cysteinylglycine, vitamin B12 and folate were measured at week 0, 4 and 12. Changes from week 0 to week 4 and from week 0 to week 12 were calculated.\n Folate administration reduced serum levels of total homocysteine in the folate group as compared with the placebo group by 13.9% (P < 0.01) and 21.7% (P < 0.001) at week 4 and 12, respectively. In the folate group versus the placebo group serum levels of vitamin B12 increased by 9.9% (P = 0.010) and 9.6% (P = 0.043) while folate levels increased by 96.9 and 89.9% at week 4 and 12, respectively.\n The present study indicates that the homocysteine-increasing effect of metformin can be counteracted by folate administration.", "Elevated plasma total homocysteine (tHcy) concentrations are associated with increased risk of vascular disease, and there is a strong inverse association between dietary and blood folate and blood tHcy concentrations. Increased folate consumption may lower the risk of tHcy-mediated cardiovascular disease.\n The objective was to determine the most appropriate means of increasing dietary folate to reduce plasma tHcy.\n Sixty-five free-living subjects aged 36-71 y with tHcy concentrations >/=9 micromol/L participated in a randomized, controlled trial to compare 3 approaches for increasing dietary folate to approximately 600 microg/d: folic acid supplementation, consumption of folic acid-fortified breakfast cereals, and increased consumption of folate-rich foods.\n An intake of 437 microg folic acid/d from supplements resulted in a 27-nmol/L increase in serum folate and a 21% reduction in tHcy, relative to the change in a control group. In subjects who consumed folic acid-fortified breakfast cereal, folate intake increased by an average of 298 microg, serum folate increased by 21 nmol/L, and tHcy concentrations decreased by 24%. Increased intakes of folate-rich foods resulted in a 418-microg increase in dietary folate, a 7-nmol/L increase in serum folate, and a 9% reduction in tHcy concentrations. The decrease in tHcy was negatively correlated (r = -0.66) with the increase in serum folate.\n Daily consumption of folic acid-fortified breakfast cereals and the use of folic acid supplements appear to be the most effective means of reducing tHcy concentrations. The reduction in tHcy was significantly negatively correlated with the increase in serum folate, which may be a useful marker for measuring dietary change." ]	This updated Cochrane review found no evidence to suggest that homocysteine-lowering interventions in the form of supplements of vitamins B6, B9 or B12 given alone or in combination should be used for preventing cardiovascular events. Furthermore, there is no evidence suggesting that homocysteine-lowering interventions are associated with an increased risk of cancer.
CD005984	[ "1773955", "17059514" ]	[ "Controlled trial comparing two types of enteral nutrition in treatment of active Crohn's disease: elemental versus polymeric diet.", "Effectiveness of an 'half elemental diet' as maintenance therapy for Crohn's disease: A randomized-controlled trial." ]	[ "To determine whether an elemental diet or a polymeric defined formula diet would be more effective for treating active Crohn's disease, we conducted a prospective randomised clinical trial in 30 patients with active Crohn's disease unresponsive to steroids and/or complicated by malnutrition. They received a four to six week enteral nutrition course with either an elemental diet or a polymeric diet. Clinical remission occurred in 10 of the 15 patients on elemental diet compared with 11 of the 15 patients assigned to polymeric diet. Both groups showed similar improvements in nutritional status, biological inflammation, alpha 1 antitrypsin clearance, and colonoscopic lesions (diminished in 17 out of 24 patients). Most patients relapsed during the year after discharge. We conclude that enteral nutrition, whatever the diet, is an efficient primary therapy for active Crohn's disease but does not influence the long term outcome.", "Although thiopurines have a proven role in maintenance therapy for Crohn's disease, an alternative therapy is needed for patients intolerant or resistant to thiopurines.\n To evaluate the effectiveness of home enteral nutrition as a maintenance therapy regimen in which half of the daily calorie requirement is provided by an elemental diet and the remaining half by a free diet. We refer to this home enteral nutrition therapy as 'half elemental diet'.\n Between 2002 and 2005, 51 patients in remission from two hospitals were randomly assigned to a half elemental diet group (n = 26) or a free diet group (n = 25). The primary outcome measure of this study was the occurrence of relapse over the 2-year period.\n The relapse rate in the half elemental diet group was significantly lower [34.6% vs. 64.0%; multivariate hazard ratio 0.40 (95% CI: 0.16-0.98)] than that in the free diet group after a mean follow-up of 11.9 months. Compliance was similar in the two groups. No adverse event occurred in any of the patients throughout the study.\n This randomized-controlled trial shows the effectiveness of an half elemental diet, which is a promising maintenance therapy for Crohn's disease patients." ]	The available evidence suggests that supplementary enteral nutritional may be effective for maintenance of remission in Crohn's disease. Whilst larger studies are needed to confirm these findings, enteral nutritional supplementation could be considered as an alternative or as an adjunct to maintenance drug therapy in Crohn's disease.
CD002842	[ "10667738", "17166313", "19825502" ]	[ "Effects of cognitive treatment in psychiatric rehabilitation.", "Cognitive rehabilitation in the elderly: effects on strategic behavior in relation to goal management.", "Efficacy and specificity of intensive cognitive rehabilitation of attention and executive functions in multiple sclerosis." ]	[ "Ninety subjects with severe and disabling psychiatric conditions, predominantly schizophrenia, participated in a controlled-outcome trial of the cognitive component of Integrated Psychological Therapy (IPT), a group-therapy modality intended to reestablish basic neurocognitive functions. The cognitive therapy was delivered to subjects in the experimental condition during intensive 6-month treatment periods. Control subjects received supportive group therapy. Before, during, and after the intensive treatment period, all subjects received an enriched regimen of comprehensive psychiatric rehabilitation, including social and living skills training, optimal pharmacotherapy, occupational therapy, and milieu-based behavioral treatment. IPT subjects showed incrementally greater gains compared with controls on the primary outcome measure, the Assessment of Interpersonal Problem-Solving Skills, suggesting that procedures that target cognitive impairments of schizophrenia spectrum disorders can enhance patients' response to standard psychiatric rehabilitation, at least in the short term, in the domain of social competence. There was equivocal evidence for greater improvement in the experimental condition on the Brief Psychiatric Rating Scale disorganization factor and strong evidence for greater improvement on a laboratory measure of attentional processing. There was significant improvement in both conditions on measures of attention, memory, and executive functioning, providing support for the hypothesis that therapeutic procedures that target impaired cognition enhance response to conventional psychiatric rehabilitation modalities over a 6-month timeframe.", "Executive functions are highly sensitive to the effects of aging and other conditions affecting frontal lobe function. Yet there are few validated interventions specifically designed to address executive functions, and, to our knowledge, none validated in a healthy aging sample. As part of a large-scale cognitive rehabilitation randomized trial in 49 healthy older adults, a modified Goal Management Training program was included to address the real-life deficits caused by executive dysfunction. This program emphasized periodic suspension of ongoing activity to establish goal hierarchies and monitor behavioral output. Tabletop simulated real-life tasks (SRLTs) were developed to measure the processes targeted by this intervention. Participants were randomized to two groups, one of which received the intervention immediately and the other of which was wait-listed prior to rehabilitation. Results indicated improvements in SRLT performance and self-rated executive deficits coinciding with the training in both groups. These gains were maintained at long-term follow-up. Future research will assess the specificity of these effects in patient groups.", "To evaluate the efficacy of a computer-based intensive training program of attention, information processing and executive functions in patients with clinically-stable relapsing-remitting (RR) multiple sclerosis (MS) and low levels of disability. DESIGN, PATIENTS AND INTERVENTIONS: A total of 150 patients with RR MS and an Expanded Disability Status Scale (EDSS) score of < or =4 were examined. Information processing, working memory and attention were assessed by the Paced Auditory Serial Addition Test (PASAT) and executive functions by the Wisconsin Card Sorting Test (WCST). Twenty patients who scored below certain cut-off measures in both tests were included in this double-blind controlled study. Patients were casually assigned to a study group (SG) or a control group (CG) and underwent neuropsychological evaluation at baseline and after 3 months. Patients in the SG received intensive computer-assisted cognitive rehabilitation of attention, information processing and executive functions for 3 months; the CG did not receive any rehabilitation.\n Ambulatory patients were sent by the MS referral center.\n Improvement in neuropsychological test and scale scores.\n After rehabilitation, only the SG significantly improved in tests of attention, information processing and executive functions (PASAT 3'' p=0.023, PASAT 2'' p=0.004, WCSTte p=0.037), as well as in depression scores (MADRS p=0.01). Neuropsychological improvement was unrelated to depression improvement in regression analysis.\n Intensive neuropsychological rehabilitation of attention, information processing and executive functions is effective in patients with RR MS and low levels of disability, and also leads to improvement in depression." ]	The effectiveness of cognitive rehabilitation remains unconfirmed. The results suggest there may be a short-term effect on attentional abilities, but future studies need to assess the persisting effects and measure attentional skills in daily life. Trials also need to have higher methodological quality and better reporting.
CD003297	[ "15154663", "11165126", "15015612", "16619567", "15774341", "12050495", "15898977" ]	[ "The standardised mistletoe extract PS76A2 improves QoL in patients with breast cancer receiving adjuvant CMF chemotherapy: a randomised, placebo-controlled, double-blind, multicentre clinical trial.", "The effect of an adjuvant mistletoe treatment programme in resected head and neck cancer patients: a randomised controlled clinical trial.", "Impact of complementary mistletoe extract treatment on quality of life in breast, ovarian and non-small cell lung cancer patients. A prospective randomized controlled clinical trial.", "Quality of life is improved in breast cancer patients by Standardised Mistletoe Extract PS76A2 during chemotherapy and follow-up: a randomised, placebo-controlled, double-blind, multicentre clinical trial.", "A pilot study of a supervised group exercise programme as a rehabilitation treatment for women with breast cancer receiving adjuvant treatment.", "Evaluation of an unconventional treatment modality with mistletoe lectin to prevent recurrence of superficial bladder cancer: a randomized phase II trial.", "Immunotherapy with depigmented glutaraldehyde-polymerized extracts: changes in quality of life." ]	[ "Patients with breast cancer receiving adjuvant chemotherapy frequently suffer from a restricted quality of life (QoL) due to the side-effects of chemotherapy and the consequences of coping with the diagnosis. Therefore, the objective of this clinical study was to investigate the impact of PS76A2, an aqueous mistletoe extract standardised to the galactoside-specific mistletoe lectin, on QoL by performing a placebo-controlled trial. Overall, 272 patients with breast cancer receiving adjuvant CMF chemotherapy (cyclophosphamide-methotrexate-fluorouracil) were enrolled and randomised to groups receiving placebo or PS76A2 at concentrations of 10, 30 or 70 ng mistletoe lectin (ML) per ml. The patients received 0.5 ml study medication twice weekly subcutaneously for 15 consecutive weeks (4 CMF cycles). Primary variables were the self-assessment QoL scores GLQ-8 (Global Life Quality) and Spitzer's uniscale. As a result, statistically significant effects on QoL were obtained with the medium dose (15 ng ML/0.5 ml). The treatment difference between the medium dose and placebo with regard to the GLQ-8 sum was 60.8 mm (95% confidence interval: 19.3 to 102.0 mm). The treatment effect for Spitzer's uniscale between the medium dose and placebo was 16.4 mm (95% confidence interval: 6.3 to 26.6 mm). The results on QoL were supported by an increase of T helper lymphocytes (CD4+) and the CD4+/CD8+ ratio (p<0.05). Overall, PS76A2 was well tolerated. Local reactions at the injection sites occurred dose-dependently, but were mild at the low and medium dose levels.", "The effect of an adjuvant mistletoe extract treatment was tested in a prospective, randomised controlled clinical trial involving 477 patients with head and neck squamous cell carcinoma. The patients were stratified into two treatment groups that underwent surgery or surgery followed by radiotherapy and both groups were randomised for additional treatment with mistletoe extract. Patients treated with a mistletoe lectin-1 (ML-1) standardised mistletoe preparation had no lower risk of local/locoregional recurrences, distant metastases or second primaries. In the main analysis based on 202 patients treated with surgery and 275 patients treated with surgery and radiotherapy the adjusted hazard ratio for the disease-free survival (DFS) was 0.959 (95% confidence interval (CI) 0.725-1.268). The 5-year survival rates of patients from the mistletoe group were no better than the survival rates of patients from the control group. Furthermore, no significant changes in the cellular immune reaction or in quality of life could be detected. We conclude that the used mistletoe preparation has no indication in the adjuvant treatment of patients with head and neck cancer.", "Standardized aqueous mistletoe extracts have been applied to cancer patients for several decades as complementary medicine. A multicentric, randomized, open, prospective clinical trial was conducted in three oncological centers in the People's Republic of China in Bejing, Shenyang and Tianjin. Following the guidelines of \"Good Clinical Practice\" (GCP) this study was performed to get information on efficacy safety and side-effects of the standardized mistletoe extract (sME). Two hundred and thirty-three patients with breast (n=68), ovarian (n=71) and non-small cell lung cancer (NSCLC; n=94) were enrolled into this study. Two hundred and twenty-four patients fulfilled the requirements for final analysis (n=115 treated with sME HELIXOR A; n=109 comprising the control group being treated with the approved immunomodulating phytopharmacon Lentinan). All patients were provided with standard tumor-destructive treatment schedules and complementarily treated with sME or Lentinan during chemotherapy according to treatment protocol. Biometrically, the patients of the control and sME treatment group were comparable regarding distribution, clinical classification (WHO) and treatment protocols. Analysis was performed according to the \"Intention to treat principle\". Quality of life (QoL) was significantly (p<0.05) improved for patients who were complementarily treated with sME, as determined by the questionnaires FLIC (Functional Living Index-Cancer), TCM (Traditional Chinese Medicine Index) and the KPI (Karnofsky Performance Index) in comparison to the control group. Additionally, the occurrence of adverse events (AEs) was less frequent in the sME than in the control group (total number of AEs 52 versus 90 and number of serious AEs 5 versus 10 in study and control group, most of them due to chemotherapy). Only one serious AE was allocated to complementary treatment in each group (1 angioedema in sME group). All other side-effects of the sME (7 harmless local inflammatory reactions at subcutaneous injection site, 4 cases with fever) were self-limiting and did not demand therapeutic intervention. This study showed that complementary treatment with sME can beneficially reduce the side-effects of chemotherapy in cancer patients and thus improve quality of life.", "The objective of this randomised, multicentre, double-blind clinical trial was to investigate the impact of PS76A2, an aqueous mistletoe extract standardised to mistletoe lectins, on quality of life (QoL) in breast cancer patients. A total of 352 patients were randomly allocated to 2 groups receiving PS76A2 (15 ng mistletoe lectin/0.5 ml) or matching placebo twice weekly for 4 to 6 cycles of CMF (cyclophosphamide, methotrexate, fluorouracil) chemotherapy followed by 2 months follow-up. The primary efficacy end-point was the change from baseline of 3 FACT-G subscales (physical, emotional and functional well-being) during the fourth CMF cycle. Secondary measures included GLQ-8 (8 linear analogue self-assessment scales), Spitzer's uniscale and haematological variables. The main variables of safety analysis were adverse events, including injection site reactions and clinical laboratory tests. The results showed that physical, emotional and functional well-being improved upon PS76A2, but deteriorated following placebo. The treatment differences were statistically significant for the 3 subscales as well as for the summary score FACT-G, which was analysed as O'Brien's rank sum of its 3 subscales: The total score increased by 4.40 +/- 11.28, indicating a higher QoL after PS76A2, but decreased by 5.11 +/- 11.77 with placebo (p<0.0001). The GLQ-8 sum of 8 LASA scales was analysed as a summary score of GLQ-5 (sum of item nos. 1, 5, 6, 7, 8) and GLQ-3 (sum of item nos. 2, 3, 4). GLQ-5 characterises typical aspects of QoL, while GLQ-3 consists of 3 side-effects of CMF (feeling sick, numbness or pins and needles, loss of hair). GLQ-5 decreased by 42.9 +/- 125.0 upon PS76A2, indicating an improvement in QoL, but increased by 60.3 +/- 94.0 upon placebo (p<0.0001). GLQ-3 deteriorated in both groups (PS76A2: 13.9 +/- 52.4; placebo: 34.5 +/- 57.0), but the differences in favour of PS76A2 were, nevertheless, statistically significant (p=0.0007). The total score GLQ-8 improved by 28.9 +/- 154.6 after PS76A2 and deteriorated by 94.8 +/- 141.1 after placebo (p<0.0001). Spitzer's uniscale improved by 12.2 +/- 30.7 upon PS76A2 and deteriorated by 10.8 +/- 26.1 with placebo (p<0.0001). After follow-up without chemotherapy, a significant treatment difference in favour of PS76A2 was determined by means of FACT-G, GLQ-8 and Spitzer's uniscale. PS76A2 was well tolerated in this trial, with the exception of slight local reactions in 17.6% of the PS76A2 group. In conclusion, PS76A2 (15 ng mistletoe lectin/0.5 ml twice weekly) was shown to be safe and effective in improving QoL in breast cancer patients during chemotherapy and follow-up.", "This pilot study examined whether exercise as an adjunctive rehabilitation therapy could benefit women who have early stage breast cancer and are currently receiving chemotherapy/radiotherapy. The study was designed as a randomised controlled trial (RCT). Physical functioning, fatigue and Quality of Life (QoL) outcomes were evaluated pre and post a 12-week intervention. The results showed that after 12 weeks the women who participated in the exercise programme (n = 12) displayed significantly higher levels of physical functioning and reported higher QoL scores than the controls (n = 10). Changes in fatigue and satisfaction with life favoured the intervention group but did not reach significance. These results are encouraging and suggest that a structured group exercise programme during adjuvant treatment is a safe, well tolerated and effective way of providing physical and psychological health benefits to women during treatment for early stage breast cancer. Since this was a pilot study the numbers did not allow appropriately powered analyses of some variables of interest and favoured relatively young and socio-economically advantaged women. Future studies need to address these issues and determine if these short-term benefits can be sustained.", "The indication for topic chemotherapy or immunotherapy for well differentiated, noninvasive superficial bladder cancer remains controversial. Side effects of these treatments promoted use of unconventional therapies with cytokines, immunomodulators and mistletoe extracts. However, there are no controlled clinical data available on the efficacy of these extracts for bladder cancer. We evaluate the influence of subcutaneously applicated mistletoe lectin on bladder tumor recurrence after transurethral resection.\n The study consists of 45 patients with pTa G1-2 bladder cancer treated with transurethral resection during a 3-year period. Median patient age was 65 years and 33 patients were male. The study cohort was randomly divided into a treatment group receiving adjuvant therapy with mistletoe lectin and a control group receiving no additional treatment. Patients in the treatment group received mistletoe lectin according to schedule 2 weeks after transurethral resection. Clinical followup was assessed 3, 6, 9, 12 and 18 months after the initial resection, and included uretherocystoscopy.\n Both study arms comprised similar patients with regard to total number of previous tumors (mean 2.6 versus 2.9), number of primary lesions (14 versus 12) and number of recurrent tumors (8 versus 11). After followup of 18 months the recurrence-free interval in both study arms was similar (p = 0.76) and the total number of recurrences comparable (p = 0.48).\n Subcutaneous use of mistletoe lectin as adjuvant treatment after transurethral resection does not seem to affect the time to first recurrence, total number of recurrences or recurrence-free outcome.", "Immunotherapy (IT) with modified allergens reduces allergic rhinitis (AR) symptoms and medications requirements. Improvement of quality of life (QOL) is a key point in the treatment of AR. The aim of this study was to provide evidence of changes related to the patient's QOL (well-being) induced by a modified (depigmented glutaraldehyde-polymerized) therapeutic vaccine and of its safety.\n Fifty-three patients with a well-documented clinical history of seasonal AR sensitized to Dactylis glomerata and Olea europaea pollens were included in a randomized clinical trial. Twenty-five patients (Group-A) received a mixture of D. glomerata and O. europaea pollen extracts and 28 patients received placebo (group-C). Any adverse event was recorded and graded in accordance with EAACI guidelines. RQLQ was recorded before the treatment (pollen season 2000) and after 1 year of treatment (pollen season 2001). Dose-response skin prick test with each allergen extract was conducted at baseline and at the end of the study.\n Each patient received 17 injections during this period. All patients completed the trial and no systemic adverse reactions were recorded. Symptom scores (P<0.001) and medication requirements (P<0.001) were significantly reduced in the IT group during the pollen season. This patient group also experienced greater and statistically significant improvement in overall RQLQ score and in five of the seven domains, all of them surpassing the threshold of 'minimal important difference' of 0.5 points.\n Results of this study provided evidence that IT with depigmented, glutaraldehyde-modified allergen extracts was well-tolerated and added beneficial effects to AR treatment in pollen allergic patients eliciting an improvement in QOL enough to justify a change in the patient's treatment." ]	The evidence from RCTs to support the view that the application of mistletoe extracts has impact on survival or leads to an improved ability to fight cancer or to withstand anticancer treatments is weak. Nevertheless, there is some evidence that mistletoe extracts may offer benefits on measures of QOL during chemotherapy for breast cancer, but these results need replication. Overall, more high quality, independent clinical research is needed to truly assess the safety and effectiveness of mistletoe extracts. Patients receiving mistletoe therapy should be encouraged to take part in future trails.
CD006979	[ "11517199" ]	[ "A randomised control study comparing the Infant Flow Driver with nasal continuous positive airway pressure in preterm infants." ]	[ "To compare the effectiveness of the Infant Flow Driver (IFD) with single prong nasal continuous positive airway pressure (nCPAP) in preterm neonates affected by respiratory distress syndrome.\n Randomised controlled study.\n Between September 1997 and March 1999, 36 preterm infants who were eligible for CPAP treatment were randomly selected for either nCPAP or IFD and studied prospectively for changes in oxygen requirement and/or respiratory rate. The requirement for mechanical ventilation, complications of treatment, and effects on mid-term outcome were also evaluated.\n Use of the IFD had a significantly beneficial effect on both oxygen requirement and respiratory rate (p < 0.0001) when compared with nCPAP. Moreover, O(2) requirement and respiratory rate were significantly decreased by four hours (p < 0.001 and p < 0.03 respectively). The probability of remaining supplementary oxygen free over the first 48 hours of treatment was significantly higher in patients treated with the IFD than with nCPAP (p < 0.02). IFD treated patients had a higher success (weaning) rate (94% v 72 %) and shorter duration of treatment (49.3 (31) v 56 (29.7) hours respectively; mean (SD)), although the difference was not significant.\n IFD appears to be a feasible device for managing respiratory distress syndrome in preterm infants, and benefits may be had with regard to oxygen requirement and respiratory rate when compared with nCPAP. The trend towards reduced requirement for mechanical ventilation, shorter clinical recovery time, and shorter duration of treatment requires further evaluation in a multicentre randomised clinical trial." ]	Infants who have their NCPAP pressure weaned to a predefined level and then stop NCPAP completely have less total time on NCPAP and shorter durations of oxygen therapy and hospital stay compared with those that have NCPAP removed for a predetermined number of hours each day. Future trials of withdrawing NCPAP should compare proposed strategies with weaning NCPAP pressure to a predefined level and then stopping NCPAP completely. Clear criteria need to be established for the definition of stability prior to attempting to withdraw NCPAP.
CD000086	[ "12463661", "16452734" ]	[ "Hemiarthroplasty versus internal fixation for displaced intracapsular hip fractures in the elderly. A randomised trial of 455 patients.", "Randomized comparison of reduction and fixation, bipolar hemiarthroplasty, and total hip arthroplasty. Treatment of displaced intracapsular hip fractures in healthy older patients." ]	[ "A total of 455 patients aged over 70 years with a displaced intracapsular fracture of the proximal femur was randomised to be treated either by hemiarthroplasty or internal fixation. The preoperative characteristics of the patients in both groups were similar. Internal fixation has a shorter length of anaesthesia (36 minutes versus 57 minutes, p < 0.0001), lower operative blood loss (28 ml versus 177 ml, p < 0.0001) and lower transfusion requirements (0.04 units versus 0.39 units, p < 0.0001). In the internal fixation group 90 patients required 111 additional surgical procedures while only 15 additional operations on the hip were needed in 12 patients in the arthroplasty group. There was no statistically significant difference in mortality between the groups at one year (61/226 versus 63/229, p = 0.91), but there was a tendency for an improved survival in the older less mobile patients treated by internal fixation. For the survivors assessed at one, two and three years from injury there were no differences with regard to the outcome for pain and mobility. Limb shortening was more common after internal fixation (7.0 mm versus 3.6 mm, p = 0.004). We recommend that displaced intracapsular fractures in the elderly should generally be treated by arthroplasty but that internal fixation may be appropriate for those who are very frail.", "Orthopaedic surgeons vary in their management of displaced intracapsular fractures of the hip in healthy older patients. The aim of this investigation was to determine the functional, clinical, and resource consequences of three different types of surgical treatment.\n The study was a multicenter randomized controlled trial. Reduction and fixation was compared with bipolar hemiarthroplasty with cement and total hip replacement with cement. Participating surgeons elected to randomize their patients to be treated with either one of the three types of procedures or with either fixation or bipolar hemiarthroplasty. Functional outcomes were measured with a hip-rating questionnaire and the EuroQol health status measure. Clinical outcomes included mortality and complications. The direct health service costs were compared. Participants were followed up for two years.\n Two hundred and seven patients were randomized to be treated with one of the three operations, and ninety-one were randomized to be treated with either fixation or bipolar hemiarthroplasty. There were no differences in the mortality rates among the treatment groups. The rate of secondary surgery was highest in the fixation group (39% compared with 5% in the group treated with bipolar hemiarthroplasty and 9% in the group treated with total hip replacement). The fixation group had the worst hip-rating-questionnaire and EuroQol scores at four and twelve months. The total hip replacement group had significantly better functional outcome scores at twenty-four months than the other two groups. Although fixation was initially the least costly procedure, this short-term advantage was eroded by significantly higher costs for subsequent hip-related hospital admissions.\n Arthroplasty is more clinically effective and cost-effective than reduction and fixation in healthy older patients with a displaced intracapsular fracture of the hip. The long-term results of total hip replacement may be better than those of bipolar hemiarthroplasty." ]	There is insufficient evidence from randomised trials to determine whether replacement arthroplasty has any advantage over internal fixation for extracapsular hip fractures. Further larger well-designed randomised trials comparing arthroplasty versus internal fixation for the treatment of unstable fractures are required.
CD004149	[ "15832550", "17172550" ]	[ "Effects of constraint-induced movement therapy in young children with hemiplegic cerebral palsy: an adapted model.", "Constraint-induced movement therapy during early stroke rehabilitation." ]	[ "The aim of this study was to evaluate the effects of a modified version of constraint-induced (CI) movement therapy on bimanual hand-use in children with hemiplegic cerebral palsy (CP; age range 18 mo to 4 y) and to make a comparison with conventional paediatric treatment. Twenty-one children (13 females, eight males) completed the CI therapy programme and 20 children (12 males, eight females) served as a control group. Children in the CI therapy group were expected to wear a restraint glove for 2 hours each day over a period of 2 months. The training was based on principles of motor learning used in play and in motivational settings. To evaluate the effect of treatment, the Assisting Hand Assessment (AHA) was used. Assessments took place on three occasions: at onset, after 2 months, and 6 months after the first assessment. A significant interaction was found between group and AHA measure (ANOVA, F(2,74) = 5.64, p = 0.005). The children who received CI therapy improved their ability to use their hemiplegic hand significantly more than the children in the control group after 2 months, i.e. after treatment. Effect size was high after treatment and remained medium at 6 months. As the treatment was tailored to each child's capacity and interests, little frustration was experienced by the children.", "Limited data are available about the effectiveness of early rehabilitation after stroke.\n This is the 1st randomized controlled trial of constraint-induced movement therapy (CIMT) in subacute stroke to investigate neurophysiologic mechanisms and long-term outcome.\n Within 2 weeks after stroke, 23 patients with upper extremity (UE) weakness were randomized to 2 weeks of CIMT or traditional therapy at an equal frequency of up to 3 h/day. Motor function of the affected UE was blindly assessed before treatment, after treatment, and 3 months after stroke. Transcranial magnetic stimulation (TMS) measured the cortical area evoking movement of the affected hand.\n Long-term improvement in motor function of the affected UE did not differ significantly between patients who received CIMT versus intensive traditional therapy. All outcome comparisons showed trends favoring CIMT over intensive traditional therapy, but none was statistically significant except for improvements in the Fugl-Meyer (FM) UE motor scale immediately following treatment and in reported quality of hand function at 3 months. Improvement in UE motor function on the FM was associated with a greater number of sites on the affected cerebral hemisphere where responses of the affected hand were evoked by TMS.\n Future trials of CIMT during early stroke rehabilitation need greater statistical power, more inclusive eligibility criteria, and improved experimental control over treatment intensity. The relationship between changes in motor function and in evoked motor responses suggests that motor recovery during the 1st 3 months after stroke is associated with increased motor excitability of the affected cerebral hemisphere." ]	This systematic review found a significant treatment effect using modified CIMT in a single trial. A positive trend favouring CIMT and Forced Use was also demonstrated. Given the limited evidence, the use of CIMT, modified CIMT and Forced Use should be considered experimental in children with hemiplegic cerebral palsy. Further research using adequately powered RCTs, rigorous methodology and valid and reliable outcome measures is essential to provide higher level support of the effectiveness of CIMT for children with hemiplegic cerebral palsy.
CD003404	[ "2792781" ]	[ "Effect of exercise on postural sway in the elderly." ]	[ "Fifty female subjects, aged 72-92 (mean 82) years, were enrolled in a 12-week (36 classes) exercise program aimed at increasing postural stability. Subjects were residents of sheltered apartments, rest homes or nursing homes, well enough and mobile enough to participate in the classes. The subjects were randomized into an exercise or a control group. Their postural sway, standing at rest on a force platform, was measured with eyes open and eyes closed. The groups were well matched in all respects. The results showed no improvement in the postural sway as a result of the exercise program. We hypothesize that increasing postural sway in the elderly represents a deterioration in, for the most part, the nervous system and may at this extreme of life indicate an irreversible loss of function. For this reason no improvement in postural sway may be possible." ]	When the possible side-effects of standard treatment (hypnotics) are considered, there is an argument to be made for clinical use of alternative treatments in the elderly. Exercise, though not appropriate for all in this population, may enhance sleep and contribute to an increased quality of life. Research involving exercise programmes designed with the elderly in mind is needed.
CD004508	[ "9649101", "9916954" ]	[ "A randomized controlled trial of early postoperative feeding in gynecologic oncology patients undergoing intra-abdominal surgery.", "Early feeding compared with nasogastric decompression after major oncologic gynecologic surgery: a randomized study." ]	[ "To evaluate the safety and efficacy of early oral feeding after intra-abdominal surgery in gynecologic oncology patients.\n During a 1-year period, 200 gynecologic oncology patients undergoing intra-abdominal surgery were enrolled in a randomized controlled trial of early compared with traditional oral postoperative feeding. Patients allocated to early postoperative oral feeding began a clear liquid diet on the first postoperative day and then advanced to a regular diet as tolerated. Patients allocated to traditional postoperative oral feeding received nothing by mouth until return of bowel function (defined as the passage of flatus in the absence of vomiting or abdominal distention), then began a clear liquid diet, and advanced to a regular diet as tolerated.\n Age, case distribution, surgery length, blood loss, and first passage of flatus were similar in the early and traditional feeding groups. Significantly more patients in the early group developed nausea. Despite this, the incidence of vomiting, abdominal distention, incidence and duration of nasogastric tube use, and percentage of patients who tolerated clear liquid and regular diets on the first attempt were comparable in both groups. Time to development of bowel sounds, time to initiation of clear liquid and regular diets, and hospital stay were significantly longer in the traditional group. Major complications (eg, pneumonia, atelectasis, and wound complications) and febrile morbidity occurred equally in both groups. There were no known anastamotic complications or aspirations in either group. Postoperative changes in hematologic indices and electrolytes were comparable in both groups.\n Early postoperative feeding in gynecologic oncology patients undergoing intra-abdominal surgery is safe and well tolerated.", "To evaluate the feasibility, safety, and tolerance of early feeding in patients undergoing surgery for gynecologic malignancies.\n Patients were stratified according to operative time and type of tumor and were randomized into two arms: A) early oral feeding and B) nasogastric decompression followed by feeding at the first passage of flatus. Variables assessed included nausea, vomiting, time to first passage of flatus and stool, time elapsed before adequate tolerance of a regular diet, postoperative stay, and complications.\n Sixty-one patients were randomized into each arm. The types of tumor, the surgical procedures performed, and the operative times were similar in both groups. Early oral feeding in patients in arm A was associated with a significantly faster resolution of postoperative ileus (P < .01), with a more rapid return to a regular diet (P < .01), with an earlier first passage of stool (P < .01), and with a shorter postoperative stay (P < .05) than patients in arm B. Rates of nausea and vomiting were similar in both arms. Hindered deglutition and nasal soreness caused by the nasogastric tube were observed in 88% of patients in arm B. Insertion of a nasogastric tube was necessary in six patients in arm A (10%), and three of these had postoperative complications. Thus, early feeding was feasible in 95% of patients and did not seem to be related to preoperative chemotherapy, tumor type, or lymphadenectomy.\n Early feeding is feasible and well tolerated and is associated with reduced postoperative discomfort and a more rapid recovery in patients undergoing major surgery for gynecologic malignancies." ]	Early feeding after major abdominal gynaecologic surgery is safe however associated with the increased risk of nausea and a reduced length of hospital stay. Whether to adopt the early feeding approach should be individualised. Further studies should focus on the cost-effectiveness, patient's satisfaction, and other physiological changes.
CD006250	[ "14581438", "15134985", "9700583", "12215552", "12885803", "12359855", "2462069", "8418243" ]	[ "Combined analysis of two multicenter, randomized, placebo-controlled studies of pamidronate disodium for the palliation of bone pain in men with metastatic prostate cancer.", "Samarium-153-Lexidronam complex for treatment of painful bone metastases in hormone-refractory prostate cancer.", "A double blind randomized study of oral clodronate in the treatment of bone metastases from tumors poorly responsive to chemotherapy.", "The PLACORHEN study: a double-blind, placebo-controlled, randomized radionuclide study with (186)Re-etidronate in hormone-resistant prostate cancer patients with painful bone metastases. Placebo Controlled Rhenium Study.", "Repeated bone-targeted therapy for hormone-refractory prostate carcinoma: tandomized phase II trial with the new, high-energy radiopharmaceutical rhenium-188 hydroxyethylidenediphosphonate.", "A randomized, placebo-controlled trial of zoledronic acid in patients with hormone-refractory metastatic prostate carcinoma.", "Palliation of painful bone metastases from prostate cancer using sodium etidronate: results of a randomized, prospective, double-blind, placebo-controlled study.", "Double-blind controlled trial of oral clodronate in patients with bone metastases from breast cancer." ]	[ "Bone metastases occur in approximately 80% of patients with advanced prostate cancer. Pain is common in these patients. The purpose of this study was to evaluate the effect of an intravenous bisphosphonate, pamidronate disodium, on pain control in metastatic prostate cancer patients.\n Two multicenter, double-blind, randomized, placebo-controlled trials were conducted in patients with bone pain due to metastatic prostate cancer, with disease progression after first-line hormonal therapy. Intravenous pamidronate disodium (90 mg) or placebo was administered every 3 weeks for 27 weeks. Efficacy was measured via self-reported pain score (Brief Pain Inventory), analgesic use, the proportion of patients with a skeletal-related event (SRE; defined as pathologic fracture, radiation or surgery to bone, spinal cord compression, or hypercalcemia), and a pilot quantitative measurement of mobility. Laboratory evaluations included serum prostate-specific antigen, interleukin-6, bone alkaline phosphatase, and urinary bone resorption markers.\n Results of the two trials were pooled. There were no sustained significant differences between the pamidronate and placebo groups in self-reported pain measurements, analgesic use, proportion of patients with an SRE, or mobility at week 9 or 27. Urinary bone resorption markers were suppressed in the pamidronate group compared with placebo.\n Pamidronate disodium failed to demonstrate a significant overall treatment benefit compared with placebo in palliation of bone pain or reduction of SREs. Evaluation of more potent bisphosphonates in patients with prostate cancer is warranted.", "A Phase III randomized trial was designed to assess the effectiveness of samarium-153 (153Sm)-lexidronam for palliation of bone pain in patients with hormone-refractory prostate cancer.\n A total of 152 men with hormone-refractory prostate cancer and painful bone metastases were enrolled in a prospective, randomized, double-blind trial comparing radioactive (153Sm) versus nonradioactive (152Sm) lexidronam complexes. Patients were randomized (2:1) to the radioactive (153Sm) agent. Patient diaries recording daily pain and analgesic use were completed during a planned 16-week evaluation period. Nonresponders were informed of the treatment received after 4 weeks of treatment and, if initially treated with placebo, were allowed to receive 153Sm-lexidronam in an open-label fashion. Pain was measured using validated patient-derived visual analog scales and pain descriptor scales.\n 153Sm-lexidronam had positive effects on measures of pain relief compared with placebo within 1 to 2 weeks. Reductions in opioid use were recorded at weeks 3 and 4. Because nonresponders were unblinded at week 4, statistical comparisons between the arms beyond week 4 were not possible. Mild, transient bone marrow suppression was the only adverse event associated with 153Sm-lexidronam administration. The mean nadir white blood cell and platelet count (3 to 4 weeks after treatment) was 3800/microL and 127,000/microL, respectively. Counts recovered to baseline after approximately 8 weeks. No grade 4 decreases in either platelets or white bloods cells were documented.\n These findings demonstrate that 1 mCi/kg 153Sm-lexidronam is both safe and effective for the palliation of painful bone metastases in patients with hormone-refractory prostate cancer.", "Bisphosphonates are used in oncology as a means of decreasing complications due to bone metastases, in association with anticancer treatment, especially in patients with breast cancer, prostate cancer and myeloma. Little is known about the effects of bisphosphonates on bone metastases from other tumors and in particular from tumors for which no effective treatment is available. We conducted a randomized, double-blind placebo-controlled trial of oral clodronate in patients with bone metastases from tumors poorly responsive to chemotherapy, with the aims of evaluating the effects of this drug on symptoms control and bone metastases evolution. Sixty-six patients with poorly responsive tumors such as non-small cell lung cancer (NSCLC), bladder cancer, gastrointestinal cancers, kidney cancer, melanoma and metastatic carcinoma of unknown origin entered the study. Patients were randomized to receive either clodronate 1,600 mg/day for one year or identical placebo-containing tablets. Various parameters such as Karnofsky performance status, pain score (measured by a visual-analogue scale) and analgesic requirement were recorded at monthly intervals. Of the 66 patients enrolled, 9 were observed for one month or less; 7 were followed for two months; only 50 patients were followed for more than 2 months and could be adequately evaluated. At 3 months both clodronate and placebo-treated patients had a decrease in Karnofsky performance status, with the decrease being more evident in the placebo group. Mean pain scores showed an increase of pain in patients receiving placebo and a decrease of pain in patients receiving clodronate, although the difference failed to be statistically significant. Analgesics requirement increased in both groups, but significantly more in patients receiving placebo (p = 0.042), in whom increase in opioid requirements was particularly evident. Toxicity was low, with occasional gastroenteric discomfort in both groups. The main problem of this study was the difficulty in recruiting an adequate number of patients and following them for a sufficient period of time: general conditions rapidly deteriorated in many patients, and approximately 25% of the 66 enrolled were not considered evaluable; few patients survived for the length of the study, one year. This might partly account for the lack of significance of some of the parameters under study. With these limits, oral clodronate demonstrated some efficacy in symptom control and in reducing the need for analgesics.", "(186)Re-1,1-hydroxyethylidene diphosphonate (etidronate) can be used for the palliative treatment of metastatic bone pain. A randomized, placebo-controlled study using (186)Re-etidronate was conducted on end-stage prostate cancer patients with metastatic bone pain.\n Pain relief was assessed using an electronic diary containing questions reflecting the multidimensional character of chronic pain. The diary was marked twice daily for a maximum of 14 wk (2 wk before and 12 wk after the injection). Pain response was determined using a specific decision rule in which pain intensity, medication index, and daily activities were the core determinants. A positive response day was defined as a day on which pain intensity was reduced > or = 25% compared with baseline values, while medication index and daily activities were at least constant, or on which pain intensity was reduced < 25% and medication index or daily activities improved > or = 25%, without worsening of the remaining factor. The total response (%) was defined as the number of positive response days divided by the number of days of follow-up.\n Of the 111 included patients, 79 were evaluable (43 (186)Re-etidronate, 36 placebo). Thirty-two patients were excluded from the analysis because of incomplete datasets. The total response of the patients treated with (186)Re-etidronate varied from 0% to 96% (mean, 27%, or 23/84 d). In the placebo group, the total response varied from 0% to 80% (mean, 13%, or 11/84 d; Mann-Whitney U test, P < 0.05). The number of patients who requested radiotherapy was higher in the placebo group (67%) than in the (186)Re-etidronate group (44%) (relative risk, 1.51; Fisher's exact test, P = 0.069).\n This randomized controlled trial confirmed that, compared with placebo, (186)Re-etidronate resulted in a significantly longer pain response in the treatment of bone pain from metastasized prostate cancer.", "We investigated the effect of repeated bone-targeted therapy with rhenium-188 hydroxyethylidenediphosphonate (HEDP) in patients with progressive, hormone-resistant prostate carcinoma and bone pain. The aim of this study was to determine the pain palliation and the antitumor effect of rhenium-188 HEDP treatments.\n Sixty-four patients were randomly assigned to one of two groups for radionuclide therapy with rhenium-188 HEDP; patients of group A received a single injection, patients of group B received two injections (interval, 8 weeks). After therapy, patients were followed-up by assessment of pain palliation and clinical outcome until death.\n In both groups, toxicity was low, with moderate thrombopenia and leukopenia (maximum common toxicity criteria grade of 2). The effectiveness of rhenium-188 HEDP for pain palliation was better in the repeated treatment group (group B), with a response rate and time of response of 92% and 5.66 months, respectively (P =.006 and P =.001). In group B, 11 (39%) of 28 patients had a prostate-specific antigen decrease of more than 50% for at least 8 weeks, compared with two (7%) of 30 patients in the single-injection group (group A). The median times to progression of group A and group B were 2.3 months (range, 0 to 12.2 months) and 7.0 months (range, 0 to 24.1 months), respectively (P =.0013), and the median overall survival times were 7.0 months (range, 1.3 to 36.7 months) and 12.7 months (range, 4.1 to 32.2 months), respectively (P =.043).\n Compared with single-injection therapy, repeated bone-targeted therapy with rhenium-188 HEDP administered to patients with advanced progressive hormone-refractory prostate carcinoma enhanced pain palliation and improved progression-free and overall survival. Larger studies are justified to further evaluate the use of rhenium-188 HEDP.", "Bone metastases are a common cause of morbidity in patients with prostate carcinoma. We studied the effect of a new bisphosphonate, zoledronic acid, which blocks bone destruction, on skeletal complications in prostate cancer patients with bone metastases.\n Patients with hormone-refractory prostate cancer and a history of bone metastases were randomly assigned to a double-blind treatment regimen of intravenous zoledronic acid at 4 mg (N = 214), zoledronic acid at 8 mg (subsequently reduced to 4 mg; 8/4) (N = 221), or placebo (N = 208) every 3 weeks for 15 months. Proportions of patients with skeletal-related events, time to the first skeletal-related event, skeletal morbidity rate, pain and analgesic scores, disease progression, and safety were assessed. All statistical tests were two-sided.\n Approximately 38% of patients who received zoledronic acid at 4 mg, 28% who received zoledronic acid at 8/4 mg, and 31% who received placebo completed the study. A greater proportion of patients who received placebo had skeletal-related events than those who received zoledronic acid at 4 mg (44.2% versus 33.2%; difference = -11.0%, 95% confidence interval [CI] = -20.3% to -1.8%; P =.021) or those who received zoledronic acid at 8/4 mg (38.5%; difference versus placebo = -5.8%, 95% CI = -15.1% to 3.6%; P =.222). Median time to first skeletal-related event was 321 days for patients who received placebo, was not reached for patients who received zoledronic acid at 4 mg (P =.011 versus placebo), and was 363 days for those who received zoledronic acid at 8/4 mg (P =.491 versus placebo). Compared with urinary markers in patients who received placebo, urinary markers of bone resorption were statistically significantly decreased in patients who received zoledronic acid at either dose (P =.001). Pain and analgesic scores increased more in patients who received placebo than in patients who received zoledronic acid, but there were no differences in disease progression, performance status, or quality-of-life scores among the groups. Zoledronic acid at 4 mg given as a 15-minute infusion was well tolerated, but the 8-mg dose was associated with renal function deterioration.\n Zoledronic acid at 4 mg reduced skeletal-related events in prostate cancer patients with bone metastases.", "Sodium etidronate is a diphosphonate compound that inhibits bone resorption and mineralization. The drug has been reported to be highly effective for the palliation of painful bone metastasis from prostatic cancer. Fifty-seven patients were entered into a randomized, prospective, double-blind, placebo-controlled study of sodium etidronate. All patients had hormone refractory metastatic prostatic cancer and bone pain requiring analgesics. No difference was seen in the symptomatic response rate or analgesic requirement between patients treated with sodium etidronate and placebo. With the dose scheme used in this study sodium etidronate was ineffective for palliation of bone pain from prostatic cancer.", "Osteolytic metastases often give rise to hypercalcemia, fracture, and bone pain, and occur commonly in patients with recurrent breast cancer. We assessed the bisphosphonate, clodronate, which has proven to be a useful treatment for hypercalcemia and may be a potent inhibitor of tumor-induced osteolysis, for its effect on reducing the osseous complications of metastatic breast cancer.\n We studied 173 patients with bone metastases due to breast cancer in a randomized, double-blind, placebo-controlled trial of oral clodronate 1,600 mg/d (85 patients) compared with an identical placebo (88 patients).\n The patients in each wing were comparable in their clinical, radiologic, and biochemical characteristics at trial entry. In patients who received clodronate, there was a significant reduction compared with placebo in the total number of hypercalcemic episodes (28 v 52; P < .01), in the number of terminal hypercalcemic episodes (seven v 17; P < .05), in the incidence of vertebral fractures (84 v 124 per 100 patient-years; P < .025), and in the rate of vertebral deformity (168 v 252 per 100 patient-years; P < .001). The combined rate of all morbid skeletal events was significantly reduced (218.6 v 304.8 per 100 patient-years; P < .001). Trends were seen in favor of clodronate for nonvertebral fracture rates and radiotherapy requirements for bone pain (particularly spinal pain). No significant survival differences and no significant differences in side effects were observed between the two groups.\n These findings indicate that oral clodronate has a beneficial effect on the skeletal morbidity associated with breast cancer and should be considered as antiosteolytic therapy in affected patients. It deserves further investigation as an adjuvant therapy in operable breast cancer and in patients with nonosseous recurrence who are at high risk for bone metastases." ]	Bisphosphonates should be considered for patients with metastatic prostate cancer for the treatment of refractory bone pain and prevention of skeletal events. More research is needed to guide the choice of bisphosphonates, optimal treatment schedule as well as cost-benefit comparisons. Combining results from different studies is difficult because different tools were used to assess pain, and also, bisphosphonates vary considerably in potency. This review highlights the need for standardisation and co-ordination among researchers in cancer pain studies.
CD000448	[ "16555167", "11434406", "7498868", "10591711", "15605620", "15538592", "23196026", "10759336", "10823363", "15708844", "12008860", "7857503", "10968813", "15744631", "12153829", "16796730", "11939866", "7592505", "9342765", "2239134", "3882677", "6370980" ]	[ "Comparative efficacy and safety of a once-daily dosage of hypericum extract STW3-VI and citalopram in patients with moderate depression: a double-blind, randomised, multicentre, placebo-controlled study.", "Efficacy and tolerability of hypericum extract WS 5572 versus placebo in mildly to moderately depressed patients. A randomized double-blind multicenter clinical trial.", "[Treatment of depressive symptoms with a high concentration hypericum preparation. A multicenter placebo-controlled double-blind study].", "Hypericum extract versus imipramine or placebo in patients with moderate depression: randomised multicentre study of treatment for eight weeks.", "Efficacy and tolerability of Hypericum extract STW 3-VI in patients with moderate depression: a double-blind, randomized, placebo-controlled clinical trial.", "Hypericum extract LI 160 and fluoxetine in mild to moderate depression: a randomized, placebo-controlled multi-center study in outpatients.", "Clinical significance of hyperforin for the efficacy of Hypericum extracts on depressive disorders of different severities.", "Equivalence of St John's wort extract (Ze 117) and fluoxetine: a randomized, controlled study in mild-moderate depression.", "Comparison of an extract of hypericum (LI 160) and sertraline in the treatment of depression: a double-blind, randomized pilot study.", "Acute treatment of moderate to severe depression with hypericum extract WS 5570 (St John's wort): randomised controlled double blind non-inferiority trial versus paroxetine.", "Hypericum perforatum versus fluoxetine in the treatment of mild to moderate depression.", "Effectiveness and tolerance of the hypericum extract LI 160 compared to maprotiline: a multicenter double-blind study.", "Comparison of St John's wort and imipramine for treating depression: randomised controlled trial.", "Efficacy and tolerability of hypericum extract STW3 in long-term treatment with a once-daily dosage in comparison with sertraline.", "Efficacy of St. John's wort extract WS 5570 in major depression: a double-blind, placebo-controlled trial.", "Superior efficacy of St John's wort extract WS 5570 compared to placebo in patients with major depression: a randomized, double-blind, placebo-controlled, multi-center trial [ISRCTN77277298].", "Effect of Hypericum perforatum (St John's wort) in major depressive disorder: a randomized controlled trial.", "A double-blind comparison of Org 3770, amitriptyline, and placebo in major depression.", "Efficacy and tolerability of St. John's wort extract LI 160 versus imipramine in patients with severe depressive episodes according to ICD-10.", "A randomized, within-patient, cross-over, placebo-controlled trial on the efficacy and tolerability of the tricyclic antidepressants chlorimipramine and nortriptyline in central pain.", "A comparison of fluoxetine, imipramine, and placebo in patients with major depressive disorder.", "A two-center double-blind study of nomifensine, imipramine, and placebo in depressed geriatric outpatients." ]	[ "The objective of this double-blind, randomised, placebo-controlled, multicentre clinical study was to demonstrate the non-inferiority and safety of the hypericum extract STW3-VI in a once-daily dosage regime in the treatment of moderate depression. During the 6-week treatment phase, the course of depression was documented by use of HAMD (items 1-17), the von Zerssen's Adjective Mood Scale (BfS) and the CGI scales. The primary objective of this 3-arm design study was to demonstrate the non-inferiority of hypericum extract STW3-VI (900 mg) to the SSRI citalopram (20 mg) and superiority of hypericum over placebo.\n Outpatients (N = 388) suffering from moderate depression were enrolled. The safety and tolerability of hypericum extract in comparison to citalopram and placebo was investigated on the basis of CGI, the occurrence of adverse events and the investigation of laboratory parameters and vital signs.\n From almost identical baseline values of 21.9 +/- 1.2 points (hypericum extract), 21.8 +/- 1.2 points (citalopram) and 22.0 +/- 1.2 points (placebo), the HAMD score was reduced to 10.3 +/- 6.4 (hypericum extract), 10.3 +/- 6.4 (citalopram) and 13.0 +/- 6.9 (placebo), respectively. Based on this data, the statistical significant therapeutic equivalence of hypericum extract STW3-VI to citalopram (p < 0.0001) and the superiority of this hypericum extract over placebo (p < 0.0001) was demonstrated. At the end of treatment 54.2 % (hypericum extract), 55.9 % (citalopram) and 39.2 % (placebo) of the patients were assessed as therapy responders. The secondary efficacy parameters, change in BfS, CGI and amount of therapy responders showed that the hypericum group was not statistically different from the citalopram group, and significantly superior to the placebo group. Significantly more adverse events with \"certain\", \"probable\" or \"possible\" relation to study medication were documented in the citalopram group (hypericum: 17.2 %, citalopram: 53.2 %, placebo: 30 %). In most cases, the investigators assessed the tolerability of hypericum extract, citalopram and placebo as \"good\" or \"very good\".\n The non-inferiority of hypericum extract as compared to citalopram and the superiority of both active compounds to placebo were demonstrated, as well as a better safety and tolerability of hypericum extract in comparison to citalopram. These results revealed that hypericum extract STW3-VI is a good alternative to chemically defined antidepressants in the treatment of outpatients with moderate depression.", "We have investigated the antidepressant efficacy and safety of Hypericum perforatum (St. John's wort) extract WS5572 in a double-blind, placebo-controlled multicenter clinical trial. 72 patients (WS 5572: 37, placebo: 35) with a diagnosis of mild to moderate major depressive disorder (according to DSM-IV criteria) were randomized in 42 days of treatment with either 300 mg WS5572 t.i.d. or placebo. The primary efficacy variable was the change of the 17-item Hamilton Depression Scale (HAMD) total score between baseline and double-blind treatment. The study was conducted with an adaptive interim analysis, which led to early stopping because convincing treatment efficacy could already be demonstrated. Group differences in favor of WS 5572 were descriptively apparent as early as day 7 of randomized treatment and were statistically significant at days 28 (p = 0.011) and day 42 (p < 0.001). Between baseline and treatment end, the HAMD total score decreased from 19.7 +/- 3.4 to 8.9 +/- 4.3 points in the Hypericum group and from 20.1 +/- 2.6 to 14.4 +/- 6.8 points in the placebo group (mean +/- SD). Responder rates were consistently higher in the Hypericum group. Comparable group differences in favor of WS 5572 were also found for von Zerssen's Depression Scale (D-S; self-rating), Clinical Global Impressions (CGI) and a global patient's self-assessment (GPA). Tolerability was very good in both groups, with no adverse drug reactions and no clinically relevant changes in safety parameters. The results indicate that Hypericum extract WS 5572 is an effective and well-tolerated drug for the treatment of mild to moderate major depressive disorder.", "In a multicenter, placebo-controlled double-blind trial, the effect on depression (ICD 10 F 32.1) of treatment with an innovative highly concentrated hypericum preparation was investigated. The study contained 97 outpatients who received 100 to 120 mg of the hypericum extract bid. The course of the illness was assessed with the Hamilton Depression Scale (HAMD), the von Zerssen Depressivity Scale (D-S) and the Clinical Global Impression Scale (CGIS). Treatment resulted in an appreciable improvement in the symptoms of depression, and the 70% response rate (n = 43), corresponded to that of chemical antidepressants. The preparation also showed an anxiolytic effect. The substance was extremely well tolerated, and no side-effects were reported by any of the patients.", "To assess the efficacy and safety of hypericum extract (STEI 300, Steiner Arzneimittel, Berlin) compared with imipramine and placebo in patients in primary care with a current episode of moderate depression.\n Randomised, double blind, multicentre, parallel group trial for 8 weeks.\n Trained panel of 18 general practitioners from four German states: Bavaria, Berlin, Rhineland Palatinate, and Saxony.\n 263 patients (66 men, 197 women) with moderate depression according to ICD-10 (international classification of diseases, 10th revision) codes F32. 1 and F33.1.\n 1050 mg hypericum extract (350 mg three times daily), 100 mg imipramine (50 mg, 25 mg, and 25 mg daily), or placebo three times daily.\n Change from baseline score on the 17 item version of the Hamilton depression scale, the Hamilton anxiety scale, the clinical global impressions scale, Zung's self rating depression scale, and SF-36, and adverse events profile.\n Hypericum extract was more effective at reducing Hamilton depression scores than placebo and as effective as imipramine (mean -15.4 (SD 8.1), -12.1 (7.4), and -14.2 (7.3) respectively). Comparable results were found for Hamilton anxiety and clinical global impressions scales and were most pronounced for the Zung self rating depression scale. Quality of life was more improved in the standardised mental component scale of the SF-36 with both active treatments than with placebo but in the physical component scale was improved only by hypericum extract compared with placebo. The rate of adverse events with hypericum extract was in the range of the placebo group but lower than that of the imipramine group (0.5, 0.6, and 1.2 events per patient respectively).\n At an average dose of 350 mg three times daily hypericum extract was more effective than placebo and at least as effective as 100 mg imipramine daily in the treatment of moderate depression. Treatment with hypericum extract is safe and improves quality of life.", "In this double-blind, randomized, placebo-controlled, prospective study, the clinical efficacy and tolerability of oral Hypericum extract STW 3-VI (Laif) 900 mg once daily was compared with that of placebo. A total of 140 outpatients (94 women; 46 men) with moderate depressive disorders and a 17-item Hamilton Depression Scale (HAMD-17) score of 20 to 24 were enrolled in this study. Following a single-blind placebo run-in period of 7 days, the patients were randomized to Hypericum extract 900 mg or placebo for the 6-week treatment period. Nineteen patients have been excluded from the per protocol collective because of violations of protocol regarding the scheduling of study visits and intake of study medication. The primary endpoint for treatment efficacy was the change in total HAMD-17 score at the end of the 6-week treatment period. The HAMD-17 total score decreased significantly from baseline by approximately 11.1 +/- 4.5 points (from 22.8 +/- 1.1 to 11.8 +/- 4.4) in the Hypericum group and by approximately 3.4 +/- 3.9 points (from 22.6 +/- 1.2 to 19.2 +/- 3.8) in the placebo group (P < .001). Comparable group differences in favor of Hypericum were revealed by an additional responder analysis, the von Zerssen's Adjective Mood Scale, the Clinical Global Impressions scale, and a global efficacy assessment. Tolerability was very good in both groups; neither serious adverse events nor clinically relevant changes in safety parameters were observed, and only 2 cases demonstrated a possible connection between an adverse event and the study medication. The final safety assessment showed no differences between the Hypericum extract and placebo groups. The study provided evidence that Hypericum extract STW 3-VI in a once-daily dosing regimen may be an effective and well-tolerated option for patients with moderate depressive disorders.", "Efficacy and tolerability of Hypericum LI 160 was compared to fluoxetine and placebo in mild to moderate Major Depression (DSM-IV) in a 4-week randomized, double-blind trial. One hundred and sixty-three outpatients from 15 general practitioner centers received either 900 mg Hypericum LI 160, 20 mg fluoxetine, or placebo daily. Amelioration was measured by the Hamilton and the Montgomery-Asberg Depression scales. Response and remission rates and global ratings by investigators and patients were measured. Adverse event reports, laboratory screening, vital signs, physical exams and ECG were collected. No significant differences could be observed regarding efficacy measures except for remission rate (Hypericum 24%; fluoxetine 28%; placebo 7 %). Hypericum was significantly better tolerated than fluoxetine. Hypericum LI 160 or fluoxetine were not more effective in short-term treatment in mild to moderate depression than placebo.", "In a randomized, double-blind, placebo-controlled, multicenter study, the clinical efficacy and safety of two different extracts of St. John's wort were investigated in 147 male and female out-patients suffering from mild or moderate depression according to DSM-IV criteria. Fifty-six (38.1%) of them had an initial total score ≥ 22 points on the Hamilton Rating Scale for Depression (HAMD, 17-item version). Following a placebo run-in period of three to seven days, the patients were randomized to one of three treatment groups: During the 42-day treatment period, they received 3×1 tablet of either placebo, Hypericum extract WS 5573 (300mg, with a content of 0.5% hyperforin), or Hypericum extract WS 5572 (300 mg, with a content of 5% hyperforin). The manufacturing process for both Hypericum preparations was identical, they only differed with regard to their content of hyperforin. Efficacy regarding depressive symptoms was assessed on days 0, 7,14,28, and 42. The last observation of patients withdrawn from the trial prematurely was carried forward. At the end of the treatment period (day 42), the patients receiving WS 5572 (5% hyperforin) exhibited the largest HAMD reduction versus day 0 (10.3 ± 4.6 points; mean ± SD), followed by the WS 5573 group (0.5% hyperforin; HAMD reduction 8.5 ± 6.1 points) and the placebo group (7.9 ± 5.2 points). The monotonie trend was significant (Jonckheere-Terpstra test; p = 0.017). In patients with an initial HAMD total score ≥ 22, the HAMD reduction was even by 16.5% larger than in the total study group receiving WS 5572. More severely depressed patients treated with WS 5573, however, showed a 22.4% lower reduction of the HAMD total score than the entire WS 5573 treatment group. In patients with HAMD ≥ 22, WS 5572 showed a 53.8% larger HAMD reduction than placebo, whereas WS 5573 was not relevantly different from the placebo level. The mean HAMD reductions, treatment end versus baseline, for the more severely depressed patients were 12.0 (3.7) points, 6.6 (7.7) points and 7.8 (5.4) points [mean (SD)] for WS 5S72, WS 5573 and placebo, respectively. The results of a responder analysis support these findings. The data point to a dose-response relationship between the antidepressant efficacy of Hypericum extract and its hyperforin content. The extract with a higher content of hyperforin was particularly effective in patients who were more severely depressed.\n Copyright © 1998 Gustav Fischer Verlag. Published by Elsevier GmbH.. All rights reserved.", "Treatment with St John's wort extract tablets (hypericum Ze 117) and the commonly used slow serotonin reuptake inhibitor (SSRI) fluoxetine was compared in patients with mild-moderate depression with entry Hamilton Depression Scale (HAM-D) (21-item) in the range 16-24, in a randomized, double-blind, parallel group comparison in 240 subjects; fluoxetine: 114 (48%), hypericum: 126 (52%). After 6 weeks' treatment, mean HAM-D at endpoint decreased to 11.54 on hypericum and to 12.20 on fluoxetine (P < 0.09), while mean Clinical Global Impression (CGI) item I (severity) was significantly (P < 0.03) superior on hypericum, as was the responder rate (P = 0.005). Hypericum safety was substantially superior to fluoxetine, with the incidence of adverse events being 23% on fluoxetine and 8% on hypericum. The commonest events on fluoxetine were agitation (8%), GI disturbances (6%), retching (4%), dizziness (4%), tiredness, anxiety/nervousness and erectile dysfunction (3% each), while on hypericum only GI disturbances (5%) had an incidence greater than 2%. We concluded that hypericum and fluoxetine are equipotent with respect to all main parameters used to investigate antidepressants in this population. Although hypericum may be superior in improving the responder rate, the main difference between the two treatments is safety. Hypericum was superior to fluoxetine in overall incidence of side-effects, number of patients with side-effects and the type of side-effect reported.", "Hypericum (St. John's wort) has been shown to be as efficacious and well tolerated as standard antidepressants in the treatment of depression but has not been compared with selective serotonin reuptake inhibitors (SSRIs).\n This study compared hypericum and the SSRI sertraline in the treatment of depression.\n In a double-blind, randomized study conducted in a community hospital, 30 male and female outpatients (19 women, 11 men; mean age, 45.5 years) with mild to moderate depression received 600 mg/d of a standardized extract of hypericum (LI 160) or 50 mg/d sertraline for I week, followed by hypericum 900 mg/d or sertraline 75 mg/d for 6 weeks.\n The severity of symptoms, as assessed by scores on the Hamilton Rating Scale for Depression (HAM-D) and the Clinical Global Impression scale, was significantly reduced in both treatment groups (P < 0.01). Clinical response (defined as a > or =50% reduction in HAM-D scores) was noted in 47% of patients receiving hypericum and 40% of those receiving sertraline. The difference was not statistically significant. Both agents were well tolerated. A post hoc power analysis indicated that failure to reach statistical significance between treatments resulted primarily from an absence of clinical differences rather than the small sample size.\n The hypericum extract was at least as effective as sertraline in the treatment of mild to moderate depression in a small group of outpatients.", "To investigate the efficacy of hypericum extract WS 5570 (St John's wort) compared with paroxetine in patients with moderate to severe major depression.\n Randomised double blind, double dummy, reference controlled, multicentre non-inferiority trial.\n 21 psychiatric primary care practices in Germany.\n 251 adult outpatients with acute major depression with total score > or = 22 on the 17 item Hamilton depression scale.\n 900 mg/day hypericum extract WS 5570 three times a day or 20 mg paroxetine once a day for six weeks. In initial non-responders doses were increased to 1800 mg/day hypericum or 40 mg/day paroxetine after two weeks.\n Change in score on Hamilton depression scale from baseline to day 42 (primary outcome). Secondary measures were change in scores on Montgomery-Asberg depression rating scale, clinical global impressions, and Beck depression inventory.\n The Hamilton depression total score decreased by mean 14.4 (SD 8.8) points, corresponding to 56.6% (SD 34.3%) of the baseline value, in the hypericum group and by 11.4 (SD 8.6) points (44.8% (SD 33.5%) of baseline value) in the paroxetine group (intention to treat analysis; similar results were observed in the per protocol analysis). The intention to treat analysis (lower one sided 97.5% confidence limit 1.5 points for the difference hypericum minus paroxetine) and the per protocol analysis (lower confidence limit 0.7 points) showed non-inferiority of hypericum and statistical superiority over paroxetine. The lower limits in both cases exceeded the pre-specified non-inferiority margin of -2.5 points and the superiority margin of 0. The incidence of adverse events was 0.035 and 0.060 events per day of exposure for hypericum and paroxetine, respectively.\n In the treatment of moderate to severe major depression, hypericum extract WS 5570 is at least as effective as paroxetine and is better tolerated.", "In a randomized, controlled, double-blind trial, 70 patients (mean age, 49.7 years) suffering from mild to moderate depression received one tablet of either St. John's Wort (Hypericum perforatum) extract (Calmigen) or fluoxetine hydrochloride (Prozac) twice a day for 6 weeks. Efficacy was determined according to the 17-item Hamilton Rating Scale for Depression (HAMD), the von Zerssen depression scale (DS), Clinical Global Impression (CGI), and patients' overall evaluation. Significant decreases (P<.001) of 50% in the Hypericum group and 58% in the fluoxetine group in the HAMD score and of 42% and 52% on the DS spoke to the efficacy of both medications. The Hypericum extract achieved 83% of the efficacy of fluoxetine on the HAMD and 78% on the DS. Assessments by physicians (CGI) and patients indicated considerable improvement with no between-treatment differences. Of the 9 dropouts (13%), 2 in the Hypericum group and 2 in the fluoxetine group were due to adverse reactions. Safety evaluations demonstrated only minor changes. The Hypericum preparation tested in this study is therapeutically equivalent to fluoxetine and is therefore a rational alternative to synthetic antidepressants.", "A randomized, double-blind study examining the effectiveness and tolerance of a standardized hypericum preparation when compared to maprotiline was performed in a group of 102 patients with depression, in accordance with ICD-10, F 32.1. The study was conducted in the offices of neurology and psychiatry specialists. The patients received, over a period of 4 weeks, either 3 x 300 mg of the hypericum extract or 3 x 25 mg maprotiline pills of identical appearance. Effectiveness was determined using the Hamilton Depression Scale (HAMD), the Depression Scale according to von Zerssen (D-S), and the Clinical Global Impression Scale (CGI). The total score of the HAMD scale dropped during the 4 weeks of therapy in both treatment groups by about 50%. The mean values of the D-S scale and the CGI scale showed similar results, and after 4 weeks of therapy, no significant differences in either treatment group were noticed. The onset of the effects occurred up to the second week of treatment, but were observed earlier with maprotiline than with the hypericum extract. On the other hand, maprotiline treatment resulted in more cases of tiredness, mouth dryness, and heart complaints.", "To compare the efficacy and tolerability of Hypericum perforatum (St John's wort extract) with imipramine in patients with mild to moderate depression.\n Randomised, multicentre, double blind, parallel group trial.\n 40 outpatient clinics in Germany. Participants: 324 outpatients with mild to moderate depression.\n 75 mg imipramine twice daily or 250 mg hypericum extract ZE 117 twice daily for 6 weeks.\n Hamilton depression rating scale, clinical global impression scale, and patient's global impression scale.\n Among the 157 participants taking hypericum mean scores on the Hamilton depression scale decreased from 22.4 at baseline to 12.00 at end point; among the 167 participants taking imipramine they fell from 22.1 to 12.75. Mean clinical global impression scores at end point were 2.22 out of 7 for the hypericum group and 2.42 for the imipramine group. On the 7 point self assessments of global improvement completed by participants (score of 1 indicating \"very much improved\" and 7 indicating \"very much deteriorated\") mean scores were 2.44 in the hypericum group and 2.60 in the imipramine group. None of the differences between treatment groups were significant. However, the mean score on the anxiety-somatisation subscale of the Hamilton scale (3.79 in the hypericum group and 4.26 in the imipramine group) indicated a significant advantage for hypericum relative to imipramine. Mean scores on the 5 point scale used by participants to assess tolerability (score of 1 indicating excellent tolerability and 5 indicating very poor tolerability) were better for hypericum (1.67) than imipramine (2.35). Adverse events occurred in 62/157 (39%) participants taking hypericum and in 105/167 (63%) taking imipramine. 4 (3%) participants taking hypericum withdrew because of adverse events compared with 26 (16%) taking imipramine.\n This Hypericum perforatum extract is therapeutically equivalent to imipramine in treating mild to moderate depression, but patients tolerate hypericum better.", "The objective of this double-blind, multi-center clinical study was to demonstrate the non-inferiority of hypericum extract versus sertraline in the treatment of moderate depression.\n A total of 241 patients with a diagnosis of moderate depressive disorder (according to ICD-10 criteria) were randomized with either 50 mg sertraline or 612 mg hypericum extract (hypericum group n = 123; sertraline group n = 118). According to the study protocol, 200 patients were treated for at least 12 weeks ( n = 102 hypericum extract; n = 98 sertraline); 81 patients in the hypericum group and 80 in the sertraline group were treated after week 12 for an additional 12 weeks. Thus, most patients were treated for a period of 6 months. The primary efficacy variable was the 17-item HAMD total score at the end of the first 12-week double-blind treatment period.\n After the first 12-week treatment period, the HAMD score decreased from almost identical initial values (22.0 +/- 1.1 for hypericum and 22.1 +/- 1.1 points for sertraline) to 8.3 +/- 5.5 points (hypericum) and 8.1 +/- 5.6 points (sertraline) (mean +/- SD) in the patients treated per-protocol (PP) population. The statistical test for non-inferiority (boundary delta = 3) revealed that hypericum extract is not inferior to sertraline ( P < 0.0001). The mean difference between the treatments was 0.1995 points, with a corresponding one-sided 97.5 % confidence interval (-infinity, 1.3772). In patients who continued treatment in the follow-up phase, the HAMD score at the end of the study was 5.7 +/- 4.8 points (hypericum group) and 7.1 +/- 6.3 points (sertraline group). Comparable improvement was also found for the von Zerssen's Adjective Mood Scale (BfS) and CGI during the first and second 12-week treatment period in both treatment groups. With 68.6 % of patients in the hypericum group and 70.4 % in the sertraline group, the percentage of patients rated as responders did not differ significantly between treatment groups (12 weeks). The adverse events of 12 patients in the hypericum group (9.8 %) and of 16 patients in the sertraline group (13.6 %) were possibly related to study medication. No basic differences in the treatment groups were observed and no interaction with concomitant medication was documented. In most cases , the investigators assessed the tolerability of hypericum extract and sertraline as \"good\" or \"very good.\"\n The results indicate that hypericum extract STW 3 is not inferior to sertraline and that it is a well-tolerated drug for the treatment of moderate depression. These favorable effects were achieved with a once-daily dose of 612 mg of hypericum extract given for up to 24 weeks.", "In a double-blind, randomized, placebo-controlled trial with 375 patients the authors investigated the antidepressant efficacy and safety of 300 mg t.i.d. of hydroalcoholic Hypericum perforatum extract WS 5570.\n The study participants were male and female adult outpatients with mild to moderate major depression (single or recurrent episode, DSM-IV criteria). After a single-blind placebo run-in phase, the patients were randomly assigned, 186 to WS 5570 and 189 to placebo, after which they received double-blind treatment for 6 weeks. Follow-up visits were held after 1, 2, 4, and 6 weeks. The primary outcome measure was the change from baseline in the total score on the 17-item Hamilton Depression Rating Scale. In addition, analyses of responders (patients with at least a 50% reduction in Hamilton total score) and patients with remissions (patients with a total score of 6 or less on the Hamilton scale at treatment end) were carried out, and subscale/subgroup analyses were conducted. The design included an adaptive interim analysis performed after random assignment of 169 patients with options for group size adjustment or early termination.\n Compared to placebo, WS 5570 produced a significantly greater reduction in total score on the Hamilton depression scale and significantly more patients with treatment response or remission. It was more effective in patients with higher baseline Hamilton scores and led to global reduction of depression-related core symptoms, assessed with the melancholia subscale of the Hamilton scale. The placebo and WS 5570 groups had comparable adverse events.\n H. perforatum extract WS 5570 was found to be safe and more effective than placebo for the treatment of mild to moderate depression.", "The aim of the current study was to assess the antidepressant efficacy and safety of Hypericum perforatum (St. John's wort) extract WS 5570 at doses of 600 mg/day in a single dose and 1200 mg/day in two doses.\n The participants in this double-blind, randomized, placebo-controlled, multi-center clinical trial were male and female adult out-patients with an episode of mild or moderate major depressive episode (single or recurrent episode, DSM-IV criteria). As specified by the relevant guideline, the study was preceded by a medication-free run-in phase. For the 6-week treatment, 332 patients were randomized: 123 to WS 5570 600 mg/day, 127 to WS 5570 1200 mg/day, and 82 to placebo. The primary outcome measure was the change in total score on the Hamilton Rating Scale for Depression (HAM-D, 17-item version) between baseline and endpoint. Additional measures included the number of responders, the number of patients in remission, and several other standard rating scales. Efficacy and safety were assessed after 2 and 6 weeks. The design included an interim analysis performed after randomization with the option of early termination.\n After 6 weeks of treatment, mean +/- standard deviation decreases in HAM-D total scores of 11.6 +/- 6.4, 10.8 +/- 7.3, and 6.0 +/- 8.1 points were observed for the WS 5570 600 mg/day, 1200 mg/day and placebo groups, respectively (endpoint analysis). Secondary measures of treatment efficacy also showed that both WS 5570 groups were statistically superior to placebo. Significantly more patients in the WS 5570 treatment groups than in the placebo group showed treatment response and remission. WS 5570 was consistently more effective than placebo in patients with either less severe or more severe baseline impairment. The number of patients who experienced remission was higher in the WS 5570 1200 mg/day group than the WS 5570 600 mg/day group. The incidence of adverse events was low in all groups. The adverse event profile was consistent with the known profile for Hypericum extract preparations.\n Hypericum perforatum extract WS 5570 at doses of 600 mg/day (once daily) and 1200 mg/day (600 mg twice daily) were found to be safe and more effective than placebo, with comparable efficacy of the WS 5570 groups for the treatment of mild to moderate major depression.", "Extracts of Hypericum perforatum (St John's wort) are widely used for the treatment of depression of varying severity. Their efficacy in major depressive disorder, however, has not been conclusively demonstrated.\n To test the efficacy and safety of a well-characterized H perforatum extract (LI-160) in major depressive disorder.\n Double-blind, randomized, placebo-controlled trial conducted in 12 academic and community psychiatric research clinics in the United States.\n Adult outpatients (n = 340) recruited between December 1998 and June 2000 with major depression and a baseline total score on the Hamilton Depression Scale (HAM-D) of at least 20.\n Patients were randomly assigned to receive H perforatum, placebo, or sertraline (as an active comparator) for 8 weeks. Based on clinical response, the daily dose of H perforatum could range from 900 to 1500 mg and that of sertraline from 50 to 100 mg. Responders at week 8 could continue blinded treatment for another 18 weeks.\n Change in the HAM-D total score from baseline to 8 weeks; rates of full response, determined by the HAM-D and Clinical Global Impressions (CGI) scores.\n On the 2 primary outcome measures, neither sertraline nor H perforatum was significantly different from placebo. The random regression parameter estimate for mean (SE) change in HAM-D total score from baseline to week 8 (with a greater decline indicating more improvement) was -9.20 (0.67) (95% confidence interval [CI], -10.51 to -7.89) for placebo vs -8.68 (0.68) (95% CI, -10.01 to -7.35) for H perforatum (P =.59) and -10.53 (0.72) (95% CI, -11.94 to -9.12) for sertraline (P =.18). Full response occurred in 31.9% of the placebo-treated patients vs 23.9% of the H perforatum-treated patients (P =.21) and 24.8% of sertraline-treated patients (P =.26). Sertraline was better than placebo on the CGI improvement scale (P =.02), which was a secondary measure in this study. Adverse-effect profiles for H perforatum and sertraline differed relative to placebo.\n This study fails to support the efficacy of H perforatum in moderately severe major depression. The result may be due to low assay sensitivity of the trial, but the complete absence of trends suggestive of efficacy for H perforatum is noteworthy.", "A 6-week, double-blind, dose titration study was performed to evaluate efficacy and safety of the new antidepressant Org 3770 in comparison with amitriptyline and placebo.\n One hundred fifty outpatients of both sexes, 18 years and older, with a DSM-III diagnosis of major depressive episode, were randomly assigned to 6 weeks of treatment with Org 3770, amitriptyline, or placebo.\n At baseline, mean 17-item Hamilton Rating Scale for Depression (HAM-D) scores of all treatment groups were higher than 25, thus indicating that a large proportion of severely depressed patients entered the study. The overall mean daily doses were 22 mg/day for Org 3770, 133 mg/day for amitriptyline, and 4.9 capsules/day for placebo. The majority of times assessments were made, both active drugs produced significantly greater improvements than placebo on all efficacy variables (17-item HAM-D, Montgomery-Asberg Depression Rating Scale, Clinical Global Impressions, and Zung Self-Rating Depression Scale). After 6 weeks of treatment, significantly greater (p < or = .05) proportions of patients in both active treatment groups (70% in the Org 3770- and 58% in the amitriptyline-treatment groups) than in the placebo-treatment group (33%) were HAM-D responders. Org 3770 was well tolerated in this study; dry mouth and somnolence were the only adverse experiences that occurred significantly more frequently with Org 3770- than with placebo-treated patients. By contrast, treatment with amitriptyline was related to significantly higher rates of dry mouth, constipation, and dyspepsia as compared with both Org 3770 and placebo, and significantly higher rates of somnolence as compared with placebo.\n In this study, Org 3770 was as effective as amitriptyline in the treatment of major depression, with advantages regarding improvements of depressed mood (HAM-D Item 1), responder rates, and safety.", "The special extract of St. John's wort, LI 160, exhibited a superior antidepressant efficacy compared to placebo in several controlled trials. Two further trials demonstrated a similar reduction of depressive symptomatology under LI 160 compared to tricyclics. All these trials were performed in mildly to moderately depressed patients. The present investigation was a randomized, controlled, multicentre, 6-week trial comparing 1800 mg LI 160/die to 150 mg imipramine/die in severely depressed patients according to ICD-10. The main efficacy parameter, a reduction of the total score of the Hamilton Depression Scale, proved both treatment regimens very effective at the end of the 6 week treatment period (mean values 25.3 to 14.5 in the LI 160 group and 26.1 to 13.6 in the imipramine group), but not statistically equivalent within a a-priori defined 25% interval of deviation. The analysis of subgroups with more than a 33% and 50% reduction of the HAMD total score justified the assumption of equivalence within a 25% deviation interval. This view was also supported by the global efficacy ratings from patients and investigators. Regarding adverse events, the nonrejection of the nonequivalence hypothesis denotes a superiority of the herbal antidepressant. These main result indicate that LI 160 might be a treatment alternative to the synthetic tricyclic antidepressant imipramine in the majority of severe forms of depressions. However, more studies of this type must be performed before a stronger recommendation can be made.", "Antidepressant drugs are increasingly used in the management of chronic pain. They are mainly prescribed for cancer-related pain and central pain, e.g. phantom or stump pain, post-herpetic neuropathy. However, no controlled clinical trials have validated their in either pathology. Thus, physicians still do not know whether antidepressants are really effective and which might be best. It is still debated whether the effect of antidepressants in the management of chronic pain is limited to the amelioration of frequently concomitant depression or extends to pain itself. To verify both the analgesic effect of tricyclic antidepressants, and the possible relationship between their antidepressant effect and the relief of central pain, we carried out a randomized, within-patient (cross-over) placebo-controlled study in patients suffering from central pain. The results clearly indicate the better analgesic effect of tricyclic antidepressants over placebo (p less than 0.0001). Within the antidepressants tested, chlorimipramine, a blocker of serotonin reuptake, is significantly more effective (p less than 0.0001) than notriptyline, a blocker of noradrenaline reuptake. Finally, the antinociceptive effect is independent of the effects of the two drugs on the symptoms of depression.", "The efficacy and safety of fluoxetine were compared with those of imipramine and of placebo in a 6-week randomized double-blind parallel study of patients with major depressive illness. Mean values for all efficacy measurements were improved over baseline with fluoxetine and imipramine treatment (p less than .001). More fluoxetine patients completed the study than did imipramine or placebo patients. Predominant adverse experiences reported by imipramine patients were dry mouth and dizziness/lightheadedness. Predominant adverse experiences reported by fluoxetine patients were drowsiness/sedation and excessive sweating. In a subsequent 48-week open-label study, the predominant adverse experience in the fluoxetine group was excessive sweating and in the imipramine group was still dry mouth. In this study, fluoxetine relieved the symptoms of major depressive illness effectively and significantly better than placebo and was better tolerated than imipramine.", "Both nomifensine and imipramine were superior to placebo in a 4-week double-blind study involving 63 geriatric patients (greater than 60 years) with primary affective disorder-depression. Significant improvement in the active drug groups was demonstrated on the Hamilton Depression Rating Scale, Clinical Global Impressions, Brief Psychiatric Rating Scale, and Hopkins Symptom Check List. Analysis of laboratory and physical examination data, including ECGs, revealed no clinically significant changes associated with either drug. Compared to the imipramine group, nomifensine-treated patients showed a more rapid rate of improvement and a lower incidence of discomforting side effects." ]	The available evidence suggests that the hypericum extracts tested in the included trials a) are superior to placebo in patients with major depression; b) are similarly effective as standard antidepressants; c) and have fewer side effects than standard antidepressants. The association of country of origin and precision with effects sizes complicates the interpretation.
CD000985	[ "8201703", "9171752", "21557814", "1572460", "15798610" ]	[ "A comparison of thrombolytic therapy with operative revascularization in the initial treatment of acute peripheral arterial ischemia.", "Prospective randomized trial of high-dose bolus versus low-dose tissue plasminogen activator infusion in the management of acute limb ischaemia. Thrombolysis Study Group.", "SYNTHESIS expansion: design of a nonprofit, pragmatic, randomized, controlled trial on the best fast-track endovascular treatment vs. standard intravenous alteplase for acute ischemic stroke.", "Surgical treatment versus thrombolysis in acute arterial occlusion: a randomised controlled study.", "Comparison of intravenous and intra-arterial urokinase thrombolysis for acute ischaemic stroke." ]	[ "Despite the widespread use of intraarterial thrombolytic therapy for peripheral arterial occlusive disease, a randomized study comparing its efficacy with that of operative intervention has never been performed. This study evaluates the potential of intraarterial urokinase infusion to provide clinical benefits in patients with acute peripheral arterial occlusion.\n Patients with limb-threatening ischemia of less than 7 days' duration were randomly assigned to intraarterial catheter-directed urokinase therapy or operative intervention. Anatomic lesions unmasked by thrombolysis were treated with balloon dilation or operation. The primary end points of the study were limb salvage and survival.\n A total of 57 patients were randomized to the thrombolytic therapy group, and 57 patients were randomized to the operative therapy group. Thrombolytic therapy resulted in dissolution of the occluding thrombus in 40 (70%) patients. Although the cumulative limb salvage rate was similar in the two treatment groups (82% at 12 months), the cumulative survival rate was significantly improved in patients randomized to the thrombolysis group (84% vs 58% at 12 months, p = 0.01). The mortality differences seemed to be primarily attributable to an increased frequency of in-hospital cardiopulmonary complications in the operative treatment group (49% vs 16%, p = 0.001). The benefits of thrombolysis were achieved without significant differences in the duration of hospitalization (median 11 days) and with only modest increases in hospital cost in the thrombolytic treatment arm (median $15,672 vs $12,253, p = 0.02).\n Intraarterial thrombolytic therapy was associated with a reduction in the incidence of in-hospital cardiopulmonary complications and a corresponding increase in patient survival rates. These benefits were achieved without an appreciable increase in the duration of hospitalization and with only modest increases in hospital cost, suggesting that thrombolytic therapy may offer a safe and effective alternative to operation in the initial treatment of patients diagnosed with acute limb-threatening peripheral arterial occlusion.", "Accelerated thrombolysis with high-dose bolus tissue plasminogen activator (tPA) may enable patients with more severe acute leg ischaemia to be treated without recourse to surgery. This study was a randomized comparison of two thrombolytic regimens.\n One hundred patients with acute leg ischaemia of less than 30 days' duration were randomized to receive either high-dose bolus tPA (three doses of 5 mg over 30 min, then 3.5 mg/h for up to 4 h, then 0.5-1.0 mg/h) or conventional low-dose tPA (0.5-1.0 mg/h). The groups were well matched for age, cardiovascular risk factors, duration and severity of ischaemia, site, cause and length of arterial occlusion.\n The median duration of infusion in the high-dose group was 4.0 (range 0.25-46) h compared with 20 (range 2-46) h for low-dose infusion (P < 0.0001). Successful thrombolysis was achieved in 45 of 49 high-dose and 39 of 44 low-dose infusions but significantly more adjunctive procedures were required following high-dose bolus infusion (26 versus 16 patients) (P = 0.002). Thirty days after treatment was commenced, limb salvage was achieved in 39 of 49 patients in the high-dose group compared with 37 of 44 who had a low-dose infusion of tPA. Six and two patients respectively required amputation. Four patients in the high-dose group and five in the low-dose group died. Three patients in each group suffered a major haemorrhage and one in the low-dose group had a stroke.\n High-dose bolus therapy significantly accelerated thrombolysis with tPA without compromising outcome. Some 50 per cent of patients were treated within 4 h enabling thrombolysis to be used as primary therapy for patients with acute critical ischaemia.", "Rationale Reperfusion in ischemic stroke can be pursued by either systemic intravenous thrombolysis or endovascular treatment. However, systemic intravenous thrombolysis with alteplase within 4·5 h of symptom onset in selected patients is the only medication of proven efficacy. No randomized-controlled trials have so far compared the two modalities. To explore this, after a pilot phase, we started the SYNTHESIS Expansion trial. Aims To determine whether endovascular treatment (i.e., intra-arterial thrombolysis with alteplase - if necessary, associated to or substituted by mechanical clot disruption and/or retrieval) compared with systemic intravenous thrombolysis with alteplase, administered according to European labelling, increases the proportion of independent survivors at three-months. Design SYNTHESIS Expansion is an open-label, multicenter randomized-controlled trial, with blinded follow-up. Eligibility applies to; patients with symptomatic ischemic stroke, seen within 4·5 h of onset; being able to initiate intravenous alteplase immediately, and endovascular treatment as soon as possible (not later than six-hours of stroke onset). The study is pragmatically based on the 'uncertainty principle' between endovascular treatment and systemic intravenous thrombolysis for patients eligible for intravenous alteplase. There are no prespecified clinical or instrumental criteria to further select a patient, although investigators are left free to use them. Enrollment will be completed with 350 randomized patients. Primary analysis is on an intent-to-treat basis. Study outcomes Primary: modified Rankin scale score of 0 or 1 at three-months. Secondary: neurological deficit seven-days after thrombolysis and the safety of the procedure on the basis of events reported within seven-days following thrombolysis - symptomatic cerebral hemorrhage, fatal and nonfatal stroke, death from any cause, neurological deterioration.\n © 2011 The Authors. International Journal of Stroke © 2011 World Stroke Organization.", "Thrombolytic treatment has been tried in various forms for acute limb ischaemia with varying degrees of success but is also often accompanied by bleeding problems. The present investigation compares the effect of surgical thrombectomy (TE) and thrombolysis (TL) using recombinant tissue plasminogen activator (rt-PA). Twenty patients with a need for intervention owing to ischaemia lasting more than 24 h but less than 14 days were included. Patients randomised to TE were operated under epidural anaesthesia and patients in the TL group received 30 mg rt-PA during a 3 h period through a catheter placed into the thrombus and advanced as lysis was achieved. Thrombectomy resulted in an immediate restitution of blood flow in six out of nine cases, in three cases a bypass procedure was performed, and one of these failed with a resultant amputation. Thrombolysis gave a good primary result in six cases which lasted in four of them. Three had a subsequent percutaneous transluminal angioplasty. Partial lysis was seen in two cases and a further two failed. Five went to surgery with three bypass and two fogarty procedures being necessary. There was no hospital mortality and there were no bleeding complications due to the rt-PA treatment in this series. In 19 out of 20 patients the circulation was re-established. Appropriate handling of acute ischaemic conditions implies the use of both thrombolysis and appropriate surgical procedures, including distal bypass grafts.", "Intravenous fibrinolysis (IVF) with rt-PA (alteplase) provides significant benefits in acute ischaemic stroke when it is given within the first three hours following stroke onset. Intra-arterial fibrinolysis (IAF) with pro-urokinase in PROACT II study provides quite the same benefit in the first 6 hours. IVF and IAF have never been compared. To compare the efficacy and safety of IVF and IAF with urokinase given within the first 6 hours of acute ischaemic stroke. Patients fulfilling the selection criteria were randomly assigned to receive urokinase 900,000 units via intravenous or intra-arterial routes. This randomised monocentre study was done between December 1995 and August 1997. The primary outcome was defined as the number of patients with a modified Rankin score of 2 or less. Secondary outcomes included mortality, frequency of symptomatic intracranial haemorrhage (SIH), neurological and functional scores. Fourteen patients were given IVF and 13 IAF. The study was terminated by the National Health Authorities when 27 patients had been included because of the mortality rate. Seven patients (26%) died, 4 in the IV group (oedematous infarct in 3 and recurrence in 1), 3 in the IA group (SIH in 2, and oedematous infarct in 1). Patients given IVF were treated significantly earlier (4:16 h vs 5:24 h; p=.007). Although IA patients showed greater and earlier improvement there was no significant difference in primary and secondary outcomes. Because of premature termination, the trial was too small to provide any reliable and conclusive results. Intra-arterial fibrinolysis began significantly later than IV fibrinolysis but it gave non-significantly better results in this prematurely terminated study." ]	Implications for practice Thrombolysis should be reserved for patients with limb threatening ischaemia, due to the high risk of haemorrhage or death. Greater benefit is seen when the thrombolytic agent is delivered into the thrombus. Systemic intravenous thrombolysis is less effective than intra-arterial thrombolysis and is associated with an increase in bleeding complications. 'High dose' and 'forced infusion' techniques, or adjunctive agents such as platelet glycoprotein IIb/IIIa inhibitors may speed up thrombolysis, but these are not accompanied by lower amputation rates or a decreased need for adjunctive endovascular or surgical procedures. 'Low dose continuous infusion', following initial lacing of the thrombus with a high dose of the thrombolytic agent, is the least labour intensive technique. Implications for research Only large multicentre trials with carefully controlled inclusion criteria will be sufficiently powerful to demonstrate genuine benefit for a particular thrombolytic regime.
CD003967	[ "19058760", "9297994", "2861311", "18378519", "2864374", "490882", "9635947", "20166337", "2911834", "17434094", "15901766", "19636533", "19142552", "2046107", "10703801", "8258839", "18971490", "10691121", "15274104", "14654762", "9671379" ]	[ "Controlling hypertension and hypotension immediately post-stroke (CHHIPS): a randomised, placebo-controlled, double-blind pilot trial.", "Randomised double-blind comparison of placebo and active treatment for older patients with isolated systolic hypertension. The Systolic Hypertension in Europe (Syst-Eur) Trial Investigators.", "Mortality and morbidity results from the European Working Party on High Blood Pressure in the Elderly trial.", "Treatment of hypertension in patients 80 years of age or older.", "Cardiovascular risk and risk factors in a randomized trial of treatment based on the beta-blocker oxprenolol: the International Prospective Primary Prevention Study in Hypertension (IPPPSH). The IPPPSH Collaborative Group.", "Five-year findings of the hypertension detection and follow-up program. I. Reduction in mortality of persons with high blood pressure, including mild hypertension. Hypertension Detection and Follow-up Program Cooperative Group.", "Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomised trial. HOT Study Group.", "Improving combined diabetes outcomes by adding a simple patient intervention to physician feedback: a cluster randomized trial.", "Morbidity and mortality in the Systolic Hypertension in the Elderly Program (SHEP) pilot study.", "Glucose-potassium-insulin infusions in the management of post-stroke hyperglycaemia: the UK Glucose Insulin in Stroke Trial (GIST-UK).", "Double-blind comparison of full and partial anemia correction in incident hemodialysis patients without symptomatic heart disease.", "A prospective randomised multi-centre controlled trial on tight glucose control by intensive insulin therapy in adult intensive care units: the Glucontrol study.", "Intensive perioperative glucose control does not improve outcomes of patients submitted to open-heart surgery: a randomized controlled trial.", "Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension. Final results of the Systolic Hypertension in the Elderly Program (SHEP). SHEP Cooperative Research Group.", "Effect of phenobarbital on seizure frequency and mortality in childhood cerebral malaria: a randomised, controlled intervention study.", "A phase II study of moderate hypothermia in severe brain injury.", "Early insulin therapy in very-low-birth-weight infants.", "A multicenter randomized controlled trial on the clinical impact of therapeutic drug monitoring in patients with newly diagnosed epilepsy. The Italian TDM Study Group in Epilepsy.", "Volume guarantee: stability of tidal volume and incidence of hypocarbia.", "Results of the pilot study for the Hypertension in the Very Elderly Trial.", "A prospective, randomized, and controlled study of fluid management in children with severe head injury: lactated Ringer's solution versus hypertonic saline." ]	[ "Raised blood pressure is common after acute stroke and is associated with an adverse prognosis. We sought to assess the feasibility, safety, and effects of two regimens for lowering blood pressure in patients who have had a stroke.\n Patients who had cerebral infarction or cerebral haemorrhage and were hypertensive (systolic blood pressure [SBP] >160 mm Hg) were randomly assigned by secure internet central randomisation to receive oral labetalol, lisinopril, or placebo if they were non-dysphagic, or intravenous labetalol, sublingual lisinopril, or placebo if they had dysphagia, within 36 h of symptom onset in this double-blind pilot trial. The doses were titrated up if target blood pressure was not reached. Analysis was by intention to treat. This trial is registered with the National Research Register, number N0484128008.\n 179 patients (mean age 74 [SD 11] years; SBP 181 [SD 16] mm Hg; diastolic blood pressure [DBP] 95 [SD 13] mm Hg; median National Institutes of Health stroke scale [NIHSS] score 9 [IQR 5-16] points) were randomly assigned to receive labetolol (n=58), lisinopril (n=58), or placebo (n=63) between January, 2005, and December, 2007. The primary outcome--death or dependency at 2 weeks--occurred in 61% (69) of the active and 59% (35) of the placebo group (relative risk [RR] 1.03, 95% CI 0.80-1.33; p=0.82). There was no evidence of early neurological deterioration with active treatment (RR 1.22, 0.33-4.54; p=0.76) despite the significantly greater fall in SBP within the first 24 h in this group compared with placebo (21 [17-25] mm Hg vs 11 [5-17] mm Hg; p=0.004). No increase in serious adverse events was reported with active treatment (RR 0.91, 0.69-1.12; p=0.50) but 3-month mortality was halved (9.7%vs 20.3%, hazard ratio [HR] 0.40, 95% CI 0.2-1.0; p=0.05).\n Labetalol and lisinopril are effective antihypertensive drugs in acute stroke that do not increase serious adverse events. Early lowering of blood pressure with lisinopril and labetalol after acute stroke seems to be a promising approach to reduce mortality and potential disability. However, in view of the small sample size, care must be taken when these results are interpreted and further evaluation in larger trials is needed.", "Isolated systolic hypertension occurs in about 15% of people aged 60 years or older. In 1989, the European Working Party on High Blood Pressure in the Elderly investigated whether active treatment could reduce cardiovascular complications of isolated systolic hypertension. Fatal and non-fatal stroke combined was the primary endpoint.\n All patients (> 60 years) were initially started on masked placebo. At three run-in visits 1 month apart, their average sitting systolic blood pressure was 160-219 mm Hg with a diastolic blood pressure lower than 95 mm Hg. After stratification for centre, sex, and previous cardiovascular complications, 4695 patients were randomly assigned to nitrendipine 10-40 mg daily, with the possible addition of enalapril 5-20 mg daily and hydrochlorothiazide 12.5-25.0 mg daily, or matching placebos. Patients withdrawing from double-blind treatment were still followed up. We compared occurrence of major endpoints by intention to treat.\n At a median of 2 years' follow-up, sitting systolic and diastolic blood pressures had fallen by 13 mm Hg and 2 mm Hg in the placebo group (n = 2297) and by 23 mm Hg and 7 mm Hg in the active treatment group (n = 2398). The between-group differences were systolic 10.1 mm Hg (95% CI 8.8-11.4) and diastolic, 4.5 mm Hg (3.9-5.1). Active treatment reduced the total rate of stroke from 13.7 to 7.9 endpoints per 1000 patient-years (42% reduction; p = 0.003). Non-fatal stroke decreased by 44% (p = 0.007). In the active treatment group, all fatal and non-fatal cardiac endpoints, including sudden death, declined by 26% (p = 0.03). Non-fatal cardiac endpoints decreased by 33% (p = 0.03) and all fatal and non-fatal cardiovascular endpoints by 31% (p < 0.001). Cardiovascular mortality was slightly lower on active treatment (-27%, p = 0.07), but all-cause mortality was not influenced (-14%; p = 0.22).\n Among elderly patients with isolated systolic hypertension, antihypertensive drug treatment starting with nitrendipine reduces the rate of cardiovascular complications. Treatment of 1000 patients for 5 years with this type of regimen may prevent 29 strokes or 53 major cardiovascular endpoints.", "A double-blind randomised placebo-controlled trial of antihypertensive treatment was conducted in patients over the age of 60. Entry criteria included both a sitting diastolic blood pressure on placebo treatment in the range 90-119 mm Hg and a systolic pressure in the range 160-239 mm Hg. 840 patients were randomised either to active treatment (hydrochlorothiazide + triamterene) or to matching placebo. If the blood pressure remained raised, methyldopa was added to the active regimen and matching placebo in the placebo group. An overall intention-to-treat analysis, combining the double-blind part of the trial and all subsequent follow-up, revealed a non-significant change in total mortality rate (-9%, p = 0.41) but a significant reduction in cardiovascular mortality rate (-27%, p = 0.037). The latter was due to a reduction in cardiac mortality (-38%, p = 0.036) and a non-significant decrease in cerebrovascular mortality (-32%, p = 0.16). In the double-blind part of the trial, total mortality rate was not significantly reduced (-26%, p = 0.077). Cardiovascular mortality was reduced in the actively treated group (-38%, p = 0.023), owing to a reduction in cardiac deaths (-47%, p = 0.048) and a non-significant decrease in cerebrovascular mortality (-43%, p = 0.15). Deaths from myocardial infarction were reduced (-60%, p = 0.043). Study-terminating morbid cardiovascular events were significantly reduced by active treatment (-60%, p = 0.0064). Non-terminating cerebrovascular events were reduced (-52%, p = 0.026), but the non-terminating cardiac events were not (+3%, p = 0.98). In the patients randomised to active treatment there were 29 fewer cardiovascular events and 14 fewer cardiovascular deaths per 1000 patient years during the double-blind part of the trial.", "Whether the treatment of patients with hypertension who are 80 years of age or older is beneficial is unclear. It has been suggested that antihypertensive therapy may reduce the risk of stroke, despite possibly increasing the risk of death.\n We randomly assigned 3845 patients from Europe, China, Australasia, and Tunisia who were 80 years of age or older and had a sustained systolic blood pressure of 160 mm Hg or more to receive either the diuretic indapamide (sustained release, 1.5 mg) or matching placebo. The angiotensin-converting-enzyme inhibitor perindopril (2 or 4 mg), or matching placebo, was added if necessary to achieve the target blood pressure of 150/80 mm Hg. The primary end point was fatal or nonfatal stroke.\n The active-treatment group (1933 patients) and the placebo group (1912 patients) were well matched (mean age, 83.6 years; mean blood pressure while sitting, 173.0/90.8 mm Hg); 11.8% had a history of cardiovascular disease. Median follow-up was 1.8 years. At 2 years, the mean blood pressure while sitting was 15.0/6.1 mm Hg lower in the active-treatment group than in the placebo group. In an intention-to-treat analysis, active treatment was associated with a 30% reduction in the rate of fatal or nonfatal stroke (95% confidence interval [CI], -1 to 51; P=0.06), a 39% reduction in the rate of death from stroke (95% CI, 1 to 62; P=0.05), a 21% reduction in the rate of death from any cause (95% CI, 4 to 35; P=0.02), a 23% reduction in the rate of death from cardiovascular causes (95% CI, -1 to 40; P=0.06), and a 64% reduction in the rate of heart failure (95% CI, 42 to 78; P<0.001). Fewer serious adverse events were reported in the active-treatment group (358, vs. 448 in the placebo group; P=0.001).\n The results provide evidence that antihypertensive treatment with indapamide (sustained release), with or without perindopril, in persons 80 years of age or older is beneficial. (ClinicalTrials.gov number, NCT00122811 [ClinicalTrials.gov].).\n Copyright 2008 Massachusetts Medical Society.", "Myocardial infarction, sudden cardiac death, cerebrovascular accidents, blood pressure control and treatment tolerability were studied in a randomized double-blind trial conducted in 6357 men and women aged 40-64 years with uncomplicated essential hypertension (diastolic blood pressures 100-125 mmHg). At the start of the trial 3185 patients received treatment based on a beta-blocker (oxprenolol), while in the remaining 3172 placebo replaced oxprenolol. Supplementary drugs, excluding beta-blockers, were used as necessary in both treatment groups, with the aim of reducing diastolic pressure to 95 mmHg or less. Patients were followed for 3-5 years, a total of 25 651 patient years at risk. In most respects the two groups fared equally well; sudden death (relative risk [RR] 1.08; 95% confidence interval [Cl] 0.68 and 1.72), myocardial infarction (RR 0.83; Cl 0.59 and 1.16) and cerebrovascular accident (RR 0.97; Cl 0.64 and 1.47) rates were similar. Beta-blocker based therapy was associated with significantly lower average blood pressures, earlier ECG normalization, less hypokalaemia and fewer withdrawals from double-blind treatment for uncontrolled hypertension. Doctor-elicited and patient-assessed unwanted effects demonstrated overall good tolerability. In smokers the cardiac event rate was doubled. We propose that beta-blocker treatment effects depend on smoking status, with a significant interaction benefiting non-smoking men. Lower blood pressures during treatment were associated with substantially lower rates for cardiac as well as cerebrovascular events. Proportional hazards analysis also underlines the importance of other cardiovascular risk factors. The IPPPSH stresses the need for a comprehensive approach to the management of blood pressure and other risk factors in hypertensive patients.", "The Hypertension Detection and Follow-up Program (HDFP), in a community-based, randomized controlled trial involving 10,940 persons with high blood pressure (BP), compared the effects on five-year mortality of a systematic antihypertensive treatment program (Stepped Care [SC]) and referral to community medical therapy (Referred Care [RC]). Participants, recruited by population-based screening of 158,906 people aged 30 to 69 years in 14 communities througout the United States, were randomly assigned to SC or RC groups within each center and by entry diastolic blood pressure (DBP) (90 to 104, 105 to 114, and 115 + mm Hg). Over the five years of the study, more than two thirds of the SC participants continued to receive medication, and more than 50% achieved BP levels within the normotensive range, at or below the HDFP goal for DBP. Controls of BP was consistently better for the SC than for the RC group. Five-year mortality from all causes was 17% lower for the SC group compared to the RC group (6.4 vs 7.7 per 100, P less than .01) and 20% lower for the SC subgroup with entry DBP of 90 to 104 mm Hg compared to the corresponding RC subgroup (5.9 vs 7.4 per 100, P less than .01). These findings of the HDFP indicate that the systematic effective management of hypertension has a great potential for reducing mortality for the large numbers of people with high BP in the population, including those with \"mild\" hypertension.", "Despite treatment, there is often a higher incidence of cardiovascular complications in patients with hypertension than in normotensive individuals. Inadequate reduction of their blood pressure is a likely cause, but the optimum target blood pressure is not known. The impact of acetylsalicylic acid (aspirin) has never been investigated in patients with hypertension. We aimed to assess the optimum target diastolic blood pressure and the potential benefit of a low dose of acetylsalicylic acid in the treatment of hypertension.\n 18790 patients, from 26 countries, aged 50-80 years (mean 61.5 years) with hypertension and diastolic blood pressure between 100 mm Hg and 115 mm Hg (mean 105 mm Hg) were randomly assigned a target diastolic blood pressure. 6264 patients were allocated to the target pressure < or =90 mm Hg, 6264 to < or =85 mm Hg, and 6262 to < or =80 mm Hg. Felodipine was given as baseline therapy with the addition of other agents, according to a five-step regimen. In addition, 9399 patients were randomly assigned 75 mg/day acetylsalicylic acid (Bamycor, Astra) and 9391 patients were assigned placebo.\n Diastolic blood pressure was reduced by 20.3 mm Hg, 22.3 mm Hg, and 24.3 mm Hg, in the < or =90 mm Hg, < or =85 mm Hg, and < or =80 mm Hg target groups, respectively. The lowest incidence of major cardiovascular events occurred at a mean achieved diastolic blood pressure of 82.6 mm Hg; the lowest risk of cardiovascular mortality occurred at 86.5 mm Hg. Further reduction below these blood pressures was safe. In patients with diabetes mellitus there was a 51% reduction in major cardiovascular events in target group < or =80 mm Hg compared with target group < or =90 mm Hg (p for trend=0.005). Acetylsalicylic acid reduced major cardiovascular events by 15% (p=0.03) and all myocardial infarction by 36% (p=0.002), with no effect on stroke. There were seven fatal bleeds in the acetylsalicylic acid group and eight in the placebo group, and 129 versus 70 non-fatal major bleeds in the two groups, respectively (p<0.001).\n Intensive lowering of blood pressure in patients with hypertension was associated with a low rate of cardiovascular events. The HOT Study shows the benefits of lowering the diastolic blood pressure down to 82.6 mm Hg. Acetylsalicylic acid significantly reduced major cardiovascular events with the greatest benefit seen in all myocardial infarction. There was no effect on the incidence of stroke or fatal bleeds, but non-fatal major bleeds were twice as common.", "Research on synergistic effects of patient targeted interventions combined with physician-targeted interventions has been limited.\n To compare a combined physician-patient intervention to physician feedback alone on a composite outcome of glycemic, lipid and blood pressure control.\n In this cluster study 417 patients with adult-type 2 diabetes from four primary care clinics were randomized to receive either a physician-only intervention or a combined physician-plus-patient intervention. Physicians in all clinics received diabetes-related quality performance feedback during staff meetings. Patients at combined-intervention clinics also received a letter encouraging them to remind their doctors to address essential aspects of diabetes care at the next visit. At 1 year follow-up, outcome measurements included hemoglobin A1c, low density lipoprotein-cholesterol and systolic blood pressure: namely, the proportion of patients with HbA1c 9%, LDL <130 mg/dl and SBP <140 mmHg both as separate outcomes and combined.\n After adjusting for patient characteristics and baseline measures, follow-up levels of HbA1c (7.5% vs. 7.8%, P = 0.09), LDL (104.7 vs. 110.7 mg/dl, P < 0.05) and SBP (135.6 vs. 139.9, P = 0.10) were marginally better for combined-intervention patients compared to physician-only intervention patients. Significantly more patients in the combined-intervention (38.8%) than physician-only intervention (24.2%) met all three targets (HbA1c (9%, LDL (130 mg/dl and SBP <140 mmHg) as a single combined outcome (adjusted odds ratio 2.4, P < .01).\n Compared to physician-feedback alone, a dual intervention combining a patient letter with physician feedback produced modest improvements in glycemic, lipid and blood pressure control individually, but substantial improvement in a combined measure of these three outcomes together. Using composite outcomes may detect meaningful improvements in the management of complex chronic disease.", "The pilot study of the Systolic Hypertension in the Elderly Program was a randomized, double-blind, placebo-controlled trial of drug therapy for isolated systolic hypertension. It followed 551 elderly participants with untreated blood pressures of greater than 160/less than 90 mm Hg for an average of 34 months. Mean age of the participants was 72 years; 63% were women, and 82% were white. Pretreatment blood pressures averaged 172/75 mm Hg. Participants were randomly assigned to treatment with chlorthalidone or placebo as Step I medication. Blood pressures at annual visits averaged 141/68 and 157/73 mm Hg for the drug-treated and placebo-treated groups, respectively, with 60% and 33% of the survivors on blinded medication having systolic blood pressures of less than 160 mm Hg at their last annual visit. All-cause mortality rates for the drug-treated and placebo-treated groups were 25.4 and 22.7 deaths per 1,000 participant-years of risk, and rates for definite \"first stroke\" were 8.3 and 12.8 per 1,000 years of risk. Differences between groups were significant for systolic and diastolic blood pressure but not for death or stroke rates. A full-scale study has begun to determine the effects of drug therapy for isolated systolic hypertension on stroke and mortality rates.", "Hyperglycaemia after acute stroke is a common finding that has been associated with an increased risk of death. We sought to determine whether treatment with glucose-potassium-insulin (GKI) infusions to maintain euglycaemia immediately after the acute event reduces death at 90 days.\n Patients presenting within 24 h of stroke onset and with admission plasma glucose concentration between 6.0-17.0 mmol/L were randomly assigned to receive variable-dose-insulin GKI (intervention) or saline (control) as a continuous intravenous infusion for 24 h. The purpose of GKI infusion was to maintain capillary glucose at 4-7 mmol/L, with no glucose intervention in the control group. The primary outcome was death at 90 days, and the secondary endpoint was avoidance of death or severe disability at 90 days. Additional planned analyses were done to determine any differences in residual disability or neurological and functional recovery. The trial was powered to detect a mortality difference of 6% (sample size 2355), with 83% power, at the 5% two-sided significance level. This study is registered as an International Standard Randomised Controlled Trial (number ISRCTN 31118803)\n The trial was stopped due to slow enrolment after 933 patients were recruited. For the intention-to-treat data, there was no significant reduction in mortality at 90 days (GKI vs control: odds ratio 1.14, 95% CI 0.86-1.51, p=0.37). There were no significant differences for secondary outcomes. In the GKI group, overall mean plasma glucose and mean systolic blood pressure were significantly lower than in the control group (mean difference in glucose 0.57 mmol/L, p<0.001; mean difference in blood pressure 9.0 mmHg, p<0.0001).\n GKI infusions significantly reduced plasma glucose concentrations and blood pressure. Treatment within the trial protocol was not associated with significant clinical benefit, although the study was underpowered and alternative results cannot be excluded.", "It is unclear whether physiologic hemoglobin targets lead to cardiac benefit in incident hemodialysis patients without symptomatic heart disease and left ventricular dilation. In this randomized, double-blind study, lower (9.5 to 11.5 g/dl) and higher (13.5 to 14.5 g/dl) hemoglobin targets were generated with epoetin alpha over 24 wk and maintained for an additional 72 wk. Major eligibility criteria included recent hemodialysis initiation and absence of symptomatic cardiac disease and left ventricular dilation. The primary outcome measure was left ventricular volume index (LVVI). The study enrolled 596 patients. Mean age, duration of dialysis therapy, baseline predialysis hemoglobin, and LVVI were 50.8 yr, 0.8 yr, 11.0 g/dl, and 69 ml/m2, respectively; 18% had diabetic nephropathy. Mean hemoglobin levels in the higher and lower target groups were 13.3 and 10.9 g/dl, respectively, at 24 wk. Percentage changes in LVVI between baseline and last value were similar (7.6% in the higher and 8.3% in the lower target group) as were the changes in left ventricular mass index (16.8 versus 14.2%). For the secondary outcomes, the only between-group difference was an improved SF-36 Vitality score in the higher versus the lower target group (1.21 versus -2.31; P = 0.036). Overall adverse event rates were similar in both target groups; higher (P < 0.05) rates of skeletal pain, surgery, and dizziness were seen in the lower target group, and headache and cerebrovascular events were seen in the higher target group. Normalization of hemoglobin in incident hemodialysis patients does not have a beneficial effect on cardiac structure, compared with partial correction.", "An optimal target for glucose control in ICU patients remains unclear. This prospective randomized controlled trial compared the effects on ICU mortality of intensive insulin therapy (IIT) with an intermediate glucose control.\n Adult patients admitted to the 21 participating medico-surgical ICUs were randomized to group 1 (target BG 7.8-10.0 mmol/L) or to group 2 (target BG 4.4-6.1 mmol/L).\n While the required sample size was 1,750 per group, the trial was stopped early due to a high rate of unintended protocol violations. From 1,101 admissions, the outcomes of 542 patients assigned to group 1 and 536 of group 2 were analysed. The groups were well balanced. BG levels averaged in group 1 8.0 mmol/L (IQR 7.1-9.0) (median of all values) and 7.7 mmol/L (IQR 6.7-8.8) (median of morning BG) versus 6.5 mmol/L (IQR 6.0-7.2) and 6.1 mmol/L (IQR 5.5-6.8) for group 2 (p < 0.0001 for both comparisons). The percentage of patients treated with insulin averaged 66.2 and 96.3%, respectively. Proportion of time spent in target BG was similar, averaging 39.5% and 45.1% (median (IQR) 34.3 (18.5-50.0) and 39.3 (26.2-53.6)%) in the groups 1 and 2, respectively. The rate of hypoglycaemia was higher in the group 2 (8.7%) than in group 1 (2.7%, p < 0.0001). ICU mortality was similar in the two groups (15.3 vs. 17.2%).\n In this prematurely stopped and therefore underpowered study, there was a lack of clinical benefit of intensive insulin therapy (target 4.4-6.1 mmol/L), associated with an increased incidence of hypoglycaemia, as compared to a 7.8-10.0 mmol/L target. (ClinicalTrials.gov # NCT00107601, EUDRA-CT Number: 200400391440).", "The objective of this study was to investigate the relationship between different target levels of glucose and the clinical outcomes of patients undergoing cardiac surgery with cardiopulmonary bypass.\n We designed a prospective study in a university hospital where 109 consecutive patients were enrolled during a six-month period. All patients were scheduled for open-heart surgery requiring cardiopulmonary bypass. Patients were randomly allocated into two groups. One group consisted of 55 patients and had a target glucose level of 80-130 mg/dl, while the other contained 54 patients and had a target glucose level of 160-200 mg/dl. These parameters were controlled during surgery and for 36 hours after surgery in the intensive care unit. Primary outcomes were clinical outcomes, including time of mechanical ventilation, length of stay in the intensive care unit, infection, hypoglycemia, renal or neurological dysfunction, blood transfusion and length of stay in the hospital. The secondary outcome was a combined end-point (mortality at 30 days, infection or length of stay in the intensive care unit of more than 3 days). A p-value of <0.05 was considered significant.\n The anthropometric and clinical characteristics of the patients from each group were similar, except for weight and body mass index. The mean glucose level during the protocol period was 126.69 mg/dl in the treated group and 168.21 mg/dl in the control group (p<0.0016). There were no differences between groups regarding clinical outcomes, including the duration of mechanical ventilation, length of stay in the intensive care unit, blood transfusion, postoperative infection, hypoglycemic event, neurological dysfunction or 30-day mortality (p>0.05).\n In 109 patients undergoing cardiac surgery with cardiopulmonary bypass, both protocols of glycemic control in an intraoperative setting and in the intensive care unit were found to be safe, easily achieved and not to differentially affect clinical outcomes.", "To assess the ability of antihypertensive drug treatment to reduce the risk of nonfatal and fatal (total) stroke in isolated systolic hypertension.\n Multicenter, randomized, double-blind, placebo-controlled.\n Community-based ambulatory population in tertiary care centers.\n 4736 persons (1.06%) from 447,921 screenees aged 60 years and above were randomized (2365 to active treatment, 2371 to placebo). Systolic blood pressure ranged from 160 to 219 mm Hg and diastolic blood pressure was less than 90 mm Hg. Of the participants, 3161 were not receiving antihypertensive medication at initial contact, and 1575 were. The average systolic blood pressure was 170 mm Hg; average diastolic blood pressure, 77 mm Hg. The mean age was 72 years, 57% were women, and 14% were black.\n --Participants were stratified by clinical center and by antihypertensive medication status at initial contact. For step 1 of the trial, dose 1 was chlorthalidone, 12.5 mg/d, or matching placebo; dose 2 was 25 mg/d. For step 2, dose 1 was atenolol, 25 mg/d, or matching placebo; dose 2 was 50 mg/d.\n Primary. Nonfatal and fatal (total) stroke. Secondary. Cardiovascular and coronary morbidity and mortality, all-cause mortality, and quality of life measures.\n Average follow-up was 4.5 years. The 5-year average systolic blood pressure was 155 mm Hg for the placebo group and 143 mm Hg for the active treatment group, and the 5-year average diastolic blood pressure was 72 and 68 mm Hg, respectively. The 5-year incidence of total stroke was 5.2 per 100 participants for active treatment and 8.2 per 100 for placebo. The relative risk by proportional hazards regression analysis was 0.64 (P = .0003). For the secondary end point of clinical nonfatal myocardial infarction plus coronary death, the relative risk was 0.73. Major cardiovascular events were reduced (relative risk, 0.68). For deaths from all causes, the relative risk was 0.87.\n In persons aged 60 years and over with isolated systolic hypertension, antihypertensive stepped-care drug treatment with low-dose chlorthalidone as step 1 medication reduced the incidence of total stroke by 36%, with 5-year absolute benefit of 30 events per 1000 participants. Major cardiovascular events were reduced, with 5-year absolute benefit of 55 events per 1000.", "Seizures commonly complicate cerebral malaria and are associated with an increased risk of death and neurological sequelae. We undertook a randomised study to assess the efficacy of intramuscular phenobarbital in preventing seizures in childhood cerebral malaria.\n Children with cerebral malaria admitted to one hospital in Kilifi, Kenya, were randomly assigned a single intramuscular dose of phenobarbital (20 mg/kg) or identical placebo. Clinical tolerance was assessed at the start of the trial, with particular reference to respiratory depression and hypotension. Seizures were timed and recorded, and treated in a standard way. Plasma phenobarbital concentrations were measured. Analyses were by intention to treat.\n 440 children with cerebral malaria were admitted to the hospital; 100 were not recruited to the study. Of the remaining 340, 170 received phenobarbital and 170 placebo. The drug was adequately absorbed and well tolerated. Seizure frequency was significantly lower in the phenobarbital group than in the placebo group (18 [11%] vs 46 [27%] children had three or more seizures of any duration; odds ratio 0.32 [95% CI 0.18-0.58]) but mortality was doubled (30 [18%] vs 14 [8%] deaths; 2.39 [1.28-4.64]). The frequency of respiratory arrest was higher in the phenobarbital group than in the placebo group, and mortality was greatly increased in children who received phenobarbital plus three or more doses of diazepam (odds ratio 31.7 [1.2-814]).\n In children with cerebral malaria, phenobarbital 20 mg/kg provides highly effective seizure prophylaxis but is associated with an unacceptable increase in mortality. Use of this dose cannot, therefore, be recommended.", "Forty-six patients with severe nonpenetrating brain injury [Glasgow Coma Scale (GCS) 4-7] were randomized to standard management at 37 degrees C (n = 22) and to standard management with systemic hypothermia to 32 to 33 degrees C (n = 24). The two groups were balanced in terms of age (Wilcoxon's rank sum test, p > 0.95), randomizing GCS (chi-square test, p = 0.54), and primary diagnosis. Cooling was begun within 6 h of injury by use of cooling blankets. Metocurine and morphine were given hourly during induction and maintenance of hypothermia. Rewarming was at a rate of 1 degree C per 4 h beginning 48 h after intravascular temperature had reached 33 degrees C. Muscle relaxants and sedation were continued until core temperature reached 35 degrees C. There were no cardiac or coagulopathy-related complications. Seizure incidence was lower in the hypothermia group (Fisher's exact text, p = 0.019). Sepsis was seen more commonly in the hypothermia group, but difference was not statistically significant (chi-square test). Mean Glasgow Outcome Scale (GOS) score at 3 months after injury showed an absolute increase of 16% (i.e., 36.4-52.2%) in the number of patients in the Good Recovery/Moderate Disability (GR/MD) category as compared with Severe Disability/Vegetative/Dead (SD/V/D) (chi-square test, p > 0.287). Based on evidence of improved neurologic outcome with minimal toxicity, we believe that phase III testing of moderate systemic hypothermia in patients with severe head injury is warranted.", "Studies involving adults and children being treated in intensive care units indicate that insulin therapy and glucose control may influence survival. Hyperglycemia in very-low-birth-weight infants is also associated with morbidity and mortality. This international randomized, controlled trial aimed to determine whether early insulin replacement reduced hyperglycemia and affected outcomes in such neonates.\n In this multicenter trial, we assigned 195 infants to continuous infusion of insulin at a dose of 0.05 U per kilogram of body weight per hour with 20% dextrose support and 194 to standard neonatal care on days 1 to 7. The efficacy of glucose control was assessed by continuous glucose monitoring. The primary outcome was mortality at the expected date of delivery. The study was discontinued early because of concerns about futility with regard to the primary outcome and potential harm.\n As compared with infants in the control group, infants in the early-insulin group had lower mean (+/-SD) glucose levels (6.2+/-1.4 vs. 6.7+/-2.2 mmol per liter [112+/-25 vs. 121+/-40 mg per deciliter], P=0.007). Fewer infants in the early-insulin group had hyperglycemia for more than 10% of the first week of life (21% vs. 33%, P=0.008). The early-insulin group had significantly more carbohydrate infused (51+/-13 vs. 43+/-10 kcal per kilogram per day, P<0.001) and less weight loss in the first week (standard-deviation score for change in weight, -0.55+/-0.52 vs. -0.70+/-0.47; P=0.006). More infants in the early-insulin group had episodes of hypoglycemia (defined as a blood glucose level of <2.6 mmol per liter [47 mg per deciliter] for >1 hour) (29% in the early-insulin group vs. 17% in the control group, P=0.005), and the increase in hypoglycemia was significant in infants with birth weights of more than 1 kg. There were no differences in the intention-to-treat analyses for the primary outcome (mortality at the expected date of delivery) and the secondary outcome (morbidity). In the intention-to-treat analysis, mortality at 28 days was higher in the early-insulin group than in the control group (P=0.04).\n Early insulin therapy offers little clinical benefit in very-low-birth-weight infants. It reduces hyperglycemia but may increase hypoglycemia (Current Controlled Trials number, ISRCTN78428828.)\n 2008 Massachusetts Medical Society", "To assess the clinical impact of monitoring serum concentrations of antiepileptic drugs (AEDs) in patients with newly diagnosed epilepsy.\n One-hundred eighty patients with partial or idiopathic generalized nonabsence epilepsy, aged 6 to 65 years, requiring initiation of treatment with carbamazepine (CBZ), valproate (VPA), phenytoin (PHT), phenobarbital (PB), or primidone (PRM) were randomly allocated to two groups according to an open, prospective parallel-group design. In one group, dosage was adjusted to achieve serum AED concentration within a target range (10-20 microg/ml for PHT, 15-40 microg/ml for PB, 4-11 microg/ml for CBZ, and 40-100 microg/ml for VPA), whereas in the other group, dosage was adjusted on clinical grounds. Patients were followed up for 24 months or until a change in therapeutic strategy was clinically indicated.\n Baseline characteristics did not differ between the two groups. Most patients with partial epilepsy were treated with CBZ, whereas generalized epilepsies were most commonly managed with PB or VPA. PHT was used only in a small minority of patients. A total of 116 patients completed 2-year follow-up, and there were no differences in exit rate from any cause between the monitored group and the control group. The proportion of assessable patients with mean serum drug levels outside the target range (mostly below range) during the first 6 months of the study was 8% in the monitored group compared with 25% in the control group (p < 0.01). There were no significant differences between the monitored group and the control group with respect to patients achieving 12-month remission (60% vs. 61%), patients remaining seizure free since initiation of treatment (38% vs. 41%), and time to first seizure or 12-month remission. Frequency of adverse effects was almost identical in the two groups.\n Only a small minority of patients were treated with PHT, the drug for which serum concentration measurements are most likely to be useful. With the AEDs most commonly used in this study, early implementation of serum AED level monitoring did not improve overall therapeutic outcome. and the majority of patients could be satisfactorily treated by adjusting dose on clinical grounds. Monitoring the serum levels of these drugs in selected patients and in special situations is likely to be more rewarding than routine measurements in a large clinic population.", "Excessive tidal volume (V(T)) can lead to lung injury, hypocarbia, and neurologic damage. Volume guarantee (VG) uses exhaled V(T) as the control variable to reduce the risk of volutrauma and more closely control PaCO(2). Our objective was to test the hypothesis that VG combined with assist/control (A/C) will maintain PaCO(2) and V(T) within target range more consistently than assist/control alone during the first 72 hr of life in ventilated preterm infants. Eligible infants were randomly assigned to A/C + VG or A/C alone. Data were recorded directly from the pressure and volume module of the Draeger Babylog 8000+ ventilator. Arterial blood gases were obtained every 2-6 hr, as clinically indicated. In A/C, inspiratory pressure was adjusted to achieve a V(T) of 4-6 ml/kg. In VG, the target V(T) was 5 ml/kg. Subsequent adjustments were made by the clinical team in response to arterial blood gas measurements (ABG). Proportion of breaths and PaCO(2) values outside the target range were compared by chi(2), and continuous variables by t-test. There were no differences in demographic or baseline ventilator variables between the 18 infants in the two groups. For 1,805/11,950 breaths (15.1%), V(T) was > target with A/C + VG, vs. 2,503/9,853 (25.4%) with A/C (P < 0.001). V(T) was < target for 21.7% of breaths with A/C + VG, vs. 35.7% with A/C (P < 0.001). Twenty percent of PaCO(2) values were < target, with A/C + VG vs. 36.3% with A/C, P < 0.05. The proportion of PaCO(2) values > target was similar in the two groups. Oxygenation and mean pH were not different. No complications related to mechanical ventilation were observed. In conclusion, VG significantly reduced hypocarbia and excessively large V(T). This suggests the potential to reduce pulmonary and neurologic complications of mechanical ventilation. Larger studies are needed to establish safety and demonstrate such benefits.\n Copyright 2004 Wiley-Liss, Inc.", "The risks and benefits of treating hypertension in individuals older than 80 years are uncertain. A meta-analysis has suggested that a reduction in stroke events of 36% may have to be balanced against a 14% increase in total mortality.\n To report the results of the pilot study of the Hypertension in the Very Elderly Trial (HYVET), which is in progress to address these issues.\n The HYVET-Pilot was a multicentre international open pilot trial. In 10 European countries, 1283 patients older than 80 years and with a sustained blood pressure of 160-219/90-109 mmHg were allocated randomly to one of three treatments: a diuretic-based regimen (usually bendroflumethiazide; n = 426), an angiotensin-converting enzyme inhibitor regimen (usually lisinopril; n = 431) or no treatment (n = 426). The procedure permitted doses of the drug to be titrated and diltiazem slow-release to be added to active treatment. Target blood pressure was < 150/80 mmHg and mean follow-up was 13 months.\n In the combined actively treated groups, the reduction in stroke events relative hazard rate (RHR) was 0.47 [95% confidence interval (CI) 0.24 to 0.93] and the reduction in stroke mortality RHR was 0.57 (95% CI 0.25 to 1.32). However, the estimate of total mortality supported the possibility of excess deaths with active treatment (RHR 1.23, 95% CI 0.75 to 2.01).\n The preliminary results support the need for the continuing main HYVET trial. It is possible that treatment of 1000 patients for 1 year may reduce stroke events by 19 (nine non-fatal), but may be associated with 20 extra non-stroke deaths.", "Resuscitation in severe head injury may be detrimental when given with hypotonic fluids. We evaluated the effects of lactated Ringer's solution (sodium 131 mmol/L, 277 mOsm/L) compared with hypertonic saline (sodium 268 mmol/L, 598 mOsm/L) in severely head-injured children over the first 3 days after injury.\n An open, randomized, and prospective study.\n A 16-bed pediatric intensive care unit (ICU) (level III) at a university children's hospital.\n A total of 35 consecutive children with head injury.\n Thirty-two children with Glasgow Coma Scores of <8 were randomly assigned to receive either lactated Ringer's solution (group 1) or hypertonic saline (group 2). Routine care was standardized, and included the following: head positioning at 30 degrees; normothermia (96.8 degrees to 98.6 degrees F [36 degrees to 37 degrees C]); analgesia and sedation with morphine (10 to 30 microg/kg/hr), midazolam (0.2 to 0.3 mg/kg/hr), and phenobarbital; volume-controlled ventilation (PaCO2 of 26.3 to 30 torr [3.5 to 4 kPa]); and optimal oxygenation (PaO2 of 90 to 105 torr [12 to 14 kPa], oxygen saturation of >92%, and hematocrit of >0.30).\n Mean arterial pressure and intracranial pressure (ICP) were monitored continuously and documented hourly and at every intervention. The means of every 4-hr period were calculated and serum sodium concentrations were measured at the same time. An ICP of 15 mm Hg was treated with a predefined sequence of interventions, and complications were documented. There was no difference with respect to age, male/female ratio, or initial Glasgow Coma Score. In both groups, there was an inverse correlation between serum sodium concentration and ICP (group 1: r = -.13, r2 = .02, p < .03; group 2: r = -.29, r2 = .08, p < .001) that disappeared in group 1 and increased in group 2 (group 1: r = -.08, r2 = .01, NS; group 2: r = -.35, r2 =.12, p < .001). Correlation between serum sodium concentration and cerebral perfusion pressure (CPP) became significant in group 2 after 8 hrs of treatment (r = .2, r2 = .04, p = .002). Over time, ICP and CPP did not significantly differ between the groups. However, to keep ICP at <15 mm Hg, group 2 patients required significantly fewer interventions (p < .02). Group 1 patients received less sodium (8.0 +/- 4.5 vs. 11.5 +/- 5.0 mmol/kg/day, p = .05) and more fluid on day 1 (2850 +/- 1480 vs. 2180 +/- 770 mL/m2, p = .05). They also had a higher frequency of acute respiratory distress syndrome (four vs. 0 patients, p = .1) and more than two complications (six vs. 1 patient, p = .09). Group 2 patients had significantly shorter ICU stay times (11.6 +/- 6.1 vs. 8.0 +/- 2.4 days; p = .04) and shorter mechanical ventilation times (9.5 +/- 6.0 vs. 6.9 +/- 2.2 days; p = .1). The survival rate and duration of hospital stay were similar in both groups.\n Treatment of severe head injury with hypertonic saline is superior to that treatment with lactated Ringer's solution. An increase in serum sodium concentrations significantly correlates with lower ICP and higher CPP. Children treated with hypertonic saline require fewer interventions, have fewer complications, and stay a shorter time in the ICU." ]	There was no significant difference in the risk of death for low (< 120 g/L) versus higher Hb targets (>133 g/L). Lower Hb targets were significantly associated with an increased risk for seizures but a reduced risk of hypertension. In general study quality was poor. There is a need for more adequately powered, well-designed and reported trials. Trials should be pragmatic, focusing on hard end-points (mortality, ESKD, major side effects) or outcomes which were previously not studied adequately (e.g. seizures, quality of life).
CD008946	[ "2594037", "2934438", "6175137", "3579357", "9071622", "20889234", "16518424", "14567368", "8070287", "12351592", "17107398", "356523" ]	[ "A randomized trial comparing combination electron-beam radiation and chemotherapy with topical therapy in the initial treatment of mycosis fungoides.", "Intralesional interferon in the treatment of early mycosis fungoides.", "Transfer factor therapy in mycosis fungoides: a double-blind study.", "Recombinant interferon alfa-2b in plaque-phase mycosis fungoides. Intralesional and low-dose intramuscular therapy.", "A randomized clinical trial of topical paromomycin versus oral ketoconazole for treating cutaneous leishmaniasis in Turkey.", "A phase II placebo-controlled study of photodynamic therapy with topical hypericin and visible light irradiation in the treatment of cutaneous T-cell lymphoma and psoriasis.", "A prospective, double-blind phase II study evaluating the safety and efficacy of a topical histamine gel for the prophylaxis of oral mucositis in patients post hematopoietic stem cell transplantation.", "Ciclopirox gel in the treatment of patients with interdigital tinea pedis.", "A double-blind, vehicle-controlled study of the safety and efficacy of Fungoid Tincture in patients with distal subungual onychomycosis of the toes.", "Prophylaxis of radiation-associated mucositis in conventionally treated patients with head and neck cancer: a double-blind, phase III, randomized, controlled trial evaluating the clinical efficacy of an antimicrobial lozenge using a validated mucositis scoring system.", "Prospective, randomized controlled trial on Lactobacillus rhamnosus in infants with moderate to severe atopic dermatitis.", "Prophylactic treatment with miconazole in patients highly predisposed to fungal infection. A placebo-controlled double-blind study." ]	[ "Mycosis fungoides is a T-cell lymphoma that arises in the skin and progresses at highly variable rates. Nonradomized studies have suggested that early aggressive therapy may improve the prognosis in this usually fatal disease. We studied 103 patients with mycosis fungoides, who, after complete staging, were randomly assigned to receive either combination therapy, consisting of 3000 cGy of electron-beam radiation to the skin combined with parenteral chemotherapy with cyclophosphamide, doxorubicin, etoposide, and vincristine (n = 52) or sequential topical treatment (n = 51). The prognostic factors were well balanced in the two groups. Combined therapy produced considerable toxicity: 12 patients required hospitalization for fever and transient neutropenia, 5 had congestive heart failure, and 2 were later found to have acute nonlymphocytic leukemia. Patients receiving combined therapy had a significantly higher rate of complete response, documented by biopsy, than patients receiving conservative therapy (38 percent vs. 18 percent; P = 0.032). After a median follow-up of 75 months, however, there was no significant difference between the treatment groups in disease-free or overall survival. We conclude that early aggressive therapy with radiation and chemotherapy does not improve the prognosis for patients with mycosis fungoides as compared with conservative treatment beginning with sequential topical therapies.", "Twelve patients with early mycosis fungoides were enrolled in a randomized, double-blind, placebo-controlled study. Isolated plaques were injected three times a week with recombinant alpha 2-interferon in nine patients and with the vehicle in three patients. Two additional plaques were evaluated in each patient; one was left untreated, and another was treated topically with either placebo ointment or betamethasone ointment. Biopsies were taken from an untreated, representative plaque prior to treatment and from all test sites following treatment for light microscopy and T lymphocyte subsets. Three of the nine lesions injected with interferon cleared, and all showed improvement. Thirteen of eighteen noninjected lesions improved in patients who received interferon, showing a systemic effect. In the control group, none of the injected lesions improved and only two of the noninjected lesions showed any change. Histopathologic changes confirmed the clinical impression. This study shows that intralesional interferon may be given safely and has a beneficial effect, both locally and systemically.", "Sixteen patients with mycosis fungoides (MF) were given either active transfer factor (TF) or heat-inactivated TF as additional therapy to topical nitrogen mustard or PUVA. The TF was prepared from non-selected healthy blood donors. The clinical evaluation after 2 years of therapy showed that among 8 patients treated with active TF, none went into complete remission of their disease 4 patients had partial remission, one was unchanged, 2 progressed, and one died of active MF. In the placebo-treated group, 5 patients achieved complete remission and 2 partial remission. One patient died early in the trial due to cardiac disease. Immunological studies during the first year of therapy revealed cutaneous anergy towards tuberculin in most patients. This anergy did not change during TF therapy and differed from normal lymphocyte reactivity in vitro after tuberculin stimulation. At the start of treatment the patients had diminished levels of T lymphocytes in peripheral blood. A temporary increase was observed in the total number of T lymphocytes in patients after one month of treatment with active TF. After one year the T lymphopenia had disappeared in both groups. The mitogen reactivity of lymphocytes was found to be normal (PHA, PWM) or somewhat reduced (Con A). It is concluded that under the conditions employed in this trial, TF was not able to prevent progression of early mycosis fungoides, when viewed over a period of 2 years.", "A two-part clinical trial was conducted to determine the therapeutic efficacy of recombinant interferon alfa-2b in plaque-phase mycosis fungoides. In an initial randomized double-blind study, each of six patients had two representative plaques injected intralesionally with 1 X 10(6) U of recombinant interferon alfa-2b per site and two control plaques injected with placebo three times weekly for four consecutive weeks. Complete clinical regression of disease was observed at ten of 12 recombinant interferon alfa-2b sites compared with one of 12 placebo-treated sites four weeks after treatment with injections was stopped. Subsequently, in an open-labeled study, five of these patients were treated intramuscularly with 5 X 10(6) U of recombinant interferon alfa-2b three times weekly for four weeks and two patients were treated with a second, more extended course of therapy lasting 12 to 16 weeks. Three of the five patients treated systemically showed some improvement overall, but the responses were judged not to be clinically significant. The differential response observed from intralesional and intramuscular injections may be related to differences in concentration of recombinant interferon alfa-2b achieved in lesional skin by the two methods of administration.", "An open-labeled, randomized clinical trial to evaluate the efficacy of paromomycin ointment as compared with ketoconazole was conducted on seventy-two patients of both sexes and different ages with the confirmed diagnosis of cutaneous leishmaniasis (CL). All patients had a complete clinical evaluation for other diseases. Patients were excluded if they were pregnant or nursing or if they had serious concomitant diseases. Patients were divided randomly into two treatment groups: in the first group 40 patients were treated with an ointment containing 15% paromomycin sulfate and 12% methylbenzothonium chloride in white soft paraffin (labeled as p-ointment by El-On1) twice daily for 15 days. Treated lesions were left uncovered. The second group consisted of 32 patients who received ketoconazole 400 mg/day orally for 30 days. This dosage was reduced to 200 mg/day for patients below 12 years of age. In all cases the diagnosis was based on positive smear and/or culture. Direct smears were prepared from the exudate obtained by a small incision made at the edge of the lesion with a sterile surgical blade or lancet and stained using the Giemsa method for leishmania bodies (Fig 1). In smear negative and suspected cases aspirates taken by puncturing the lesions were inoculated onto NNN (Novy, McNeal, Nicolle) medium for culture. The cultures were incubated at 28 degrees C and the development of motile promastigotes was observed. Clinical and parasitological evaluations of the patients were performed at the end of the treatment period and 4 weeks post-treatment. A cure was defined as complete healing and disappearance of the lesion or reversible hypopigmentation at the site of lesion. Incomplete or partial improvement was defined as a reduction in the size of a lesion and the absence of parasites on smear or culture. A treatment failure was defined as the absence of any changes in the lesion and persistence of parasites on smear or culture.", "Hypericin is a known photodynamic agent that has been demonstrated to induce apoptosis in normal and malignant B and T lymphocytes, and has potential to treat benign and malignant disorders of the skin, including psoriasis and cutaneous T-cell lymphoma.\n We wished to test whether topical hypericin was an effective, safe, and well-tolerated therapy for patch or plaque phase mycosis fungoides and for plaque psoriasis.\n We conducted a phase II placebo-controlled clinical study in patients who had either patch or plaque phase mycosis fungoides or plaque type psoriasis vulgaris. Representative lesions were treated twice weekly for 6 weeks with topically applied hypericin or placebo followed 24 hours later by exposure to visible light at 8 to 20 J/cm(2).\n After 6 weeks of twice-weekly therapy, several concentrations of hypericin resulted in the significant improvement of treated skin lesions among the majority of patients with cutaneous T-cell lymphoma and psoriasis whereas the placebo vehicle was ineffective.\n The clinical trial involved a small number of patients.\n Overall, the data from this study support the conclusion that topical hypericin/visible light photodynamic therapy is an effective and well-tolerated alternative to standard psoralen plus ultraviolet A treatment of these disorders.\n Copyright © 2010 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.", "The aim of this study was to evaluate the safety, tolerability and efficacy of a topical gel containing histamine dihydrochloride (HDC) versus a placebo gel in preventing oral mucositis in hematopoietic stem cell transplantation (HSCT) patients. A total of 45 patients post-HSCT were enrolled in a prospective longitudinal, placebo-controlled, double-blind study. Patients were evaluated twice weekly for oral mucositis (OMAS, NCI score), oral pain (VAS), oral function and salivary flow rate. Compliance was assessed using a patient diary. Oral mucositis developed in 85% of the HDC group and 63% of the placebo group. The mean maximal intensity for NCI score was 1.45+/-1 in the HDC group and 1.21+/-1.27 in the placebo group (P=0.37). The mean duration of oral mucositis was 4.7+/-3.6 and 2.33+/-2.23 days in the HDC and placebo groups, respectively (P=0.06). The same trends were measured with OMAS. Visual analogue scale for oral pain and oral function was not significantly different between the two groups. Histamine dihydrochloride was found to be safe. In the search for topical agents for the prevention of mucositis, we found that HDC neither improves nor worsens oral mucositis in HSCT patients. The balance between the pro- and anti-inflammatory effects of HDC should be investigated further in order to acquire a clinically effective topical medication based on its anti-inflammatory properties.", "BACKGROUND Tinea pedis (athlete's foot) is the most common fungal infection in the general population. Ciclopirox, a broad-spectrum hydroxypyridone antifungal, has proven efficacy against the organisms commonly implicated in tinea pedis; Trichophyton rubrum, T.mentagrophytes and Epidermophyton floccosum.\n Two multicenter, double-blind, clinical studies compared the efficacy and safety of ciclopirox gel with that of its vehicle base in subjects with moderate interdigital tinea pedis with or without plantar involvement.\n Three hundred and seventy-four subjects were enrolled and randomized to one of two treatment groups: ciclopirox gel 0.77%, or ciclopirox gel vehicle, applied twice daily for 28 days, with a final visit up to day 50. The primary efficacy variable was Treatment Success defined as combined mycological cure and clinical improvement >/= 75%. Secondary measures of effectiveness were Global Clinical Response, Sign and Symptom Severity Scores, Mycological Evaluation (KOH examination and final culture result), Mycological Cure (negative KOH and negative final culture results) and Treatment Cure (combined clinical and mycological cure).\n At endpoint (final post-baseline visit), 60% of the ciclopirox subjects achieved treatment success compared to 6% of the vehicle subjects. At the same time point, 66% of ciclopirox subjects compared with 19% of vehicle subjects were either cleared or had excellent improvement. Pooled data showed that 85% of ciclopirox subjects were mycologically cured, compared to only 16% of vehicle subjects at day 43, 2 weeks post-treatment.\n Ciclopirox gel 0.77% applied twice daily for 4 weeks is an effective treatment of moderate interdigital tinea pedis due to T. rubrum, T. mentagrophytes and E. floccosum and is associated with a low incidence of minor adverse effects.", "Onychomycosis is one of the most common causes of nail disease and one of the hardest to treat among fungal infections. A double-blind, vehicle-controlled study has been conducted to evaluate the safety and efficacy of Fungoid Tincture (Pedinol Pharmacal, Inc), for the treatment of fungal infection of the toenails. Ten patients with distal subungual onychomycosis were treated for twelve months with topical Fungoid Tincture. Another ten patients with the same ailment were treated with the vehicle alone. Once a month, clinical and global evaluation of the target nail was done, in addition to trimming and debridement of the nails. After twelve months of treatment, 90 percent of patients applying Fungoid Tincture showed negative results on culture. There were minimal adverse effects.", "Mucositis occurs in almost all patients treated with radiotherapy for head and neck cancer. The aim of this multicenter, double-blind, prospective, randomized trial was to evaluate the clinical efficacy of an economically viable antimicrobial lozenge (bacitracin, clotrimazole, and gentamicin [BcoG]) in the alleviation of radiation-induced mucositis in patients with head and neck cancer.\n One hundred thirty-seven eligible patients were randomized to treatment with either antimicrobial lozenge (69 patients) or placebo lozenge (68 patients). The primary end point of the study was the time to development of severe mucositis from the start of radiotherapy. Secondary end points included severity and duration of mucositis, pain measurement, radiation therapy interruption, and quality of life. Mucositis was scored using a validated mucositis scoring system.\n Toxicity profiles were similar between the two arms of the study. The median time to development of severe mucositis from the start of radiotherapy was 3.61 weeks on BCoG and 3.96 weeks on placebo (P =.61). There were no statistically significant differences between the arms in the extent of severe mucositis as measured by physician, in oral toxicities as recorded by patients, or in radiotherapy delays.\n This study was conducted on the basis of a pilot study that demonstrated the BCoG lozenge to be tolerable and microbiologically efficacious. A validated mucositis scoring system was used. However, in this group of patients treated with conventional radiotherapy, the lozenge did not impact significantly on the severity of mucositis. Whether such a lozenge would be beneficial in treatment situations where rate of severe mucositis is higher (ie, in patients treated with unconventional fractionation or with concomitant chemotherapy) is unknown.", "A reduction of symptoms of atopic dermatitis (AD) in small infants by the administration of Lactobacillus rhamnosus has been reported in a few studies. One study with older children and adolescents failed to show any effect.\n We conducted a prospective study to reassess the efficacy of orally administered L. rhamnosus strain GG (LGG) in infants with AD.\n In a randomized, double-blind, placebo-controlled study, 54 infants aged 1-55 months with moderate to severe AD were randomized to daily 10 x 10(9) colony-forming units of LGG or to placebo during an 8-week intervention phase. Emollients, class I-II topical corticosteroids and antihistamines were permitted.\n The treatment with LGG was well tolerated. At the end of treatment there were no significant differences between the groups with respect to clinical symptoms (SCORAD, pruritus, sleep loss), the use of topical corticosteroids and antihistamines, immunological parameters, or health-related quality of life of the parents.\n Our results could not confirm LGG as an effective treatment of AD in infancy.", "In a placebo-controlled double-blind study the prophylactic value of oral systemic treatment with the antimycotic agent miconazole was assessed in 30 highly predisposed patients receiving intensive cytostatic chemotherapy because of haematological malignancies. Patients colonized with Candida before treatment were not freed from this micro-organism by miconazole treatment. However, only 3 out of 6 initially non-colonized miconazole-treated patients became colonized during the study, against 10 out of 10 placebo-treated patients (p = 0.036). Seven out of 15 patients in the placebo group developed clinical mycosis, against only two out of 15 in the miconazole group. The miconazole-treated patients remained clinically free of mycosis for 252 out of 264 treatment days, while the placebo-treated patients remained free of mycosis for only 263 out or 338 treatment days (p = 0.0001). The results indicate that systemic miconazole treatment protects highly predisposed patients from colonization with Candida and prevents or postpones clinically established candidosis." ]	This review identified trial evidence for a range of different topical and systemic interventions for mycosis fungoides. Because of substantial heterogeneity in design, small sample sizes, and low methodological quality, the comparative safety and efficacy of these interventions cannot be established on the basis of the included RCTs. Taking into account the possible serious adverse effects and the limited availability of efficacy data, topical and skin-directed treatments are recommended first, especially in the early stages of disease. More aggressive therapeutic regimens may show improvement or clearance of lesions, but they also result in more adverse effects; therefore, they are to be considered with caution. Larger studies with comparable, clearly-defined end points for all stages of mycosis fungoides, and a focus on safety, quality of life, and duration of remission as part of the outcome measures, are necessary.
CD003492	[ "6143340", "6437366", "15994710", "9004053", "6810839", "15056579" ]	[ "Continuation therapy with lithium and amitriptyline in unipolar depressive illness: a randomized, double-blind, controlled trial.", "Drug therapy in the prevention of recurrences in unipolar and bipolar affective disorders. Report of the NIMH Collaborative Study Group comparing lithium carbonate, imipramine, and a lithium carbonate-imipramine combination.", "Olanzapine versus lithium in the maintenance treatment of bipolar disorder: a 12-month, randomized, double-blind, controlled clinical trial.", "Gradual discontinuation of lithium augmentation in elderly patients with unipolar depression.", "Lithium carbonate and imipramine in the prophylaxis of unipolar and bipolar II illness: a prospective, placebo-controlled comparison.", "Relapse prevention in bipolar I disorder: 18-month comparison of olanzapine plus mood stabiliser v. mood stabiliser alone." ]	[ "A detailed analysis of the results of a multi-centre clinical trial shows that, while the relapse rate following recovery from an operationally defined depressive illness was smaller among patients subsequently treated with either amitryptiline or lithium than with a placebo, there was no clinically significant difference between the prophylactic efficacy of the 2 antidepressants. An account is given of the relative adverse effects of the treatments, and the implications of the findings are discussed.", "In a double-blind, long-term follow-up study, 117 bipolar patients received lithium carbonate, imipramine hydrochloride, or both and 150 unipolar patients received lithium carbonate, imipramine, both lithium carbonate and imipramine, or placebo. With bipolar patients, lithium carbonate and the combination treatment were superior to imipramine in preventing manic recurrences and were as effective as imipramine in preventing manic recurrences and were as effective as imipramine in preventing depressive episodes. The combination treatment provided no advantage over lithium carbonate alone. With unipolar patients, imipramine and the combination treatment were more effective than lithium carbonate and placebo in preventing depressive recurrences. The combination treatment provided no advantage over imipramine alone. The lithium carbonate-treated group had fewer manic episodes than the other groups. Treatment outcome, which was evaluated primarily in terms of the occurrence of major depression or manic episodes, was significantly related to characteristics of the index episode, ie, the episode that brought the patient into the study.", "The authors compared the efficacy of olanzapine and lithium in the prevention of mood episode relapse/recurrence.\n Patients with a diagnosis of bipolar disorder (manic/mixed), a history of two or more manic or mixed episodes within 6 years, and a Young Mania Rating Scale total score > or =20 entered the study and received open-label co-treatment with olanzapine and lithium for 6-12 weeks. Those meeting symptomatic remission criteria (Young Mania Rating Scale score < or =12; 21-item Hamilton depression scale score < or =8) were randomly assigned to 52 weeks of double-blind monotherapy with olanzapine, 5-20 mg/day (N=217), or lithium (target blood level: 0.6-1.2 meq/liter) (N=214).\n Symptomatic relapse/recurrence (score > or =15 on either the Young Mania Rating Scale or Hamilton depression scale) occurred in 30.0% of olanzapine-treated and 38.8% of lithium-treated patients. The noninferiority of olanzapine relative to lithium (primary objective) in preventing relapse/recurrence was met, since the lower limit of the 95% confidence interval on the 8.8% risk difference (-0.1% to 17.8%) exceeded the predefined noninferiority margin (-7.3%). Secondary results showed that compared with lithium, olanzapine had significantly lower risks of manic episode and mixed episode relapse/recurrence. Depression relapse/recurrence occurred in 15.7% of olanzapine-treated and 10.7% of lithium-treated patients. Mean weight gain during open-label co-treatment was 2.7 kg; during double-blind monotherapy, weight gain was significantly greater with olanzapine (1.8 kg) than with lithium (-1.4 kg).\n These results suggest that olanzapine was significantly more effective than lithium in preventing manic and mixed episode relapse/recurrence in patients acutely stabilized with olanzapine and lithium co-treatment. Both agents were comparable in preventing depression relapse/recurrence.", "Recently, the therapeutic benefit of lithium augmentation in old age has come into question. These data, in light of the documented high incidence of side effects after lithium use in elderly patients, resulted in the design of a prospective, placebo-controlled lithium augmentation withdrawal study in elderly patients with unipolar depression. Twelve eligible geriatric patients (10 women and 2 men; mean [+/-SD] age, 76.2 +/- 5.7 years) with DSM-III-R unipolar depression receiving adjunct lithium therapy were randomized to receive continued lithium augmentation or matching placebo (withdrawal rate 150 mg/day/wk). At each clinic visit, patients were assessed for depression (Montgomery-Asberg Depression Rating Scale and Geriatric Depression Rating Scale) and lithium-induced toxicities (a 21-item side-effect checklist, renal and thyroid biochemistry). Over the 2-year observation period, the placebo group reported a decrease in composite 21-item side-effect score and specific lithium toxicities (e.g., urinary urgency, hand tremor, and renal/thyroid abnormalities). Two patients in the lithium maintenance group had a recurrence of depression at 61 and 96 weeks, respectively, immediately after a stressful life event (cerebrovascular accident [CVA] or death of spouse), and two patients had a recurrence in the placebo group at 7 and 92 weeks, respectively, without any apparent changes in life stresses. No other prognostic risk factors for recurrence were identified. Depression that recurred in patients who were receiving placebo was relatively resistant to reinstitution of lithium augmentation therapy. In otherwise stable geriatric patients with unipolar depression, the documented benefits of reduced side effects should be weighed against the risk of recurrence and subsequent lithium resistance before withdrawal of lithium augmentation.", "Twenty-seven patients with recurrent unipolar depression and 22 with bipolar II illness in remission for at least six months were randomly assigned on a double-blind basis to treatment regimens using lithium carbonate, imipramine hydrochloride, lithium carbonate plus imipramine, or placebo. Lithium carbonate was found to help prevent depressive relapse among patients with unipolar disease, and relapse of any type among those with bipolar II disease. No effect or interaction of imipramine was found in either group. These results add to a growing body of data that suggest the usefulness of lithium carbonate in the prophylaxis of unipolar depressive illness. The relative usefulness of lithium carbonate and imipramine requires further study.", "Few controlled studies have examined the use of atypical antipsychotic drugs for prevention of relapse in patients with bipolar I disorder. Aims To evaluate whether olanzapine plus either lithium or valproate reduces the rate of relapse, compared with lithium or valproate alone.\n Patients achieving syndromic remission after 6 weeks'treatment with olanzapine plus either lithium (0.6-1.2 mmol/l) or valproate (50-125 microg/ml) received lithium or valproate plus either olanzapine 5-20 mg/day (combination therapy) or placebo (monotherapy), and were followed in a double-masked trial for 18 months.\n The treatment difference in time to relapse into either mania or depression was not significant for syndromic relapse (median time to relapse: combination therapy 94 days, monotherapy 40.5 days; P=0.742), but was significant for symptomatic relapse (combination therapy 163 days, monotherapy 42 days; P=0.023).\n Patients taking olanzapine added to lithium or valproate experienced sustained symptomatic remission, but not syndromic remission, for longer than those receiving lithium or valproate monotherapy." ]	There was adequate efficacy evidence for lithium or antidepressants preventing relapse in unipolar affective disorder, however their relative efficacy was unknown. When considering lithium or antidepressant long-term therapy, patients and clinicians should take into account the patient's clinical history, the side-effects and the individual's likely adherence to the recommended treatment regime. Large-scale, long-term randomised trials in unselected groups of subjects with unipolar affective disorder are needed.
CD006818	[ "11099583" ]	[ "Baby CareLink: using the internet and telemedicine to improve care for high-risk infants." ]	[ "To evaluate an Internet-based telemedicine program designed to reduce the costs of care, to provide enhanced medical, informational, and emotional support to families of very low birth weight (VLBW) infants during and after their neonatal intensive care unit (NICU) stay.\n Baby CareLink is a multifaceted telemedicine program that incorporates videoconferencing and World Wide Web (WWW) technologies to enhance interactions between families, staff, and community providers. The videoconferencing module allows virtual visits and distance learning from a family's home during an infant's hospitalization as well as virtual house calls and remote monitoring after discharge. Baby CareLink's WWW site contains information on issues that confront these families. In addition, its security architecture allows efficient and confidential sharing of patient-based data and communications among authorized hospital and community users.\n A randomized trial of Baby CareLink was conducted in a cohort of VLBW infants born between November 1997 and April 1999. Eligible infants were randomized within 10 days of birth. Families of intervention group infants were given access to the Baby CareLink telemedicine application. A multimedia computer with WWW browser and videoconferencing equipment was installed in their home within 3 weeks of birth. The control group received care as usually practiced in this NICU. Quality of care was assessed using a standardized family satisfaction survey administered after discharge. In addition, the effect of Baby CareLink on hospital length of stay as well as family visitation and interactions with infant and staff were measured.\n Of the 176 VLBW infants admitted during the study period, 30 control and 26 study patients were enrolled. The groups were similar in patient and family characteristics as well as rates of inpatient morbidity. The CareLink group reported higher overall quality of care. Families in the CareLink group reported significantly fewer problems with the overall quality of care received by their family (mean problem score: 3% vs 13%). In addition, CareLink families also reported greater satisfaction with the unit's physical environment and visitation policies (mean problem score: 13% vs 50%). The frequency of family visits, telephone calls to the NICU, and holding of the infant did not differ between groups. The duration of hospitalization until ultimate discharge home was similar in the 2 groups (68.5 +/- 28.3 vs 70.6 +/- 35.6 days). Among infants born weighing <1000 g (n = 31) there was a tendency toward shorter lengths of stay (77.4 +/- 26.2 vs 93.1 +/- 35.6 days). All infants in the CareLink group were discharged directly to home whereas 6/30 (20%) of control infants were transferred to community hospitals before ultimate discharge home.\n CareLink significantly improves family satisfaction with inpatient VLBW care and definitively lowers costs associated with hospital to hospital transfer. Our data suggest the use of telemedicine and the Internet support the educational and emotional needs of families facilitating earlier discharge to home of VLBW infants. We believe that further extension of the Baby CareLink model to the postdischarge period will significantly improve the coordination and efficiency of care." ]	There is insufficient evidence to support or refute the use of telemedicine technology to support the parents of high-risk newborn infants receiving intensive care. Clinical trials are needed to assess the application of telemedicine to support parents and families of infants in NICU with length of hospital stay and their perception of NICU care as the major outcomes.
CD004248	[ "16772251", "10190777", "11936063", "10416558", "9475639", "11371683" ]	[ "Effects of a supervised home-based aerobic and progressive resistance training regimen in women infected with human immunodeficiency virus: a randomized trial.", "Moderate and high intensity exercise training in HIV-1 seropositive individuals: a randomized trial.", "Effectiveness of a home-based exercise intervention for HIV-infected adults: a randomized trial.", "Cardiopulmonary and CD4 cell changes in response to exercise training in early symptomatic HIV infection.", "The effect of exercise training on aerobic fitness, immune indices, and quality of life in HIV+ patients.", "Aerobic exercise: effects on parameters related to fatigue, dyspnea, weight and body composition in HIV-infected adults." ]	[ "Women infected with human immunodeficiency virus (HIV) increasingly demonstrate abnormalities in fat distribution and metabolism; however, the effects of a home-based exercise regimen in this group have not been investigated.\n We conducted a 16-week randomized intervention study of a supervised home-based progressive resistance training and aerobic exercise program in 40 HIV-infected women with increased waist-hip ratio and self-reported fat redistribution. Cross-sectional muscle area and muscle attenuation were measured by computed tomography. Cardiorespiratory fitness was determined by calculated maximum oxygen consumption (VO2max) and strength by 1-repetition maximum.\n Cardiorespiratory fitness (VO2max) was markedly lower at baseline (median [95% confidence interval], 15.4 [8.3-25.2] mL x kg(-1) x min(-1)) than reported values for healthy female subjects (26-35 mL x kg(-1) x min(-1)). Subjects randomized to exercise had significant improvement in mean +/- SEM VO2max (1.5 +/- 0.8 vs -2.5 +/- 1.6 mL x kg(-1) x min(-1); P<.001) and endurance (1.0 +/- 0.3 vs -0.6 +/- 0.3 minute; P<.001). Strength increased at the knee extensors, pectoralis, knee flexors, shoulder abductors, ankle plantar flexors, and elbow flexors (all P<.001). Total muscle area (6 +/- 1 vs 2 +/- 1 cm2; P = .02) and attenuation (2 +/- 1 vs -1 +/- 1 Hounsfield unit; P = .03) increased in the exercise group. No significant difference was seen in lipid levels, blood pressure, or abdominal visceral fat between the groups, but subjects randomized to exercise reported improved energy and appearance.\n A 16-week, supervised, home-based exercise regimen improved measures of physical fitness in HIV-infected women. The effects on strength were most significant, but improvements in cardiorespiratory fitness, endurance, and body composition were also seen.", "HIV-infected individuals are frequently active, but guidelines for exercise in this population lack scientific support, since studies on the effects of exercise training on immunologic variables of HIV-1 positive individuals have shown conflicting results. Exercise capacity, immunologic markers (CD4, CD8 and CD4:CD8 ratio), anthropometric measurements, and depression scores were evaluated to compare the effects of two intensities of aerobic exercise on HIV-1 seropositive individuals. Twenty-one healthy subjects (14 men, 7 women), carriers of the HIV-1 virus (CD4>200 cells x mm(-3)), and inactive for at least 6 months, completed a 12 week exercise training program (36 sessions of 1 h, 3 times per week), in a moderate intensity group (60+/-4% of maximal heart rate) or a high intensity group (84+/-4% of maximal heart rate). Exercise capacity estimated by treadmill time was increased significantly in both moderate intensity (680+/-81 s before; 750+/-151 s after) and high intensity (651+/-122 s before; 841+/-158 s after) groups, but the high intensity group presented a significantly larger increment (p<0.01). There were no significant changes in the immunologic variables, anthropometric measurements or depression scores. Thus, HIV-seropositive individuals that participate in moderate and high intensity exercise programs are able to increase their functional capacity without any detectable changes in immunologic variables, anthropometric measurements or depression scores.", "The authors conducted a randomized controlled trial to assess the impact of a 15-week (20 minutes three times per week) home-based aerobic exercise intervention versus usual care on the physical endurance, immune status, and self-reported health status of 99 HIV-infected adults. In the exercise group, there was no improvement in physical endurance or health-related quality of life (HRQOL), except in the Medical Outcomes Study-HIV Health Survey Overall Health subscale (difference = 12.1, 95% confidence interval = 2.0-22.2, p = .02). Although physical endurance levels were maintained at baseline levels in the intervention group and declined in the control group, differences between the groups were small and not significant. There were also no significant changes in CD4+ T-lymphocyte counts. Exercise appears to be safe in HIV-infected patients. Improvements in physical endurance and HRQOL might result if the exercise protocol is longer or progressive. Further research is needed to establish guidelines for exercise in patients on highly active antiretroviral therapy.", "The purposes of the present study were to assess the effects of a 12-wk laboratory based aerobic exercise program on cardiopulmonary function, CD4 cell count, and physician-assessed health status among symptomatic pre-AIDS HIV-infected individuals (N = 28) and to assess the degree to which ill health was associated with exercise relapse.\n Responses to graded exercise test, physician-assessed health status, and CD4 cell counts were determined at baseline and 12-wk follow-up for participants randomly assigned to exercise or control conditions, and reasons for exercise noncompliance were recorded.\n Approximately 61% of exercise-assigned participants complied (> 50% attendance) with the exercise program, and analyses of exercise relapse data indicated that obesity and smoking status, but not exercise-associated illness, differentiated compliant from noncompliant exercisers. Compliant exercisers significantly improved peak oxygen consumption (VO2peak; 12%), oxygen pulse (O2pulse; 13%), tidal volume (TV; 8%), ventilation (VE; 17%), and leg power (25%) to a greater degree than control participants and noncompliant exercisers (all P < 0.05). Although no group differences in health status were found, a significant interaction effect indicated that noncompliant exercisers' CD4 cells declined (18%) significantly, whereas compliant exercisers' cell counts significantly increased (13%; P < 0.05).\n We conclude that although aerobic exercise can improve cardiopulmonary functioning in symptomatic HIV-infected individuals with minimal health risks, attention to factors associated with exercise adherence is warranted.", "Thirty four HIV+ patients participated in a 6-wk aerobic exercise training program to determine whether exercise improved aerobic fitness, immune indices, and quality of life.\n Subjects were assigned to three groups: control (no regular aerobic exercise), moderate exercise, and heavy exercise training. At study entry and exit (in each subject) we evaluated aerobic function with a symptom limited cardiopulmonary exercise test, immune indices with CD4 counts and Candida skin tests, viral replication with plasma HIV RNA measurements, and quality of life with a HIV+ population validated questionnaire.\n Aerobic fitness increased significantly in both exercise groups relative to the control group; immune indices changed very little among all three groups; however, the Candida skin tests (mm2) increased significantly in the moderate group; viral replication was essentially unchanged in all three groups; quality of life (QOL) markers improved in both exercising groups but not the control group. There were no opportunistic infections during the study.\n Exercise training resulted in a substantial improvement in aerobic function while immune indices were essentially unchanged. Quality of life markers improved significantly with exercise. Exercise training is safe and effective in this patient group and should be promoted for HIV+ patients.", "The purpose of the study was to examine the effects of aerobic exercise on physiological fatigue (time on treadmill), dyspnea [rate of perceived exertion (RPE) and forced expiratory volume at 1 s (FEV1)], weight, and body composition in HIV-1-infected adults (200-499 x 106 CD4+ cells/l).\n The study was a randomized, wait-listed, controlled clinical trial of aerobic exercise in HIV-1-infected adults on signs and symptoms associated with HIV-1 infection or its treatment.\n Sixty subjects were recruited and randomized to two groups. Experimental subjects completed a 12-week supervised exercise program. Control subjects continued usual activity from baseline to week 12 and were then were enrolled in the exercise program.\n At baseline, the groups were similar in age, weight, body mass index [mean body mass index (BMI) > 27], time since diagnosis, number of symptoms, CD4+ cell count, and number on protease inhibitor therapy (n = 7). Despite disproportionate attrition from the exercise group (38%), exercise subjects were able to remain on the treadmill longer, lost weight, decreased BMI, subcutaneous fat, and abdominal girth when compared to controls. The improvement in weight and body composition occurred without a decrease in kilocalories consumed. Exercise did not seem to have an effect on RPE, a surrogate for dyspnea, and FEV1. There was no significant difference in either the change in CD4+ cell count, percentage or copies of plasma HIV-1 RNA between groups.\n We conclude that supervised aerobic exercise training safely decreases fatigue, weight, BMI, subcutaneous fat and abdominal girth (central fat) in HIV-1-infected individuals. It did not appear to have an effect on dyspnea." ]	Progressive resistive exercise or a combination of progressive resistive exercise and aerobic exercise appear to be safe and may be beneficial for adults living with HIV/AIDS. These findings are limited by the small number of studies that could be included in meta-analyses, small sample sizes and variable participant withdrawal rates among included studies. Future research would benefit from including participants at various stages of HIV infection, a greater proportion of female participants, and participants in a variety of age groups to increase the generalizability of results. Furthermore, future research would benefit from studies with larger sample sizes that conduct an "intention-to-treat" analysis (analysis of participants based on the groups to which they were originally allocated) to better understand outcomes of participants that withdraw from exercise interventions.
CD003134	[ "19996196", "19570573", "14711911", "15665326", "10528036", "1859050", "2863676", "18399862", "7589382", "16162746", "15894479", "9301350", "18669816" ]	[ "Pirfenidone in idiopathic pulmonary fibrosis.", "Effect of interferon gamma-1b on survival in patients with idiopathic pulmonary fibrosis (INSPIRE): a multicentre, randomised, placebo-controlled trial.", "A placebo-controlled trial of interferon gamma-1b in patients with idiopathic pulmonary fibrosis.", "Double-blind, placebo-controlled trial of pirfenidone in patients with idiopathic pulmonary fibrosis.", "A preliminary study of long-term treatment with interferon gamma-1b and low-dose prednisolone in patients with idiopathic pulmonary fibrosis.", "Azathioprine combined with prednisone in the treatment of idiopathic pulmonary fibrosis: a prospective double-blind, randomized, placebo-controlled clinical trial.", "Alternate-day prednisone reduces morbidity and improves pulmonary function in cystic fibrosis.", "Effects of pulmonary rehabilitation in patients with idiopathic pulmonary fibrosis.", "Recombinant human DNase I in cystic fibrosis patients with severe pulmonary disease: a short-term, double-blind study followed by six months open-label treatment.", "Anticoagulant therapy for idiopathic pulmonary fibrosis.", "Effects of inhaled HFA beclomethasone on pulmonary function and symptoms in patients with chronic obstructive pulmonary disease.", "Randomised controlled trial of inhaled corticosteroids (fluticasone propionate) in cystic fibrosis.", "Treatment of idiopathic pulmonary fibrosis with etanercept: an exploratory, placebo-controlled trial." ]	[ "Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease without proven effective therapy. A multicentre, double-blind, placebo-controlled, randomised phase III clinical trial was conducted in Japanese patients with well-defined IPF to determine the efficacy and safety of pirfenidone, a novel antifibrotic oral agent, over 52 weeks. Of 275 patients randomised (high-dose, 1,800 mg x day(-1); low-dose, 1,200 mg x day(-1); or placebo groups in the ratio 2:1:2), 267 patients were evaluated for the efficacy of pirfenidone. Prior to unblinding, the primary end-point was revised; the change in vital capacity (VC) was assessed at week 52. Secondary end-points included the progression-free survival (PFS) time. Significant differences were observed in VC decline (primary end-point) between the placebo group (-0.16 L) and the high-dose group (-0.09 L) (p = 0.0416); differences between the two groups (p = 0.0280) were also observed in the PFS (the secondary end-point). Although photosensitivity, a well-established side-effect of pirfenidone, was the major adverse event in this study, it was mild in severity in most of the patients. Pirfenidone was relatively well tolerated in patients with IPF. Treatment with pirfenidone may decrease the rate of decline in VC and may increase the PFS time over 52 weeks. Additional studies are needed to confirm these findings.", "Idiopathic pulmonary fibrosis is a fatal disease for which no effective treatment exists. We assessed whether treatment with interferon gamma-1b improved survival compared with placebo in patients with idiopathic pulmonary fibrosis and mild-to-moderate impairment of pulmonary function.\n 826 patients with idiopathic pulmonary fibrosis were enrolled from 81 centres in seven European countries, the USA, and Canada. Patients were randomly assigned (double-blind) in a 2:1 ratio to receive 200 microg interferon gamma-1b (n=551) or equivalent placebo (n=275) subcutaneously, three times per week. Eligible patients were aged 40-79 years, had been diagnosed in the past 48 months, had a forced vital capacity of 55-90% of the predicted value, and a haemoglobin-corrected carbon monoxide diffusing capacity of 35-90% of the predicted value. The primary endpoint was overall survival time from randomisation measured at the second interim analysis, when the proportion of deaths had reached 75% of those expected by the study conclusion. This study is registered with ClinicalTrials.gov, number NCT00075998.\n At the second interim analysis, the hazard ratio for mortality in patients on interferon gamma-1b showed absence of minimum benefit compared with placebo (1.15, 95% CI 0.77-1.71, p=0.497), and indicated that the study should be stopped. After a median duration of 64 weeks (IQR 41-84) on treatment, 80 (15%) patients on interferon gamma-1b and 35 (13%) on placebo had died. Almost all patients reported at least one adverse event, and more patients on interferon gamma-1b group had constitutional signs and symptoms (influenza-like illness, fatigue, fever, and chills) than did those on placebo. Occurrence of serious adverse events (eg, pneumonia, respiratory failure) was similar for both treatment groups. Treatment adherence was good and few patients discontinued treatment prematurely in either group.\n We cannot recommend treatment with interferon gamma-1b since the drug did not improve survival for patients with idiopathic pulmonary fibrosis, which refutes previous findings from subgroup analyses of survival in studies of patients with mild-to-moderate physiological impairment of pulmonary function.\n InterMune.", "Idiopathic pulmonary fibrosis is a progressive, fatal disease with no known efficacious therapy.\n In a double-blind, multinational trial, we randomly assigned 330 patients with idiopathic pulmonary fibrosis that was unresponsive to corticosteroid therapy to receive subcutaneous interferon gamma-1b or placebo.\n Over a median of 58 weeks, interferon gamma-1b therapy did not significantly affect the primary end point of progression-free survival, defined as the time to disease progression or death, and no significant treatment effect was observed on measures of lung function, gas exchange, or the quality of life. Ten percent of patients in the interferon gamma-1b group died, as compared with 17 percent of patients in the placebo group (P=0.08). Treatment with interferon gamma-1b was associated with more frequent constitutional symptoms. However, the rates of treatment adherence and premature discontinuation of treatment were similar in the two groups. More pneumonias were reported among patients in the interferon gamma-1b group, but the incidence of severe or life-threatening respiratory tract infections was similar in the two groups.\n In a well-defined population of patients with idiopathic pulmonary fibrosis, interferon gamma-1b did not affect progression-free survival, pulmonary function, or the quality of life. Owing to the size and duration of the trial, a clinically significant survival benefit could not be ruled out.\n Copyright 2004 Massachusetts Medical Society", "Idiopathic pulmonary fibrosis (IPF) is a fatal disorder without an effective therapy to date. In a double-blind, randomized, placebo-controlled trial, 107 patients were prospectively evaluated for efficacy of a novel compound, pirfenidone. The difference in the change in the lowest oxygen saturation by pulse oximetry (SpO2) during a 6-minute exercise test, the primary endpoint, from baseline to 6 months was not significant between the two groups (p = 0.0722). In a prespecified subset of patients who maintained a SpO2 greater than 80% during a 6-minute exercise test at baseline, the lowest SpO2 improved during a 6-minute exercise test in the pirfenidone group at 6 and 9 months (p = 0.0069 and 0.0305, respectively). Positive treatment effect was demonstrated in secondary endpoints: (1) change in VC measurements at 9 months (p = 0.0366) and (2) episodes of acute exacerbation of IPF occurring exclusively in the placebo group during the 9 months (p = 0.0031). Significant adverse events were associated with pirfenidone; however, adherence to treatment regimen was similar between pirfenidone and placebo groups. In conclusion, treatment with pirfenidone improved VC and prevented acute exacerbation of IPF during the 9 months of follow-up. Future long-term studies are needed to clarify the overall safety and efficacy of pirfenidone in IPF.", "Patients with idiopathic pulmonary fibrosis have progressive scarring of the lung and usually die within four to five years after symptoms develop. Treatment with oral glucocorticoids is often ineffective. We conducted an open, randomized trial of treatment with a combination of interferon gamma-1b, which has antifibrotic properties, and an oral glucocorticoid. We studied 18 patients with idiopathic pulmonary fibrosis who had not had responses to glucocorticoids or other immunosuppressive agents. Nine patients were treated for 12 months with oral prednisolone alone (7.5 mg daily, which could be increased to 25 to 50 mg daily), and nine with a combination of 200 microg of interferon gamma-1b (given three times per week subcutaneously) and 7.5 mg of prednisolone (given once a day).\n All the patients completed the study. Lung function deteriorated in all nine patients in the group given prednisolone alone: total lung capacity decreased from a mean (+/-SD) of 66+/-8 percent of the predicted value at base line to 62+/-6 percent at 12 months. In contrast, in the group receiving interferon gamma-1b plus prednisolone, total lung capacity increased (from 70+/-6 percent of the predicted value at base line to 79+/-12 percent at 12 months, P<0.001 for the difference between the groups). In the group that received interferon gamma-1b plus prednisolone, the partial pressure of arterial oxygen at rest increased from 65+/-9 mm Hg at base line to 76+/-8 mm Hg at 12 months, whereas in the group that received prednisolone alone it decreased from 65+/-6 to 62+/-4 mm Hg (P<0.001 for the difference in the change from baseline values between the two groups); on maximal exertion, the value increased from 55+/-6 to 65+/-8 mm Hg in the group that received combined treatment and decreased from 55+/-6 mm Hg to 52+/-5 mm Hg in the group given prednisolone alone (P<0.001). The side effects of interferon gamma-1b, such as fever, chills, and muscle pain, subsided within the first 9 to 12 weeks.\n In a preliminary study, 12 months of treatment with interferon gamma-1b plus prednisolone was associated with substantial improvements in the condition of patients with idiopathic pulmonary fibrosis who had had no response to glucocorticoids.", "Twenty-seven newly diagnosed patients with idiopathic pulmonary fibrosis (IPF) who were previously untreated for IPF were enrolled in a prospective, double-blind, randomized, placebo-controlled study to compare the therapeutic effect of combined prednisone/azathioprine (n = 14) with prednisone plus placebo (n = 13). Prednisone was started at 1.5 mg/kg/day (not to exceed 100 mg/day) for the first 2 wk followed by a biweekly taper to a maintenance dose of 20 mg/day. Azathioprine was administered at a daily dose of 3 mg/kg (not to exceed 200 mg/day). The patients tolerated the use of azathioprine well with few associated side effects. Changes in lung function at 1 yr, as measured by resting alveolar-arterial oxygen difference P[A-a]O2, FVC, and single breath diffusing capacity for carbon monoxide (DLCOSB), were all somewhat better in the azathioprine/prednisone group compared with the prednisone alone group, although none of these comparisons were statistically significant. Six of 14 (43%) patients randomized to prednisone plus azathioprine died during the 9-yr follow-up period, compared with 10 of 13 (77%) patients randomized to prednisone plus placebo. A Cox model survival analysis shows a nonsignificant but potentially large survival advantage for azathioprine/prednisone (hazard ratio 0.48, with 95% confidence interval increasing from 0.17 to 1.38). When adjusted for age, the survival advantage of azathioprine/prednisone becomes marginally significant (hazard ratio 0.26, with 95% confidence interval increasing from 0.08 to 0.88; p = 0.02 by large sample approximation, p = 0.05 by randomization test). We conclude that combined prednisone and azathioprine is a safe and possibly effective regimen for the treatment of IPF.(ABSTRACT TRUNCATED AT 250 WORDS)", "A randomised, double-blind, placebo-controlled study examined the effects of alternate-day prednisone therapy on morbidity and progression of lung disease in cystic fibrosis (CF). At baseline the patients (aged 1-12 years) had mild to moderate lung disease, and the prednisone group did not differ significantly from the placebo group for any values measured. After 4 years, the prednisone-treated group had significant advantages over the placebo group for height, weight, vital capacity, forced expiratory volume in 1 s, peak flow rate, erythrocyte sedimentation rate, and serum IgG. The prednisone-treated group required 9 admissions to hospital for CF-related pulmonary disease compared with 35 for the placebo group. There were no steroid-induced side-effects. To rule out bias in case selection, 69 CF clinic patients comparable in age and clinical status but not included in the study were compared with the placebo group at 4 years; no significant differences between the groups were found.", "Although pulmonary rehabilitation is effective for patients with COPD, its efficacy in patients with IPF is unknown. The purpose of this study was to evaluate the effects of pulmonary rehabilitation in IPF.\n Thirty patients diagnosed with IPF, according to the consensus statement, were randomly assigned to the rehabilitation group or the control group. The pulmonary rehabilitation mainly consisted of a 10-week programme of exercise training. Pulmonary function, blood gas analysis, 6MWD, dyspnoea rating with the baseline dyspnoea index and health-related quality of life score on the St George's Respiratory Questionnaire were evaluated at baseline and after the programme.\n Assessment of efficacy was carried out on 13 patients who completed the programme and 15 patients in the control group. There were no significant effects of the programme on measures of pulmonary function, values of arterial blood gas analysis or dyspnoea rating. Although there were some differences in the baseline 6MWD and total health-related quality of life score which were not statistically significant, marked improvements were observed in the 6MWD (mean difference 46.3 m (95% CI: 8.3-84.4), P < 0.05) and the total health-related quality of life score (-6.1 (95% CI: -11.7 to -0.5), P < 0.05).\n Pulmonary rehabilitation improves both exercise capacity and health-related quality of life in patients with IPF.", "Chronic pulmonary infection is the major cause of morbidity and mortality in cystic fibrosis (CF). Recombinant human deoxyribonuclease (rhDNase) in vitro has been shown to dramatically reduce the viscoelasticity of the sputum from CF patients. Phase II and III clinical trials have shown the drug to be safe, and that patients with a forced vital capacity (FVC) of > 40% predicted show an improvement in pulmonary function when receiving rhDNase. The current study evaluates the safety and efficacy of rhDNase in the most severly ill CF patients (FVC < 40% predicted). A double-blind, randomized, placebo-controlled trial in which patients received either 2.5 mg rhDNase twice daily or placebo for a period of 14 days followed by a 6 month open extension period (OEP) is reported. Seventy patients were recruited for the double-blind study, and 64 entered the OEP of whom 38 completed. During the OEP, all patients received 2.5 mg rhDNase twice daily. In both the double-blind period and the OEP the drug appeared to be safe. During the double-blind study, forced expiratory volume in one second (FEV1) and FVC improved in both groups but there was no statistically significant difference between the groups. In the OEP, there was mean improvement in percentage predicted FEV1 and FVC, 9 and 18%, respectively, for all patients participating. In conclusion, DNase is safe when administered in conjunction with a rigorous regimen of chest physiotherapy to severely ill patients (FVC < 40% predicted) with CF. The double-blind, 14 day study showed no significant improvement in pulmonary function but some patients may have improved after longer administration of rhDNase.", "To evaluate the effect of anticoagulant therapy on the survival of patients with idiopathic pulmonary fibrosis (IPF).\n Prospective study.\n Five hospitals located in the Miyagi prefecture in Japan, including a university hospital, a Red Cross hospital, two public general hospitals, and a municipal hospital.\n Fifty-six patients with IPF (mean age, 69.4 years; range, 47 to 89) admitted to the hospitals from April 2001 to April 2004.\n Patients were assigned to receive prednisolone alone or prednisolone plus anticoagulant therapy. The anticoagulants included oral warfarin in an outpatient setting and low-molecular-weight heparin for rehospitalized patients with severely progressive respiratory failure.\n There was no difference in baseline characteristics, including age, gender, clinical condition, pulmonary function, and plasma d-dimer level between the non-anticoagulant group and the anticoagulant group. The overall survival and hospitalization-free periods were assessed. There was a significant difference between survival curves of the non-anticoagulant group and the anticoagulant group, with a 2.9 hazard ratio (p = 0.04, Cox regression model). There was no significant difference in the probability of a hospitalization-free period between groups. The major cause of clinical deterioration was acute exacerbation during follow-up in the present study. Therefore, the mortality and plasma d-dimer levels in patients with an acute exacerbation were also assessed. The mortality associated with acute exacerbations of IPF in the anticoagulant group was significantly reduced compared to that in the non-anticoagulant group (18% vs 71%, respectively; p = 0.008, Fisher Exact Test). Furthermore, the plasma d-dimer levels in patients who died were significantly higher than those in survivors during acute exacerbation of IPF (3.3 +/- 2.3 microg/mL vs 0.9 +/- 0.7 microg/mL, p < 0.0001). Histologic analysis performed in three patients who died due to an exacerbation of IPF in the non-anticoagulant group demonstrated the features of usual interstitial pneumonia and acute lung injury.\n Our data suggested that plasma d-dimer levels are associated with mortality in patients with an acute exacerbation of IPF, and that anticoagulant therapy has a beneficial effect on survival in patients with IPF.", "Chronic obstructive pulmonary disease is characterized by progressive airflow limitation and pulmonary inflammation. Inhaled corticosteroids (ICS) have been shown to be effective in the reduction of the number of exacerbations and the rate of deterioration in health status in patients with more advanced chronic obstructive pulmonary disease (COPD). Therefore current international guidelines recommend ICS for patients with severe COPD (FEV1 < 50%) with at least one exacerbation within the last year. We determined the short-term effect of the inhaled corticosteroid beclomethasone in HFA 134 formulation (Ventolair) on Health related Quality of Life (HRQOL), pulmonary function and the release of the cytokines Interleukin-10 (IL-10), Granulocyte-Macrophage Colony-stimulating Factor (GM-CSF), Interferon-gamma (IFN-gamma) and Macrophage Inflammatory Protein-1alpha (MIP-1alpha) from peripheral blood monocytes of patients with COPD (n = 11) in a 12 week double blind cross over placebo-controlled study. Baseline lung function and the St. George Respiratory Questionnaire (SGRQ) were performed at the start and the end of each treatment phase. Monocytes were separated from blood at the end of each treatment phase. The treatment with Ventolair) resulted in an increase of PEF from 4.92 to 5.53 l/s and a decrease of RV% TLC (% predicted) values from 144.52 to 131.36. Inhaled HFA beclomethasone did not affect the cytokine release of IL-10, IFN-gamma, GM-CSF and MIP-1alpha. All cytokines were measured using commercially available Enzyme Linked Immun Sorbent Assay (ELISA) kits. The symptom score of the St. George Respiratory Questionnaire significantly decreased from 55.12 to 47.77 units in the active period compared to the placebo period after the treatment with HFA beclomethasone. The present study shows that a short-term treatment with inhaled steroid beclomethasone in fine particle HFA formulation decreases the hyperinflation and improves the PEF and the COPD symptoms.", "Controlling lung inflammation may be the key to improving morbidity and mortality in cystic fibrosis.\n To assess the effects of inhaled corticosteroids on lung inflammation in cystic fibrosis.\n Double blind placebo controlled randomised sequence crossover trial. Fluticasone propionate (400 micrograms/day) was given as a dry powder inhaler for six weeks with a four week washout period before crossover.\n Sputum inflammatory markers (interleukin-8, tumour necrosis factor-alpha (TNF-alpha) and neutrophil elastase-both free and bound to alpha 1-antiprotease), sputum interleukin-10, lung function, and symptomatology.\n Twenty three children from a regional cystic fibrosis centre were enrolled into the study, with mean age 10.3 years (range 7 to 17 years) and mean baseline forced expiratory volume in one second (FEV1) of 64% (range 21% to 102%) predicted for sex and height. One patient was excluded for non-compliance to the study protocol.\n No significant benefit was shown for the use of fluticasone propionate in any of the outcomes. For sputum interleukin-8 there was an estimated true treatment median difference of 142 pg/ml (95% confidence interval (CI) 8 to 2866 pg/ml) in favour of placebo; while for maximal expiratory flow at 25% (MEF25%) remaining forced vital capacity predicted for sex and height there was a 15 percentage points (pp) (95% CI 4 to 26 pp) mean treatment difference in favour of placebo. Sputum interleukin-10 was undetected in any samples and unaffected by fluticasone propionate. Neither atopic status, baseline FEV1, nor concomitant DNase therapy had any effect on response to treatment.\n Lack of benefit from fluticasone propionate was most likely due to failure of the drug to penetrate the viscid mucus lining the airways. It is suggested a large multicentre trial with higher doses given for a longer time by a different delivery system is required to assess efficacy.", "An efficacious medical therapy for idiopathic pulmonary fibrosis (IPF) remains elusive.\n To explore the efficacy and safety of etanercept in the treatment of IPF.\n This was a randomized, prospective, double-blind, placebo-controlled, multicenter exploratory trial in subjects with clinically progressive IPF. Primary endpoints included changes in the percentage of predicted FVC and lung diffusing capacity for carbon monoxide corrected for hemoglobin (Dl(CO(Hb))) and change in the alveolar to arterial oxygen pressure difference P(a-a)(O(2)) at rest from baseline over 48 weeks.\n Eighty-eight subjects received subcutaneous etanercept (25 mg) or placebo twice weekly as their sole treatment for IPF. No differences in baseline demographics and disease status were detected between treatment groups; the mean time from first diagnosis was 13.6 months and mean FVC was 63.9% of predicted. At 48 weeks, no significant differences in efficacy endpoints were observed between the groups. A nonsignificant reduction in disease progression was seen in several physiologic, functional, and quality-of-life endpoints among subjects receiving etanercept. There was no difference in adverse events between treatment groups.\n In this exploratory study in patients with clinically progressive IPF, etanercept was well tolerated. Although there were no differences in the predefined endpoints, a decreased rate of disease progression was observed on several measures. Further evaluation of TNF antagonists in the treatment of IPF may be warranted. Clinical trial registered with www.clinicaltrials.gov (NCT 00063869)." ]	Based on available data, partly still unpublished, pirfenidone appears to improve progression-free survival and, to a lesser extent, pulmonary function in patients with idiopathic pulmonary fibrosis. More data are needed on overall survival and quality of life on treatment. From the studies in this review, interferon gamma-1beta has not been shown to affect survival. Other agents evaluated in single studies either failed to provide evidence for a benefit or need to be assessed in larger randomised controlled trials.
CD002296	[ "14707396", "8328732", "1742504", "8607484", "2904006", "7920500", "8091141", "1905501", "11802750", "9751091", "10979111", "9712107", "8311540", "7625622", "7595718", "7611589", "11136274", "7729275", "12586320", "9494149", "10408559", "8618582", "1816217", "20380111", "8359082", "19686407", "16961439", "19086953", "1570496", "10609815", "19523014", "8791962", "10975769", "18942898", "17039120", "14530224", "17645482", "16101608", "1832313", "11252687" ]	[ "Efficacy and tolerability of pantoprazole compared with misoprostol for the prevention of NSAID-related gastrointestinal lesions and symptoms in rheumatic patients.", "Duodenal and gastric ulcer prevention with misoprostol in arthritis patients taking NSAIDs. Misoprostol Study Group.", "Misoprostol prevents NSAID-induced gastroduodenal lesions in patients with osteoarthritis and rheumatoid arthritis.", "Misoprostol and ranitidine in the prevention of NSAID-induced ulcers: a prospective, double-blind, multicenter study.", "Prevention of NSAID-induced gastric ulcer with misoprostol: multicentre, double-blind, placebo-controlled trial.", "[Misoprostol in the prevention of gastric erosions caused by nonsteroidal anti-inflammatory agents].", "Efficacy of 12 months' misoprostol as prophylaxis against NSAID-induced gastric ulcers. A placebo-controlled trial.", "Misoprostol compared with sucralfate in the prevention of nonsteroidal anti-inflammatory drug-induced gastric ulcer. A randomized, controlled trial.", "Ulcer prevention in long-term users of nonsteroidal anti-inflammatory drugs: results of a double-blind, randomized, multicenter, active- and placebo-controlled study of misoprostol vs lansoprazole.", "Preliminary study of the safety and efficacy of SC-58635, a novel cyclooxygenase 2 inhibitor: efficacy and safety in two placebo-controlled trials in osteoarthritis and rheumatoid arthritis, and studies of gastrointestinal and platelet effects.", "Gastrointestinal toxicity with celecoxib vs nonsteroidal anti-inflammatory drugs for osteoarthritis and rheumatoid arthritis: the CLASS study: A randomized controlled trial. Celecoxib Long-term Arthritis Safety Study.", "Diclofenac/misoprostol compared with diclofenac in the treatment of osteoarthritis of the knee or hip: a randomized, placebo controlled trial. Arthrotec Osteoarthritis Study Group.", "Double-blind comparison of efficacy and gastroduodenal safety of diclofenac/misoprostol, piroxicam, and naproxen in the treatment of osteoarthritis.", "Misoprostol dosage in the prevention of nonsteroidal anti-inflammatory drug-induced gastric and duodenal ulcers: a comparison of three regimens.", "Nonsteroidal antiinflammatory drugs for cancer pain: comparison between misoprostol and ranitidine in prevention of upper gastrointestinal damage.", "Misoprostol reduces serious gastrointestinal complications in patients with rheumatoid arthritis receiving nonsteroidal anti-inflammatory drugs. A randomized, double-blind, placebo-controlled trial.", "Randomized trial of low-dose misoprostol and naproxen vs. nabumetone to prevent recurrent upper gastrointestinal haemorrhage in users of non-steroidal anti-inflammatory drugs.", "Misoprostol coadministered with diclofenac for prevention of gastroduodenal ulcers. A one-year study.", "A study of co-treatment of nonsteroidal anti-inflammatory drugs (NSAIDs) with misoprostol for cervical priming before suction termination of first trimester pregnancy.", "Omeprazole compared with misoprostol for ulcers associated with nonsteroidal antiinflammatory drugs. Omeprazole versus Misoprostol for NSAID-induced Ulcer Management (OMNIUM) Study Group.", "A double-blind, placebo-controlled trial of diclofenac/misoprostol in Alzheimer's disease.", "Famotidine for the prevention of gastric and duodenal ulcers caused by nonsteroidal antiinflammatory drugs.", "Double blind, placebo controlled trial on the cytoprotective effect of misoprostol in subjects with rheumatoid arthritis, osteoarthritis and seronegative spondarthropathy on NSAIDs.", "Proton pump inhibitors after endoscopic hemostasis in patients with peptic ulcer bleeding.", "Helicobacter pylori infection, ABO blood group, and effect of misoprostol on gastroduodenal mucosa in NSAID-treated patients with rheumatoid arthritis.", "Optimal dose of intravenous pantoprazole in patients with peptic ulcer bleeding requiring endoscopic hemostasis in Korea.", "Evaluation of an automated system for prior authorization: a COX-2 inhibitor example.", "High- versus low-dose proton pump inhibitors after endoscopic hemostasis in patients with peptic ulcer bleeding: a multicentre, randomized study.", "A double-blind comparison of the gastroduodenal safety and efficacy of diclofenac and a fixed dose combination of diclofenac and misoprostol in the treatment of rheumatoid arthritis.", "Celecoxib versus diclofenac in long-term management of rheumatoid arthritis: randomised double-blind comparison.", "Oral or intravenous proton pump inhibitor in patients with peptic ulcer bleeding after successful endoscopic epinephrine injection.", "High-dose ranitidine for the prevention of recurrent peptic ulcer disease in rheumatoid arthritis patients taking NSAIDs.", "Efficacy of pantoprazole in the prevention of peptic ulcers, induced by non-steroidal anti-inflammatory drugs: a prospective, placebo-controlled, double-blind, parallel-group study.", "[Intravenous proton-pump inhibitor for acute peptic ulcer bleeding--is profound acid suppression beneficial to reduce the risk of rebleeding?].", "COX-2 specific inhibitors in the management of osteoarthritis of the knee: a placebo-controlled, randomized, double-blind study.", "Gastrointestinal tolerability and effectiveness of rofecoxib versus naproxen in the treatment of osteoarthritis: a randomized, controlled trial.", "Low-dose intravenous pantoprazole for optimal inhibition of gastric acid in Korean patients.", "Misoprostol in the management of the third stage of labour in the home delivery setting in rural Gambia: a randomised controlled trial.", "Ranitidine prevents duodenal ulcers associated with non-steroidal anti-inflammatory drug therapy.", "Tolerability profiles of rofecoxib (Vioxx) and Arthrotec. A comparison of six weeks treatment in patients with osteoarthritis." ]	[ "To compare the efficacy and tolerability of pantoprazole 20 mg once daily (o.d.) with misoprostol 200 microg twice daily (b.i.d.), administered for 6 months to rheumatic patients who required long-term therapy with nonsteroidal anti-inflammatory drugs (NSAIDs) and who were at increased risk of developing gastrointestinal lesions.\n This randomized, double-blind, multicenter, parallel group comparison study was performed with rheumatic patients (n = 515) who were likely to take NSAIDs continuously for at least 6 months. Patients were 55 years or older, at risk to develop gastrointestinal lesions, had less than five erosions/petechiae in the stomach and duodenum, no ulcers, no reflux esophagitis (endoscopy-proven), and gastrointestinal symptoms of at most moderate intensity. A minimum daily dose was defined for NSAIDs (COX-2 inhibitors were not available at the time). Patients were randomized to take either pantoprazole 20 mg o.d. (n = 257) or misoprostol 200 microg b.i.d. (n = 258) for 6 months while continuing NSAID therapy. Endoscopy was performed at baseline, 3, and 6 months.\n Pantoprazole was superior to misoprostol (p < 0.001) with regard to 'therapeutic failure' (occurrence of a peptic ulcer, ten or more erosions/petechiae in the stomach/duodenum, reflux esophagitis, severe gastrointestinal symptoms, and/or 'likely' or 'definitely' related adverse event leading to study termination). Estimated remission rates at 3 and 6 months (Kaplan-Meier life-table analysis) were, respectively, 93 and 89% (pantoprazole) and 79 and 70% (misoprostol). Pantoprazole was superior to misoprostol (p = 0.005) with regard to 'endoscopic failure' (occurrence of a peptic ulcer, ten or more erosions/petechiae in the stomach/duodenum, or reflux esophagitis) after 6 months. Estimated remission rates at 3 and 6 months were, respectively, 98 and 95% (pantoprazole) and 95 and 86% (misoprostol). Patients discontinuing the study early due to adverse events 'likely' or 'definitely' related to the study drug accounted for 13/257 (5%) in the pantoprazole and 33/258 (13%) in the misoprostol treatment groups.\n Pantoprazole 20 mg o.d. is superior to misoprostol 200 microg b.i.d. in the prevention of NSAID-induced gastrointestinal lesions and symptoms in patients on continuous long-term treatment with NSAIDs due to rheumatic diseases and at risk to develop such lesions or symptoms.\n Copyright 2003 S. Karger AG, Basel", "To determine the efficacy of misoprostol for the prevention of nonsteroidal anti-inflammatory drug (NSAID)-induced duodenal and gastric ulcers in arthritis patients receiving NSAID therapy.\n A randomized, double-blind, multicenter, placebo-controlled trial.\n Six hundred thirty-eight private, Veterans Affairs, health maintenance, and academic practices.\n Six hundred thirty-eight patients with chronic inflammatory or noninflammatory arthritis who were taking an NSAID but who did not have a gastric or duodenal ulcer on screening endoscopy received treatment with ibuprofen, piroxicam, naproxen, sulindac, tolmetin, indomethacin, or diclofenac daily for 3 months. Four hundred fifty-five (71%) patients completed the trial.\n Patients meeting the entry criteria were randomized to receive either misoprostol, 200 micrograms, or placebo, four times a day for 12 weeks.\n The endoscopy was repeated at 4, 8, and 12 weeks. The development of a duodenal or gastric ulcer (defined as a circumscribed mucosal defect > or = 0.5 cm in diameter and with perceptible depth) was regarded as prophylactic failure.\n By 12 weeks, a duodenal ulcer developed in 2 of 320 (0.6%; 95% CI, 0.2% to 3.9%) patients randomized to receive misoprostol, compared with 15 of 323 (4.6%; CI, 2.8% to 8%) patients receiving placebo (P = 0.002). A gastric ulcer developed in 6 of 320 (1.9%; (CI, 0.8% to 4.4%) patients, compared with in 25 of 323 (7.7%; CI, 5.1% to 11.4%), respectively.\n Misoprostol significantly lowers the frequency of both duodenal and gastric ulcer development in patients who require long-term therapy with NSAIDS.", "The clinical use of nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with significant adverse effects on the integrity of the gastrointestinal (GI) mucosa. A unique, double-blind, placebo-controlled, randomized, multicentre study investigated the prophylactic co-therapy with misoprostol, a novel PGE1 analog, for the prevention of the NSAID-induced gastric and duodenal mucosal lesions. The study also investigated whether the co-therapy with misoprostol could interfere with the anti-rheumatic action of the NSAIDs using detailed rheumatological assessments. Patients with osteoarthritis or rheumatoid arthritis had to be free of symptoms and significant erosive and/or haemorrhagic lesions of the upper GI tract. The patients were randomized to co-therapy with misoprostol or its matching placebo. Follow-up endoscopy and symptoms assessment were carried out within 4 weeks and compared to pre-study findings. Misoprostol significantly reduced (p less than 0.01) the incidence of erosive and/or haemorrhagic gastric and duodenal mucosal lesions. Misoprostol also reduced the proportion of patients with epigastric pain (p less than 0.01). Misoprostol was well tolerated and did not interfere with the anti-rheumatic activity of the administered NSAID. We conclude that misoprostol is safe and effective in the protection against NSAID-induced gastric and duodenal mucosal lesions and symptoms.", "To compare ranitidine to misoprostol with respect to the prevention of gastric and duodenal ulcers in patients on chronic NSAID therapy.\n A multi-center, 8-wk, randomized, double-blind study. Eligible patients were on chronic NSAID therapy and were experiencing NSAID-related upper gastrointestinal (UGI) pain without UGI endoscopic evidence of gastric or duodenal ulcers. Patients enrolled in the study were randomized to either misoprostol 200 micrograms q.i.d. or ranitidine 150 mg b.i.d.. Follow-up UGI endoscopy was performed after 4 and 8 wk of treatment. Therapeutic failure was considered the development of a gastric or duodenal ulcer > or = 0.3 cm in diameter with perceptible depth.\n Gastric ulcers were found in only 1/180 (0.56%) patient on misoprostol and in 11/194 (5.67%) patients on ranitidine, a difference that was statistically significant (p < 0.01). Duodenal ulcer rates were similar for the ranitidine (2/185 or 1.08%) and misoprostol (2/181 or 1.10%) groups.\n Misoprostol is significantly more effective than ranitidine in the prevention of NSAID-induced gastric ulcers. Ranitidine was as effective as misoprostol for the prevention of NSAID-induced duodenal ulcers. Misoprostol should be used for prophylaxis against both gastric and duodenal ulceration in patients on chronic NSAID therapy.", "A double-blind, placebo-controlled study was carried out to see whether the synthetic E prostaglandin, misoprostol, would prevent gastric ulcer induced by non-steroidal anti-inflammatory drugs (NSAIDs). 420 patients with osteoarthritis and NSAID-associated abdominal pain were studied; they were receiving ibuprofen, piroxicam, or naproxen. Endoscopy was done at entry and after 1, 2, and 3 months of continuous treatment with 100 micrograms or 200 micrograms misoprostol or placebo, given four times daily with meals and at bedtime, concurrently with the NSAID. Abdominal pain was rated independently by patients and physicians. A treatment failure was defined as development of a gastric ulcer. Gastric ulcers (0.3 cm in diameter or greater) occurred less frequently (p less than 0.001) in both misoprostol treatment groups (5.6% 100 micrograms and 1.4% 200 micrograms) than in the placebo group (21.7%). The significant difference in ulcer formation between the placebo and the misoprostol treatment groups remained when comparisons were restricted to ulcers greater than 0.5 cm in diameter (12.3% placebo, 4.2% 100 micrograms misoprostol, and 0.7% 200 micrograms misoprostol). Mild to moderate, self-limiting diarrhoea was the most frequently reported adverse effect attributed to misoprostol. These results provide the first clear indication that NSAID-induced ulcers are preventable.", "A multicenter, double-blind, placebo-controlled study was carried out to determine whether the synthetic prostaglandin E1 analog misoprostol is effective in preventing gastric and duodenal lesions induced by nonsteroidal anti-inflammatory drugs. Two hundred fifty-six patients under nonsteroidal anti-inflammatory drug treatment (diclofenac, naproxen, piroxicam, ibuprofen, indomethacin, ketoprofen, or tiaprofenic acid) for osteoarthritis, rheumatoid arthritis, or other rheumatic diseases were included in the study. None of the patients had patent gastroduodenal damage at entry (0 to 3 mucosal erosions or subepithelial hemorrhages on endoscopy). Patients were randomly assigned to treatment with misoprostol 400 micrograms/d (M 400), misoprostol 800 micrograms/d (M 800) or a placebo. Results of the follow-up endoscopy on day 28 in the 186 evaluable patients showed that gastric erosions were significantly less common (p < or = 0.02) in the two misoprostol groups (5% and 2% in the M 400 and M 800 groups respectively) than in the placebo group (19%). Similar small numbers of patients in the three groups had gastric subepithelial hemorrhages or duodenal lesions. Three patients developed gastric ulcers in the placebo group, versus none in the misoprostol groups. Misoprostol therapy did not modify the efficacy of the nonsteroidal antiinflammatory agent on pain or other rheumatologic manifestations. Diarrhea occurred in 1%, 10%, and 5% of patients in the M 400, M 800, and placebo groups, respectively. In conclusion, misoprostol given in combination with a nonsteroidal anti-inflammatory agent for 28 days significantly reduced the incidence of gastric erosions in a random sample of patients with a variety of rheumatic diseases. The daily dosage associated with the best risk/benefit ratio may be 400 micrograms/day.", "We performed a 12-month, double-blind, randomised, placebo-controlled study to determine the long term effect of misoprostol (600-800 micrograms/d) in the prevention of gastric ulcers and gastroduodenal erosions in 83 arthritis patients on chronic NSAID therapy. Patients underwent endoscopy at 0, 3, 6 and 12 months. At the initial endoscopy, 12 patients had an ulcer (11 gastric), which was healed prior to randomization. Seventy eligible patients reached the 3 month endoscopy. Four (12.5%) of the 32 patients given misoprostol developed a gastric ulcer compared with 11 (28.9%) of the 38 on placebo (p < 0.05, life-table analysis). Six of the 11 patients with an initial gastric ulcer developed a further gastric ulcer, compared to 9 of 58 patients without an initial ulcer (p < 0.05). We conclude that misoprostol decreases the cumulative development of NSAID-induced gastric ulcers. Patients with a previous NSAID-ulcer have a higher risk of further ulceration.", "To compare the efficacy and frequency of adverse experiences of misoprostol and sucralfate in the prevention of gastric ulcers in patients receiving nonsteroidal anti-inflammatory drug (NSAID) therapy.\n A prospective, randomized, single-blind, multicenter trial.\n Patients with osteoarthritis receiving treatment with ibuprofen, piroxicam, or naproxen and experiencing abdominal pain were eligible.\n Patients who were expected to receive at least 3 months of NSAID therapy and who did not have a gastric ulcer at the time of the initial screening endoscopy were randomized to receive misoprostol, 200 micrograms four times a day, or sucralfate, 1 g four times a day. A gastric ulcer was defined as a lesion of the gastric mucosa 0.3 cm or greater in diameter. Patients were followed clinically, and repeat endoscopies were performed after 4, 8, and 12 weeks.\n The development of a gastric ulcer, which was regarded as a prophylaxis failure.\n Two hundred fifty-three patients were evaluable for efficacy analysis. A gastric ulcer developed in 2 of the 122 (1.6%, 95% CI, 0.3% to 6.4%) patients on misoprostol, compared with 21 of 131 patients on sucralfate (16%, CI, 10.4% to 23.7%). The difference in ulcer rates was 14.4% (CI, 10.4% to 19.5%; P less than 0.001).\n In patients receiving chronic NSAID therapy for osteoarthritis, treatment with misoprostol for 3 months was associated with a significantly lower frequency of gastric ulcer formation, compared with treatment with sucralfate (P less than 0.001).", "Studies that report prevention of ulcer recurrence among long-term users of nonsteroidal anti-inflammatory drugs (NSAIDs) that do not stratify for Helicobacter pylori status may not be generalizable to the large population of individuals without H pylori.\n This was a prospective, double-blind, multicenter, active- and placebo-controlled study among 537 patients without H pylori who were long-term users of NSAIDs and who had a history of endoscopically documented gastric ulcer. Patients were randomized to receive placebo, 200 microg of misoprostol 4 times a day, or 15 or 30 mg of lansoprazole once daily for 12 weeks. Ulcer status was determined by endoscopy at 4, 8, and 12 weeks.\n Patients receiving lansoprazole (15 or 30 mg) remained free from gastric ulcer longer than those who received placebo (P<.001) but for a shorter time than those who received misoprostol. By week 12, the percentages of gastric ulcer-free patients were as follows: placebo, 51% (95% confidence interval [CI], 41.1%-61.3%); misoprostol, 93% (95% CI, 87.2%-97.9%); 15-mg lansoprazole, 80% (95% CI, 72.5%-87.3%); and 30-mg lansoprazole, 82% (95% CI, 75.0%-89.6%). A significantly higher proportion of patients in the misoprostol group reported treatment-related adverse events and early withdrawal from the study. When the impact of withdrawals on ulcer development was considered (as failures), therapy was successful for 69% for each of the active treatment groups and 35% for the placebo group.\n Proton pump inhibitors such as lansoprazole are superior to placebo for the prevention of NSAID-induced gastric ulcers but not superior to misoprostol, 800 microg/d. When the poor compliance and potential adverse effects associated with misoprostol are considered, proton pump inhibitors and full-dose misoprostol are clinically equivalent.", "To investigate the efficacy and safety of SC-58635 (celecoxib), an antiinflammatory and analgesic agent that acts by selective cyclooxygenase 2 (COX-2) inhibition and is not expected to cause the typical gastrointestinal (GI), renal, and platelet-related side effects associated with inhibition of the COX-1 enzyme.\n Four phase II trials were performed: a 2-week osteoarthritis efficacy trial, a 4-week rheumatoid arthritis efficacy trial, a 1-week endoscopic study of GI mucosal effects, and a 1-week study of effects on platelet function.\n The 2 arthritis trials identified SC-58635 dosage levels that were consistently effective in treating the signs and symptoms of arthritis and were distinguished from placebo on standard arthritis scales. In the upper GI endoscopy study, 19% of subjects receiving naproxen (6 of 32) developed gastric ulcers, whereas no ulcers occurred in subjects receiving SC-58635 or placebo. The study of platelet effects revealed no meaningful effect of SC-58635 on platelet aggregation or thromboxane B2 levels, whereas aspirin caused significant decreases in 2 of 3 platelet aggregation measures and thromboxane B2 levels. In all 4 trials, SC-58635 was well tolerated, with a safety profile similar to that of placebo.\n SC-58635 achieves analgesic and antiinflammatory efficacy in arthritis through selective COX-2 inhibition, without showing any evidence of 2 of the toxic effects of COX-1 inhibition associated with nonsteroidal antiinflammatory drugs.", "Conventional nonsteroidal anti-inflammatory drugs (NSAIDs) are associated with a spectrum of toxic effects, notably gastrointestinal (GI) effects, because of inhibition of cyclooxygenase (COX)-1. Whether COX-2-specific inhibitors are associated with fewer clinical GI toxic effects is unknown.\n To determine whether celecoxib, a COX-2-specific inhibitor, is associated with a lower incidence of significant upper GI toxic effects and other adverse effects compared with conventional NSAIDs.\n The Celecoxib Long-term Arthritis Safety Study (CLASS), a double-blind, randomized controlled trial conducted from September 1998 to March 2000.\n Three hundred eighty-six clinical sites in the United States and Canada.\n A total of 8059 patients (>/=18 years old) with osteoarthritis (OA) or rheumatoid arthritis (RA) were enrolled in the study, and 7968 received at least 1 dose of study drug. A total of 4573 patients (57%) received treatment for 6 months.\n Patients were randomly assigned to receive celecoxib, 400 mg twice per day (2 and 4 times the maximum RA and OA dosages, respectively; n = 3987); ibuprofen, 800 mg 3 times per day (n = 1985); or diclofenac, 75 mg twice per day (n = 1996). Aspirin use for cardiovascular prophylaxis (</=325 mg/d) was permitted.\n Incidence of prospectively defined symptomatic upper GI ulcers and ulcer complications (bleeding, perforation, and obstruction) and other adverse effects during the 6-month treatment period.\n For all patients, the annualized incidence rates of upper GI ulcer complications alone and combined with symptomatic ulcers for celecoxib vs NSAIDs were 0.76% vs 1.45% (P =.09) and 2. 08% vs 3.54% (P =.02), respectively. For patients not taking aspirin, the annualized incidence rates of upper GI ulcer complications alone and combined with symptomatic ulcers for celecoxib vs NSAIDs were 0.44% vs 1.27% (P =.04) and 1.40% vs 2.91% (P =.02). For patients taking aspirin, the annualized incidence rates of upper GI ulcer complications alone and combined with symptomatic ulcers for celecoxib vs NSAIDs were 2.01% vs 2.12% (P =.92) and 4.70% vs 6.00% (P =.49). Fewer celecoxib-treated patients than NSAID-treated patients experienced chronic GI blood loss, GI intolerance, hepatotoxicity, or renal toxicity. No difference was noted in the incidence of cardiovascular events between celecoxib and NSAIDs, irrespective of aspirin use.\n In this study, celecoxib, at dosages greater than those indicated clinically, was associated with a lower incidence of symptomatic ulcers and ulcer complications combined, as well as other clinically important toxic effects, compared with NSAIDs at standard dosages. The decrease in upper GI toxicity was strongest among patients not taking aspirin concomitantly. JAMA. 2000;284:1247-1255", "Gastric (GU) and duodenal ulcers (DU) are common adverse effects of nonsteroidal anti-inflammatory drugs (NSAID). Endoscopically diagnosed upper gastrointestinal (GI) ulceration occurs in about 24% of longterm NSAID users. Coadministration of misoprostol with the NSAID reduces the incidence of NSAID induced GU and DU and their complications. However, compliance is limited by the different dosing regimens of misoprostol and NSAID and GI symptoms associated with misoprostol at its recommended q.i.d. dose. We compared the efficacy, safety, and incidence of endoscopic upper GI ulceration associated with the administration of 2 combinations of diclofenac (50 or 75 mg) and misoprostol 200 microg (D50/M200 t.i.d., D75/M200 b.i.d.), diclofenac 75 mg b.i.d., and placebo in a 6 week, randomized, double blind study in patients with osteoarthritis (OA) of the knee or hip.\n A total of 572 patients with symptomatic OA of the knee or hip and history of GU, DU. or 10 or more erosions were randomized to receive D50/M200 t.i.d., D75/M200 b.i.d., diclofenac 75 mg b.i.d., or placebo for 6 weeks. Arthritis assessments were performed at baseline, 2, and 6 weeks, and upper GI endoscopies at baseline and end of treatment.\n All active treatment groups were significantly better than placebo, at all visits, in improving OA symptoms. There were no significant differences in arthritis efficacy between the diclofenac/ misoprostol combinations and diclofenac. However, endoscopically diagnosed GU and/or DU were significantly less frequent in patients receiving D50/M200 t.i.d. (8%), D75/M200 b.i.d. (7%), and placebo (4%) compared to diclofenac 75 mg b.i.d. (17%). Adverse events were not different between the active treatment groups, except for higher incidences of flatulence with D75/M200 and diarrhea with D50/M200.\n Diclofenac 50 mg/misoprostol 200 microg t.i.d. and diclofenac 75 mg/misoprostol 200 microg b.i.d. are as efficacious as diclofenac 75 mg b.i.d. in the treatment of OA, but are associated with a significantly lower incidence of gastric and/or duodenal ulcers.", "To compare the efficacy and gastroduodenal safety of a fixed-dose combination of diclofenac sodium 50 mg and misoprostol 200 micrograms twice daily with those of piroxicam 10 mg twice daily and naproxen 375 mg twice daily in patients with osteoarthritis.\n A 4 week, randomised, double-blind, parallel-group, multicentre study was conducted in 643 patients with symptomatic osteoarthritis of the hip and/or knee, who required continuous non-steroidal anti-inflammatory drug therapy for 4 weeks and who were without significant upper gastrointestinal damage as confirmed by endoscopy.\n For patients who had pre- and post-treatment endoscopic examinations, gastroduodenal ulcers developed in 3 (1.5%) of 200 patients treated with diclofenac/misoprostol, 21 (10.3%) of 204 piroxicam-treated patients, and 17 (8.6%) of 198 patients receiving naproxen (Chi square = 13.771, p = 0.001). The improvement in the osteoarthritis severity index was greater in the diclofenac/misoprostol group than in the piroxicam group (p = 0.004). Changes in physician and patient global assessments showed no significant differences between treatment groups. The incidences of diarrhoea and abdominal pain were higher in the diclofenac/misoprostol group than in the piroxicam and naproxen groups.\n Diclofenac/misoprostol at twice daily dosing is associated with significantly fewer gastroduodenal ulcers than either piroxicam or naproxen. The efficacy of diclofenac/misoprostol in treating the signs and symptoms of osteoarthritis is at least comparable to that of piroxicam and naproxen.", "To compare the effectiveness and tolerability of three misoprostol dosing regimens for the prevention of gastric and duodenal ulcers associated with long-term nonsteroidal anti-inflammatory drug (NSAID) therapy.\n A multicenter, 12-week, randomized, double-blind, placebo-controlled, parallel, four-limb study.\n Eligibility criteria included upper gastrointestinal symptoms during NSAID therapy and no endoscopic evidence of gastric or duodenal ulcers. A total of 1623 patients was enrolled; 1197 of these met major accession and regimen-compliance criteria and completed the trial. These 1197 patients composed the evaluable group.\n Patients were randomly assigned to one of four regimens: placebo four times daily; 200 micrograms of misoprostol twice daily and placebo twice daily; 200 micrograms of misoprostol three times daily and placebo once daily; and 200 micrograms of misoprostol four times daily.\n Upper gastrointestinal endoscopic examinations for ulcers were done after 4, 8, and 12 weeks of therapy. Tolerability and safety of the regimens were assessed by adverse-event monitoring.\n In the placebo group, the incidence of gastric ulcers was 15.7% and the incidence of duodenal ulcers was 7.5%. The incidence of gastric ulcers was significantly lower in the groups receiving misoprostol twice daily (8.1%; difference, 7.6% [95% CI, 2.7% to 12.5%]; P = 0.002), three times daily (3.9%; difference, 11.8% [CI, 7.4% to 16.3%]; P < 0.001), and four times daily (4%; difference, 11.7% [CI, 6.7% to 16.8%]; P < 0.001) compared with placebo. The gastric ulcer rate was significantly higher in patients receiving misoprostol twice daily compared with those receiving misoprostol three times daily (difference, 4.2% [95% CI, 0.7% to 7.7%]; P = 0.02). A significant (P = 0.02) misoprostol dose-response effect was noted in the prevention of gastric ulcers. The incidence of duodenal ulcers was significantly lower in the groups receiving misoprostol twice daily (2.6%; difference, 4.9% [CI, 1.5% to 8.2%]; P = 0.004), three times daily (3.3%; difference, 4.2% [CI, 0.6% to 7.7%]; P = 0.019), and four times daily (1.4%; difference, 6.1% [CI, 2.6% to 9.6%]; P = 0.007) compared with placebo. No significant difference was detected between patients receiving misoprostol twice daily and those receiving misoprostol three times daily, and no dose-response effect was noted with duodenal ulcers. The incidence of withdrawals for adverse events was significantly lower in the groups receiving misoprostol twice daily (12%) and three times daily (12%) than in the group receiving it four times daily (20%). The incidence of gastrointestinal adverse events was significantly higher in the group receiving misoprostol four times daily (74%) than in the placebo group (62%).\n Misoprostol, 200 micrograms twice or three times daily, offers substantial protection against gastric and duodenal ulcers in patients receiving long-term NSAID therapy. These dosages were better tolerated than the currently approved regimen of 200 micrograms four times daily.", "The prophylactic strategy of nonsteroidal antiinflammatory drug (NSAID)-induced upper gastrointestinal (UGI) damage has largely been studied in arthritic patients, but not in cancer patients. The efficacy of misoprostol and ranitidine in the prevention of gastroduodenal damage in patients taking diclofenac for their cancer pain has been compared in this study.\n Patients who needed high-dose (200 to 300 mg/d) diclofenac for cancer pain and without mucosal lesions at baseline gastroduodenal endoscopy were randomized to receive misoprostol (200 micrograms twice daily; M group) or ranitidine (150 mg twice daily; R group). UGI endoscopy was repeated after 4 weeks.\n Twenty-three patients treated with misoprostol and 26 treated with ranitidine concluded the study. The M group showed a significantly (P < .02) lower incidence of gastroduodenal lesions (two patients; 8.7%) than the R group (10 patients; 38.5%). Gastric ulcers occurred in one (4%) misoprostol-treated patient and in six (23%) ranitidine-treated patients. Six of seven patients with ulcers were asymptomatic. Seventy-one percent and 86% of ulcers occurred in patients older than 60 years and in those who received greater than 3.1 mg/kg of diclofenac, respectively.\n Misoprostol was significantly more effective than ranitidine in the prevention of gastroduodenal lesions in cancer patients receiving diclofenac.", "To investigate whether concurrent administration of misoprostol reduces the occurrence of serious upper gastrointestinal complications, such as perforation, gastric outlet obstruction, or bleeding, in patients with rheumatoid arthritis who are receiving nonsteroidal anti-inflammatory drugs (NSAIDs).\n 6-month randomized, double-blind, placebo-controlled trial.\n 664 clinical practices of family medicine, internal medicine, or rheumatology in the United States and Canada.\n 8843 men and women (mean age, 68 years) receiving continuous therapy with any of 10 specified NSAIDs for control of symptoms of rheumatoid arthritis. Patients were enrolled between July 1991 and August 1993.\n Patients were randomly assigned to receive 200 micrograms of misoprostol or placebo four times a day.\n Development of serious upper gastrointestinal complications detected by clinical symptoms or findings (not by scheduled endoscopy).\n Serious upper gastrointestinal complications were reduced by 40% (odds ratio, 0.598 [95% CI, 0.364 to 0.982; P = 0.049]) among patients receiving misoprostol (25 of 4404 patients) compared with those receiving placebo (42 of 4439 patients). During the first month, more patients receiving misoprostol (20%) than placebo (15%) withdrew from the study, primarily because of diarrhea and related problems (P < 0.001). Risk factors for serious upper gastrointestinal complications were increasing age, history of peptic ulcer or bleeding, and cardiovascular disease. Patients with all four risk factors would have a 9% risk for a major complication in 6 months.\n In older patients with rheumatoid arthritis, misoprostol reduced serious NSAID-induced upper gastrointestinal complications by 40% compared with placebo.", "Prophylactic misoprostol or non-steroidal anti-inflammatory drugs (NSAIDs) with low gastric toxicity (nabumetone) has been shown to reduce mucosal injury.\n To compare nabumetone vs. co-therapy of naproxen with low-dose misoprostol for secondary prevention of upper gastrointestinal bleeding in NSAID users.\n NSAID users presenting with upper gastrointestinal bleeding were enrolled if they required long-term NSAIDs. After ulcer healing, they were randomized to receive: naproxen (500-1000 mg/day) and misoprostol (200 microg b.d.), or nabumetone (1000-1500 mg/day) and placebo misoprostol for 24 weeks. The primary end-point was recurrent upper gastrointestinal bleeding. The secondary end-point was the proportion of patients suffering from major gastrointestinal events including ulcer bleeding, symptomatic ulcers and severe dyspepsia.\n A total of 90 patients were included in the intention-to-treat analysis (misoprostol/naproxen 45, nabumetone 45). Recurrent bleeding occurred in 10 patients (22.2%) receiving misoprostol/naproxen compared with three (6.7%) receiving nabumetone (relative risk 3.33, 95% CI: 0.98-11.32, P=0.069). The proportion of patients suffering from major gastrointestinal events at 24 weeks was 31.1% in the misoprostol/naproxen group and 28.9% in the nabumetone group.\n Misoprostol/naproxen is not superior to nabumetone for secondary prevention of upper gastrointestinal bleeding. Neither low-dose misoprostol nor nabumetone is adequate for high-risk NSAID users.", "The objective of this study was to determine the long-term efficacy of misoprostol in preventing diclofenac-induced gastroduodenal ulcers in rheumatoid arthritis and osteoarthritis patients. Three hundred eighty-four patients who had an endoscopically confirmed gastric or duodenal lesion that had healed with misoprostol therapy were randomized to receive misoprostol or placebo coadministered with diclofenac for up to 52 weeks. Endoscopic examinations were repeated at weeks 12, 24, and 52. The development of a gastric and/or duodenal ulcer was considered a prophylaxis failure. Results in the evaluable cohort of patients demonstrated that gastroduodenal ulcer incidences were lower with misoprostol than placebo for all study periods (0-12 weeks, 7% vs 23%; 0-24 weeks, 11% vs 26%; and 0-52 weeks, 15% vs 31%). Misoprostol did not interfere with the antiarthritic effects of diclofenac. In conclusion, misoprostol coadministered with diclofenac for 12 months to patients with rheumatoid arthritis or osteoarthritis significantly reduced the incidence of diclofenac-induced gastroduodenal ulcers (P < or = 0.018).", "This double-blind randomized control study was conducted to evaluate whether a nonsteroidal anti-inflammatory drug (NSAID) could act as an effective pain control method during first trimester suction abortion, and whether co-treatment of NSAID with misoprostol will decrease the efficacy of the cervical ripening effect of misoprostol. Subjects were randomized to receive misoprostol alone or misoprostol together with diclofenac sodium. Both groups of subjects suffered from similar incidence of preoperative side effects. Co-treatment of NSAID with misoprostol did not attenuate the cervical ripening efficacy of misoprostol. There was no significant pain reduction in the group treated with NSAID, except that a marginal benefit was found in the subgroup of multiparous women. About two thirds of the subjects in both treatment groups found that this was a satisfactory pain relief method during the procedure.", "Misoprostol is effective for ulcers associated with the use of nonsteroidal antiinflammatory drugs (NSAIDs) but is often poorly tolerated because of diarrhea and abdominal pain. We compared the efficacy of omeprazole and misoprostol in healing and preventing ulcers associated with NSAIDs.\n In a double-blind study, we randomly assigned 935 patients who required continuous NSAID therapy and who had ulcers or more than 10 erosions in the stomach or duodenum (or both) to receive 20 mg or 40 mg of omeprazole orally in the morning or 200 microg of misoprostol orally four times daily. Patients were treated for four weeks or, in the absence of healing, eight weeks. Treatment success was defined as the absence of ulcers and the presence of fewer than five erosions at each site and not more than mild dyspepsia. We then randomly reassigned 732 patients in whom treatment was successful to maintenance therapy with 20 mg of omeprazole daily, 200 microg of misoprostol twice daily, or placebo for six months.\n At eight weeks, treatment was successful in 76 percent of the patients given 20 mg of omeprazole (233 of 308), 75 percent of those given 40 mg of omeprazole (237 of 315), and 71 percent of those given misoprostol (212 of 298). The rates of gastric-ulcer healing were significantly higher with 20 mg of omeprazole (but not 40 mg of omeprazole) than with misoprostol. Healing rates among patients with duodenal ulcers were higher with either dose of omeprazole than with misoprostol, whereas healing rates among patients with erosions alone were higher with misoprostol. More patients remained in remission during maintenance treatment with omeprazole (61 percent) than with misoprostol (48 percent, P=0.001) and with either drug than with placebo (27 percent, P<0.001). There were more adverse events during the healing phase in the misoprostol group than in the groups given 20 mg and 40 mg of omeprazole (59 percent, 48 percent, and 46 percent, respectively).\n The overall rates of successful treatment of ulcers, erosions, and symptoms associated with NSAIDs were similar for the two doses of omeprazole and misoprostol. Maintenance therapy with omeprazole was associated with a lower rate of relapse than misoprostol. Omeprazole was better tolerated than misoprostol.", "Previous studies suggest a potential benefit from nonsteroidal anti-inflammatory drugs (NSAIDs) in Alzheimer's disease (AD). Prescribing NSAIDs, however, carries the risk of significant gastrointestinal adverse events.\n To study whether treatment with an NSAID prevents expected decline in AD patients and evaluate whether co-administration of the gastro-protective agent, misoprostol, with an NSAID is safe in AD.\n The efficacy and safety of diclofenac in combination with misoprostol (D/M) was evaluated in 41 patients with mild-moderate AD in a prospective 25-week, randomized, double-blind placebo-controlled trial. Efficacy measures comprised the Alzheimer's Disease Assessment Scale cognitive and noncognitive subsections, Global Deterioration Scale, Clinical Global Impression of Change, Mini-Mental State Examination, Instrumental Activities of Daily Living, Physical Self-Maintenance Scale, and a caregiver-rated Global Impression of Change.\n There were no group differences with any of the outcome measures in an intent-to-treat analysis. There were some nonsignificant trends for the placebo group to have deteriorated more than the D/M-treated patients. Withdrawal rates were 12 of 24 in the D/M group and 2 of 17 in the placebo group. There were no serious drug-related adverse events.\n This pilot study, with small treatment numbers, did not demonstrate a significant effect of NSAID treatment in AD, but the trends observed justify further investigations with a larger number of participants. D/M is safe in AD patients, but its tolerability is not optimal.", "Acid suppression with famotidine, a histamine H2-receptor antagonist, provides protection against gastric injury in normal subjects receiving short courses of aspirin or naproxen. The efficacy of famotidine in preventing peptic ulcers in patients receiving long-term therapy with nonsteroidal antiinflammatory drugs (NSAIDs) is not known.\n We studied the efficacy of two doses of famotidine (20 mg and 40 mg, each given orally twice daily), as compared with placebo, in preventing peptic ulcers in 285 patients without peptic ulcers who were receiving long-term NSAID therapy for rheumatoid arthritis (82 percent) or osteoarthritis (18 percent). The patients were evaluated clinically and by endoscopy at base line and after 4, 12, and 24 weeks of treatment. The evaluators were unaware of the treatment assignment. The primary end point was the cumulative incidence of gastric or duodenal ulceration at 24 weeks.\n The cumulative incidence of gastric ulcers was 20 percent in the placebo group, 13 percent in the group of patients receiving 20 mg of famotidine twice daily (P = 0.24 for the comparison with placebo), and 8 percent in the group receiving 40 mg of famotidine twice daily (P = 0.03 for the comparison with placebo). The proportion of patients in whom duodenal ulcers developed was significantly lower with both doses of famotidine than with placebo (13 percent in the placebo group, 4 percent in the low-dose famotidine group [P = 0.04], and 2 percent in the high-dose famotidine group [P = 0.01]). Both doses of famotidine were well tolerated.\n Treatment with high-dose famotidine significantly reduces the cumulative incidence of both gastric and duodenal ulcers in patients with arthritis receiving long-term NSAID therapy.", "Ninety arthritic patients were randomly allotted to receive misoprostol 200 micrograms thrice daily or placebo, for 4 weeks, while they were started on various NSAIDs. While upper gastrointestinal symptoms occurred equally in both groups, patients on placebo had significantly more post-therapy abnormal endoscopy findings. Misoprostol was well tolerated without any adverse side effects; it did not interfere with the therapeutic efficacy of the NSAIDs. Arthritic patients requiring long term NSAID therapy appear to benefit from misoprostol because of its cytoprotective effect on the gastrointestinal mucosa.", "Peptic ulcer bleeding is a common and potentially fatal condition. For patients with bleeding peptic ulcers that display major endoscopic stigmata of recent hemorrhage, a combination of endoscopic and pharmacologic therapy is the current standard management.\n To show our experience with management of peptic ulcer bleeding.\n Patients who presented with gastrointestinal bleeding caused by peptic ulcer or recent history (< 24 h before presentation) of hematemesis and/or melena admitted to our hospital emergency departments, and patients whose ulcer hemorrhage started after hospitalization for an unrelated medical or surgical condition.\n Patients with actively bleeding ulcers and those with nonbleeding visible vessel or adherent clot were treated with epinephrine injection and/or endoscopic hemoclips, and randomized to receive intravenous pantoprasole according to the continuous regimen (dose of 5 x 40 mg in continuous infusion of 8 mg/h for 72 h) or the standard regimen (40 mg bolus of PPI twice daily for 3 days). After the infusion, all patients were given 40 mg PPI twice daily orally. The primary end point was the in-hospital rebleeding rate, as discovered by the repeated endoscopy.\n Bleeding recurred in 5 of 34 patients (14.7%) receiving the intensive regimen, and in 8 of 35 (22.8%) patients receiving the standard regimen. Hemoglobin (g/l) rate in standard regimen group was 93.5 +/- 23.8, and in intensive regimen group 106.6 +/- 22.4 (P = 0.042). Mean units of blood transfused for all patients in group were 71.8 +/- 45.8 in the intensive and 45.3 +/- 50.2 in the standard regimen group (P = 0.0257). The duration of hospital stay was 6.4 +/- 2.8 in standard group and 5.8 +/- 2.8 in the intensive group (P = 0.40).\n In patients with bleeding peptic ulcers with successful endoscopic hemostasis the standard PPI regimen had advantage on transfusion requirements, but no advantage with respect to in-hospital rates of rebleeding rates, need for surgery, length of hospital stay, or death, which corresponds with recent studies.", "Our aim was to investigate the effect of misoprostol on NSAID-induced gastroduodenal mucosal damage in patients with rheumatoid arthritis. The study included 40 patients, and it was designed as a double-blind, placebo-controlled trial. Misoprostol significantly reduced the gastroduodenal mucosal lesions found at endoscopy (P < 0.05) and prevented the development of ulcers. The cumulative incidence of ulcers at four weeks was 5% in the placebo group and 0% in the misoprostol group. The basal and pentagastrin-stimulated acid output as evaluated after 23 days of treatment with misoprostol was not significantly affected. Forty-one percent of the patients had signs of current Helicobacter pylori infection, 33% had positive serology only, and 26% had no evidence of infection. Most of the patients with current infection belonged to blood group O (P < 0.05). Misoprostol treatment did not affect the occurrence of Helicobacter pylori or the rheumatic disease activity. It is concluded that the protective actions of misoprostol on the gastroduodenal mucosa of NSAID-treated patients are largely mediated by mechanisms other than inhibition of acid secretion. The relationship among active Helicobacter pylori infection, blood group O, and peptic ulcer may be helpful to identify a subpopulation of patients taking NSAIDs at risk of developing peptic ulcers.", "The lowest effective dose of proton pump inhibitors (PPI) for prevention of peptic ulcer rebleeding remains unclear. The objective of the present study was to evaluate whether low-dose PPI has a similar efficacy to high-dose i.v. administration for maintaining intragastric pH above 6.\n Sixty-one patients with bleeding ulcers were randomized into one of three groups after endoscopic hemostasis: pantoprazole 80 mg bolus followed by 8 mg/h; 40 mg, 4 mg/h infusion; and bolus injection of 40 mg every 24 h. Intragastric pH values and rebleeding rates were measured. In addition, pharmacokinetic parameters and association with CYP2C19 polymorphisms and H. pylori infection were assessed.\n Mean percentage of time with intragastric pH > 6, and the proportion of patients with pH > 6 for more than 60% of the time were significantly higher in the 40 mg, 4 mg/h infusion group compared to the 40 mg bolus injection. There was no significant difference between the 80 mg, 8 mg/h and the 40 mg, 4 mg/h groups. In the H. pylori (-) group, only 40% of patients that received continuous infusion reached the target pH > 6 for more than 60% of the time; this was significantly lower than the H. pylori (+) group, 87.5% (P = 0.026).\n A continuous infusion, regardless of high or low dose, was more effective for acid suppression than a 40 mg bolus PPI injection in Korea. H. pylori infection was an important factor for the maintenance of an intragastric pH > 6.", "To evaluate the effectiveness of an automated prior authorization (PA) system (SmartPA) in reducing use of and expenditures for cyclooxygenase-2 (COX-2) inhibitors.\n Before and after with control group.\n After implementation of SmartPA in Missouri, changes in use of and expenditures for COX-2 inhibitors, COX-2 substitutes (traditional nonsteroidal anti-inflammatory drugs [NSAIDs] and other products for pain), and gastrointestinal (GI) protective agents were compared between the Medicaid program of Missouri and that of a state with no PA program for COX-2 inhibitors. Subjects were continuously enrolled for the 24-month study period and had a claim for a COX-2 inhibitor in the 12-month baseline period. Analyses included comparison of means and linear regression. Regressions controlled for age, sex, risk for GI complications, severity of illness, and the interaction between state and risk.\n Changes in expenditures for COX-2 inhibitors, NSAIDs, other pain drugs, and GI-protective drugs were $256 higher, $56 lower, $21 higher, and $198 higher, respectively, in the control state among low-risk patients. Changes in expenditures were $102 higher, $12 lower, $21 lower, and $185 higher, respectively, in the control state among high-risk patients. Results were similar for drug utilization.\n Implementation of SmartPA resulted in reduced use of and expenditures for COX-2 inhibitors and reduced net expenditures for all pain and GI-protective medications. These effects were greatest for patients at low risk for GI complications.", "The most effective schedule of proton pump inhibitor (PPI) administration following endoscopic hemostasis of bleeding ulcers remains uncertain.\n Patients with actively bleeding ulcers and those with nonbleeding visible vessel or adherent clot were treated with epinephrine injection and/or thermal coagulation, and randomized to receive intravenous PPIs according to an intensive regimen (80 mg bolus followed by 8 mg/h as continuous infusion for 72 h) or a standard regimen (40 mg bolus daily followed by saline infusion for 72 h). After the infusion, all patients were given 20 mg PPI twice daily orally. The primary end point was the in-hospital rebleeding rate, as ascertained at the repeat endoscopy.\n Bleeding recurred in 28 of 238 patients (11.8%) receiving the intensive regimen, and in 19 of 236 (8.1%) patients receiving the standard regimen (P= 0.18). Most rebleeding episodes occurred during the initial 72-h infusion: 18 (7.6%) and 19 events (8.1%) in the intensive and standard groups, respectively (P= 0.32). Mean units of blood transfused were 1.7 +/- 2.1 in the intensive and 1.5 +/- 2.1 in the standard regimen group (P= 0.34). The duration of hospital stay was <5 days for 88 (37.0%) and 111 patients (47.0%) in the intensive and standard groups (P= 0.03). There were fewer surgical interventions in the standard versus intensive regimen (1 vs 3). Five patients in each treatment group died.\n Following endoscopic hemostasis of bleeding ulcers, standard-dose PPIs infusion was as effective as a high-dose regimen in reducing the risk of recurrent bleeding. (ClinicalTrials.gov number, NCT00374101).", "This double-blind, parallel group study was conducted to evaluate the gastroduodenal safety and antiarthritic efficacy of a fixed combination of diclofenac sodium 50 mg and misoprostol 200 mcg, compared with a combination of diclofenac 50 mg and placebo. Three hundred and thirty-nine patients with rheumatoid arthritis and no significant gastric or duodenal mucosal damage were enrolled and received study medication (diclofenac/misoprostol, 164; diclofenac/placebo, 175) BID or TID for 12 weeks. Posttreatment gastroduodenal endoscopic examinations revealed ulcers in 11% of the diclofenac/placebo group, compared with only 4% of the diclofenac/misoprostol group (p = 0.034). Four-weekly assessments of arthritic condition revealed no clinically or statistically significant treatment differences. It was concluded that diclofenac/misoprostol caused significantly less gastroduodenal damage than diclofenac, but was as effective as diclofenac alone in the treatment of rheumatoid arthritis.", "Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit cyclo-oxygenase (COX), which leads to suppression of COX-1-mediated production of gastrointestinal-protective prostaglandins. Gastrointestinal injury is a common outcome. We compared the efficacy, safety, and tolerability of long-term therapy with celecoxib, a COX-1 sparing inhibitor of COX-2, with diclofenac, a non-specific COX inhibitor.\n 655 patients with adult-onset rheumatoid arthritis of at least 6 months' duration were randomly assigned oral celecoxib 200 mg twice daily or diclofenac SR 75 mg twice daily for 24 weeks. Anti-inflammatory and analgesic activity and tolerability were assessed at baseline, every 4 weeks, and at week 24. We assessed gastrointestinal safety by upper-gastrointestinal endoscopy within 7 days of the last treatment dose at centres where the procedure was available. Analysis was by intention-to-treat.\n 430 patients underwent endoscopy (celecoxib n=212, diclofenac n=218). The two drugs were similar in management of rheumatoid arthritis pain and inflammation. Gastroduodenal ulcers were detected endoscopically in 33 (15%) patients treated with diclofenac and in eight (4%) in the celecoxib group (p<0.001). The rate of withdrawal for any gastrointestinal-related adverse event, most commonly abdominal pain, diarrhoea, and dyspepsia, was nearly three times higher in the diclofenac-treated group than in the celecoxib group (16 vs 6%; p<0.001).\n Celecoxib showed sustained anti-inflammatory and analgesic activity similar to diclofenac, with a lower frequency of upper gastrointestinal ulceration or gastrointestinal adverse events, and tolerability was better.", "We aimed to assess the clinical effectiveness of oral vs. intravenous (i.v.) regular-dose proton pump inhibitor (PPI) after endoscopic injection of epinephrine in patients with peptic ulcer bleeding.\n Peptic ulcer patients with active bleeding, nonbleeding visible vessels, or adherent clots were enrolled after successful endoscopic haemostasis achieved by epinephrine injection. They were randomized to receive either oral rabeprazole (RAB group, 20 mg twice daily for 3 days) or i.v. omeprazole (OME group, 40 mg i.v. infusion every 12 h for 3 days). Subsequently, the enrolled patients receive oral PPI for 2 months (rabeprazole 20 mg or esomeprazole 40 mg once daily). The primary end-point was recurrent bleeding up to 14 days. The hospital stay, blood transfusion, surgery and mortality within 14 days were compared as well.\n A total of 156 patients were enrolled, with 78 patients randomly allocated in each group. The two groups were well matched for factors affecting the clinical outcomes. Primary end-points (recurrent bleeding up to 14 days) were reached in 12 patients (15.4%) in the OME group and 13 patients (16.7%) in the RAB group [95% confidence interval (CI) of difference -12.82, 10.22]. All the rebleeding events occurred within 3 days of enrolment. The two groups were not different in hospital stay, volume of blood transfusion, surgery or mortality rate (1.3% of the OME group and 2.6% of the RAB group died, 95% CI of difference -5.6, 3.0).\n Oral rabeprazole and i.v. regular-dose omeprazole are equally effective in preventing rebleeding in patients with high-risk bleeding peptic ulcers after successful endoscopic injection with epinephrine.", "Continuous therapy with low-dose ranitidine (150 mg b.d.) is known to be effective for the prevention of recurrent nonsteroidal anti-inflammatory drug (NSAID)-associated duodenal ulcer but not for gastric ulcer.\n To investigate, in a double-blind placebo-controlled study, the preventive effect of a high dose of ranitidine (300 mg b.d.) on the recurrence of both duodenal ulcers and gastric ulcers in rheumatoid arthritis patients with a continuous need for NSAIDs.\n Rheumatoid arthritis patients with a history of peptic ulcer disease were randomized to receive either ranitidine 300 mg b.d. or placebo for 12 months. Endoscopy was performed at study entry and after 6 and 12 months. End-point was the recurrence of gastric or duodenal ulcers.\n The study was stopped after a blinded interim analysis; at that time 10 of the 15 included patients in each treatment group were evaluable. Recurrent duodenal ulcers had occurred in four patients treated with placebo and none of the patients treated with ranitidine (Fisher's exact one-tailed P = 0.04; 95% CI, - 0.70 to -0.10). Recurrent gastric ulcers had occurred in six patients in the placebo group and three patients in the ranitidine group (Fisher's exact one-tailed P = 0.18; 95% CI, -0.72 to 0.12). Two patients in the placebo group had developed both duodenal ulcers and gastric ulcers. No adverse events were observed.\n High dose ranitidine is effective for the prevention of recurrent duodenal ulcer but not for recurrent gastric ulcer in rheumatoid arthritis patients taking NSAIDs.", "To evaluate the efficacy of pantoprazole in preventing gastrointestinal lesions in patients with rheumatic diseases receiving continuous, long-term treatment with non-steroidal anti-inflammatory drugs.\n This was a prospective, randomised, double-blind, unbalanced, placebo-controlled, parallel group study. Outpatients (n= 104, age range 22-80 years, mean age 59.5) with rheumatoid arthritis or osteoarthritis, requiring chronic intake of NSAIDs (at least 8 weeks prior to the start of the study), were randomised and enrolled to receive either 40 mg pantoprazole (n=70) or placebo (n=34) once daily, for 12 weeks. Patients had endoscopically confirmed gastric and duodenal lesions grade 0, 1 or 2 (Lanza classification grade 0: normal to hyperaemic mucosa; grade 1: 1 to 3 erosions, submucosal haemorrhage or petechiae, grade 2: 4 to 10 erosions, submucosal haemorrhages or petechiae). Clinical and endoscopic evaluations were performed at baseline, after 4, and 12 weeks. The primary end-point of the study was the incidence of gastric or duodenal ulcers after 4 and 12 weeks of treatment.\n Patients (n=95) were evaluated: 65 in the pantoprazole group and 30 in the placebo group. When considering all patients (those with Lanza score grade 0, 1, 2 at baseline), the overall proportion of patients in remission was 82% and 77% after 4 weeks, and 72% and 59% after 12 weeks in pantoprazole and placebo groups, respectively (cumulative survival analysis according to Kaplan-Meier). The difference between the treatment groups was even more marked when only those patients with normal mucosa at baseline (grade 0) were considered. After 12 weeks, the proportion of patients in remission was 82% (95% confidence limits 70% - 94% in the pantoprazole and 55% (95% confidence limits 33% - 77%) in the placebo treatment group, p=O.036. Adverse events were reported in 4% and 6% of patients in pantoprazole and placebo treatment groups, respectively\n Pantoprazole 40 mg once daily was well tolerated and is more effective than placebo in the prevention of peptic ulcers in patients with rheumatic diseases who require continuous, long-term, treatment with NSAIDs.", "To compare two regimens of pantoprazole administered intravenously in patients with ulcerative gastrointestinal bleeding (UGB), and a high risk of presenting with persitent or recurrent hemorrhage.\n Patients were randomized into two groups: group 0--treatment with a 80 mg bolus of pantoprazole administered intravenously, followed by continuous infusion of 8 mg/h for 72 hours; group 1--treatment with 40 mg of pantoprazole administered intravenously on a daily basis. The percentage of hemorrhagic persistence/recurrence in both groups was analyzed, as were transfusion requirements, need for surgery, and mortality resulting from the hemorrhagic episode.\n There were 20 patients in group 0 and 21 in group 1. No differences were found between groups in terms of gender, age, smoking habits, use of NSAIDs, presence of hemodynamic instability or stigmata in ulcer crater (Forrest Ia: 5 vs. 14.3%, p = 0.322; Forrest Ib: 30 vs. 33.3%, p = 0.819; Forrest IIa: 60 vs. 50.1%, p = 0.753). In group 0, 90% of patients received endoscopic treatment, versus 100% in group 1, p = 0.232. In group 0, 50% of patients had a transfusion, as compared to 52.4% in group 1, p = 0.879. In group 0, 2 patients (10.5%) presented with recurrent hemorrhage, versus 3 patients (14.3%) in group 1. Surgery was required by 1 person from each group, and 1 patient in group 0 died.\n Maximum acid inhibition with a bolus and then a continuous infusion of pantoprazole does not yield better results than treatment with conventional doses in acute hemorrhagic episodes.", "COX-2 specific inhibitors have demonstrated significant safety advantages and comparable efficacy in osteoarthritis (OA) compared with conventional nonsteroidal anti-inflammatory drugs (NSAIDs), but no direct comparative trials between COX-2 specific inhibitors have been published. In this double-blind, placebo-controlled, parallel group, multicenter study, 182 patients (> or =40 years old) with OA of the knee were randomly assigned to treatment with celecoxib 200 mg q.d. (n = 63), rofecoxib 25 mg q.d. (n = 59), or placebo (n = 60) for 6 weeks. Arthritis assessments were performed at baseline and Weeks 3 and 6, or at early termination. At Week 6, celecoxib and rofecoxib treatment resulted in similar mean changes from baseline (p > 0.55) in arthritis pain visual analogue scale, patient's global assessment, and total score for WOMAC; all changes were superior to placebo (p < 0.05). In the patient's global assessment of arthritis pain at Week 6, 79% of celecoxib-treated and 78% of rofecoxib-treated patients improved by > or =1 grade, compared with 50% of placebo patients (celecoxib, p = 0.025; rofecoxib, p = 0.020). Adverse event incidences were similar among the active comparators; however, celecoxib-treated patients had significantly fewer adverse gastrointestinal symptoms compared with rofecoxib-treated patients, which suggests that celecoxib may have a better gastrointestinal tolerability profile than rofecoxib at these doses. Adverse events that prompted withdrawal occurred in fewer than 7% of patients, and the overall incidences were similar between the active agents. Once-daily doses of celecoxib 200 mg and rofecoxib 25 mg offer comparable efficacy and are an effective alternative to conventional NSAIDs in the management of OA.", "Gastrointestinal (GI) toxicity mediated by dual cyclooxygenase (COX)-1 and COX-2 inhibition of nonsteroidal anti-inflammatory drugs (NSAIDs) can cause serious alterations of mucosal integrity or, more commonly, intolerable GI symptoms that may necessitate discontinuation of therapy. Unlike NSAIDs, rofecoxib targets only the COX-2 isoform.\n To assess the tolerability of rofecoxib compared with naproxen for treatment of osteoarthritis.\n Randomized, controlled trial.\n 600 office and clinical research sites.\n 5557 patients (mean age, 63 years) with a baseline diagnosis of osteoarthritis of the knee, hip, hand, or spine.\n Rofecoxib, 25 mg/d, or naproxen, 500 mg twice daily. Use of routine medications, including aspirin, was permitted.\n Discontinuation due to GI adverse events (primary end point) and use of concomitant medication to treat GI symptoms (secondary end point). Efficacy was determined by patient-reported global assessment of disease status and the Australian/Canadian Osteoarthritis Hand Index, as well as discontinuations due to lack of efficacy. Patients were evaluated at baseline and at weeks 6 and 12.\n Rates of cumulative discontinuation due to GI adverse events were statistically significantly lower in the rofecoxib group than in the naproxen group (5.9% vs. 8.1%; relative risk, 0.74 [95% CI, 0.60 to 0.92]; P = 0.005), as were rates of cumulative use of medication to treat GI symptoms (9.1% vs. 11.2%; relative risk, 0.79 [CI, 0.66 to 0.96]; P = 0.014]). Subgroup analysis of patients who used low-dose aspirin (13%) and those who previously discontinued using arthritis medication because of GI symptoms (15%) demonstrated a relative risk similar to the overall sample for discontinuation due to GI adverse events (relative risk, 0.56 [CI, 0.31 to 1.01] and 0.53 [CI, 0.34 to 0.84], respectively). No statistically significant difference was observed between treatments for efficacy in treating osteoarthritis or for occurrence of other adverse events.\n In patients with osteoarthritis treated for 12 weeks, rofecoxib, 25 mg/d, was as effective as naproxen, 500 mg twice daily, but had statistically significantly superior GI tolerability and led to less use of concomitant GI medications. Benefits of rofecoxib in subgroup analyses were consistent with findings in the overall sample.", "Proton-pump inhibitor (PPI) therapy for bleeding ulcers is more efficacious in Asian patients than in non-Asian patients. The aim of this study was to evaluate the efficacy of various doses of pantoprazole on intragastric acidity in Korean patients.\n A prospective randomized study was conducted in 52 patients either with bleeding peptic ulcers after successful endotherapy or who received endoscopic mucosal resection for gastric neoplasms. Patients were randomized into two doses of intravenous pantoprazole: 40 mg q.d. and 40 mg b.i.d. We compared these results with our preliminary study utilizing high-dose pantoprazole (80 mg + 8 mg/h). The potential contribution of CYP2C19 genetic polymorphisms and the presence of Helicobacter pylori were also assessed.\n Pantoprazole 40 mg b.i.d. and high-dose pantoprazole demonstrated better inhibition of intragastric acid than pantoprazole q.d. (P < 0.05). The pantoprazole 40 mg q.d. group exhibited significant variations in acid inhibition correlating with CYP2C19 genotype. Median 24 h pH values did not differ significantly between the pantoprazole b.i.d. and high-dose pantoprazole groups, regardless of H. pylori infection status. A median intragastric pH < 6.0 was observed in only three of 28 patients in the 40 mg b.i.d. group; these three patients were extensive metabolizers.\n A 40 mg b.i.d. dose of pantoprazole is sufficient to maintain pH > 6.0 in Korean patients, except for patients with extensive metabolizing CYP2C19 genotypes.", "To assess the effectiveness of 600 microg oral misoprostol on postpartum haemorrhage (PPH) and postpartum anaemia in a low income country home birth situation.\n Double blind randomised controlled trial.\n Twenty-six villages in rural Gambia with 52 traditional birth attendants (TBAs).\n One thousand, two hundred and twenty-nine women delivering at home under the guidance of a trained TBA.\n Active management of the third stage of labour using three 200-microg misoprostol tablets and placebo or four 0.5-mg ergometrine tablets (standard treatment) and placebo. Tablets were taken orally immediately after delivery.\n Measured blood loss, postpartum haemoglobin (Hb), difference between Hb at the last antenatal care visit and three to five days postpartum.\n The misoprostol group experienced lower incidence of measured blood loss > or =500 mL and postpartum Hb <8 g/dL, but the differences were not statistically significant. The reduction in postpartum (compared with pre-delivery) Hb > or = 2 g/dL was 16.4% with misoprostol and 21.2% with ergometrine [relative risk 0.77; 95% confidence interval (CI) 0.60-0.98; P= 0.02]. Shivering was significantly more common with misoprostol, while vomiting was more common with ergometrine. Only transient side effects were observed.\n Six hundred micrograms of oral misoprostol is a promising drug to prevent life-threatening PPH in this setting.", "The results of four similarly designed, randomized, double-blind, placebo-controlled studies conducted to evaluate ranitidine as prophylaxis for NSAID-associated damage are reviewed. A total of 673 patients receiving therapeutic dosages of NSAIDs for arthritic or musculoskeletal conditions also received either ranitidine 150 mg twice daily (n = 343) or placebo (n = 330) for four weeks (two studies) or eight weeks (two studies). Endoscopic grading of mucosal lesions was based on a modified Lanza scoring system. All patients had normal baseline endoscopies. After four weeks of treatment a significant protective effect against duodenal mucosal lesions including duodenal ulcers (three studies) and gastric mucosal lesions including gastric ulcers (one study) was observed in patients who received ranitidine compared with those who received placebo. A meta-analysis of the four studies confirmed that significantly fewer patients receiving ranitidine than placebo developed duodenal ulcers (1% vs. 6%, P = 0.01). Endoscopic data at eight weeks from the two longer-term studies showed that duodenal ulcers occurred in ranitidine- and placebo-treated patients at a rate of 1% (2/137) vs. 8% (10/126) (P = 0.02), respectively, in one trial, and 0% (0/57) vs. 8% (4/49) (P = 0.02), respectively, in the other trial. No protective effect in the stomach was evident at eight weeks. We conclude that ranitidine is effective in preventing NSAID-associated duodenal ulcers and may be appropriate prophylaxis for certain high-risk patients.", "To compare the incidence of selected spontaneously reported adverse events (AEs) in patients with osteoarthritis (OA) treated with rofecoxib (VIOXX, 12.5 mg qd) or Arthrotec (diclofenac 50 mg/misoprostol 200 mcg bid).\n Double-blind, parallel-group, 6-week study of patients aged > or = 40 years with a clinical diagnosis of OA treated with rofecoxib or Arthrotec. Primary endpoint: self-reported diarrhea; secondary endpoints: abdominal pain, discontinuations due to AEs, GI AEs and NSAID-type GI AEs (ie., acid reflux, dyspepsia, epigastric discomfort, heartburn, nausea, vomiting).\n Among 483 patients (80.3% females, mean age 62.1), the rofecoxib group vs the Arthrotec group respectively reported diarrhea 6.2% vs 16.2% (p<0.001); drug-related diarrhea 3.7% vs 16.2% (p<0.001); one or more clinical AEs 52.9% vs 73.0% (p<0.001); GI AEs 28.9% vs 48.5% (p<0.001); NSAID-type GI AEs 18.6% vs 29.9% (p=0.004); discontinuations due to abdominal pain 0.4% vs 3.7% (p<0.05); and discontinuations due to any AE 4.1% vs 9.1% (p=0.029). No significant differences were observed in efficacy.\n Rofecoxib 12.5 mg qd has improved GI tolerability and similar efficacy compared to Arthrotec (diclofenac 50 mg/misoprostol 200 mcg bid)." ]	Misoprostol, PPIs, and double dose H2RAs are effective at preventing chronic NSAID related endoscopic gastric and duodenal ulcers. Lower doses of misoprostol are less effective and are still associated with diarrhoea. In patients with previous NSAID bleeds, a COX-2 inhibitor alone is equivalent to a tNSAID+PPI, though the re-bleeding rates with both strategies are still relatively high. A strategy of a COX-2 inhibitor+PPI appears to offer the greatest GI safety in high risk patients.
CD003445	[ "7683942", "9093725", "10213009" ]	[ "Randomised comparison of combination chemotherapy plus supportive care with supportive care alone in patients with metastatic colorectal cancer.", "Randomized comparison between chemotherapy plus best supportive care with best supportive care in advanced gastric cancer.", "A phase III study of irinotecan (CPT-11) versus best supportive care in patients with metastatic colorectal cancer who have failed 5-fluorouracil therapy. V301 Study Group." ]	[ "To compare the length of survival and quality of life in patients given combination chemotherapy in addition to supportive care and in patients given only supportive care.\n Randomised study.\n Gastrointestinal oncology departments.\n 40 previously untreated patients with histologically confirmed, measurable colorectal cancer that was locally recurrent or metastatic.\n Patients were allocated randomly to receive chemotherapy or only supportive care in a ratio of 2:1 according to performance status, metastatic disease of the liver, and weight loss in the six months before entering the study. Chemotherapy consisted of four week cycles of intravenous leucovorin (200 mg/m2/day) followed by 5-fluorouracil (550 mg/m2/day) and cisplatin (20 mg/m2/day), each drug being given on the first four days of the cycle.\n Length of survival and quality of life score with an optimised functional living index-cancer scale.\n Overall survival was significantly longer for patients given chemotherapy (11.0 months) than for those receiving supportive care alone (5.0 months; p = 0.006). Despite common association of chemotherapy with mild to moderate gastrointestinal symptoms, there was no significant difference between the two groups in global or subgroup quality of life scores. In patients with abnormal scores before treatment, quality of life seemed better in the chemotherapy arm.\n In this sample of patients with disseminated colorectal cancer the chemotherapy regimen was an effective form of palliative treatment.", "The extent to which chemotherapy may relieve tumour-related symptoms, improve quality of life and prolong survival in patients with gastric cancer is not known in spite of the extensive use of this treatment modality. The aim of this study was to estimate any gain in the quantity and quality of life produced by chemotherapy in these patients.\n Between January 1991 and February 1995, 61 patients with gastric cancer were randomized to either chemotherapy in addition to best supportive care or to best supportive care. Chemotherapy was allowed in the latter group if the supportive measures did not lead to palliation. Chemotherapy was the ELF-regimen consisting of 5-fluorouracil, leucovorin and etoposide, or, in elderly patients with poor performance, a 5-fluorouracil/leucovorin regimen (FLv). Quality of life was evaluated with the EORTC-QLQ-C30 instrument.\n More patients in the chemotherapy group (45%, 14/31) had an improved or prolonged high quality of life for a minimum period of 4 months compared to those in the best supportive care group (20%, 6/30, P < 0.05). A similar difference was seen in the treating physician's evaluation of whether the patient was subjectively improved or continued to do well for at least 4 months (17/31, 55% versus 6/30, 20%, P < 0.01). Overall survival was longer in the chemotherapy group (median 8 vs. 5 months) although the difference was not statistically significant (P = 0.12). After corrections for imbalances in pretreatment characteristics, chemotherapy treatment was, however, associated with a survival benefit (P = 0.003). Also, the quality-adjusted survival time and time to disease progression were longer for patients randomized to chemotherapy (median 5 vs. 2 months, P = 0.03).\n The results show that chemotherapy can add to both quantity and quality of life in advanced gastric cancer. The number of patients who benefit from treatment is, however, still rather limited.", "In a prospective multicenter trial, 279 patients with metastatic colorectal cancer who had failed 5-fluorouracil therapy were randomized 2:1 to receive either best supportive care (BSC) plus treatment with the topoisomerase I inhibitor, irinotecan (CPT-11; Rhône-Poulenc Rorer, Antony, France), at a dose of 350 mg/m2 every 3 weeks or BSC alone. Overall survival, the primary end point of the study, was significantly improved in patients receiving the irinotecan treatment. Only 14% of patients receiving BSC alone were alive at 1 year compared with 36% in the irinotecan group. After adjustment for prognostic factors such as performance status, the difference in survival favoring irinotecan remained highly significant (P = .001). The benefit of irinotecan was also observed through significantly longer survival without performance status deterioration, longer survival without more than 5% weight loss, and longer duration of pain-free survival. Appreciable deterioration in global quality of life (50% reduction from baseline) occurred significantly later in the irinotecan-treated patients than in the controls. Additionally, quality of life analyses of all symptoms, except diarrhea, mean scores were significantly in favor of patients assigned to irinotecan treatment than those assigned to BSC. This is the first time that the benefit of second-line chemotherapy has been demonstrated by a randomized controlled trial in advanced colorectal cancer." ]	Overall the results show that for most of the studies included in this review, certain forms of chemotherapy plus supportive care improve both survival and quality of life in patients with gastrointestinal cancer (gastric and colorectal cancers) compared to receiving supportive care alone. Trials involving BSC/SC in patients with advanced gastrointestinal cancer require careful evaluation. Oncologists and researchers alike should strive for improvements in trial design and reporting. Future trials should focus on clearer definitions of supportive care. The EORTC definition of supportive care can be used as a guide. BSC/SC trials should use standardised validated outcome measures for symptom control, quality of life, toxicity and other useful palliative measures.
CD007720	[ "17710485", "3943336", "2233916", "8625660", "9713447" ]	[ "Efficacy of corticosteroids in the treatment of community-acquired pneumonia requiring hospitalization.", "Role of corticosteroids in the development of pneumonia in mechanically ventilated head-trauma victims.", "Corticosteroids as adjunctive therapy for severe Pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome. A double-blind, placebo-controlled trial.", "Effects of long-term treatment with corticosteroids in COPD.", "Randomised controlled trial of inhaled corticosteroids in patients with chronic obstructive pulmonary disease." ]	[ "Recent studies suggested that administration of corticosteroids may improve clinical outcomes in patients with severe pneumonia.\n The aim of this study was to assess the effectiveness of corticosteroids as an adjunctive therapy in community-acquired pneumonia (CAP) requiring hospitalization.\n An open label, prospective, randomized control study was conducted from September 2003 to February 2004 in a community general hospital in Japan.\n Thirty-one adult CAP patients who required hospitalization were enrolled.\n Fifteen patients received 40 mg of prednisolone intravenously for 3 days (steroid group). Sixteen patients did not receive prednisolone (control group). Both groups were also evaluated for their adrenal function. The primary endpoint was length of hospital stay. Secondary endpoints were duration of intravenous (IV) antibiotics and time required to stabilize vital signs. Both groups demonstrated similar baseline characteristics and length of hospital stay, and yet a shorter duration of IV antibiotics was observed in the steroid group (p < 0.05). In addition, vital signs were stabilized earlier in the steroid group (p < 0.05). These differences were more prominent in the moderate-severe subgroup but not as significant in the mild-moderate subgroup. The prevalence of relative adrenal insufficiency (RAI) in both groups was high (43%), yet there was no difference in baseline characteristics between patients, with or without RAI. In multiple regression models, RAI seemed to have no influence on clinical courses.\n In moderate-severe CAP, administration of corticosteroids promotes resolution of clinical symptoms and reduces the duration of intravenous antibiotic therapy.", "The development of pneumonia was monitored in head-trauma patients requiring mechanical ventilation. Of the 66 patients studied, 15 (23%) developed pneumonia within 14 days after ICU admission. In each case the diagnosis was based on x-ray evidence and at least two of the following: increased white blood cell count, increased fever, and/or increased sputum production with a predominant organism on the sputum stain. Coagulase-positive Staphylococcus aureus was the most common etiologic agent. There was no difference in the occurrence of pneumonia between patients treated with no steroids or with low, moderate, or high steroid doses. Although there was an association between thiopental use and the development of pneumonia, dexamethasone treatment was not a significant risk factor in the development of pneumonia in this patient population.", "Preliminary reports suggest that patients with the acquired immunodeficiency syndrome (AIDS) and Pneumocystis carinii pneumonia may benefit from the addition of corticosteroid treatment to antibiotic therapy.\n We conducted a double-blind, placebo-controlled trial to assess the efficacy of adjunctive corticosteroids in patients with AIDS and severe P. carinii pneumonia. Patients with marked abnormalities in gas exchange who had been treated with antibiotics for less than 72 hours were randomly assigned to receive either methylprednisolone (40 mg) or placebo every 6 hours for 7 days, in addition to treatment for 21 days with trimethoprim-sulfamethoxazole. The primary outcome measures were survival until hospital discharge and the development of respiratory failure.\n Twenty-three patients were enrolled in the study; there were no significant differences in base-line clinical or laboratory measures between the two treatment groups. Of 12 patients treated with corticosteroids, 9 (75 percent) survived until hospital discharge, as compared with only 2 of 11 placebo recipients (18 percent) (P less than 0.008). Respiratory failure developed in nine placebo recipients, as compared with only three patients treated with corticosteroids (P less than 0.008). No patient required the interruption or discontinuation of corticosteroid or antibiotic treatment because of toxicity or a complicating event. Because of the marked difference in survival, it was deemed unethical to continue the trial, and the study was terminated.\n Early adjunctive corticosteroid therapy can improve survival and decrease the occurrence of respiratory failure in patients with AIDS and severe P. carinii pneumonia.", "To determine the effectiveness of treatment with corticosteroids in patients with COPD.\n In this study, we investigated the effect of a 2-year treatment with corticosteroids on clinical symptoms and the decline of lung function in 58 nonallergic patients with COPD. Subjects were treated in a double-blind, randomized, placebo-controlled, parallel way with inhaled budesonide (bud), 1,600 micrograms/d; inhaled budesonide, 1,600 micrograms/d, plus oral prednisolone, 5 micrograms/d (bud + pred); or placebo (plac). Clinical assessment (history, physical examination, and spirometry) was carried out every 2 months. The rate of decline in FEV1 was assessed by calculating individual regression co-efficients from linear regression of FEV1 on time for each subject.\n Eleven patients dropped out. The number of withdrawals due to pulmonary problems was significantly higher in the plac group (n = 5 out of 18) than in the actively treated groups (n = 2 out of 40). Treatment with corticosteroids significantly reduced pulmonary symptoms. Median decline of FEV1 was 60 mL/yr in the plac group, 40 mL/yr in the bud + pred group, and 30 mL/yr in the bud group. Variation was large and differences were not statistically significant. No treatment effect was found on frequency or duration of exacerbations, possibly because of the high number of withdrawals due to pulmonary deterioration in the plac group. Treatment with a combination of inhaled plus oral corticosteroids was not more effective than inhaled corticosteroids alone. Morning plasma cortisol levels remained within the normal range in all three groups.\n Our study shows beneficial effects of long-term daily treatment with inhaled corticosteroids in patients with COPD with regard to symptoms and drop out due to pulmonary problems. Lung function decline tends to decrease during treatment with inhaled corticosteroids. The observed effects are limited but warrant further studies on the effectiveness of corticosteroids in larger numbers of patients with COPD.", "Inhaled corticosteroids are known to be beneficial for patients with asthma, but their role in treating patients with stable chronic obstructive pulmonary disease (COPD) remains controversial. A study was undertaken to determine whether inhaled corticosteroids are of functional benefit in patients who did not show improvement with a trial of oral corticosteroids.\n In phase I patients with stable COPD were given a two week course of oral placebo followed by two weeks of prednisone 40 mg per day in a single blind manner to distinguish between responders and non-responders to oral corticosteroids. In phase II a double blind, randomised, parallel group trial of inhaled budesonide 1600 micrograms per day versus placebo was carried out in 79 nonresponders to oral corticosteroids. The primary outcome measure was forced expiratory volume in one second (FEV1), and secondary outcome measures were exercise capacity, dyspnoea with exertion, quality of life, peak expiration flow rate, and respiratory symptoms.\n Randomisation allocated 39 subjects to inhaled corticosteroids and 40 to placebo. There was no difference in the change in FEV1 from baseline between the treatment and placebo groups; mean difference -12 ml (95% CI -88 to 63) at three months and -4 ml (95% CI -95 to 87) at six months. The proportion of patients with a 15% or greater improvement was no higher among those receiving inhaled corticosteroids than in the placebo group at any of the follow up visits. Changes in secondary outcomes were also no different.\n Inhaled corticosteroids, even at high doses, were of no physiological or functional benefit in these patients with advanced COPD." ]	In most patients with pneumonia, corticosteroids are generally beneficial for accelerating the time to resolution of symptoms. However, evidence from the included studies was not strong enough to make any recommendations.
CD003927	[ "16489694", "8885732", "8688399", "10521736", "6988006", "6990761", "9259905", "1879595", "17272618", "18275573", "8238130", "2657045" ]	[ "Ritodrine in oral maintenance of tocolysis after active preterm labor: randomized controlled trial.", "The clinical efficacy of oral tocolytic therapy.", "Double-blind evaluation of ritodrine sustained release for oral maintenance of tocolysis after active preterm labour.", "Maintenance oral nifedipine for preterm labor: a randomized clinical trial.", "The influence of betamethasone and orciprenaline on the incidence of respiratory distress syndrome in the newborn after preterm labour.", "Oral ritodrine maintenance in the treatment of preterm labor.", "A placebo-controlled randomized trial of the terbutaline pump for prevention of preterm delivery.", "The use of micronized progesterone in the treatment of menace of preterm delivery.", "Randomized trial of a single repeat dose of prenatal betamethasone treatment in imminent preterm birth.", "Progesterone for maintenance tocolytic therapy after threatened preterm labour: a randomised controlled trial.", "Antibiotic treatment of preterm labor with intact membranes: a multicenter, randomized, double-blinded, placebo-controlled trial.", "Randomized comparison of oral terbutaline and ritodrine for preventing recurrent preterm labor." ]	[ "To assess the efficacy of oral ritodrine in the form of sustained-release capsules for maintenance of uterine quiescence after successful treatment of threatened preterm labor.\n We randomized 120 women with singleton pregnancy who were successfully treated for threatened preterm labor before 34 completed weeks to receive either maintenance tocolysis with two 40 mg ritodrine sustained release capsules three times a day (study group, n=62) or no treatment (control group, n=58) for three days. The primary outcome measure was the recurrent episode of threatened preterm labor within 72 hours, which was defined as regular palpable uterine contractions and change in cervical effacement or cervical dilatation on clinical examination. Secondary outcome measures included the incidence of preterm birth, neonatal adverse outcomes, and maternal side effects.\n There was no difference in the frequency of recurrent episodes of threatened preterm labor requiring another course of intravenous treatment between the study (8/62) and control (6/58) group of women (P=0.879). No differences were found between the study and control groups in any of the predefined secondary outcome measures, ie, delivery before 37 weeks (13/62 vs 7/58, respectively; P=0.288), delivery before 34 weeks (3/62 vs 1/58, respectively; P=0.682) and birth weight (3037-/+573 g vs 3223-/+423 g, respectively, P=0.862). There were more reported maternal side effects in the study group than in control group (47/62 vs 23/58, respectively; P(<0.001).\n Additional maintenance ritodrine therapy was unnecessary in women with singleton pregnancy who had an episode of threatened preterm labor successfully treated with intravenous tocolytic therapy.\n ClinicalTrials.gov Identifier: NCT00290173.", "Our purpose was to determine whether maintenance oral tocolytic therapy after preterm labor stabilization decreases uterine activity, reduces the rate of recurrent preterm labor and subsequent preterm birth, or improves neonatal outcome.\n Women with documented idiopathic preterm labor stabilized with acute tocolytic therapy were randomized to three groups: placebo, terbutaline 5 mg, or magnesium chloride 128 mg, all given orally every 4 hours. Patients and providers were blinded to group assignment. All subjects were enrolled in a comprehensive system of preterm birth prevention that included preterm labor education, weekly clinic visits, home uterine contraction assessment, daily phone contact, and 24-hour perinatal nurse access.\n Of the 248 patients who were randomized, 39 were delivered before discharge and 4 were lost to follow-up, leaving 205 for final analysis: 68 placebo, 72 terbutaline, and 65 magnesium. The terbutaline group had significantly more side effects than the placebo group did. All groups had otherwise similar perinatal outcomes when confounding variables were controlled for. Overall, the three groups had a preterm birth rate < 37 weeks of 55.6% delivery, < 34 weeks of 15.6%, a 20.4% rate of newborn intensive care unit admission, and a mean neonatal length of stay of 6.3 days.\n Maintenance oral tocolytic therapy did not decrease uterine activity, reduce the rate of recurrent preterm labor or preterm birth, or improve perinatal outcome. Overall improvement in perinatal outcome may be achieved with a comprehensive program of preterm birth prevention without the use of maintenance oral tocolytic therapy.", "To evaluate the effect of ritodrine sustained release capsules for maintaining uterine quiescence after successful treatment of active preterm labour.\n Multicentre placebo-controlled trial.\n Five teaching hospitals in the Netherlands.\n Women (n = 95) at less than 35 weeks of gestation in whom active preterm labour had been stopped with intravenous ritodrine.\n Women received either two 40 mg ritodrine sustained release capsules (n = 50) or identical placebo capsules (n = 45) three times a day for seven days.\n The proportion of women who received another course of active treatment was significantly smaller with the sustained release than with placebo (1 of 50 versus 11 of 45: P = 0.003) as was the number delivering because of preterm labour during treatment (0 of 50 versus 4 of 45: P = 0.04). There were no other significant differences between the two groups.\n Maintenance treatment with ritodrine sustained release capsules after arrest of preterm labour reduces the risk of recurrences of preterm labour that necessitate treatment or precipitate delivery.", "This study was undertaken to evaluate the efficacy of maintenance oral nifedipine in patients initially treated with intravenous magnesium sulfate for preterm labor.\n Patients with a diagnosis of preterm labor between 24 and 33.9 weeks' gestation were randomly assigned to receive either maintenance tocolytic therapy with oral nifedipine (20 mg every 4-6 hours) or no treatment (control) after discontinuation of magnesium tocolysis. Pregnancy and neonatal outcomes were evaluated. A sample size of 50 patients was required to detect a 10-day difference in mean time gained (beta =.2, alpha =.05). Statistical analyses were based on intent to treat. The t, chi(2), and Fisher exact tests were performed.\n Seventy-four patients were randomly assigned to receive either oral nifedipine (n = 37) or no treatment (n = 37). There were no statistically significant differences in age, race, parity, preterm delivery risk factors, enrollment gestational age, results of cervical examination, delivery gestational age, time gained, or neonatal complications between the groups. Delivery gestational age (mean +/- SD) was 35.4 +/- 3.2 weeks for patients randomly assigned to receive nifedipine and 35.3 +/- 3.2 weeks for patients who received no treatment (P =.9). Time gained during pregnancy was 37 +/- 23.9 days in the nifedipine group and 32.8 +/- 20.4 days in the control group (P =.4).\n Maintenance therapy with oral nifedipine does not significantly prolong pregnancy in patients initially treated with intravenous magnesium sulfate for preterm labor.", "In a randomized double-blind trial on antenatal corticosteroid treatment for the prevention of respiratory distress syndrome (RDS) a corticosteroid related beneficial effect was found. Possibly of more significance was the finding that the children born within 12 hours of their mother's admission to hospital showed a higher incidence of RDS than those born between 12 hours and one week after admission even in the placebo and untreated groups. Bèta-adrenergic drugs seemed to exert no other influence on the occurrence of RDS than can be explained by the delay of delivery. Prolonged ruptured membranes appeared to decrease the incidence of RDS to the same extent as other symptoms of threatened preterm labour.", "Seventy patients with preterm labor and intact membranes were initially treated with ritodrine hydrochloride to delay preterm delivery. Tocolysis beyond 24 hours was achieved in 59 patients. Fifty-five of the 59 patients were then placed on either oral ritodrine or placebo as maintenance therapy in a randomized double-blind manner. If preterm labor recurred, the sequence of intramuscular and then oral treatment was repeated. The number of days gained after initiation of intramuscular treatment was similar in both groups (oral ritodrine = 34 days, oral placebo = 36 days). In those 55 patients receiving oral treatment, there was a smaller number of relapses requiring repeat intramuscular treatment in the oral ritodrine group (1.11 in the ritodrine patient vs. 2.71 in the placebo patient, p less than 0.05), and the mean interval between beginning oral treatment and the first relapse/delivery was 5.8 days in the oral placebo group and 25.9 in those receiving oral ritodrine (p less than 0.05). Cardiovascular side effects, notably maternal tachycardia and palpitations were frequent but well tolerated. The results suggest that oral ritodrine maintenance will decrease the incidence of recurrent preterm labor in patients who have had initial successful tocolysis.", "To determine the efficacy of the terbutaline pump for the prevention of preterm delivery, patients in preterm labor defined by progressive cervical change underwent intravenous magnesium sulfate tocolysis (with or without oral indomethacin, as necessary), and once labor was arrested, were randomized to one of three treatment arms: terbutaline by pump, saline by pump (blinded), or oral terbutaline. If recurrent preterm labor occurred despite maximization of therapy, the treatment arm was determined and therapy was changed; saline pump and oral terbutaline were switched to terbutaline pump, terbutaline pump was switched to oral terbutaline. Patients who continued to labor were readmitted for aggressive intravenous therapy. Women randomized to the terbutaline pump (n = 15), saline pump (n = 12), and oral terbutaline (n = 15) groups were similar in terms of gravidity, parity, days of tocolysis before study entry, gestational age at entry, and cervical dilatation at entry. The mean gestational age at delivery was the same in all three groups (35 weeks), as were neonatal outcomes. Terbutaline by pump, saline by pump, and oral terbutaline appear equivalent for the prevention of preterm delivery. The terbutaline pump should remain experimental.", "The results of a study concerning the treatment of acute menace of preterm labor are given: beta-mimetics were administered intravenously in all cases (44) and micronized progesterone or placebo was administered orally after classical double-blind randomization (22 cases in each group). The mean index of pregnancy prolongation was the same in both groups. However the mean duration of the intravenous perfusion and the mean quantity of beta-mimetics administered intravenously were significantly reduced in the progesterone group (P less than 0.01). The mean duration of hospital stay was also significantly reduced (P less than 0.05). Cost and risks are finally significantly lessened.", "A single dose of prenatal betamethasone treatment decreases neonatal morbidity rates when administered within 7 days before preterm delivery. A single repeat dose or booster dose of betamethasone before delivery has been proposed to be effective, but its efficacy has not been subjected to a randomized, blinded trial.\n Women with imminent delivery before 34.0 gestational weeks were eligible if they remained without delivery for >7 days after a single course of betamethasone. After stratification, a single repeat dose of betamethasone (12 mg) or placebo was administered. The primary outcome was survival without respiratory distress syndrome or severe intraventricular hemorrhage (grade 3 or 4).\n A total of 249 mothers had been enrolled by the time the study was discontinued. All of the 159 infants in the betamethasone group and 167 in the placebo group were born before 36 weeks of gestation. The intact survival rate was unaffected and was lower than anticipated, because the gestational age-adjusted incidence of respiratory distress syndrome was higher than the population incidence. The requirement for surfactant therapy in respiratory distress syndrome was increased in the betamethasone group. According to posthoc analysis of the data for 206 infants who were delivered within 1 to 24 hours, the betamethasone booster tended to increase the risk of respiratory distress syndrome and to decrease intact survival rates.\n According to this study, a single booster dose of betamethasone just before preterm birth may perturb respiratory adaptation. These results caution against uncontrolled use of a repeat dose of glucocorticoid in high-risk pregnancies.", "Women with preterm labour that is arrested with tocolytic therapy are at increased risk of recurrent preterm labour. The efficacy of maintenance tocolytic therapy after successful arrest of preterm labour remains controversial.\n The purpose of this study was to determine whether supplementation of vaginal progesterone after inhibition of preterm labour is associated with an increased latency period and a decreased recurrent of preterm labour.\n This trial was conducted in 70 women who presented with symptoms of threatened preterm labour, who after arrest of uterine activity were then randomised to progesterone therapy or no treatment. Treatment group received progesterone suppository (400 mg) daily until delivery and control group received no treatment.\n Longer mean latency until delivery (36/11 +/- 17/9 vs 24/52 +/- 27/2) (mean + standard deviation) days; respiratory distress syndrome 4 (10.8%) vs 12 (36.4%) P = 0.021; low birthweight 10 (27%) vs 17 (51.5%) P = 0.04; and birthweight (3101.54 +/- 587.9 g vs r 2609.39 +/- 662.9 g, P = 0.002), were significantly different between the two groups. No significant differences were found between recurrent preterm labour 13 (35.1%) vs 19 (57.6%), P = 0.092; admission to intensive care unit 9 (24.3%) vs 13 (39.4%), P= 0.205 ; and neonatal sepsis 2 (5.4%) vs 6 (18.2%) P = 0.136, for the progesterone and control groups, respectively.\n The use of vaginal progesterone suppository after successful parenteral tocolysis associated with a longer latency preceding delivery but failed to reduce the incidence of readmission for preterm labour.", "Although an association between subclinical intrauterine infection and preterm birth is well established, there is conflicting evidence regarding the benefits of antibiotic administration to women in preterm labor with intact membranes. We attempted to determine the effect of ampicillin-amoxicillin and erythromycin treatment on prolongation of pregnancy, the rate of preterm birth, and neonatal morbidity in patients with preterm labor and intact membranes.\n A multicenter, randomized, double-blinded, placebo-controlled trial was designed and implemented by the Maternal-Fetal Medicine Units Network of the National Institute of Child Health and Human Development. Two hundred seventy-seven women with singleton pregnancies and preterm labor with intact membranes (24 to 34 weeks) were randomly allocated to receive either antibiotics or placebos.\n Of the 2373 patients screened for participation in this study in six medical centers, 277 women were enrolled (n = 133 for antibiotics group vs n = 144 for placebo group). In each study group, 60% of patients completed all the study medications. The overall prevalence of microbial invasion of the amniotic cavity was 5.8% (14/239). No significant difference between the antibiotic group and the placebo group was found in maternal outcomes, including duration of randomization-to-delivery interval, frequency of preterm delivery (< 37 weeks), frequency of preterm premature rupture of membranes, clinical chorioamnionitis, endometritis, and number of subsequent admissions for preterm labor. Similarly, no significant difference in neonatal outcomes could be detected between the two groups including respiratory distress syndrome, bronchopulmonary dysplasia, intraventricular hemorrhage, sepsis, and admission and duration of newborn intensive special care unit hospitalization.\n The results of this study do not support the routine use of antibiotic administration to women in preterm labor with intact membranes.", "We compared oral ritodrine and terbutaline for the prevention of recurrent preterm labor. Women between 20 and 35 weeks' gestation who successfully completed a course of intravenous tocolysis were eligible for inclusion. One hundred two patients were randomized to oral ritodrine (20 mg every four hours) or oral terbutaline (5 mg every four hours). The groups showed no significant differences with respect to recognized risk factors for preterm labor or prognostic factors for the failure of tocolysis. Initial treatment failures occurred more frequently in the ritodrine group (nine vs. two, P = .0527). There were no statistically significant differences in the treatment results or frequency of side effects. We conclude that ritodrine appears to be less effective than terbutaline upon the initiation of oral therapy and that oral ritodrine and terbutaline are equivalent in safety and efficacy when used on a long-term basis for preventing recurrent preterm labor." ]	Available evidence does not support the use of oral betamimetics for maintenance therapy after threatened preterm labour.
MR000016	[ "9676667", "14996698", "12038932", "8942777", "9708752", "9872878", "10789326", "12701945", "9676668", "8198342", "8928603", "17473138", "1727960", "12038910", "12161081", "9310565", "8015120", "9737493", "19775439", "15161896", "7853047", "1315663", "12876092", "17115429", "9676666", "8721797" ]	[ "Effect on the quality of peer review of blinding reviewers and asking them to sign their reports: a randomized controlled trial.", "Effects of training on quality of peer review: randomised controlled trial.", "Comparison of review articles published in peer-reviewed and throwaway journals.", "Readers' evaluation of effect of peer review and editing on quality of articles in the Nederlands Tijdschrift voor Geneeskunde.", "The Medical Journal of Australia Internet peer-review study.", "Effect of open peer review on quality of reviews and on reviewers' recommendations: a randomised trial.", "Open peer review: a randomised controlled trial.", "Publication bias and meta-analyses: a practical example.", "Does masking author identity improve peer review quality? A randomized controlled trial. PEER Investigators.", "Manuscript quality before and after peer review and editing at Annals of Internal Medicine.", "How does the peer review process influence AANA journal article readability?", "Commercially funded and United States-based research is more likely to be published; good-quality studies with negative outcomes are not.", "Factors influencing publication of research results. Follow-up of applications submitted to two institutional review boards.", "Effect of written feedback by editors on quality of reviews: two randomized trials.", "The reporting of methodological factors in randomized controlled trials and the association with a journal policy to promote adherence to the Consolidated Standards of Reporting Trials (CONSORT) checklist.", "Publication bias: evidence of delayed publication in a cohort study of clinical research projects.", "Effects of peer review and editing on the readability of articles published in Annals of Internal Medicine.", "Effect of attendance at a training session on peer reviewer quality and performance.", "A randomized controlled trial evaluating the impact of knowledge translation and exchange strategies.", "Empirical evidence for selective reporting of outcomes in randomized trials: comparison of protocols to published articles.", "Cumulative meta-analysis of clinical trials builds evidence for exemplary medical care.", "Impact of random assignment on study outcome: an empirical examination.", "Factors associated with failure to publish large randomized trials presented at an oncology meeting.", "Examination of the analytic quality of behavioral health randomized clinical trials.", "Effect of blinding and unmasking on the quality of peer review: a randomized trial.", "Assessing the quality of reports of randomized clinical trials: is blinding necessary?" ]	[ "Anxiety about bias, lack of accountability, and poor quality of peer review has led to questions about the imbalance in anonymity between reviewers and authors.\n To evaluate the effect on the quality of peer review of blinding reviewers to the authors' identities and requiring reviewers to sign their reports.\n Randomized controlled trial.\n A general medical journal.\n A total of 420 reviewers from the journal's database.\n We modified a paper accepted for publication introducing 8 areas of weakness. Reviewers were randomly allocated to 5 groups. Groups 1 and 2 received manuscripts from which the authors' names and affiliations had been removed, while groups 3 and 4 were aware of the authors' identities. Groups 1 and 3 were asked to sign their reports, while groups 2 and 4 were asked to return their reports unsigned. The fifth group was sent the paper in the usual manner of the journal, with authors' identities revealed and a request to comment anonymously. Group 5 differed from group 4 only in that its members were unaware that they were taking part in a study.\n The number of weaknesses in the paper that were commented on by the reviewers.\n Reports were received from 221 reviewers (53%). The mean number of weaknesses commented on was 2 (1.7, 2.1, 1.8, and 1.9 for groups 1, 2, 3, and 4 and 5 combined, respectively). There were no statistically significant differences between groups in their performance. Reviewers who were blinded to authors' dentities were less likely to recommend rejection than those who were aware of the authors' identities (odds ratio, 0.5; 95% confidence interval, 0.3-1.0).\n Neither blinding reviewers to the authors and origin of the paper nor requiring them to sign their reports had any effect on rate of detection of errors. Such measures are unlikely to improve the quality of peer review reports.", "To determine the effects of training on the quality of peer review.\n Single blind randomised controlled trial with two intervention groups receiving different types of training plus a control group.\n Reviewers at a general medical journal. Interventions Attendance at a training workshop or reception of a self taught training package focusing on what editors want from reviewers and how to critically appraise randomised controlled trials.\n Quality of reviews of three manuscripts sent to reviewers at four to six monthly intervals, evaluated using the validated review quality instrument; number of deliberate major errors identified; time taken to review the manuscripts; proportion recommending rejection of the manuscripts.\n Reviewers in the self taught group scored higher in review quality after training than did the control group (score 2.85 v 2.56; difference 0.29, 95% confidence interval 0.14 to 0.44; P = 0.001), but the difference was not of editorial significance and was not maintained in the long term. Both intervention groups identified significantly more major errors after training than did the control group (3.14 and 2.96 v 2.13; P < 0.001), and this remained significant after the reviewers' performance at baseline assessment was taken into account. The evidence for benefit of training was no longer apparent on further testing six months after the interventions. Training had no impact on the time taken to review the papers but was associated with an increased likelihood of recommending rejection (92% and 84% v 76%; P = 0.002).\n Short training packages have only a slight impact on the quality of peer review. The value of longer interventions needs to be assessed.", "To compare the quality, presentation, readability, and clinical relevance of review articles published in peer-reviewed and \"throwaway\" journals.\n We reviewed articles that focused on the diagnosis or treatment of a medical condition published between January 1 and December 31, 1998, in the 5 leading peer-reviewed general medical journals and high-circulation throwaway journals. Reviewers independently assessed the methodologic and reporting quality, and evaluated each article's presentation and readability. Clinical relevance was evaluated independently by 6 physicians.\n Of the 394 articles in our sample, 16 (4.1%) were peer-reviewed systematic reviews, 135 (34.3%) were peer-reviewed nonsystematic reviews, and 243 (61.7%) were nonsystematic reviews published in throwaway journals. The mean (SD) quality scores were highest for peer-reviewed articles (0.94 [0.09] for systematic reviews and 0.30 [0.19] for nonsystematic reviews) compared with throwaway journal articles (0.23 [0.03], F(2,391) = 280.8, P<.001). Throwaway journal articles used more tables (P =.02), figures (P =.01), photographs (P<.001), color (P<.001), and larger font sizes (P<.001) compared with peer-reviewed articles. Readability scores were more often in the college or higher range for peer-reviewed journals compared with the throwaway journal articles (104 [77.0%] vs 156 [64.2%]; P =.01). Peer-reviewed article titles were judged less relevant to clinical practice than throwaway journal article titles (P<.001).\n Although lower in methodologic and reporting quality, review articles published in throwaway journals have characteristics that appeal to physician readers.", "Academic biomedical journals use peer review and editing to help to select and improve the quality of articles. We have investigated whether articles accepted by the Nederlands Tijdschrift voor Geneeskunde, the Dutch Journal of Medicine, were improved after peer review and editing (post-acceptance scientific and copy editing).\n 400 readers of the journal (100 each of medical students, recent medical graduates, general practitioners, and specialists) were invited to participate in a questionnaire survey. The first 25 from each group who agreed to participate were included. We posted a pack containing a set of identically appearing typescripts (ie, blinding) of the submitted, accepted, and published versions of 50 articles that had been published in Ned Tijdschr Geneeskd. Each evaluator received two of the sets of versions, and each set was evaluated by one person from each group. The package also included two questionnaires: the first was used to compare the submitted with the accepted version (25 questions), the second compared the accepted with the published version (17 questions). The questions were answered on five-point scales, and were about the quality of the articles or were general/overall scores. We analysed the data as scores of 3-5 (ie, improvement) versus 1-2.\n After peer review, the quality in 14 of 23 questions (61%) was significantly improved (p = 0.03 or smaller). In particular, the overall score and general medical value were significantly improved (p = 0.00001 for each). Editing led to significant improvement in 11 of 16 questions (69%, p = 0.017 or smaller), and especially in style and readability (p = 0.001 and p = 0.004). Generally, we found no differences between the scores of the four categories of evaluators. 72% of the evaluators correctly identified which version was which.\n Evaluations by readers of the Ned Tijdschr Geneeskd indicated significant improvement of published articles after both peer review and editing. We think that peer review and editing are worthwhile tasks. We also think that possible biases would have had a negligible effect on our results (including the fact that we selected the first 25 evaluators who responded, that some evaluators may have read the published version, and that one questionnaire may have looked more scientific than the other, more editorial one).", "Peer review of medical papers is a confidential consultancy between the reviewer and the journal editor, and has been criticised for its potential bias and inadequacy. We explored the potential of the internet for open peer review to see whether this approach improved the quality and outcome of peer review.\n Research and review articles that had been accepted for publication in The Medical Journal of Australia (MJA) were published together with the reviewers' reports on the worldwide web, with the consent of authors and referees. Selected readers' e-mailed comments were electronically published as additional commentary; authors could reply or revise their paper in response to readers' comments. Articles were edited and published in print after this open review.\n 60 (81%) of 74 authors agreed to take part in the study, together with 150 (92%) of 162 reviewers. There was no significant difference in the performance of commissioned reviewers before and during the study. Four articles were not included because of insufficient time before print publication. Of the remaining 56 papers, 28 received 52 comments from 42 readers (2% of readers submitted comments). Most readers' comments were short and specific, and seven articles were changed by the authors in response.\n Open peer review is acceptable to most authors and reviewers. Postpublication review by readers on the internet is no substitute for commissioned prepublication review, but can provide editors with valuable input from individuals who would not otherwise be consulted. Readers also gain insight into the processes of peer review and publication.", "To examine the effect on peer review of asking reviewers to have their identity revealed to the authors of the paper.\n Randomised trial. Consecutive eligible papers were sent to two reviewers who were randomised to have their identity revealed to the authors or to remain anonymous. Editors and authors were blind to the intervention.\n The quality of the reviews was independently rated by two editors and the corresponding author using a validated instrument. Additional outcomes were the time taken to complete the review and the recommendation regarding publication. A questionnaire survey was undertaken of the authors of a cohort of manuscripts submitted for publication to find out their views on open peer review.\n Two editors' assessments were obtained for 113 out of 125 manuscripts, and the corresponding author's assessment was obtained for 105. Reviewers randomised to be asked to be identified were 12% (95% confidence interval 0.2% to 24%) more likely to decline to review than reviewers randomised to remain anonymous (35% v 23%). There was no significant difference in quality (scored on a scale of 1 to 5) between anonymous reviewers (3.06 (SD 0.72)) and identified reviewers (3.09 (0.68)) (P=0.68, 95% confidence interval for difference - 0.19 to 0.12), and no significant difference in the recommendation regarding publication or time taken to review the paper. The editors' quality score for reviews (3.05 (SD 0.70)) was significantly higher than that of authors (2.90 (0.87)) (P<0.005, 95%confidence interval for difference - 0.26 to - 0.03). Most authors were in favour of open peer review.\n Asking reviewers to consent to being identified to the author had no important effect on the quality of the review, the recommendation regarding publication, or the time taken to review, but it significantly increased the likelihood of reviewers declining to review.", "Most scientific journals practise anonymous peer review. There is no evidence, however, that this is any better than an open system.\n To evaluate the feasibility of an open peer review system.\n Reviewers for the British Journal of Psychiatry were asked whether they would agree to have their name revealed to the authors whose papers they review; 408 manuscripts assigned to reviewers who agreed were randomised to signed or unsigned groups. We measured review quality, tone, recommendation for publication and time taken to complete each review.\n A total of 245 reviewers (76%) agreed to sign. Signed reviews were of higher quality, were more courteous and took longer to complete than unsigned reviews. Reviewers who signed were more likely to recommend publication.\n This study supports the feasibility of an open peer review system and identifies such a system's potential drawbacks.", "Publication bias is widely appreciated, but considerable time and effort are needed to locate and obtain data from unpublished randomized controlled trials (RCTs), those published in non-English language journals or those reported in the gray literature; for this publication, we will call this collection of trials the \"gray+literature.\" However, excluding such trials from systematic reviews could introduce bias and give rise to misleading conclusions.\n We aimed to explore and quantify the impact of inclusion of gray+ literature on the results of all completed individual patient data (IPD) reviews coordinated by our group (13 meta-analyses). For each IPD review, results were calculated for RCTs fully published in English language journals and RCTs fully published in English language journals and the gray+literature.\n The IPD meta-analyses based only on RCTs that were fully published in English language journals tended to give more favorable results than those that included RCTs from the gray+literature. Although in most cases the addition of gray+data gave less encouraging results, moving the estimated treatment effect toward a null result, the direction of effect was not always predictable.\n We recommend that all systematic reviews should at least attempt to identify trials reported in the gray+literature and, where possible, obtain data from them.", "All authors may not be equal in the eyes of reviewers. Specifically, well-known authors may receive less objective (poorer quality) reviews. One study at a single journal found a small improvement in review quality when reviewers were masked to author identity.\n To determine whether masking reviewers to author identity is generally associated with higher quality of review at biomedical journals, and to determine the success of routine masking techniques.\n A randomized controlled trial performed on external reviews of manuscripts submitted to Annals of Emergency Medicine, Annals of Internal Medicine, JAMA, Obstetrics & Gynecology, and Ophthalmology.\n Two peers reviewed each manuscript. In one study arm, both peer reviewers received the manuscript according to usual masking practice. In the other arm, one reviewer was randomized to receive a manuscript with author identity masked, and the other reviewer received an unmasked manuscript.\n Review quality on a 5-point Likert scale as judged by manuscript author and editor. A difference of 0.5 or greater was considered important.\n A total of 118 manuscripts were randomized, 26 to usual practice and 92 to intervention. In the intervention arm, editor quality assessment was complete for 77 (84%) of 92 manuscripts. Author quality assessment was complete on 40 (54%) of 74 manuscripts. Authors and editors perceived no significant difference in quality between masked (mean difference, 0.1; 95% confidence interval [CI], -0.2 to 0.4) and unmasked (mean difference, -0.1; 95% CI, -0.5 to 0.4) reviews. We also found no difference in the degree to which the review influenced the editorial decision (mean difference, -0.1; 95% CI,-0.3 to 0.3). Masking was often unsuccessful (overall, 68% successfully masked; 95% CI, 58%-77%), although 1 journal had significantly better masking success than others (90% successfully masked; 95% CI, 73%-98%). Manuscripts by generally known authors were less likely to be successfully masked (odds ratio, 0.3; 95% CI, 0.1-0.8). When analysis was restricted to manuscripts that were successfully masked, review quality as assessed by editors and authors still did not differ.\n Masking reviewers to author identity as commonly practiced does not improve quality of reviews. Since manuscripts of well-known authors are more difficult to mask, and those manuscripts may be more likely to benefit from masking, the inability to mask reviewers to the identity of well-known authors may have contributed to the lack of effect.", "To evaluate the effects of peer review and editing on manuscript quality.\n Editorial offices of Annals of Internal Medicine.\n Masked before-after study. MANUSCRIPTS: 111 consecutive original research manuscripts accepted for publication at Annals between March 1992 and March 1993.\n We used a manuscript quality assessment tool of 34 items to evaluate the quality of the research report, not the quality of the research itself. Each item was scored on a 1 to 5 scale. Forty-four expert assessors unaware of the design or aims of the study evaluated the manuscripts, with different persons evaluating the two versions of each manuscript (before and after the editorial process).\n 33 of the 34 items changed in the direction of improvement, with the largest improvements seen in the discussion of study limitations, generalizations, use of confidence intervals, and the tone of conclusions. Overall, the percentage of items scored three or more increased by an absolute 7.3% (95% CI, 3.3% to 11.3%) from a baseline of 75%. The average item score improved by 0.23 points (CI, 0.07 to 0.39) from a baseline mean of 3.5. Manuscripts rated in the bottom 50% showed two- to threefold larger improvements than those in the top 50%, after correction for regression to the mean.\n Peer review and editing improve the quality of medical research reporting, particularly in those areas that readers rely on most heavily to decide on the importance and generalizability of the findings.", "This study examined the readability of the AANA Journal, quantifying the effect of peer review on case and research reports published from 1992 to 1994. Gunning and Flesch index-based computer analysis, as well as human comparative analysis, was undertaken. Computer and human assessment of readability revealed improvement as papers evolved from submitted to published versions; however, at publication the manuscripts remained in the \"difficult\" readability range. Although this study provides evidence that peer review improves readability, it may be that, due to a professed need for scientific purity and an imposed sense of scholarship, nursing and other biomedical journals may overemphasize a style and approach that paradoxically make transfer of information unreasonably difficult.", "Prior studies implying associations between receipt of commercial funding and positive (significant and/or pro-industry) research outcomes have analyzed only published papers, which is an insufficiently robust approach for assessing publication bias. In this study, we tested the following hypotheses regarding orthopaedic manuscripts submitted for review: (1) nonscientific variables, including receipt of commercial funding, affect the likelihood that a peer-reviewed submission will conclude with a report of a positive study outcome, and (2) positive outcomes and other, nonscientific variables are associated with acceptance for publication.\n All manuscripts about hip or knee arthroplasty that were submitted to The Journal of Bone and Joint Surgery, American Volume, over seventeen months were evaluated to determine the study design, quality, and outcome. Analyses were carried out to identify associations between scientific factors (sample size, study quality, and level of evidence) and study outcome as well as between non-scientific factors (funding source and country of origin) and study outcome. Analyses were also performed to determine whether outcome, scientific factors, or nonscientific variables were associated with acceptance for publication.\n Two hundred and nine manuscripts were reviewed. Commercial funding was not found to be associated with a positive study outcome (p = 0.668). Studies with a positive outcome were no more likely to be published than were those with a negative outcome (p = 0.410). Studies with a negative outcome were of higher quality (p = 0.003) and included larger sample sizes (p = 0.05). Commercially funded (p = 0.027) and United States-based (p = 0.020) studies were more likely to be published, even though those studies were not associated with higher quality, larger sample sizes, or lower levels of evidence (p = 0.24 to 0.79).\n Commercially funded studies submitted for review were not more likely to conclude with a positive outcome than were nonfunded studies, and studies with a positive outcome were no more likely to be published than were studies with a negative outcome. These findings contradict those of most previous analyses of published (rather than submitted) research. Commercial funding and the country of origin predict publication following peer review beyond what would be expected on the basis of study quality. Studies with a negative outcome, although seemingly superior in quality, fared no better than studies with a positive outcome in the peer-review process; this may result in inflation of apparent treatment effects when the published literature is subjected to meta-analysis.", "--To investigate factors associated with the publication of research findings, in particular, the association between \"significant\" results and publication.\n --Follow-up study.\n --Studies approved in 1980 or prior to 1980 by the two institutional review boards that serve The Johns Hopkins Health Institutions--one that serves the School of Medicine and Hospital and the other that serves the School of Hygiene and Public Health.\n --A total of 737 studies were followed up.\n --Of the studies for which analyses had been reported as having been performed at the time of interview, 81% from the School of Medicine and Hospital and 66% from the School of Hygiene and Public Health had been published. Publication was not associated with sample size, presence of a comparison group, or type of study (eg, observational study vs clinical trial). External funding and multiple data collection sites were positively associated with publication. There was evidence of publication bias in that for both institutional review boards there was an association between results reported to be significant and publication (adjusted odds ratio, 2.54; 95% confidence interval, 1.63 to 3.94). Contrary to popular opinion, publication bias originates primarily with investigators, not journal editors: only six of the 124 studies not published were reported to have been rejected for publication.\n --There is a statistically significant association between significant results and publication.", "Better peer review is needed, but proven methods to improve quality are unknown. Our objective was to determine whether written feedback to reviewers improves subsequent reviews.\n Eligible reviewers were randomized to intervention or control (receiving other reviewers' unscored reviews and the editor's decision letter). Study 1 (September 1998-September 2000) included reviewers with a median quality score of 3 or lower; study 2 (April 2000-January 2002), reviewers with median score of 4 or lower. Study 1 was designed with a power of 0.80 to detect a difference in score of 1; study 2, with a power of 0.80 to detect a difference of 0.5. All reviewers were at a peer-reviewed journal (Annals of Emergency Medicine). The main outcome measure was the editor's routine quality rating (1-5) of all reviews (blinded to study enrollment).\n For study 1, 51 reviewers were eligible and randomized and 35 had sufficient data (182 reviews) for analysis. The mean individual reviewer rating change was 0.16 (95% confidence interval [CI], -0.26 to 0.58) for control and -0.13 (-0.49 to 0.23) for intervention. For study 2, 127 reviewers were eligible and randomized, and 95 had sufficient data (324 reviews). Controls had a mean individual rating change of 0.12 (95% CI, -0.20 to 0.26) and intervention reviewers, 0.06 (-0.19 to 0.31).\n In study 1, minimal feedback from editors on review quality had no effect on subsequent performance of poor-quality reviewers, and the trend was toward a negative effect. In study 2, feedback to average reviewers was more extensive and supportive but produced no improvement in reviewer performance. Simple written feedback to reviewers seems to be an ineffective educational tool.", "The \"Consolidated Standards of Reporting Trials\" (CONSORT) was developed to improve the suboptimal reporting of randomized controlled trials (RCTs). However, little is known about the quality of reporting since this publication. We undertook an observational study to determine the quality of reporting key methodological factors in RCTs since the publication of the CONSORT statement and if a journal policy to promote adherence to the CONSORT checklist was associated with superior reporting. We recorded the reporting of 11 key methodological factors in 105 RCTs from 29 medical journals published subsequent to the CONSORT statement. We examined the quality of reporting in relation to whether a journal was a \"CONSORT promoter\" as defined by inclusion of the CONSORT checklist in a journal's \"information to authors\" section or a requirement that authors, manuscript reviewers, or copy editors complete the CONSORT checklist. Multivariate analysis controlled for journal impact factor, study outcome, and time of publication. Six of the 11 methodological factors were reported <50% of the time. The number of methodological factors reported was greater in CONSORT promoters than in journals not promoting CONSORT in both unadjusted (6.0 and 5.1, respectively, p-value = 0.03) and adjusted (6.4 and 4.8 of the 11 methodological factors, respectively, p-value = 0.0001) analyses. While journals that promote CONSORT demonstrate superior reporting of RCTs, persistent inadequacies in reporting remain. Until these inadequacies are resolved health-care providers will remain limited in their ability to make informed inferences about the validity of the studies upon which they base their clinical practice.", "To determine the extent to which publication is influenced by study outcome.\n A cohort of studies submitted to a hospital ethics committee over 10 years were examined retrospectively by reviewing the protocols and by questionnaire. The primary method of analysis was Cox's proportional hazards model.\n University hospital, Sydney, Australia.\n 748 eligible studies submitted to Royal Prince Alfred Hospital Ethics Committee between 1979 and 1988.\n Time to publication.\n Response to the questionnaire was received for 520 (70%) of the eligible studies. Of the 218 studies analysed with tests of significance, those with positive results (P < 0.05) were much more likely to be published than those with negative results (P > or = 0.10) (hazard ratio 2.32 (95% confidence interval 1.47 to 3.66), P = 0.0003), with a significantly shorter time to publication (median 4.8 v 8.0 years). This finding was even stronger for the group of 130 clinical trials (hazard ratio 3.13 (1.76 to 5.58). P = 0.0001), with median times to publication of 4.7 and 8.0 years respectively. These results were not materially changed after adjusting for other significant predictors of publication. Studies with indefinite conclusions (0.05 < or = P < 0.10) tended to have an even lower publication rate and longer time to publication than studies with negative results (hazard ratio 0.39 (0.13 to 1.12), P = 0.08). For the 103 studies in which outcome was rated qualitatively, there was no clear cut evidence of publication bias, although the number of studies in this group was not large.\n This study confirms the evidence of publication bias found in other studies and identifies delay in publication as an additional important factor. The study results support the need for prospective registration of trials to avoid publication bias and also support restricting the selection of trials to those started before a common date in undertaking systematic reviews.", "To measure the effect of the peer review and editorial processes on the readability of original articles.\n Comparison of manuscripts before and after the peer review and editorial processes.\n Annals of Internal Medicine between March 1 and November 30, 1992. MANUSCRIPTS: One hundred one consecutive manuscripts reporting original research.\n Assessment of readability by means of two previously validated indexes: the Gunning fog index (units of readability in the fog index roughly correlate to years of education) and the Flesch reading ease score. Each manuscript was analyzed for readability and length on receipt and after it had passed through the peer review and editorial processes. Text and abstracts were analyzed similarly but separately. Mean readability scores were compared by two-tailed t tests for paired observations.\n Mean (+/- SD) initial readability scores of manuscripts and abstracts by the Gunning fog index were 17.16 +/- 1.55 and 16.65 +/- 2.80, respectively. At publication, scores were 16.85 +/- 1.42 and 15.64 +/- 2.42 (P = .0005 and P < .0001 for before-after differences, respectively). By comparison, studies of other print media showed scores of about 11 for the New York Times editorial page and about 18 for a typical legal contract. Similar changes were found for the Flesch scores. The median length of the manuscripts increased by 2.6% and that of the abstracts by 4.2% during the processes.\n The peer review and editorial processes slightly improved the readability of original articles and their abstracts, but both remained difficult to read at publication. Better readability scores may improve readership.", "To determine whether attendance at a voluntary training workshop improves quality ratings of medical journal peer reviewers.\n Peer reviewers for Annals of Emergency Medicine who completed two or more reviews during the 20 months before or the 20 months after October 1995 were eligible. Reviews were routinely rated by editors on a subjective 5-point quality scale. Comparisons were made between reviewers who chose to attend a 4-hour workshop on peer review sponsored by the journal in 1995 (attendees) and 2 groups of reviewers who did not attend: controls matched for review quality and number of reviews completed before the workshop, and unmatched controls. Guest reviewers were excluded.\n A total of 298 reviewers completed 1906 reviews before the workshop and 2,194 after the workshop; 2,117 of these reviews were rated by editors. Forty-five attendees participated in the workshop, 39 of whom had sufficient ratings for analysis. Matched controls were almost identical in performance to attendees, but unmatched controls had performed fewer reviews and had lower average ratings before the workshop. There was no significant change in any performance measurement after the workshop, including average quality rating, percent change in quality rating, odds ratio for recommending acceptance, and odds ratio for congruence with editor's decision.\n In a self-selected group of experienced reviewers who attended a 4-hour workshop on peer review, no effect could be identified in subsequent performance as measured by editors' quality ratings or reviewer performance statistics.", "Significant resources and time are invested in the production of research knowledge. The primary objective of this randomized controlled trial was to evaluate the effectiveness of three knowledge translation and exchange strategies in the incorporation of research evidence into public health policies and programs.\n This trial was conducted with a national sample of public health departments in Canada from 2004 to 2006. The three interventions, implemented over one year in 2005, included access to an online registry of research evidence; tailored messaging; and a knowledge broker. The primary outcome assessed the extent to which research evidence was used in a recent program decision, and the secondary outcome measured the change in the sum of evidence-informed healthy body weight promotion policies or programs being delivered at health departments. Mixed-effects models were used to test the hypotheses.\n One hundred and eight of 141 (77%) health departments participated in this study. No significant effect of the intervention was observed for primary outcome (p < 0.45). However, for public health policies and programs (HPPs), a significant effect of the intervention was observed only for tailored, targeted messages (p < 0.01). The treatment effect was moderated by organizational research culture (e.g., value placed on research evidence in decision making).\n The results of this study suggest that under certain conditions tailored, targeted messages are more effective than knowledge brokering and access to an online registry of research evidence. Greater emphasis on the identification of organizational factors is needed in order to implement strategies that best meet the needs of individual organizations.\n The trial registration number and title are as follows: ISRCTN35240937 -- Is a knowledge broker more effective than other strategies in promoting evidence-based physical activity and healthy body weight programming?", "Selective reporting of outcomes within published studies based on the nature or direction of their results has been widely suspected, but direct evidence of such bias is currently limited to case reports.\n To study empirically the extent and nature of outcome reporting bias in a cohort of randomized trials.\n Cohort study using protocols and published reports of randomized trials approved by the Scientific-Ethical Committees for Copenhagen and Frederiksberg, Denmark, in 1994-1995. The number and characteristics of reported and unreported trial outcomes were recorded from protocols, journal articles, and a survey of trialists. An outcome was considered incompletely reported if insufficient data were presented in the published articles for meta-analysis. Odds ratios relating the completeness of outcome reporting to statistical significance were calculated for each trial and then pooled to provide an overall estimate of bias. Protocols and published articles were also compared to identify discrepancies in primary outcomes.\n Completeness of reporting of efficacy and harm outcomes and of statistically significant vs nonsignificant outcomes; consistency between primary outcomes defined in the most recent protocols and those defined in published articles.\n One hundred two trials with 122 published journal articles and 3736 outcomes were identified. Overall, 50% of efficacy and 65% of harm outcomes per trial were incompletely reported. Statistically significant outcomes had a higher odds of being fully reported compared with nonsignificant outcomes for both efficacy (pooled odds ratio, 2.4; 95% confidence interval [CI], 1.4-4.0) and harm (pooled odds ratio, 4.7; 95% CI, 1.8-12.0) data. In comparing published articles with protocols, 62% of trials had at least 1 primary outcome that was changed, introduced, or omitted. Eighty-six percent of survey responders (42/49) denied the existence of unreported outcomes despite clear evidence to the contrary.\n The reporting of trial outcomes is not only frequently incomplete but also biased and inconsistent with protocols. Published articles, as well as reviews that incorporate them, may therefore be unreliable and overestimate the benefits of an intervention. To ensure transparency, planned trials should be registered and protocols should be made publicly available prior to trial completion.", "Cumulative meta-analysis of clinical trials (a Bayesian interpretation for accumulating evidence) will profoundly affect medical care by summarizing evidence in the assessment of technology innovations. Application of the technique to the randomized control trials (RCTs) of streptokinase treatment of acute myocardial infarction, reduction of peri-operative mortality by antibiotic prophylaxis, and prevention of death from bleeding peptic ulcers has revealed efficacy years before it was suspected by any other means. Arrangement of the trials according to event rate in the controls, effect sizes, quality of the trials or according to covariables of interest has supplied unique information. If carried out prospectively the technique supplies invaluable information regarding indications for another trial, the number of patients necessary to determine the validity of past trends, and the type of patients who might be benefitted. Careful examination in a cumulative manner of the prior trials can reduce the need for future large trials.", "Sixty research investigations published in the biomedical literature were analyzed to examine the effect of design attributes on outcome. All 60 studies included a controlled trial involving a pretest, a therapeutic intervention, and a posttest across at least two groups. Thirty of the trials used random assignment of participants to treatment or control conditions and 30 trials employed some nonrandom method of subject assignment. Trial results were aggregated and evaluated by comparing effect sizes for the primary statistical test of the hypothesis. Data analysis revealed that the trial results, as measured by effect size, did not vary across therapeutic trials using random assignment versus those using nonrandom allocation of subjects. The impact of design attributes in the interpretation of multiple clinical trials addressing a similar research question is examined. The argument is made that various design attributes frequently associated with methodological quality should be considered as important moderator variables and their influence on trial outcome should not be assumed a priori but rather examined empirically.", "Large clinical trials are the criterion standard for making treatment decisions, and nonpublication of the results of such trials can lead to bias in the literature and contribute to inappropriate medical decisions.\n To determine the rate of full publication of large randomized trials presented at annual meetings of the American Society of Clinical Oncology (ASCO), quantify bias against publishing nonsignificant results, and identify factors associated with time to publication.\n Survey of 510 abstracts from large (sample size, > or =200), phase 3, randomized controlled trials presented at ASCO meetings between 1989 and 1998. Trial results were classified as significant (P< or =.05 for the primary outcome measure) or nonsignificant (P>.05 or not reported), and the type of presentation and sponsorship were identified. Subsequent full publication was identified using a search of MEDLINE and EMBASE, completed November 1, 2001; the search was updated in November 2002, using the Cochrane Register of Controlled Trials. Authors were contacted if the searches did not find evidence of publication.\n Publication rate at 5 years; time from presentation to full publication.\n Of 510 randomized trials, 26% were not published in full within 5 years after presentation at the meeting. Eighty-one percent of the studies with significant results had been published by this time compared with 68% of the studies with nonsignificant results (P<.001). Studies with oral or plenary presentation were published sooner than those not presented (P =.002), and studies with pharmaceutical sponsorship were published sooner than studies with cooperative group sponsorship or studies for which sponsorship was not specified (P =.02). These factors remained significant in a multivariable model. The most frequent reason cited by authors for not publishing was lack of time, funds, or other resources.\n A substantial number of large phase 3 trials presented at an international oncology meeting remain unpublished 5 years after presentation. Bias against publishing nonsignificant results is a problem even for large randomized trials. Nonpublication breaks the contract that investigators make with trial participants, funding agencies, and ethics boards.", "Adoption of evidence-based practice (EBP) policy has implications for clinicians and researchers alike. In fields that have already adopted EBP, evidence-based practice guidelines derive from systematic reviews of research evidence. Ultimately, such guidelines serve as tools used by practitioners. Systematic reviews of treatment efficacy and effectiveness reserve their strongest endorsements for treatments that are supported by high-quality randomized clinical trials (RCTs). It is unknown how well RCTs reported in behavioral science journals fare compared to quality standards set forth in fields that pioneered the evidence-based movement. We compared analytic quality features of all behavioral health RCTs (n = 73) published in three leading behavioral journals and two leading medical journals between January 2000 and July 2003. A behavioral health trial was operationalized as one employing a behavioral treatment modality to prevent or treat an acute or chronic physical disease or condition. Findings revealed areas of weakness in analytic aspects of the behavioral health RCTs reported in both sets of journals. Weaknesses were more pronounced in behavioral journals. The authors offer recommendations for improving the analytic quality of behavioral health RCTs to ensure that evidence about behavioral treatments is highly weighted in systematic reviews.\n (c) 2006 Wiley Periodicals, Inc.", "Little research has been conducted into the quality of peer review and, in particular, the effects of blinding peer reviewers to authors' identities or masking peer reviewers' identities.\n To determine whether concealing authors' identities from reviewers (blinding) and/or revealing the reviewer's identity to a coreviewer (unmasking) affects the quality of reviews, the time taken to carry out reviews, and the recommendation regarding publication.\n Randomized trial of 527 consecutive manuscripts submitted to BMJ, which were randomized and each sent to 2 peer reviewers.\n Manuscripts were randomized as to whether the reviewers were unmasked, masked, or uninformed that a study was taking place. Two reviewers for each manuscript were randomized to receive either a blinded or an unblinded version.\n Mean total quality score, time taken to carry out the review, and recommendation regarding publication.\n Of the 527 manuscripts entered into the study, 467 (89%) were successfully randomized and followed up. The mean total quality score was 2.87. There was little or no difference in review quality between the masked and unmasked groups (scores of 2.82 and 2.96, respectively) and between the blinded and unblinded groups (scores of 2.87 and 2.90, respectively). There was no apparent Hawthorne effect. There was also no significant difference between groups in the recommendations regarding publication or time taken to review.\n Blinding and unmasking made no editorially significant difference to review quality, reviewers' recommendations, or time taken to review. Other considerations should guide decisions as to the form of peer review adopted by a journal, and improvements in the quality of peer review should be sought via other means.", "It has been suggested that the quality of clinical trials should be assessed by blinded raters to limit the risk of introducing bias into meta-analyses and systematic reviews, and into the peer-review process. There is very little evidence in the literature to substantiate this. This study describes the development of an instrument to assess the quality of reports of randomized clinical trials (RCTs) in pain research and its use to determine the effect of rater blinding on the assessments of quality. A multidisciplinary panel of six judges produced an initial version of the instrument. Fourteen raters from three different backgrounds assessed the quality of 36 research reports in pain research, selected from three different samples. Seven were allocated randomly to perform the assessments under blind conditions. The final version of the instrument included three items. These items were scored consistently by all the raters regardless of background and could discriminate between reports from the different samples. Blind assessments produced significantly lower and more consistent scores than open assessments. The implications of this finding for systematic reviews, meta-analytic research and the peer-review process are discussed." ]	At present, little empirical evidence is available to support the use of editorial peer review as a mechanism to ensure quality of biomedical research. However, the methodological problems in studying peer review are many and complex. At present, the absence of evidence on efficacy and effectiveness cannot be interpreted as evidence of their absence. A large, well-funded programme of research on the effects of editorial peer review should be urgently launched.
CD005339	[ "9531581", "7760868", "8683249", "7048657", "6790985", "10735900" ]	[ "A placebo-controlled study of recombinant human granulocyte-macrophage colony-stimulating factor administered during and after induction treatment for de novo acute myelogenous leukemia in elderly patients. Groupe Ouest Est Leucémies Aiguës Myéloblastiques (GOELAM).", "Granulocyte-macrophage colony-stimulating factor after initial chemotherapy for elderly patients with primary acute myelogenous leukemia. Cancer and Leukemia Group B.", "Granulocyte-macrophage colony-stimulating factor associated with induction treatment of acute myelogenous leukemia: a randomized trial by the European Organization for Research and Treatment of Cancer Leukemia Cooperative Group.", "Prophylactic granulocyte transfusions: results of a randomized controlled trial in patients with acute myelogenous leukemia.", "A controlled trial of prophylactic granulocyte transfusions during initial induction chemotherapy for acute myelogenous leukemia.", "Use of recombinant human granulocyte colony-stimulating factor to increase chemotherapy dose-intensity: a randomized trial in very high-risk childhood acute lymphoblastic leukemia." ]	[ "The complete remission (CR) rate after intensive chemotherapy for acute myelogenous leukemia (AML) remains low in elderly patients, mainly because of a higher infectious mortality rate related to neutropenia and an increased incidence of adverse prognostic factors. Granulocyte-macrophage colony-stimulating factor (GM-CSF) has been shown to potentially recruit leukemic blasts into cell cycle and improve cytotoxic effects when given during chemotherapy, and to shorten the duration of neutropenia when administered after chemotherapy. Two hundred forty patients aged 55 to 75 years who had newly diagnosed AML were randomly assigned to receive placebo or Escherichia coli-derived GM-CSF (5 micrograms/kg/d by 6-hour intravenous infusion) starting during induction chemotherapy on day 1 and continued through and after chemotherapy until recovery of neutrophils, or evidence of regrowth of leukemia, or up to day 28. Induction chemotherapy consisted of idarubicin (8 mg/m2/d on days 1 to 5) and cytarabine (100 mg/m2/d on days 1 to 7). The study drug was not administered subsequent to the induction course. Patients who achieved a CR received continuous maintenance therapy for 1 year with four quarterly reinduction courses; in the 55- to 64-year age subgroup, patients were randomly assigned to receive or not a consolidation course before maintenance therapy. The CR rate was similar in the GM-CSF and placebo groups (63% and 60.5%, respectively; P = .79). The mortality, rate of resistant disease, and rate of regrowth of leukemia were also similar in both groups. The time to neutrophil recovery was shorter in patients who received GM-CSF (24 v 29 days; P = .0001), but the incidence and characteristics of infectious events were not different. The 2-year disease-free survival (DFS) rate was significantly improved in the GM-CSF group (48% v 21% in the placebo group; P = .003). This effect was highly significant in the cohort of patients aged 55 to 64, but only marginal in patients >/=65 years of age. There was a trend toward a longer overall survival (OS) in the GM-CSF group (P = .082). In summary, the administration of GM-CSF, concomitantly with chemotherapy and thereafter during induction course in AML, shortened the time to neutrophil recovery, but did not improve the CR rate in patients aged 55 to 75. Nonetheless, DFS and OS were significantly prolonged in patients aged 55 to 64 treated with GM-CSF. These results are promising and further evaluation of myeloid growth factors in AML is warranted.", "Elderly patients with primary acute myelogenous leukemia (AML) are less likely to enter remission than younger adults, in part because of a higher mortality rate related to severe myelosuppression. Granulocyte-macrophage colony-stimulating factor (GM-CSF) has been shown to shorten the duration of neutropenia and decrease infectious complications when administered after chemotherapy to patients with lymphomas and solid tumors.\n We randomly assigned 388 patients 60 years of age or older who had newly diagnosed primary AML to receive placebo or GM-CSF (5 micrograms per kilogram of body weight per day intravenously over a period of six hours) in a double-blind manner, beginning the day after the completion of three days of daunorubicin (45 mg per square meter of body-surface area per day) and seven days of cytarabine (200 mg per square meter per day by continuous intravenous infusion). If leukemia cells persisted in the marrow three weeks after the initiation of chemotherapy, further daunorubicin (two days) and cytarabine (five days) were administered. GM-CSF or placebo was given daily until the neutrophil count was at least 1000 per cubic millimeter, there was evidence of the regrowth of leukemia, or severe toxic effects attributable to the study infusion occurred. Patients who had a complete remission were then randomly assigned to receive one of two intensification regimens.\n Of 388 patients (median age, 69 years), 193 were randomly assigned to receive GM-CSF and 195 to placebo. The rate of complete remission was 51 percent (95 percent confidence interval, 44 to 59 percent) among those assigned to GM-CSF and 54 percent (95 percent confidence interval, 47 to 61 percent) among those assigned to receive placebo (P = 0.61). The reasons for failure (early death, death during marrow hypoplasia, and persistent leukemia), the incidence of severe or lethal infection, and the incidence of the regrowth of leukemia (2 percent overall) were similar in the two groups. The median duration of neutropenia was slightly shorter (P = 0.02) in the patients who received GM-CSF (15 days) than in those who received placebo (17 days), but the clinical importance of this result was minimal because the growth factor failed to lower the treatment-related mortality rate or improve the rate of complete remission.\n GM-CSF, in the dose and schedule we used, does not stimulate the regrowth of leukemia, but it also does not decrease the severe myelosuppressive consequences of initial chemotherapy or improve the response rate in patients 60 years of age or older with primary AML. It should not be recommended for use in such patients.", "To assess the value of granulocyte-macrophage colony-stimulating factor (GM-CSF) for induction treatment of acute myeloid leukemia (AML), both for priming of leukemic cells and for acceleration of hematopoietic recovery.\n GM-CSF was administered 5 micrograms/kg/d by continuous intravenous (i.v.) infusion during induction therapy with daunorubicin (DNR) (days 1 to 3) and cytarabine (ARA-C) (days 1 to 7). A total of 102 patients were randomized onto four arms, as follows: (1) GM-CSF 24 hours before and during chemotherapy (arm +/-); (2) GM-CSF after chemotherapy until day 28 or recovery of polymorphonuclear leukocytes (PMNs) (arm -/+);(3) GM-CSF before, during, and after chemotherapy (arm +/+); or (4) no GM-CSF (arm -/-). Stopping rules were applied in case of an initial WBC count greater than 30 x 10(9)/L or a secondary increase of circulating blast cells. Analyses were performed according to the intention-to-treat principle.\n The complete remission (CR) rates were 77% (arm -/-), 72% (arm +/-), 48% (arm -/+), and 46% (arm +/+). Patients randomized to receive GM-CSF after induction (arms -/+ and +/+) had a significantly lower CR rate (P = .008) and a trend toward accelerated recovery of neutrophils, but no fewer infections or induction deaths. The lower CR rate appeared to be related to an increased resistance rate, with persistent leukemia. The main side effects of GM-CSF were fluid retention and hypotension.\n GM-CSF administered during induction treatment of AML with a DNR/Ara-C combination did not provide any clinical benefit. Furthermore, there was a significant decrease in the CR rate with more persistent leukemia when GM-CSF was administered during the hypoplastic phase after the chemotherapy courses.", "A prospective randomized and controlled clinical trial of prophylactic granulocyte transfusions was conducted in an attempt to reduce the mortality from infection in newly diagnosed adults with acute myelogenous leukemia. Granulocytes were harvested from normal donors by cytapheresis, and transfused patients received a median of 1.45 x 10(10) granulocytes (range 0.28--3.45 x 10(10)) on alternate days during marrow aplasia caused by initial induction chemotherapy. Transfusion were started if the absolute peripheral granulocyte count was less than 500 microliters. Thirteen patients received from one to 12 granulocyte transfusions, and 11 control patients received no granulocytes. No significant advantage was demonstrated in the transfused patients compared with controls with regard to the following: 1) deaths due to infection, 2) reduction in the frequency of febrile episodes, 3) delay in the onset of fever, 4) reduction in the length of febrile episodes, or 5) reduction in the frequency of proven infection.", "To evaluate the role of prophylactic granulocyte transfusions during remission-induction chemotherapy for acute myelogenous leukemia (AML) we randomized 102 infected patients either to receive daily granulocyte transfusions when blood granulocytes fell below 0.5 x 10(9) per liter (54 patients) or not to receive them (48). Although the percentage of patients acquiring any infection was similar in the transfusion and control groups (46 and 42 per cent, respectively), granulocyte transfusions decreased the proportion of patients with bacterial septicemia (9 per cent of those with transfusions vs. 27 per cent of the controls; P = 0.01). Granulocyte transfusions did not reduce the incidence of other infections or improve bone-marrow recovery, remission rate and duration, or survival. Seventy-two per cent of the patients given transfusions had transfusion reactions. Pulmonary infiltrates were more common in the transfusion group than in the control group (57 per cent vs. 27 per cent; P = 0.002). Thirty-five per cent of the patients with pulmonary filtrates died, as compared with 5 per cent of those without filtrates. We conclude that prophylactic granulocyte transfusions should not be used during remission-induction chemotherapy in AML because the risks outweigh the benefits.", "To determine whether the use of a recombinant human granulocyte colony-stimulating factor ([G-CSF] lenogastrim) can increase the chemotherapy dose-intensity (CDI) delivered during consolidation chemotherapy of childhood acute lymphoblastic leukemia (ALL).\n Sixty-seven children with very high-risk ALL were randomized (slow early response to therapy, 55 patients; translocation t(9;22) or t(4;11), 12 patients). Consolidation consisted of six courses of chemotherapy; the first, third, and fifth courses were a combination of high-dose cytarabine, etoposide, and dexamethasone (R3), whereas the second, fourth, and sixth courses included vincristine, prednisone, cyclophosphamide, doxorubicin, and methotrexate (COPADM). G-CSF was given after each course, and the next scheduled course was started as soon as neutrophil count was > 1 x 10(9)/L and platelet count was > 100 x 10(9)/L. CDI was calculated using the interval from day 1 of the first course to hematologic recovery after the fifth course (100% CDI = 105-day interval).\n CDI was significantly increased in the G-CSF group compared with the non-G-CSF group (mean +/- 95% confidence interval, 105 +/- 5% v 91 +/- 4%; P <.001). This higher intensity was a result of shorter post-R3 intervals in the G-CSF group, whereas the post-COPADM intervals were not statistically reduced. After the R3 courses, the number of days with fever and intravenous antibiotics and duration of hospitalization were significantly decreased by G-CSF, whereas reductions observed after COPADM were not statistically significant. Duration of granulocytopenia was reduced in the G-CSF group, but thrombocytopenia was prolonged, and the number of platelet transfusions was increased. Finally, the 3-year probability of event-free survival was not different between the two groups.\n G-CSF can increase CDI in high-risk childhood ALL. Its effects depend on the chemotherapy regimen given before G-CSF administration. In our study, a higher CDI did not improve disease control." ]	Currently, there is inconclusive evidence from RCTs to support or refute the generalised use of granulocyte transfusion therapy in the most common neutropenic patient populations, that is caused by myeloablative chemotherapy with or without haematopoietic stem cell support. Contemporary well designed prospective trials are required to evaluate the efficacy of this intervention in these patient populations and to establish definitively whether it has clinical benefit. In such studies, average numbers of collected granulocytes for adults should be (at least) greater than 1x1010.
CD005107	[ "14965404", "9779530", "1535495", "15770171" ]	[ "Implementation of RCGP guidelines for acute low back pain: a cluster randomised controlled trial.", "Capacity of the clinical picture to characterize low back pain relieved by facet joint anesthesia. Proposed criteria to identify patients with painful facet joints.", "Controlled trial of balneotherapy in treatment of low back pain.", "Implementation of the Dutch low back pain guideline for general practitioners: a cluster randomized controlled trial." ]	[ "The Royal College of General Practitioners (RCGP) has produced guidelines for the management of acute low back pain in primary care.\n To investigate the impact on patient management of an educational strategy to promote these guidelines among general practitioners (GPs).\n Group randomised controlled trial, using the health centre as the unit of randomisation.\n Primary care teams in north-west England.\n Twenty-four health centres were randomly allocated to an intervention or control arm. Practices in the intervention arm were offered outreach visits to promote national guidelines on acute low back pain, as well as access to fast-track physiotherapy and to a triage service for patients with persistent symptoms.\n Twenty-four centres were randomised. Two thousand, one hundred and eighty-seven eligible patients presented with acute low back pain during the study period: 1049 in the intervention group and 1138 in the control group. There were no significant differences between study groups in the proportion of patients who were referred for X-ray, issued with a sickness certificate, prescribed opioids or muscle relaxants, or who were referred to secondary care, but significantly more patients in the intervention group were referred to physiotherapy or the back pain unit (difference in proportion = 12.2%, 95% confidence interval [CI] = 2.8% to 21.6%).\n The management of patients presenting with low back pain to primary care was mostly unchanged by an outreach educational strategy to promote greater adherence to RCGP guidelines among GPs. An increase in referral to physiotherapy or educational programmes followed the provision of a triage service.", "Prospective randomized study to compare the efficacy of facet joint injection with lidocaine and facet joint injection with saline in two groups of patients with low back pain, with and without clinical criteria that were determined in a previous study to implicate the facet joint as the primary source of the pain.\n To assess the efficacy of single facet joint anesthesia versus placebo (saline injections) and to determine clinical criteria that are predictive of significant relief of LBP after injection.\n There is no syndrome that discriminates between lower back pain caused by facet joint and that caused by other structures. Single or double facet joint anesthesia, and single photon emission computed tomography are expensive and time-consuming procedures for selecting patients in controlled clinical trials with large populations.\n Results of a previous study showed that seven clinical characteristics were more frequent in patients who responded to facet joint anesthesia than in those who did not. In the current study, a group of 43 patients with lower back pain who met at least five criteria were compared with 37 patients who met fewer criteria. Patients randomly received injection of either lidocaine or saline into the lower facet joints. The result was considered positive if more than 75% pain relief was determined by visual analog scale. The patient, the radiologist, and the investigator were blinded. An analysis of variance was used to seek an interaction between clinical group effect and injection effect, and logistic regression analysis to select the best set of variables that would be predictive of minimum pain relief of 75% after the injection.\n There was a significant interaction between clinical group and injection effect (P = 0.003). In patients with back pain, lidocaine provided greater lower-back pain relief than saline (P = 0.01). Lidocaine also-provided greater pain relief in the back pain group than in the nonpain group (P = 0.02). The presence of five among seven variables (age greater than 65 years and pain that was not exacerbated by coughing, not worsened by hyperextension, not worsened by forward flexion, not worsened when rising from flexion, not worsened by extension-rotation, and well-relieved by recumbency), always including the last item, distinguished 92% of patients responding to lidocaine injection and 80% of those not responding in the lidocaine group.\n A set of five clinical characteristics can be used in randomized studies to select lower back pain that will be well relieved by facet joint anesthesia. These characteristics should not, however, be considered as definite diagnostic criteria of lower back pain originating from facet joints.", "Three treatments for non-specific lumbar pain--balneotherapy, underwater traction bath, and underwater massage--were assessed in a randomised prospective controlled trial in 158 outpatients. Each group was treated for four weeks and patients were reviewed at the end of this period and at 12 months after entry to the trial. The prescription of analgesics and the pain score were significantly reduced in all three treated groups, but there was no difference between the three groups. No significant change occurred in spinal motion and the straight leg raising test. After one year only the analgesic consumption was significantly lower than in the control group.", "Cluster randomized controlled trial for a multifaceted implementation strategy.\n To assess the effectiveness of tailored interventions (multifaceted implementation strategy) to implement the Dutch low back pain guideline for general practitioners with regard to adherence to guideline recommendations.\n Guidelines for the management of low back pain in primary care have been developed in various countries, but little is known about the optimal implementation strategy. A multifaceted implementation strategy was developed to overcome identified barriers to the implementation of the Dutch low back pain guideline for general practitioners.\n General practitioners were randomized to an intervention or a control group. The general practitioners in the intervention group (n = 21) received tailored interventions consisting of the Dutch low back pain guideline for general practitioners, a 2-hour educational and clinical practice workshop; two scientific articles on low back pain management; the guideline for occupational physicians; a tool for patient education; and a tool for reaching agreement on low back care with physical, exercise, and manual therapists. The control group (n = 20) received no intervention. The participating general practitioners were asked to recruit consecutive patients with a new episode of low back pain as the main reason for consultation. General practitioners completed registration forms of each individual consultation with regard to the main outcome measures: advice and information, referral to other health-care providers, and prescription of medication.\n Forty-one of the 67 randomized general practitioners reported on a total of 616 consultations for 531 patients with nonspecific low back pain. The advice and explanation provided by the general practitioners, the prescription of paracetamol or nonsteroidal anti-inflammatory drugs, and prescription of pain medication on atime contingent or a pain contingent basis showed no statistically significant differences between the intervention and control groups. There were also no differences in overall referral rate. However, in follow-up consultations fewer patients were referred to a physical or exercise therapist by the general practitioners in the intervention group than in the control group.\n The multifaceted intervention strategy modestly improved implementation (for parts of the recommendations in) the Dutch low back pain guideline by general practitioners and produced small concomitant changes in patient management. The implementation strategy produced fewer referrals to therapists during follow-up consultations." ]	Based on the heterogeneity of the populations, interventions and comparison groups, we conclude that there are insufficient data to draw firm conclusions on the clinical effect of LLLT for low-back pain. There is a need for further methodologically rigorous RCTs to evaluate the effects of LLLT compared to other treatments, different lengths of treatment, wavelengths and dosages.
CD007268	[ "17786128", "12441803", "20515418", "15909273", "20163349", "15630469" ]	[ "A randomized controlled trial of therapeutic drug monitoring in treatment-naive and -experienced HIV-1-infected patients.", "PharmAdapt: a randomized prospective study to evaluate the benefit of therapeutic monitoring of protease inhibitors: 12 week results.", "Abacavir/lamivudine/zidovudine maintenance after standard induction in antiretroviral therapy-naïve patients: FREE randomized trial interim results.", "A randomized controlled trial to evaluate antiretroviral salvage therapy guided by rules-based or phenotype-driven HIV-1 genotypic drug-resistance interpretation with or without concentration-controlled intervention: the Resistance and Dosage Adapted Regimens (RADAR) study.", "Results of a community-based antiretroviral treatment program for HIV-1 infection in Western Uganda.", "Randomized, controlled trial of therapy interruption in chronic HIV-1 infection." ]	[ "To improve the utility of therapeutic drug monitoring (TDM) by defining the proportion of patients with and predictors of above or below target protease inhibitor (PI) or nonnucleoside reverse transcriptase inhibitor (NNRTI) concentrations.\n This 48-week, multicenter, open-label clinical trial randomized patients to TDM versus standard of care (SOC). Serial pharmacokinetics, including a week-2 3-sample sparse collection, and expert committee TDM recommendations were given to TDM-arm patients' providers.\n Seventy-four (39%) of 190 patients had week-2 concentrations outside of targets and 122 (64%) of 190 had nontarget exposure at least once over 48 weeks. Providers accepted 75% of TDM recommendations. Among patients with below-target concentrations, more TDM-arm than SOC-arm patients achieved targets (65% vs. 45%; P = 0.09). Increased body weight and efavirenz or lopinavir/ritonavir use were significant predictors of nontarget concentrations. Patients at target and patients who achieved targets after TDM-directed dose modifications trended toward greater viral load reductions at week 48 than patients with below-target exposures (HIV RNA reductions: 2.4, 2.3, and 1.9 log10 copies/mL, respectively; P = 0.09).\n Most patients had nontarget PI and/or NNRTI concentrations over 48 weeks. TDM recommendations were well accepted and improved exposure. Patients below TDM targets trended toward worse virologic response.", "A randomized study to evaluate the usefulness of protease inhibitor (PI) therapeutic drug monitoring (TDM) in antiretroviral-experienced HIV-infected patients.\n In the control arm, treatment was modified according to genotypic resistance testing. In the TDM arm, therapy was modified on the basis of genotypic resistance testing and at week 8 according to PI plasma trough levels measured at week 4. The major endpoint was the change in HIV-RNA levels at week 12.\n A total of 183 patients, 96 in the control arm and 87 in the TDM arm, were included in the study. Low-dose ritonavir to enhance the associated PI was prescribed to 62.5% of patients in the control arm and 65.5% of patients in the TDM arm. Using our PI concentration targets, 17/81 patients (21%) in the TDM arm were considered to have suboptimal or partly optimal PI plasma levels at week 4. Physician and protocol-driven PI modifications were performed in 18/85 patients (23.5%) in the TDM arm, and in seven of 94 patients (7%) in the control arm (P < 0.01). Week 12 HIV RNA dropped 2 log10 copies/ml in the control arm and 1.7 log10 copies/ml in the TDM arm, respectively.\n We found no statistically significant difference between the TDM arm and control arm in virological outcome at week 12. The utility of TDM could be dependent on the presence of low-dose ritonavir as a booster and the antiretroviral experience of the studied population. Effective non-toxic target concentrations for resistant viruses have still to be determined.\n Copyright 2002 Lippincott Williams & Wilkins", "Maintenance with a triple nucleoside reverse transcriptase Inhibitor (NRTI) regimen after successful induction with a dual NRTI/protease inhibitor (PI) combination may be advantageous, because of low pill burden, favorable lipids, and less drug interactions. This strategy to become free of PI-related problems without losing viral efficacy has not been formally tested. We performed a randomized, open-label, multicenter, 96-week comparative study in antiretroviral therapy (ART)-naïve patients with CD4 <or=350 cells/mm(3) and HIV-1 RNA concentrations (viral load [VL]) greater than 30,000 copies per milliliter. Patients were randomized after reaching VL less than 50 copies per milliliter on two consecutive occasions between 12 and 24 weeks after start of zidovudine/lamuvidine and lopinavir/ritonavir combination. Eligible subjects switched to abacavir/lamivudine/zidovudine (TZV) or continued the PI-containing regimen. Here we present the 48-week data with virologic success rate (failure: VL > 50 copies per milliliter). Two hundred seven patients had similar baseline (BL) characteristics: median CD4 180 cells/mm(3), median VL 5.19 log(10) copies per milliliter. One hundred twenty subjects (58%) met randomization criteria. Baseline VL differed significantly between dropouts and randomized subjects (median 5.41 versus 5.06 log(10) copies per milliliter, p = 0.017), as did CD4 cells (median 160 and 200 cells/mm(3), p = 0.044). Sixty-one subjects received TZV and 59 subjects continued NRTIs/PI. At week 48, 2 patients in the TZV group and 5 in the PI group did not have a sustained virologic suppression (log rank test; p = 0.379). CD4 counts increased significantly in both arms. In ART-naïve patients, TZV maintenance had similar antiviral efficacy compared to continued standard ART at 48 weeks after baseline. Patients on successful standard ART can be safely switched to a NRTI-only regimen, at least for the tested time period.", "It is not well defined whether concentration-controlled intervention (CCI) and rules-based human immunodeficiency virus (HIV) type 1 genotype drug-resistance interpretation (GI) or virtual phenotype drug-resistance interpretation (VPI) may improve the outcome of HIV salvage therapy.\n In a prospective, randomized, controlled trial, patients were randomized (on a factorial basis) to change treatment after either GI or VPI, and they then were further randomized to the control arm (no CCI) or the CCI arm. Protease inhibitor (PI) and nonnucleoside reverse-transcriptase inhibitor (NNRTI) trough concentration (Ctrough) values were determined at weeks 1, 4, 12, and 24 of the study.\n Among 230 patients, virological benefit (defined by an HIV RNA load of <400 copies/mL at week 24) was not statistically different, either between patients in the GI and VPI arms or between patients in the CCI and control arms. A virological benefit was found for patients in the CCI arm, compared with patients in the control arm, but this benefit was not statistically significant (56.8% vs. 64.3% at week 4 and 63.6% vs. 74% at week 12). Dosage adaptation was possible for only a fraction of patients, because of low rates of treatment adherence or patient refusal to increase dosages. In the logistic regression analysis, independent predictors of virological response at week 24 were a PI Ctrough value and/or an NNRTI Ctrough value in the higher quartiles (or above cutoff levels) and a low number of PIs previously received. Moreover, receipt of a regimen that contained PIs boosted with ritonavir was an independent predictor of virological response.\n The present study did not support the routine use of CCI for patients undergoing salvage treatment, probably as a result of existing difficulties associated with its clinical application. However, a higher Ctrough value appeared to be correlated with treatment response. No major differences were found between VPI or GI when they are used together with expert advice for the selection of salvage treatment combinations.", "To compare the treatment outcomes and mortality in a rural community-based ART (CBART) program with a hospital-based ART program in the same district.\n The study design was a non-randomized cohort study consisting of 185 persons living with HIV (PLWHIV) in the CBART cohort and 200 PLWHIV in the hospital cohort. Eligibility for both cohorts was: being HIV-infected and eligible for ART, being treatment naïve, age 18 years or older, and being a resident of Rwimi sub-county. The intervention consisted of a community-based program which included weekly home visits to patients by trained volunteers who delivered antiretroviral drugs (ARVs), monitored and supported adherence to treatment, and identified and reported adverse reactions and other clinical symptoms. Outcome variables were compared to patients in a hospital-based cohort who received the standard care delivered to all other HIV patients in the hospital. The main outcome measures were HIV-1 RNA viral load (VL), CD4 cell count and mortality after six months of treatment.\n Successful ART treatment outcome as measured by virological suppression (VL<400 copies/ml) in the CBART cohort were similar to those in the hospital-based cohort (90.1% vs 89.3%, p=0.47). The median CD4 cell count increased significantly in both cohorts (community-based cohort 159 cells/microl vs 145 cells/microl in the hospital-based cohort). Mortality was not significantly different in both cohorts (community-based cohort 11.9%, hospital-based cohort 9.0%).\n The findings show that outcomes of a CBART intervention in a rural area compare favorably to outcomes of hospital-based care. If the study results are sustainable over a longer time period, this model could be considered for ART roll-out to impoverished rural/remote populations in Uganda and elsewhere.", "Approaches to limiting exposure to antiretroviral therapy (ART) drugs are an active area of HIV therapy research. Here we present longitudinal follow-up of a randomized, open-label, single-center study of the immune, viral, and safety outcomes of structured therapy interruptions (TIs) in patients with chronically suppressed HIV-1 infection as compared to equal follow-up of patients on continuous therapy and including a final therapy interruption in both arms.\n Forty-two chronically HIV-infected patients on suppressive ART with CD4 counts higher than 400 were randomized 1:1 to either (1) three successive fixed TIs of 2, 4, and 6 wk, with intervening resumption of therapy with resuppression for 4 wk before subsequent interruption, or (2) 40 wk of continuous therapy, with a final open-ended TI in both treatment groups. Main outcome was analysis of the time to viral rebound (>5,000 copies/ml) during the open-ended TI. Secondary outcomes included study-defined safety criteria, viral resistance, therapy failure, and retention of immune reconstitution. There was no difference between the groups in time to viral rebound during the open-ended TI (continuous therapy/single TI, median [interquartile range] = 4 [1-8] wk, n = 21; repeated TI, median [interquartile range] = 5 [4-8] wk, n = 21; p = 0.36). No differences in study-related adverse events, viral set point at 12 or 20 wk of open-ended interruption, viral resistance or therapy failure, retention of CD4 T cell numbers on ART, or retention of lymphoproliferative recall antigen responses were noted between groups. Importantly, resistance detected shortly after initial viremia following the open-ended TI did not result in a lack of resuppression to less than 50 copies/ml after reinitiation of the same drug regimen.\n Cycles of 2- to 6-wk time-fixed TIs in patients with suppressed HIV infection failed to confer a clinically significant benefit with regard to viral suppression off ART. Also, secondary analysis showed no difference between the two strategies in terms of safety, retention of immune reconstitution, and clinical therapy failure. Based on these findings, we suggest that further clinical research on the long-term consequences of TI strategies to decrease drug exposure is warranted." ]	Our review does not support routine use of ARV TDM in ARV-naive or -experienced patients on either boosted PI or NNRTI ART regimens. TDM in treatment-naive participants on a PI-based ART regimen, particularly if unboosted by ritonavir, may improve virological outcomes. Trials were underpowered with small sample sizes, short durations of follow-up and generally poor uptake of TDM recommendations. As these trials were conducted in higher income earning countries, results may not be generalisable to resource-limited countries where the burden of HIV is heaviest.
CD003879	[ "9668994" ]	[ "The effect of extraction of third molars on late lower incisor crowding: a randomized controlled trial." ]	[ "The problem of late mandibular incisor crowding is a well established phenomenon, the cause of which has been the substance of considerable debate over the years. A central issue is the possible role of the third molars though no definitive conclusions have been consistently drawn. This prospective study was designed to investigate the effects of randomly assigned early extraction of third molars on late crowding of the mandibular incisors. One-hundred-and-sixty-four patients entered the study from 1984 following completion of retention after orthodontic treatment. Seventy-seven patients (47%) returned for records up to a mean of 66 months later, and their start and finish study casts were digitized on a reflex microscope to determine Little's index of irregularity, intercanine width and arch length. Forty-four of the patients had been randomized to have third molars removed. There was no evidence of responder bias. Where third molars were extracted the mean increase in lower labial segment irregularity was reduced by 1.1 mm from a mean of 2.1 mm for the group where third molars were retained (P = 0.15, not statistically significant). This difference was also not considered to be clinically significant. The principal conclusion drawn from this randomized prospective study is that the removal of third molars to reduce or prevent late incisor crowding cannot be justified." ]	Insufficient evidence was found to support or refute routine prophylactic removal of asymptomatic impacted wisdom teeth in adults. A single trial comparing removal versus retention found no evidence of a difference on late lower incisor crowding at 5 years, however no other relevant outcomes were measured. Watchful monitoring of asymptomatic third molar teeth may be a more prudent strategy.
CD005537	[ "10474848", "17066964", "16643264", "17513815", "11689579", "9638782", "12096294" ]	[ "A group cognitive behaviour therapy programme with metastatic breast cancer patients.", "Randomized clinical trial on cognitive therapy for depression in women with metastatic breast cancer: psychological and immunological effects.", "Does routine assessment and real-time feedback improve cancer patients' psychosocial well-being?", "Impact of a peer-delivered telephone intervention for women experiencing a breast cancer recurrence.", "Randomized trial of coordinated psychosocial interventions based on patient self-assessments versus standard care to improve the psychosocial functioning of patients with cancer.", "Reducing distress in cancer patients with an orientation program.", "Intervention to improve psychological functioning for newly diagnosed patients with cancer." ]	[ "One-hundred and twenty-four patients with metastatic breast cancer were randomised to either a group Cognitive Behaviour Therapy (CBT) intervention, or to a no-therapy control group condition. Both groups received standard oncological care; however, therapy recipients also attended eight weekly sessions of group CBT, followed by a family night, and three further monthly sessions. Patients completed the 'Profile of Mood States' (POMS) and the Coopersmith Self-esteem Inventory (CSI) before and after therapy, and at 3 and 6 month follow-up periods. Outcome data in the period following therapy showed reduced depression and total mood disturbance, as well as improved self-esteem amongst therapy participants, relative to a no-therapy control group. These improvements were no longer evident at the 3 or 6 month follow-up assessments. We also report on the difficulties associated with conducting a group intervention with this patient cohort.", "Depression is particularly prevalent in patients with advanced cancer. Cognitive therapy (CT) is an empirically supported treatment for depression in the general population. However, efficacy remains to be demonstrated in patients with advanced cancer. A prior controlled trial of CT in a group format showed improvements in depression, mood disturbance, and self-esteem; however, these effects were not maintained over time. Studies examining the efficacy of individual format CT interventions that may ensure more long-term maintenance of benefits are necessary. This study assessed the efficacy of CT for depression administered individually in women with metastatic breast cancer and its effect on immune function.\n Forty-five women were randomly assigned to either individual CT or to a waiting-list control (WLC) condition. CT was composed of eight weekly sessions of CT and three booster sessions administered at 3-week intervals following the end of treatment.\n Patients treated with CT had significantly lower scores on the Hamilton Depression Rating Scale at posttreatment compared to untreated patients. Pooled data from both groups indicated significant reductions of depressive symptoms from pre- to posttreatment, as well as reduction of associated symptoms including anxiety, fatigue, and insomnia symptoms. These effects were well sustained at the 3- and 6-month follow-up evaluations. CT for depression did not appear to have a significant impact on immune functioning.\n Findings of this study support the efficacy of CT for depression in this population and suggest that the administration of individual and booster sessions after treatment termination may be instrumental in sustaining the treatment effects over time.", "This study examined the effectiveness of giving medical oncologists immediate feedback about cancer patients' self-reported psychosocial well-being in reducing those patients' levels of anxiety, depression, perceived needs and physical symptoms. Cancer patients attending one cancer centre for their first visit were allocated to intervention (n = 42) or control (n = 38) groups. All patients completed a computerized survey assessing their psychosocial well-being while waiting to see the oncologist. Intervention patients' responses were immediately scored and summary reports were placed in each patient's file for follow-up. A total of 48 participants (25 intervention and 23 control) completed the survey four times. Intervention patients who reported a debilitating physical symptom at visit 2 were significantly less likely to report a debilitating physical symptom at visit 3 compared with control patients (OR = 2.8, P = 0.04). Reductions in levels of anxiety, depression and perceived needs among intervention patients were not significantly different to control patients. Repeated collection and immediate feedback of patient-reported health information to oncologists has potential to improve patients' symptom control, but has little impact upon emotional well-being, including those at high risk. Future research should consider providing the feedback to other health professionals and patients, and monitor the impact on the process of individual patient care.", "A first breast cancer recurrence creates considerable distress, yet few psychosocial interventions directed at this population have been reported. The Southwest Oncology Group conducted a phase III randomized trial to evaluate the effectiveness of a brief telephone intervention.\n Three hundred five women experiencing a first recurrence of breast cancer were randomly assigned to standard care or intervention. The intervention consisted of four to eight telephone calls delivered over a 1-month period. The calls were conducted by trained peer counselors at a breast cancer advocacy organization, the Y-ME National Breast Cancer Organization, and followed a standard curriculum. Psychosocial distress (Cancer Rehabilitation Evaluation System-Short Form [CARES-SF]) and depressive symptoms (Center for Epidemiologic Studies Depression Scale [CES-D]) outcomes were assessed at baseline and 3 and 6 months. The 3-month assessment was the primary end point and is the focus of this article.\n Analysis revealed no differences in distress or depressive symptoms at 3 months between the intervention and control groups; at 3 months, 70% of control patients and 66% of intervention patients reported psychosocial distress, and 40% of control patients and 47% of intervention patients exhibited depressive symptoms.\n Telephone peer counseling did not lead to better psychosocial outcomes. The persistent distress in these women supports the urgent need for the development and testing of more intensive or different supportive interventions for this group of patients.", "To determine whether making patient-reported cancer needs, quality-of-life (QOL), and psychosocial information available to the health care team, allowing coordinated specifically targeted psychosocial interventions, resulted in reduced cancer needs, improved QOL, and increased satisfaction with care received.\n Self-reported cancer needs, QOL, and psychosocial information was collected from 450 people with cancer, using standardized questionnaires via a touch-screen computer. For a randomly chosen two thirds, this information was made available to the health care team who coordinated targeted psychosocial interventions. Information from the remaining one third was not seen. Patients were assessed 2 and 6 months after randomization for changes in their cancer needs, QOL, and psychosocial functioning and satisfaction with overall care received.\n There were no significant differences between the two arms with respect to changes in cancer needs, QOL, or psychosocial functioning between the baseline and follow-up assessments, nor with respect to satisfaction with care. However, for the subgroup of patients who were moderately or severely depressed at baseline, there was a significant reduction in depression for the intervention arm relative to the control arm at the 6-month assessment (P =.001).\n Making patient-reported cancer needs, QOL, and psychosocial data available to the health care team at a single consultation together with coordinated psychosocial interventions does not seem to reduce cancer needs nor improve QOL, psychosocial functioning, or satisfaction with the care received. However, identification of patients with moderate or severe levels of depression may be valuable in reducing subsequent levels of depression.", "The purpose of this study was to test a brief orientation program for reducing anxiety, depressive symptoms, and overall distress in cancer patients at their initial clinic visit. One hundred and fifty consecutively referred patients seen in an oncology outpatient clinic were randomly assigned to an intervention or usual care control group. The intervention group received a clinic tour, general information about clinic operations, and a question and answer session with an oncology counselor. Outcome measures included the State-Trait Anxiety Inventory (STAI), the Brief Profile of Mood States (POMS), the Center for Epidemiologic Studies-Depression (CES-D) Scale, and an oncology clinic questionnaire which were administered at the initial clinic visit and follow-up. There were no statistically significant clinical or demographic differences between groups at initial assessment. At follow-up, the intervention group had lower state anxiety, lower overall distress, and fewer patients reporting depressive symptoms. Patients in the intervention group demonstrated significantly more knowledge about clinic operations and greater satisfaction with care. These data provide evidence that anxiety, distress and depressive symptoms can be reduced with an orientation program. This finding has particular relevance in the early stages of diagnosis where patients may suffer symptoms of anxiety and depression.", "To test the effects of a computer-based nursing intervention designed to provide patients and family caregivers with concrete, objective information on symptom management; provide education about disease and treatment; coordinate medical resources; and provide emotional support and counseling.\n Two-site, randomized clinical trial.\n A large, urban, midwestern, tertiary-cancer center and a community-based cancer center in a medium-sized midwestern city.\n 109 patients newly diagnosed with breast, colon, or lung cancer who were receiving chemotherapy; 54 received standard care, and 55 participated in the intervention group.\n Outcome data were collected via structured telephone interviews at three time points: baseline, midway through the intervention, and one month postintervention. The intervention consisting of nine visits, five in person and four by telephone, was conducted over 18 weeks by advanced practice oncology nurses.\n Psychosocial functioning, anxiety, and depression.\n Patients who received the intervention had significantly less depression between baseline and the midway point, as well as less anxiety and greater improvement in the role-emotional and mental health subscales of the Medical Outcomes Study 36 Short Form.\n Cancer-care nursing interventions can decrease psychosocial morbidity and improve quality of life for newly diagnosed patients with cancer undergoing treatment. Additional research is needed to understand who benefited most from the intervention.\n This nurse-directed intervention resulted in improved mental health for patients; however, physical subscales were not changed. Further work is needed to determine why depression and mental health were affected yet physical health and symptoms did not differ between groups. Results support the important role of nurses in addressing mental health issues in patients and families experiencing cancer." ]	Evidence from RCTs of moderate quality suggest that psychotherapy is useful for treating depressive states in advanced cancer patients. However, no evidence supports the effectiveness of psychotherapy for patients with clinically diagnosed depression.
CD009498	[ "7954233" ]	[ "Treatment of liver metastases from colorectal cancer with hepatic artery occlusion, intraportal 5-fluorouracil infusion, and oral allopurinol. A randomized clinical trial." ]	[ "Regional therapy for colorectal liver metastases aimed at prolonging survival has not been tested fully in a randomized trial with untreated control subjects. This study explored the efficacy of temporary hepatic artery occlusion followed by intraportal infusion of 5-fluorouracil (5-FU) and oral allopurinol as biochemical modulators in prolonging the survival of patients with nonresectable liver metastases and no extrahepatic cancer.\n Eighty-four patients were considered for randomization, of whom 24 were excluded at laparotomy because of extrahepatic cancer (n = 17) or resectable lesions (n = 5). In two patients, no cancer was identified in the liver. Thirty-two patients were allocated to receive treatment, and 28 were allocated to receive no regional or systemic treatment. Six patients were excluded after randomization because of major protocol violations.\n The median survival time for patients was 17 months (range, 0-66), and for control subjects, the median was 8 months (range, 0-31). Log rank analysis demonstrated a significant survival benefit for treatment versus no treatment (P = 0.0039). (In two patients, early death was due to toxicity from the wrong dose of 5-FU and the wrong route of administration, respectively; the mean and median survival were reduced by 1 month).\n This study identified a treatment modality that prolongs survival in patients with nonresectable liver metastases and no extrahepatic metastases from colorectal cancer, suggesting that control subjects receiving no therapy may not be necessary in future randomized trials." ]	On the basis of one small randomised trial that did not describe sequence generation, allocation concealment or blinding, it can be concluded that in patients with liver metastases no significant survival benefit or benefit on extrahepatic recurrence was found in the embolisation group in comparison with the palliation group. The probability for selective outcome reporting bias in the trial is high. At present, transarterial (chemo)embolisation cannot be recommended outside randomised clinical trials.
CD002848	[ "8545227", "9386673", "9652561", "1651610", "8920706", "9002329", "16148848", "15602194", "1326741", "7491235", "7707626", "1321858", "16621194", "9337376", "11740320", "14760258", "2541168", "2154925", "8699054", "8933551", "16088807", "7603812", "3894608", "2160516", "1995721", "3009634", "2330930", "16394298", "6143964", "22520136", "10426173", "2845349", "16394299", "10418923", "2157737", "2161038", "17200266", "20692031", "20107214", "14551493", "15933555", "20692030", "8408569", "3031574", "10440305", "2852792", "8393606", "22008819", "22520141", "22520135", "8046423", "22520137", "18037080", "22520140", "3009633", "19679216", "1975333", "2536789", "1650128", "1852084" ]	[ "Safety and efficacy of high-dose rhesus-human reassortant rotavirus vaccines--report of the National Multicenter Trial. United States Rotavirus Vaccine Efficacy Group.", "Efficacy and safety of high-dose rhesus-human reassortant rotavirus vaccine in Native American populations.", "Randomised placebo-controlled trial of rhesus-human reassortant rotavirus vaccine for prevention of severe rotavirus gastroenteritis.", "Immunogenicity and safety of rhesus-human rotavirus reassortant vaccines with serotype 1 or 2 VP7 specificity.", "Immunogenicity, safety and protective efficacy of one dose of the rhesus rotavirus vaccine and serotype 1 and 2 human-rhesus rotavirus reassortants in children from Lima, Peru.", "Immunogenicity, safety and efficacy of tetravalent rhesus-human, reassortant rotavirus vaccine in Belém, Brazil.", "Evaluation of safety, immunogenicity and efficacy of an attenuated rotavirus vaccine, RIX4414: A randomized, placebo-controlled trial in Latin American infants.", "Efficacy of RIX4414 live attenuated human rotavirus vaccine in Finnish infants.", "Protective efficacy against serotype 1 rotavirus diarrhea by live oral rhesus-human reassortant rotavirus vaccines with human rotavirus VP7 serotype 1 or 2 specificity.", "Comparison of immunogenicity and efficacy of rhesus rotavirus reassortant vaccines in breastfed and nonbreastfed children. US Rotavirus Vaccine Efficacy Group.", "Evaluation of rhesus rotavirus monovalent and tetravalent reassortant vaccines in US children. US Rotavirus Vaccine Efficacy Group.", "Field trial of rhesus rotavirus or human-rhesus rotavirus reassortant vaccine of VP7 serotype 3 or 1 specificity in infants. The Elmwood, Panorama, and Westfall Pediatric Groups.", "Effects of the potency and composition of the multivalent human-bovine (WC3) reassortant rotavirus vaccine on efficacy, safety and immunogenicity in healthy infants.", "Efficacy of the rhesus rotavirus-based quadrivalent vaccine in infants and young children in Venezuela.", "Safety and immunogenicity of tetravalent rhesus-based rotavirus vaccine in Bangladesh.", "Safety, efficacy, and immunogenicity of a live, quadrivalent human-bovine reassortant rotavirus vaccine in healthy infants.", "Reactions to and antigenicity of two human-rhesus rotavirus reassortant vaccine candidates of serotypes 1 and 2 in Venezuelan infants.", "Rhesus Rotavirus candidate vaccine. Clinical trial in children vaccinated between 2 and 5 months of age.", "Safety, immunogenicity, and protective efficacy of one and three doses of the tetravalent rhesus rotavirus vaccine in infants in Lima, Peru.", "Comparative evaluation of reactogenicity and immunogenicity of two dosages of oral tetravalent rhesus rotavirus vaccine. US Rhesus Rotavirus Vaccine Study Group.", "Evaluation of RIX4414, a live, attenuated rotavirus vaccine, in a randomized, double-blind, placebo-controlled phase 2 trial involving 2464 Singaporean infants.", "Evaluation of the protective efficacy of a serotype 1 bovine-human rotavirus reassortant vaccine in infants.", "Clinical efficacy of the RIT 4237 live attenuated bovine rotavirus vaccine in infants vaccinated before a rotavirus epidemic.", "Prospective study of diarrheal diseases in Venezuelan children to evaluate the efficacy of rhesus rotavirus vaccine.", "A field study of the safety and efficacy of two candidate rotavirus vaccines in a Native American population.", "A comparative trial of rhesus monkey (RRV-1) and bovine (RIT 4237) oral rotavirus vaccines in young children.", "An efficacy trial of the rhesus rotavirus vaccine in Maryland. The Clinical Study Group.", "Safety and efficacy of an attenuated vaccine against severe rotavirus gastroenteritis.", "Protection of infants against rotavirus diarrhoea by RIT 4237 attenuated bovine rotavirus strain vaccine.", "Efficacy and immunogenicity of two or three dose rotavirus-vaccine regimen in South African children over two consecutive rotavirus-seasons: a randomized, double-blind, placebo-controlled trial.", "Concurrent administration of rhesus rotavirus tetravalent (RRV-TV) vaccine with pentavalent diphtheria-pertussis-tetanus-Haemophilus influenzae beta-inactivated polio and hepatitis B vaccines.", "Field trial of rhesus rotavirus vaccine in infants.", "Safety and efficacy of a pentavalent human-bovine (WC3) reassortant rotavirus vaccine.", "Safety and immunogenicity of live attenuated human-bovine (UK) reassortant rotavirus vaccines with VP7-specificity for serotypes 1, 2, 3 or 4 in adults, children and infants.", "Clinical studies of a quadrivalent rotavirus vaccine in Venezuelan infants.", "Immune protection of infants against rotavirus gastroenteritis by a serotype 1 reassortant of bovine rotavirus WC3.", "Efficacy, immunogenicity, and safety of a pentavalent human-bovine (WC3) reassortant rotavirus vaccine at the end of shelf life.", "Efficacy of pentavalent rotavirus vaccine against severe rotavirus gastroenteritis in infants in developing countries in Asia: a randomised, double-blind, placebo-controlled trial.", "Effect of human rotavirus vaccine on severe diarrhea in African infants.", "Safety, immunogenicity and efficacy in healthy infants of G1 and G2 human reassortant rotavirus vaccine in a new stabilizer/buffer liquid formulation.", "Comparative evaluation of safety and immunogenicity of two dosages of an oral live attenuated human rotavirus vaccine.", "Efficacy of pentavalent rotavirus vaccine against severe rotavirus gastroenteritis in infants in developing countries in sub-Saharan Africa: a randomised, double-blind, placebo-controlled trial.", "Reactogenicity and immunogenicity of a high-titer rhesus rotavirus-based quadrivalent rotavirus vaccine.", "Neonatal rotavirus vaccination with RIT 4237 bovine rotavirus vaccine: a preliminary report.", "Efficacy of live, attenuated, human rotavirus vaccine 89-12 in infants: a randomised placebo-controlled trial.", "Reactogenicity and antigenicity of rhesus rotavirus vaccine (MMU-18006) in newborn infants in Venezuela.", "A comparative evaluation of the safety and immunogenicity of a single dose of unbuffered oral rhesus rotavirus serotype 3, rhesus/human reassortant serotypes 1, 2 and 4 and combined (tetravalent) vaccines in healthy infants.", "Horizontal transmission of a human rotavirus vaccine strain--a randomized, placebo-controlled study in twins.", "Secondary efficacy endpoints of the pentavalent rotavirus vaccine against gastroenteritis in sub-Saharan Africa.", "Efficacy of human rotavirus vaccine against severe gastroenteritis in Malawian children in the first two years of life: a randomized, double-blind, placebo controlled trial.", "Evaluation of the antigenicity and reactogenicity of varying formulations of the rhesus rotavirus-based quadrivalent and the M37 rotavirus vaccine candidates.", "Efficacy of pentavalent rotavirus vaccine in a high HIV prevalence population in Kenya.", "Efficacy of human rotavirus vaccine against rotavirus gastroenteritis during the first 2 years of life in European infants: randomised, double-blind controlled study.", "Efficacy of the oral pentavalent rotavirus vaccine in Mali.", "Evaluation of rhesus rotavirus vaccine (MMU 18006) in infants and young children.", "Safety and efficacy of human rotavirus vaccine during the first 2 years of life in Asian infants: randomised, double-blind, controlled study.", "Comparison of reactogenicity and antigenicity of M37 rotavirus vaccine and rhesus-rotavirus-based quadrivalent vaccine.", "Protection of Peruvian children against rotavirus diarrhea of specific serotypes by one, two, or three doses of the RIT 4237 attenuated bovine rotavirus vaccine.", "Immunogenicity of tetravalent rhesus rotavirus vaccine administered with buffer and oral polio vaccine.", "Efficacy of two doses of RIT 4237 bovine rotavirus vaccine for prevention of rotavirus diarrhoea." ]	[ "Rotavirus is a leading cause of morbidity and mortality from dehydrating gastroenteritis in infants and young children worldwide. Virtually every child is infected by age 4 years, justifying universal childhood immunization when a safe and effective vaccine is available. We report the results of a multicenter, placebo-controlled field trial in the United States of monovalent serotype 1 and tetravalent (TV) rhesus-human reassortant rotavirus vaccines (RRVs).\n In this randomized, double-blind trial, 1278 healthy infants ages 5 to 25 weeks received three oral doses of RRV serotype 1, RRV-TV, or a placebo at approximately 2, 4, and 6 months of age. Vaccines contained 4 x 10(5) plaque-forming units of virus. Gastroenteritis episodes were monitored, and severity was graded throughout one rotavirus season. Two stool specimens per episode were tested for rotavirus.\n The incidence of reactions did not differ among treatment groups during the 5-day, postvaccination safety surveillance period for any of the three doses. Both vaccines significantly reduced the incidence of rotavirus gastroenteritis. Vaccination was most protective against serious rotavirus illness; RRV-TV prevented 49% of rotavirus episodes, 80% of very severe episodes, and 100% of dehydrating rotavirus illness. Reduction of rotavirus disease by RRV-TV resulted in significantly fewer total episodes of gastroenteritis of all causes and an 82% reduction in all cases of dehydrating diarrhea.\n RRV-TV is highly protective against very severe, dehydrating rotavirus gastroenteritis.", "We compared the efficacy, safety, and immunogenicity of a rhesus rotavirus tetravalent vaccine (RRV-TV), a rhesus rotavirus monovalent (serotype 1) vaccine (RRV-S1), and placebo in healthy American Indian infants for two rotavirus seasons.\n Infants aged 6 to 24 weeks were enrolled in a randomized, double-blind efficacy study. Infants were orally administered RRV-TV (4 x 10(5) plaque-forming units per dose), RRV-S1 (4 x 10(5) plaque-forming units per dose), or placebo at 2, 4, and 6 months of age. Stools collected during episodes of gastroenteritis were tested for detection of rotavirus antigen. A total of 1185 infants received at least one dose of a study vaccine or placebo, and 1051 received all three doses according to the protocol.\n During the first year of surveillance, the estimates of vaccine efficacy (with 95% confidence interval) for preventing rotaviral gastroenteritis were 50% (26, 67) for RRV-TV and 29% (-1, 50) for RRV-S1. In this population only 6% of rotaviral gastroenteritis episodes among placebo recipients were associated with type G1 disease. For severe disease the estimates of vaccine efficacy were higher: 69% (29, 88) for RRV-TV and 48% (-4, 75) for RRV-S1.\n These data indicate that RRV-TV is moderately efficacious in preventing all episodes of gastroenteritis caused by rotavirus and is most efficacious against the severe disease characteristic of rotaviral illness.", "Rotavirus is the most common cause of acute childhood gastroenteritis. Vaccination with live oral heterologous rotavirus vaccines may prevent rotavirus gastroenteritis. We assessed the efficacy of rhesus-human reassortant rotavirus tetravalent vaccine (RRV-TV) against severe rotavirus gastroenteritis in Finnish children in a randomised placebo-controlled double-blind trial.\n Placebo or RRV-TV (titre 4x10(5) plaque-forming units) was given to infants at ages 2, 3, and 5 months. The children were followed up for one or two rotavirus epidemic seasons. The main outcome measure was protection against severe rotavirus gastroenteritis (score > or =11 on a 20-point severity scale). 2398 children were enrolled and received at least one dose of RRV-TV (n=1191) or placebo (n=1207). The primary efficacy analysis was based on children who received three doses of RRV-TV (n=1128) or placebo (n=1145).\n 256 episodes of rotavirus gastroenteritis occurred at any time during the study; 65 were among 1191 RRV-TV recipients, and 191 among 1207 placebo recipients (vaccine efficacy 66% [95% CI 55-74]; intention-to-treat analysis). 226 episodes were included in the primary efficacy analysis of fully vaccinated children (54 among 1128 RRV-TV recipients, 172 among 1145 placebo recipients; vaccine efficacy 68% [57-76]). 100 episodes were severe, eight in RRV-TV recipients and 92 in placebo recipients (vaccine efficacy 91% [82-96]).\n RRV-TV vaccine was highly effective against severe rotavirus gastroenteritis in young children. Incorporation of this vaccine into routine immunisation schedules of infants could reduce severe rotavirus gastroenteritis by 90% and severe gastroenteritis of all causes in young children by 60%.", "Rhesus-human rotavirus reassortants incorporating the gene expressing the VP7 surface protein of human rotavirus serotypes 1 or 2, and the remaining ten genes from rhesus rotavirus (RRV) were evaluated as candidate oral vaccines in 2-4-month-old infants. A single dose of the serotype 1 reassortant vaccine which had a titre of 10(4) plaque-forming units (p.f.u.) induced a fourfold or greater antibody response in 81% of the recipients by a combination of ELISA and neutralization assays; 51% of the vaccinees developed a neutralizing antibody response to the vaccine strain. A single dose of the serotype 2 vaccine (10(4) p.f.u.) induced a seroresponse in all vaccinees by the combination of assays whereas 67% developed neutralizing antibodies to the vaccine strain. A combination of these two vaccines (0.5 x 10(4) p.f.u. of each) induced an overall seroresponse in 95% of the recipients but only 48% and 24% response in neutralizing antibodies to serotypes 1 and 2, respectively. A trivalent combination which included the two reassortants and RRV (0.33 x 10(4) p.f.u. of each strain) induced an overall response in 82% of the vaccinees, but only 30%, 20% and 65% developed a neutralizing antibody response to serotype 1, serotype 2, and RRV, respectively. Febrile reactions on days 2-5 after vaccination were seen in 23-45% of the infants receiving the various vaccines and combinations and in 5% of the placebo group. It is concluded that rhesus-human reassortant rotaviruses may be combined with each other and with RRV as a polyvalent vaccine, but the VP7-specific neutralizing antibody responses are likely to be lower after combined vaccination than following vaccination with a single reassortant rotavirus.", "In a four cell trial, a single 10(4) plaque-forming unit dose of rhesus rotavirus (RRV) vaccine (serotype G3), a human rotavirus-rhesus rotavirus reassortant vaccine with serotype G1 specificity, a similar vaccine with serotype G2 specificity, or a placebo was administered with buffer orally at 2 months of age to 800 Peruvian infants. Only the RRV vaccine was associated with a febrile response (< 38 degrees C) that occurred in 9% of the infants on day 4 after vaccination. Diarrhea or other side-effects were not associated with administration of vaccine. Vaccine strains were shed by only 12-18% of the infants as determined by examination of a single stool specimen obtained on days 4 or 5 after vaccination. Fifty per cent of vaccines developed an IgA ELISA seroresponse; however, a serotype-specific seroresponse by plaque reduction neutralization was demonstrated in < 20% of the participants against each of the three candidate vaccine strains. Vaccine efficacy was evaluated by twice-weekly home surveillance for diarrheal diseases during 24 months post-immunization. Rotavirus diarrheal episodes were identified by ELISA. Only the RRV vaccine had a significant protective efficacy (29%, p = 0.03, chi-square test) against rotavirus diarrhea. Analysis of vaccine efficacy against rotavirus episodes of any severity in which no other enteropathogen was isolated showed a trend towards higher vaccine efficacy. In addition, a similar trend was observed in rotavirus-only episodes in which there was some degree of dehydration or when health services were utilized. Serotype G1 or G2 rotavirus strains were most prevalent during surveillance. Neither serotype G1 or serotype G2 vaccines were protective against serotype 1 or 2 rotavirus diarrhea, respectively. The serotype G2 vaccine was 84% protective against serotype 1 and 2 dehydrating rotavirus diarrhea in the small numbers of individuals evaluated. We conclude that one dose of 10(4) p.f.u. of the RRV, serotype G1, or serotype G2 rotavirus vaccine failed to induce either an adequate serotype-specific seroresponse or serotype-specific protection in children immunized at 2 months of age. Only the RRV vaccine induced a low level of protection against rotavirus diarrhea mainly of serotype G1 specificity. Future studies need to explore whether higher vaccine dose and/or more than one dose would increase the immunogenicity and efficacy of the rotavirus vaccine, especially in developing countries with a high level of baseline rotavirus antibodies.", "A tetravalent rhesus-human reassortant rotavirus (RRV-TV) vaccine (4 x 10(4) plaque-forming units/dose) was evaluated for safety, immunogenicity and efficacy in a prospective, randomized, double-blind, placebo-controlled trial involving 540 Brazilian infants. Doses of vaccine or placebo were given at ages 1, 3 and 5 months. No significant differences were noted in the occurrence of diarrhoea or vomiting in vaccine and placebo recipients following each dose. Low-grade fever occurred on days 3-5 in 2-3% of vaccinees after the first dose, but not after the second or third doses of vaccine. An IgA antibody response to rhesus rotavirus (RRV) occurred in 58% of vaccinees and 33% of placebo recipients. Neutralizing antibody responses to individual serotypes did not exceed 20% when measured by fluorescent focus reduction, but exceeded 40% when assayed by plaque reduction neutralization. There were 91 cases of rotavirus diarrhoea among the 3-dose (vaccine or placebo) recipients during two years of follow-up, 36 of them among children given the vaccine. Overall vaccine efficacy was 8% (P = 0.005) against any diarrhoea and 35% (P = 0.03) against any rotavirus diarrhoea. Protection during the first year of follow-up, when G serotype 1 rotavirus predominated, was 57% (P = 0.008), but fell to 12% in the second year. Similar results were obtained when analysis was restricted to episodes in which rotavirus was the only identified pathogen. There was a tendency for enhanced protection by vaccine against illness associated with an average of 6 or more stools per day. These results are sufficiently encouraging to warrant further studies of this vaccine in developing countries using a higher dosage in an attempt to improve its immunogenicity and efficacy.", "A live attenuated monovalent rotavirus vaccine RIX4414 was developed with a human strain of G1P1A P[8] specificity to reduce the rotavirus burden in children.\n A double blind, randomized, placebo-controlled study evaluated the efficacy, immunogenicity, safety and reactogenicity of 2 oral doses of RIX4414 (10(4.7), 10(5.2) or 10(5.8) focus-forming units) at 2 and 4 months coadministered with routine vaccinations and oral poliovirus vaccine given for study purposes at least 14 days apart. The 2155 infants (1618 vaccine/537 placebo) enrolled in Brazil, Mexico and Venezuela were followed until 1 year of age.\n Antirotavirus IgA seroconversion rates 2 months after dose 2 ranged between 61% (10(4.7) ffu group) and 65% (10(5.8) ffu group), and most of the infants had seroprotective levels of antibodies to coadministered routine vaccinations. The reactogenicity profile of RIX4414 was similar to that of the placebo, and no vaccination-related serious adverse events were reported. Protective efficacy against severe and any rotavirus gastroenteritis from 15 days post-dose 2 was highest in the 10(5.8) ffu group [86%; 95% confidence interval (95% CI), 63-96% and 70% (95% CI 46-84%), P < 0.001, 2-sided Fisher's exact test]. The efficacy against hospitalization was 79% (95% CI 48-92%) for pooled vaccine groups. Multiple rotavirus serotypes [G1 (50%), G9 (40%), G2, G3 and G4] were identified from gastroenteritis stools (enzyme-linked immunosorbent assay and reverse transcription-polymerase chain reaction) during the study period. For severe gastroenteritis caused by G9 serotypes, the protection reached 77% (95% CI 18-96%) in the 10(5.8) ffu group, providing proof of concept that the monovalent G1P1A P[8] human rotavirus vaccine elicits cross-protection against the G9 strain. A reduction in any and severe rotavirus gastroenteritis was already observed at post-dose 1 (period: day of dose 1 to 14 days post-dose 2) in vaccinees compared with placebo recipients.\n Two doses of RIX4414 are highly efficacious, providing cross-protection (G1 and G9 strains, prevalent during this study) and early protection against any and severe rotavirus gastroenteritis and hospitalization to infants in Latin America.", "Rotavirus gastroenteritis, a major cause of mortality and morbidity worldwide, is a vaccine-preventable disease. New safe and effective candidate rotavirus vaccines are needed to replace the withdrawn rhesus rotavirus-based oral vaccine.\n We evaluated a monovalent human rotavirus vaccine, serotype G1, strain RIX4414, for efficacy, immunogenicity and safety in a randomized, double blind, placebo-controlled trial in Finland. We randomly allocated 405 healthy infants to receive 2 doses of vaccine or placebo (ratio 2:1) at approximately 2 and 4 months of age. The infants were followed during 2 rotavirus epidemic seasons (2000-2002) for acute gastroenteritis. Rotaviruses in diarrheal stool samples were primarily detected by enzyme-linked immunosorbent assay and confirmed and G-typed by reverse transciption-polymerase chain reaction.\n The vaccine was well-tolerated. No vaccine-related serious adverse events were observed during the study period. Rotavirus IgA (enzyme-linked immunosorbent assay) seroconversion rate was 80% after 2 doses. Thirty-eight cases of rotavirus gastroenteritis were detected during the entire follow-up period; 35 of these were of the G1 type. RIX4414 vaccine significantly decreased the occurrence of any rotavirus compared with placebo. Efficacy during the first rotavirus epidemic season was 73% [95% confidence interval (95% CI), 27-91%] and 90% (95% CI 10-100%) against any and severe rotavirus gastroenteritis, respectively, and during the entire follow-up period 72% (95% CI 42-87%) against any and 85% (95% CI 42-97%) against severe rotavirus gastroenteritis (P < 0.05 for all comparisons).\n RIX4414 strain of G1 human rotavirus vaccine was well-tolerated, immunogenic and efficacious in infants against rotavirus gastroenteritis during a 2-year period. To further increase vaccine \"take\" and efficacy, a higher dose of this vaccine may be considered for future efficacy trials.", "Rhesus-human rotavirus (RV) reassortant vaccine strains D x RRV or DS 1 x RRV with VP7 serotype 1 or 2 specificity were evaluated for safety, immunogenicity and protective efficacy in a double blind placebo-controlled three cell trial involving 359 infants ages 2 to 5 months. The titer of the D x RRV vaccine was 10(4) and that of the DS 1 x RRV vaccine was 10(5) plaque-forming units/1-ml dose. The vaccines were acceptably reactogenic, each inducing a transient febrile response in fewer than one-third of the vaccinees. Seroconversion by RV enzyme-linked immunosorbent assay IgA antibody was detected in 61 and 75% of the vaccinees receiving a single dose of the serotype 1 or 2 reassortant vaccine, respectively. Efficacy against RV diarrhea was evaluated in two successive epidemic seasons; RV serotype 1 was prevalent in both. Clinical efficacy was observed with both vaccines and was associated with seroconversion after vaccination; considering only such vaccinees both vaccines showed equal efficacy. The overall rates of protection for the two vaccines combined against clinical RV disease in children with seroconversion after vaccination were 92 and 59% in the first and second RV epidemic seasons, respectively. Protection against asymptomatic RV infection, as measured by serologic responses, was 59% in the first season and nil in the second season. It is concluded that each of the reassortant RV vaccines was effective in inducing protection against symptomatic RV disease associated with RV serotype 1.", "To evaluate whether breastfeeding affected the immunogenicity and/or efficacy of candidate rhesus-human rotavirus reassortant vaccines.\n A total of 989 healthy infants between 4 and 26 weeks of age were enrolled into a 23-center, prospective, randomized, double-masked, controlled study of the safety, immunogenicity, and efficacy of three doses (4 x 10(4) plaque-forming units) of monovalent rhesus-human viral protein 7, or G, serotype 1 reassortant vaccine, (RRV-S1) or tetravalent vaccine (RRV-TV) consisting of rhesus-human reassortant G serotypes 1, 2, and 4, and the parent RRV G serotype 3. Vaccine efficacy was compared in the breastfed and nonbreastfed children as well as seroconversion rates and postvaccination geometric mean titers (GMTs) of neutralizing antibodies to human serotypes 1, 2, 3, and 4, RRV, and immunoglobulin A to RRV. GMTs in the two feeding groups were compared with and without adjustment for age at initiation of vaccination, prevaccination antibody titers, and the age and prevaccination titer interaction.\n The seroconversion rates to both vaccines by one or more assays were similar for the breastfed and the nonbreastfed groups (RRV-S1, 84% and 85%, respectively; RRV-TV, 94% and 93%, respectively). There were no significant differences in postvaccination GMTs to either vaccine, measured by any serologic assay, in the two feeding groups. The efficacy of the RRV-S1 vaccine was not significantly lower among the breastfed children than the nonbreastfed children (28% and 39%, respectively). RRV-TV, which is the vaccine being further evaluated for licensure, was equally protective in breastfed and nonbreastfed infants (50% and 51%, respectively). Logistic regression analysis, taking into account differences in age at vaccination and day 1 titer, revealed no evidence of differential vaccine efficacy in the two feeding groups for either vaccine.\n These results indicate that the RRV-TV vaccine, given as three doses of 4 x 10(4) plaque-forming units, induces similar seroresponses and protection in breastfed and nonbreastfed US children.", "To determine the safety and relative efficacy of two reassortant rhesus rotavirus vaccines over two rotavirus seasons.\n A prospective, double-masked, placebo-controlled trial.\n Twenty-three centers in the United States.\n A total of 1006 healthy infants between 4 and 26 weeks of age were enrolled, and 898 received three doses of vaccine or placebo.\n Reactogenicity was determined by comparing the incidence of fever, diarrhea, and/or vomiting for 5 days after each dose of vaccine. Rotavirus IgA and neutralizing antibody to rhesus rotavirus and four rotavirus serotypes were measured in a subset of subjects. Relative efficacy was determined by comparing the incidence of rotavirus gastroenteritis after three doses of vaccine or placebo over two rotavirus seasons.\n Adverse reactions were mild and limited to a small but significant increase in the incidence of fever after the first dose of tetravalent but not monovalent vaccine. The relative efficacy against rotavirus disease over the 2 years of observation was 40% (98.3% confidence interval, 7% to 62%) for the monovalent and 57% (98.3% confidence interval, 29% to 74%) for the tetravalent vaccine. In post hoc analyses, the relative efficacy against very severe rotavirus gastroenteritis was 73% and 82% for monovalent and tetravalent vaccine recipients, respectively. Also, a 67% and 78% reduction in medical visits for rotavirus gastroenteritis was observed. Both vaccines protected against disease caused by serotype 1 rotavirus, but only the tetravalent vaccine reduced the incidence of disease caused by non-serotype 1 rotavirus infection detected in the second season. It is unclear, however, whether this result represents serotype-specific protection or a difference in the duration of protection.\n Vaccination with both vaccines was safe and significantly reduced the incidence of rotavirus gastroenteritis, but only the tetravalent vaccine provided protection against disease caused by non-serotype 1 rotaviruses during the second year of follow-up.", "Orally administered live rhesus monkey rotavirus vaccine (RRV, VP7 serotype 3) and human-rhesus reassortant rotavirus vaccine (DxRRV, VP7 serotype 1) were evaluated in a placebo-controlled field trial of 223 infants 2-4 months old. Both vaccines were mildly reactogenic but were generally well tolerated in the 10 days after vaccination. RRV and DxRRV were immunogenic, inducing serum antibody responses in 78% and 71% of the vaccines, respectively. Efficacy of RRV vaccine was 66% (P = .01) and of DxRRV vaccine 77% (P = .002) against rotavirus-associated illness in the first season after vaccination. Efficacy of RRV vaccine against rotavirus-associated illness over three rotavirus seasons was 51.2% (P = .045) and of DxRRV vaccine was 67.3% (P = .006). RRV vaccine provided heterotypic protection of 58.5% (P = .041) and DxRRV vaccine provided homotypic protection of 72.8% (P = .005) over three seasons against the predominant serotype 1 rotavirus.", "Rotavirus gastroenteritis, which causes substantial infant mortality and morbidity worldwide, is a vaccine-preventable disease. The purpose of this study was to evaluate different compositions and potencies (vaccine virus titers) of a live multivalent human-bovine (WC3) reassortant rotavirus vaccine in order to select the potency and composition of the vaccine for further development.\n The efficacy, safety, and immunogenicity of a G1, G2, G3, G4, and P1A pentavalent composition at three different potencies, a G1, G2, G3, G4 quadrivalent composition, and a P1A monovalent composition of an oral human-bovine (WC3) reassortant rotavirus vaccine were compared in a blinded, placebo-controlled trial conducted between 1998 and 2001 enrolling 1,946 healthy Finnish infants 2-8 months of age.\n All potencies of the pentavalent and quadrivalent vaccines were efficacious (58-74%) against wild-type rotavirus gastroenteritis of any severity and 100% protective against severe rotavirus disease caused by vaccine G-serotypes through the first rotavirus season post-vaccination. The monovalent P1A vaccine was 53% efficacious against moderate-and-severe rotavirus gastroenteritis. Protection against rotavirus gastroenteritis of any severity was demonstrated through two and three rotavirus seasons for all vaccine compositions. After the third dose, the percentage of infants with >or=3-fold rise in baseline serum neutralizing antibody titers against G1 ranged from 62% to 86% for recipients of the pentavalent vaccine, depending on the potency. The incidence of fever, irritability, vomiting, and diarrhea did not significantly differ between vaccine and placebo groups. A 7-month-old male developed intussusception 9 days after the first dose of the low-potency pentavalent vaccine.\n Based on the results of this trial, a pentavalent composition (G1, G2, G3, G4, and P1A) of human-bovine (WC3) reassortant rotavirus vaccine with a potency similar to that of the middle-potency pentavalent vaccine ( approximately 8 x 10(6) plaque-forming units/dose) was selected for further development.", "Rotaviruses are the principal known etiologic agents of severe diarrhea among infants and young children worldwide. Although a rhesus rotavirus-based quadrivalent vaccine is highly effective in preventing severe diarrhea in developed countries, in developing countries its efficacy has been less impressive. We thus conducted a catchment study in Venezuela to assess the efficacy of the vaccine against dehydrating diarrhea.\n In this randomized, double-blind, placebo-controlled trial, 2207 infants received three oral doses of the quadrivalent rotavirus vaccine (4x10(5) plaque-forming units per dose) or placebo at about two, three, and four months of age. During approximately 19 to 20 months of passive surveillance, episodes of gastroenteritis were evaluated at the hospital.\n The vaccine was safe, although 15 percent of the vaccinated infants had febrile episodes (rectal temperature, > or =38.1 degrees C) during the six days after the first dose, as compared with 7 percent of the controls (P<0.001). However, the vaccine gave 88 percent protection against severe diarrhea caused by rotavirus and 75 percent protection against dehydration, and produced a 70 percent reduction in hospital admissions. Overall, the efficacy of the vaccine against a first episode of rotavirus diarrhea was 48 percent. Horizontal transmission of vaccine virus was demonstrated in 15 percent of the vaccine recipients and 13 percent of the placebo recipients with rotavirus-positive diarrhea.\n In this study in a developing country, the quadrivalent rhesus rotavirus-based vaccine induced a high level of protection against severe diarrheal illness caused by rotavirus.", "Rotavirus is the most common cause of severe gastroenteritis among children worldwide.\n To compare the safety, immunogenicity and shedding patterns of rhesus rotavirus (RRV)-tetravalent vaccine vs. placebo among infants in rural Bangladesh.\n A double blinded, placebo-controlled trial was conducted in which infants (n = 120) were randomly assigned to receive three doses of either vaccine or placebo administered at approximately 6, 10 and 14 weeks of age together with routine immunizations. Data on possible adverse effects of vaccinations were collected daily for 7 days after each dose. Stool samples were collected after each dose, and serum samples were obtained before the first and after the third vaccination.\n Fever (> or = 38 degrees C), as measured by study assistants, was noted more frequently among vaccinees (15%) than among placebo recipients (2%) during the 7 days after vaccination but was not reported more frequently by parents of vaccinees vs. placebo recipients. Overall 87% of vaccinees had an antibody response (measured by IgA or anti-RRV-neutralizing antibodies) after vaccination compared with 32% of placebo recipients. Rates of seroconversion were higher among subjects with lower levels of prevaccination antibodies and those who shed rotavirus after vaccination. Vaccine strain viruses were detected in stools from placebo vaccine recipients who had evidence of IgA seroconversion.\n In this population RRV-tetravalent vaccine was comparably immunogenic and safe as in trials conducted in developed countries, where this vaccine has been proved effective in preventing severe rotavirus diarrhea. These data support continued evaluation of rotavirus vaccines in developing countries.", "To investigate safety, efficacy, and immunogenicity of live quadrivalent rotavirus vaccine (QRV) containing human-bovine (WC3) reassortant rotavirus serotypes G1, G2, G3, and P1a.\n This was a randomized, double-blinded, placebo-controlled trial. During 1993 to 1994, at 10 US study sites, 439 healthy infants approximately 2 to 6 months of age, were enrolled to receive 3 doses of oral QRV or placebo at approximately 8-week intervals.\n The vaccine was generally well tolerated; no serious vaccine-related adverse experiences were reported. Risk differences and 95% confidence intervals suggested no differences between vaccine and placebo recipients in the incidences of fever, irritability, vomiting, or diarrhea during the 14 days after any dose. QRV was 74.6% efficacious (95% CI: 49.5%, 88.3%) in preventing rotavirus acute gastroenteritis (AGE), regardless of severity and 100% efficacious (95% CI: 43.5%, 100%) in preventing severe rotavirus AGE through one rotavirus season. Serotype G1 was identified in most infants with rotavirus AGE. A >or=3-fold rise in serum neutralizing antibody to G1 was observed in 57% (45/79) of vaccinees. A >or=3-fold rise in serum anti-rotavirus IgA and fecal anti-rotavirus IgA was observed in 88% (162/185) and 65% (104/159) of vaccinees, respectively.\n QRV was generally well tolerated, immungenic, and highly effective against rotavirus gastroenteritis.", "The reactions to and antigenicity of two human-rhesus rotavirus (RRV) reassortants (human rotavirus strain D x RRV and human rotavirus strain DS1 x RRV) with the VP7 neutralization specificity of a serotype 1 or serotype 2 rotavirus were evaluated in a placebo-controlled double-blind trial in 116 1- to 5-month-old infants in Caracas, Venezuela. The children were randomly divided into five groups to receive orally the following inocula: (i) 10(4) PFU of D x RRV reassortant; (ii) 10(4) PFU of DS1 x RRV reassortant; (iii) 10(4) PFU of RRV; (iv) 5 x 10(3) PFU of D x RRV and 5 x 10(3) PFU of RRV; and (v) placebo. The children were examined daily for 7 days following vaccine administration; 8 to 26% of the vaccinated infants developed a mild febrile reaction which in most cases lasted only 1 day. Seroresponses to rotavirus were observed in 39 to 65% of the vaccinees by plaque neutralization assay and in 57 to 88% by an immunoglobulin A enzyme-linked immunosorbent assay. Vaccine shedding was detected in 53 to 86% of the vaccinees. Analysis of neutralization antibody responses indicates that the VP4 protein represents an important component of the response induced by the vaccines.", "Live attenuated oral rhesus Rotavirus candidate vaccine (strain MMU 18006 [lot RRV-1]) was evaluated for immunogenicity, safety, and clinical protection in a double-blind, placebo-controlled trial involving 200 infants aged 2 to 5 months when vaccinated. Vaccine-induced fourfold or greater rise of Rotavirus antibodies was seen in 62% of the infants. Febrile reactions of short duration on days 3 and/or 4 after vaccination occurred in 26% of the vaccine recipients. The clinical follow-up covered two Rotavirus seasons, in which serotypes 1 and 4 were prevalent. There were 16 cases of confirmed Rotavirus diarrhea in the placebo-treated group and 10 in the vaccine-treated group; from this a vaccine protection rate of 38% was derived. Clinical severity of Rotavirus diarrhea was assessed by a score; 13 cases in the placebo-treated group and 5 in the vaccine-treated group were regarded as severe or moderately severe, giving a vaccine protection rate of 67%. The rhesus Rotavirus vaccine induces partial protection against heterotypic Rotavirus disease, but the level of protection achieved with the present vaccine dose in this age group appears to be insufficient for a general Rotavirus vaccination.", "An oral rhesus-human rotavirus tetravalent (RRV-TV) vaccine (10(4) pfu of rhesus rotavirus [type G3] and of 3 human-rhesus reassortants [G1, G2, and G4]) was evaluated in a field trial in Lima, Peru. At 2, 3, and 4 months of age, infants received either a dose of RRV-TV, an initial dose of vaccine followed by a dose of placebo at 3 and 4 months, or a dose of placebo. Rotavirus-specific IgA responses were detected by ELISA in 75% of the three-dose vaccine group, 59% of the one-dose vaccine group (P = .05), and 24% of the placebo group (P < .001): 64%, 48%, and 12% of each group, respectively, had a neutralizing antibody response to at least 1 serotype. Both one and three doses of vaccine failed to induce a significant level of protection against rotavirus diarrhea; however, they did provide some protection (range, 35%-66%) against more severe rotavirus diarrhea, especially for episodes caused by type G1.", "To compare the safety and immunogenicity of two dosages of tetravalent rhesus rotavirus vaccine (RRV-TV) and the effect of age at dosing.\n A total of 195 infants were stratified by age into 2 groups, 6 to 12 weeks and 16 to 24 weeks, and randomly assigned to receive a single dose of placebo or RRV-TV containing either 4 x 10(5) or 4 x 10(6) plaque-forming units (pfu). Symptoms were recorded for 5 days after vaccination. Anti-rotavirus IgA and neutralizing antibody to human rotavirus serotypes G1 to G4 and RRV were measured in serum obtained pre- and postvaccination.\n Rates of fever > 38 degrees C (9%), diarrhea (6%) and vomiting (8%) were similar in all groups. IgA (69% vs. 49%, P = 0.02) and RRV (85% vs. 66%, P = 0.004) seroconversion rates were significantly higher in the 4 x 10(6) pfu vaccine group as were antibody titers to RRV (440.2 vs. 263.7, P = 0.04). Older infants demonstrated significantly higher seroconversion rates and antibody titers for IgA (71% vs. 52%, P = 0.03; and 110.6 vs. 54.8, P = 0.004) and RRV (92% vs. 66%, P = 0.05 and 498.3 vs. 205.6, P = 0.01) at either dose level than did the younger infants. There were no significant differences in seroconversion rates or antibody titers to human rotavirus types G1 to G4 between the two vaccination groups.\n RRV-TV at a dose of 4 x 10(6) pfu can be safely administered to infants 6 to 24 weeks of age. A single dose of 4 x 10(6) pfu of RRV-TV was significantly more immunogenic than a single dose of 4 x 10(5) pfu but did not improve responses to the human serotypes. Older vaccine recipients demonstrated significantly higher IgA and neutralizing antibody seroconversion rates and antibody titers than younger infants independent of dosage.", "At present, no rotavirus vaccine is commercially available for use worldwide. Hence, a live, attenuated monovalent vaccine was developed with human strain RIX4414 (G1P1A P[8] specificity). Vaccination trials involving infants are ongoing in developed and developing countries.\n This study was a randomized, double-blind, placebo-controlled trial conducted at pediatric hospitals and polyclinics in Singapore for the evaluation of the immunogenicity, reactogenicity, and efficacy of 2 oral doses of RIX4414. In total, 2464 healthy infants (who were 11-17 weeks old when the first dose was administered, which is in accordance with the local immunization schedule) were enrolled to receive RIX4414 at 3 concentrations of virus (10(4.7), 10(5.2), or 10(6.1) focus-forming units) or placebo at 1-month intervals, concomitantly with routinely administered infant vaccines.\n The RIX4414 vaccine was highly immunogenic, and virtually all vaccine recipients (98%-100%) experienced \"vaccine take\" (i.e., a combined immunogenicity end point based on seroconversion and/or shedding of RIX4414 in postvaccination stool samples) after receipt of 2 doses at all 3 dosage levels. Depending on the virus concentration, the anti-rotavirus IgA seroconversion rate varied from 76% (95% confidence interval [CI], 68%-83%) to 91% (95% CI, 85%-95%). Two doses of RIX4414 were well tolerated, with no increase in high fever, severe diarrhea, or vomiting after either dose or with increased viral concentration, compared with placebo. There was no observed interference with routine vaccinations of infants when RIX4414 was coadministered. The calculated efficacy of RIX4414 against rotavirus gastroenteritis was 82% (P = .046); however, this result was considered to be of limited conclusive value because of the low number of rotavirus gastroenteritis episodes identified during the follow-up period.\n The live, attenuated rotavirus vaccine (RIX4414) was well tolerated and highly immunogenic in Singaporean infants. The immunogenicity of routinely administered infant vaccines was not impaired by concomitant administration of RIX4414 vaccine.", "The objective of this study was to evaluate the efficacy of a live, attenuated bovine (strain WC3) x human (strain WI79, serotype G1) rotavirus reassortant (WI79-9) virus vaccine for prevention of symptomatic rotavirus gastroenteritis in infants. The study was a prospective, randomized, double-blind, placebo-controlled trial, conducted over a single rotavirus season in 325 infants who were 2 to 8 months old at enrollment. Subjects were randomized to receive either placebo or WI79-9 virus vaccine at 10(7.3) plaque-forming units in three oral doses each separated by 2 months. Subjects were followed for 7 days after each dose for occurrence of adverse events and during the subsequent winter for development of rotavirus gastroenteritis. Administration of WI79-9 virus vaccine was well-tolerated, and the rates of low grade fever after each dose were no higher in vaccine recipients (8 to 21%) than in placebo recipients (14 to 19%). The protective efficacy of the WI79-9 vaccine during a subsequent epidemic of predominantly serotype G1 rotavirus was 87.0% (95% confidence limits, 62.6 to 95.5%) against relatively severe rotavirus gastroenteritis (rotavirus gastroenteritis with a clinical severity score of > 8) and was 64.1% (95% confidence limits 35.9 to 79.9%) against all symptomatic rotavirus episodes. The WI79-9 vaccine was safe and effective in prevention of homotypic human rotavirus infection in infants. Further studies of reassortant vaccines based on the bovine WC3 rotavirus should be performed.", "In a randomized, double-blind, placebo-controlled trial, 331 infants aged 6 to 12 months received orally, at an interval of 1 month, either two doses of live attenuated bovine rotavirus vaccine strain RIT 4237 or equivalent placebo. The vaccinations were carried out during September to November, a non-rotavirus season; only three cases of rotavirus diarrhea occurred in the study group before the vaccinations were completed. During the epidemic season from December to May, 31 patients with clinically significant rotavirus diarrhea required therapy. Five of these were among the 168 vaccine recipients, and 26 among the 160 placebo recipients (P less than 0.001), giving a vaccine protection rate of 82%. The incidence of clinically significant diarrhea from all causes was reduced by 76% in the vaccinees. As determined by an enzyme immunoassay antibody test with homologous virus antigen, seroconversion after vaccination was obtained in 53% of the initially seronegative infants. Clinical protection correlated well with seroconversion, but the vaccinees who failed to seroconvert also had less rotavirus diarrhea than the placebo recipients, suggesting that immunity may be mediated by factors other than serum EIA antibody. Seventeen of the 23 rotavirus isolates in the epidemic season that were typed were of serotype 1, two were of serotype 2, and four were of serotype 3. The protection rates against clinically significant diarrhea were 72%, 100%, and 100% for serotypes 1, 2, and 3, respectively. We conclude that epidemic infantile winter diarrhea associated with human rotaviruses can be significantly reduced by vaccination with the live attenuated RIT 4237 bovine rotavirus vaccine before the epidemic season.", "The efficacy of a rhesus rotavirus vaccine (MMU 18006, serotype 3) against infantile diarrhea was evaluated by active home surveillance of a group of 320 children 1-10 months of age in Caracas, Venezuela. During a 1 year period following oral administration of vaccine or placebo under a double-masked code, over 600 diarrheal episodes were detected. Etiologic studies revealed that heat-stable toxin (ST) producing enterotoxigenic E. coli (ETEC) was the most common diarrheal agent detected (34%) followed by enteropathogenic E. coli (EPEC, 10.9%), heat-labile toxin (LT) producing ETEC (7.6%), rotavirus (6.9%), Cryptosporidium (4.8%) and Campylobacter (1.3%). ST-producing ETEC were also recovered from over 20% of control stool specimens obtained during diarrhea-free periods, whereas EPEC, rotavirus, Cryptosporidium, and Campylobacter were rarely detected in such control specimens. Rotavirus was responsible for about one-half of the more severe cases of diarrhea. Twenty-two of 151 infants who received placebo (14.6%) and eight of 151 receiving a 10(4) PFU dose of vaccine (5.3%) had rotavirus diarrhea during the follow-up period for an efficacy level of 64% against any rotavirus diarrhea. However, vaccine efficacy reached 90% against the more severe cases of rotavirus diarrhea and was noticeably high in the 1-4 month age group. Serotypic analysis of the rotaviruses detected suggests that the resistance induced by the vaccine was type specific since significant protection was only evident against serotype 3 rotaviruses. A 10(3) PFU dose tested initially in 18 children did not appear to protect against rotavirus diarrhea.", "A double-blind, randomized, placebo-controlled trial was conducted to evaluate the safety and efficacy of a rhesus rotavirus vaccine and RIT 4237, a bovine rotavirus vaccine, in a Navajo population. Infants aged 2-5 months were randomized to receive one dose of either 10(4) pfu of the rhesus rotavirus vaccine or 10(8) pfu of the RIT 4237 vaccine or placebo. Eleven (10.2%) of 108 infants in the rhesus vaccine group, 11 (10.4%) of 106 in the RIT 4237 group, and 9 (8.4%) of 107 in the placebo group experienced rotavirus diarrhea during the follow-up period of 17 months. Thus, in this population, neither vaccine was efficacious in preventing rotavirus diarrhea.", "Heterologous live, oral rotavirus vaccines of rhesus monkey (RRV-1) and bovine (RIT 4237) origin were tested for immunogenicity, excretion of virus, and clinical reactions in six- to eight-month-old infants. Antibody response, indicating infection with the vaccine virus, was detected in 21 (88%) of 24 children receiving the RRV-1 vaccine and in 18 (75%) of 24 receiving the RIT 4237 vaccine. Excretion of virus in the stools within one week after vaccination was demonstrable in 84% of the RRV-1 and in 21% of the RIT 4237 vaccinees. RRV-1 vaccination was associated with a febrile response (over 38 C) that clustered on days 3 or 4 postvaccination in 64% of the recipient children. In addition, 20% of the RRV-1 vaccinees had watery stools on days 4 or 5. Fever on days 3 and 4 and loose stools were not seen in the RIT 4237 vaccinees. We concluded that in young children the RRV-1 (rhesus monkey) rotavirus vaccine is more immunogenic than the RIT 4237 (bovine) rotavirus vaccine, but vaccination with RRV-1 is associated with significant adverse reactions.", "A double-blind, placebo-controlled trial of oral rhesus rotavirus vaccine at a dose of 10(4) plaque-forming units was performed in 114 young infants in Maryland. Significantly more vaccinees than controls had fever and vomiting during the week after vaccination, but these reactions were mild. Of the vaccinees, 83% had a fourfold or greater rise in neutralizing antibody to rhesus rotavirus vaccine and 69% shed vaccine virus. Seventeen percent of the vaccinees and 24% of controls had rotavirus-positive diarrhea during the 2 years of surveillance. Vaccine efficacy was therefore 29% (95% confidence limits, -31% to +66%). Stools from 12 of 13 episodes containing sufficient antigen to type were serotype 1. We conclude that rhesus rotavirus vaccine was infective, immunogenic, and probably acceptably attenuated but that this serotype 3 vaccine provided little heterotypic protection during serotype 1 outbreaks in the community.", "The safety and efficacy of an attenuated G1P[8] human rotavirus (HRV) vaccine were tested in a randomized, double-blind, phase 3 trial.\n We studied 63,225 healthy infants from 11 Latin American countries and Finland who received two oral doses of either the HRV vaccine (31,673 infants) or placebo (31,552 infants) at approximately two months and four months of age. Severe gastroenteritis episodes were identified by active surveillance. The severity of disease was graded with the use of the 20-point Vesikari scale. Vaccine efficacy was evaluated in a subgroup of 20,169 infants (10,159 vaccinees and 10,010 placebo recipients).\n The efficacy of the vaccine against severe rotavirus gastroenteritis and against rotavirus-associated hospitalization was 85 percent (P<0.001 for the comparison with placebo) and reached 100 percent against more severe rotavirus gastroenteritis. Hospitalization for diarrhea of any cause was reduced by 42 percent (95 percent confidence interval, 29 to 53 percent; P<0.001). During the 31-day window after each dose, six vaccine recipients and seven placebo recipients had definite intussusception (difference in risk, -0.32 per 10,000 infants; 95 percent confidence interval, -2.91 to 2.18; P=0.78).\n Two oral doses of the live attenuated G1P[8] HRV vaccine were highly efficacious in protecting infants against severe rotavirus gastroenteritis, significantly reduced the rate of severe gastroenteritis from any cause, and were not associated with an increased risk of intussusception. (ClinicalTrials.gov numbers, NCT00139347 and NCT00263666.)\n Copyright 2006 Massachusetts Medical Society.", "A randomised, double-blind, placebo-controlled trial was conducted to evaluate the ability of RIT 4237 live attenuated bovine rotavirus (subgroup 1) vaccine strain to protect against natural rotavirus infection in children. 178 infants aged 8 to 11 months received a single oral dose of RIT 4237 vaccine or placebo and were followed up serologically and clinically during a subgroup 2 rotavirus epidemic. No side-effects attributable to the vaccine were observed. During the 5 months' observation after vaccination 2 of the 86 vaccine recipients and 18 of 92 placebo recipients had rotavirus diarrhoea lasting more than 24 h (p less than 0.001). The vaccine-protection rate was thus 88%. The 2 children in the vaccine group with rotavirus diarrhoea were regarded as primary vaccine failures since they had no detectable serum antibody responses after vaccination. Vaccine prepared from RIT 4237 strain of attenuated bovine rotavirus thus seems to protect children against heterologous subgroup 2 rotavirus diarrhoea.", "Human rotavirus vaccine (HRV; i.e., Rotarix) reduced the incidence of severe rotavirus gastroenteritis (RVGE) by 77% (95% Confidence interval: 56-88%) during the first year of life in South Africa. Persistence of HRV-derived protection against RVGE during subsequent rotavirus seasons, although evident in industrialized settings, remains to be established in African settings. This study reports on the efficacy of HRV against severe RVGE over two consecutive rotavirus seasons in South African children.\n A prospective, double-blind, placebo controlled multi-centered trial in South Africa and Malawi randomly assigned infants in a 1:1:1 ratio to receive either two (10 and 14 weeks; HRV_2D) or three (6, 10 and 14 weeks; HRV_3D) doses of HRV or placebo. The primary analysis involved pooling of HRV_2D and HRV_3D arms. Episodes of gastroenteritis caused by wild-type rotavirus were identified through active follow-up surveillance and graded by the Vesikari scale.\n 1339 infants (447 in the HRV_2D group, 447 in the HRV_3D group and 445 in the placebo group) were enrolled in Year 2 of the study, including 1035 (77.3%) who were followed up over two consecutive rotavirus seasons (i.e., Cohort 2 subjects). Rotarix was associated with ongoing protection against severe RVGE, preventing 2.5 episodes per 100 vaccinated children over two consecutive rotavirus seasons; vaccine efficacy: 59% (95% Confidence interval: 1-83%). An exploratory analysis indicated better immunogenicity (among Cohort 1 subjects) and a higher point-efficacy estimate over two seasons in the HRV_3D compared to HRV_2D arms of the study in Cohort 2 subjects.\n Rotarix is associated with significant reductions in severe gastroenteritis episodes through 2 years of life among South African children. Further research is needed to determine the optimal dosing schedule of Rotarix in providing long-term protection against rotavirus illness in African children.\n Copyright © 2011 Elsevier Ltd. All rights reserved.", "To investigate the incorporation of oral rhesus-human reassortant rotavirus tetravalent (RRV-TV) vaccine into a routine immunization programme, RRV-TV or oral placebo was coadministered with a pentavalent diphtheria-tetanus-whole-cell pertussis-Haemophilus influenzae b (Hib)-inactivated polio vaccine and hepatitis B vaccine following a 3-4-5-mo schedule in a double-blind trial involving 249 infants. Seroconversion rates after 3 doses of rotavirus vaccine were 80% for rotavirus immunoglobulin A (IgA) and 93% for RRV neutralizing antibodies. Rotavirus vaccine did not interfere with the immune responses to diphtheria, tetanus, pertussis, Hib, poliovirus 1, 2 and 3, or hepatitis B. Following the first, second and third doses of vaccine, fever >38 degrees C on the day of vaccination was seen in 31%, 24% and 24%, respectively, with no difference between RRV-TV- and placebo-vaccinated children. This fever was presumably due to the whole-cell pertussis vaccine. Those vaccinees who received concomitant RRV-TV vaccine had another peak of fever around d 4 after the first dose, when 25% of them had fever >38 degrees C and 3% >39 degrees C. It is concluded that RRV-TV rotavirus vaccine can be given concurrently with other childhood immunizations following a 3-4-5-mo vaccination schedule. However, febrile reactions to RRV-TV rotavirus vaccine are common when the first dose is given at the age of 3 mo.", "Orally administered rhesus rotavirus vaccine (RRV) was evaluated in a placebo-controlled study in 176 infants (ages 2 to 4 months). Eighty-eight infants received a dose of 10(4) plaque-forming units of the vaccine, and 88 received the placebo. RRV was well-tolerated but mildly reactogenic in the 10 days after vaccination. There were mild febrile reactions (greater than or equal to 38 degrees C rectally) in 40% of the vaccinees and in 16% of the placebo recipients (P = 0.001). More of the vaccinees had loose stools than did the placebo recipients (P less than 0.05). RRV was immunogenic and induced a 4-fold or greater rise in serum neutralizing antibody responses in 67% of the vaccinees; however, breast-fed infants were less likely to develop a seroresponse than infants who were not breast-fed. Despite the good immunogenicity of RRV the overall incidence of rotavirus-associated illnesses was similar between the vaccine and placebo recipients. The failure of RRV in Rochester may be related to the fact that the circulating rotaviruses were predominantly serotype 1 and RRV is a serotype 3 rotavirus. Because the serotypes of rotavirus that predominate may vary from year to year, a polyvalent preparation may be necessary to provide effective vaccination against rotaviruses.", "Rotavirus is a leading cause of childhood gastroenteritis and death worldwide.\n We studied healthy infants approximately 6 to 12 weeks old who were randomly assigned to receive three oral doses of live pentavalent human-bovine (WC3 strain) reassortant rotavirus vaccine containing human serotypes G1, G2, G3, G4, and P[8] or placebo at 4-to-10-week intervals in a blinded fashion. Active surveillance was used to identify subjects with serious adverse and other events.\n The 34,035 infants in the vaccine group and 34,003 in the placebo group were monitored for serious adverse events. Intussusception occurred in 12 vaccine recipients and 15 placebo recipients within one year after the first dose including six vaccine recipients and five placebo recipients within 42 days after any dose (relative risk, 1.6; 95 percent confidence interval, 0.4 to 6.4). The vaccine reduced hospitalizations and emergency department visits related to G1-G4 rotavirus gastroenteritis occurring 14 or more days after the third dose by 94.5 percent (95 percent confidence interval, 91.2 to 96.6 percent). In a nested substudy, efficacy against any G1-G4 rotavirus gastroenteritis through the first full rotavirus season after vaccination was 74.0 percent (95 percent confidence interval, 66.8 to 79.9 percent); efficacy against severe gastroenteritis was 98.0 percent (95 percent confidence interval, 88.3 to 100 percent). The vaccine reduced clinic visits for G1-G4 rotavirus gastroenteritis by 86.0 percent (95 percent confidence interval, 73.9 to 92.5 percent).\n This vaccine was efficacious in preventing rotavirus gastroenteritis, decreasing severe disease and health care contacts. The risk of intussusception was similar in vaccine and placebo recipients. (ClinicalTrials.gov number, NCT00090233.)\n Copyright 2006 Massachusetts Medical Society.", "Live rotavirus vaccine candidates representing VP7 serotypes 1, 2, 3 or 4 derived by reassortment between bovine UK rotavirus and human rotavirus strains D, DS-1, P or ST3 were evaluated for safety and immunogenicity in adults, children and infants. Infection was defined by evidence of rotavirus shed in stools or a 4-fold or greater increase in serum rotavirus-specific IgA or IgG ELISA or plaque reduction neutralization antibody. A single oral dose (10(5.3) or 10(5.8) pfu) of reassortant virus was well tolerated and infected most infants: 10/20 (50%) by D x UK; 9/11 (82%) by DS-1 x UK; 8/10 (80%) by P x UK and 13/14 (93%) by ST3 x UK. All 14 infants given two doses of D x UK were infected. These findings demonstrating satisfactory levels of attenuation, safety, infectivity and immunogenicity of each reassortant in infants warrant additional studies of a candidate vaccine containing these four strains.", "Phase I studies of an oral quadrivalent rotavirus vaccine were conducted in 130 Venezuelan infants 10 to 20 weeks of age. The vaccine consists of a mixture of equal amounts of rhesus rotavirus (RRV) vaccine (serotype 3 [VP7]) and each of three human rotavirus-RRV reassortant strains: D x RRV (serotype 1 [VP7]), DS1 x RRV (serotype 2 [VP7]), and ST3 x RRV (serotype 4 [VP7]). Three different doses of the quadrivalent vaccine (0.25 x 10(4), 0.5 x 10(4), and 10(4) PFU of each component) were evaluated sequentially for safety and antigenicity in placebo-controlled, double-blind trials. Starting the day after vaccination, the infants were monitored by daily home visits for 7 days. Only minor reactions were observed during this period; these were limited to mild transient febrile episodes which began day 2 or 3 after vaccination and lasted 1 to 2 days in 15 to 30% of the infants. Serological studies demonstrated that 68 to 96% of the infants developed a rotavirus serum immunoglobulin A response following vaccination. However, when tested by plaque reduction neutralization assay against individual human rotavirus serotype 1, 2, 3, or 4, the response rates ranged from 4 to 23% with the low dose, 21 to 33% with the medium dose, and 32 to 58% with the high dose. Most (73 to 79%) infants developed neutralizing antibodies to RRV following administration of each dose schedule. Vaccine virus shedding was analyzed by utilizing tissue culture isolation of virus from stool. All of the infants who received the lower of medium dose and 89% of those fed the high dose shed one or more components of the vaccine. Analyses of rotavirus serotypes isolated from the stool of infants who received the 0.25 x 10(4) -PFU dose revealed that DS1 x RRV was the most commonly shed vaccine component, followed by RRV, D x RRV, and ST3 x RRV in that order.", "The safety and protective efficacy of a serotype 1 reassortant of bovine rotavirus WC3, disignated strain WI79-9, was evaluated in a double-blind placebo-controlled trial. Rotavirus reassortant WI79-9 contains a gene segment 9 coding for the surface structural protein vp7 of a human serotype 1 rotavirus, with all other gene segments derived from WC3 rotavirus, which had previously been shown to be safe and immunogenic in infants. Infants 2-11 months of age were given two doses of vaccine (10(7.3) plaque-forming units/dose) or of placebo 28 days apart. Adverse reactions to the vaccine were not detected. The incidence of serum plaque reduction neutralization antibody responses to two doses of vaccine was serotype 6, 97%; serotype 3, 68%; and serotype 1, 22%. Active surveillance during the subsequent rotavirus season revealed 8 cases of rotavirus gastroenteritis in 39 placebo control infants and no cases in 38 WI79-9 vaccine recipients (protection = 100%, P = .003). Six cases of rotavirus gastroenteritis were caused by type 1 and two by type 3 virus. Although vaccination with WI79-9 affected only the incidence of rotavirus gastroenteritis, the vaccinated infants exhibited a significantly reduced incidence of total days of diarrhea, fever, and illness associated with gastroenteritis in general.", "Rotavirus is the leading cause of dehydrating acute gastroenteritis in infants worldwide. Previous studies of a live pentavalent human-bovine reassortant rotavirus vaccine have shown it to be efficacious across a range of potencies.\n Our goal was to evaluate the efficacy, immunogenicity, and safety of pentavalent rotavirus vaccine at the end of shelf life in healthy infants.\n During 2002-2004, 1312 healthy infants approximately 6 to 12 weeks old from the United States (47%) and Finland (53%) were randomly assigned to receive 3 oral doses of vaccine (vaccine at approximately 1.1 x 10(7) infectious U per dose) or placebo approximately 4 to 10 weeks apart. Infants were to be followed for acute gastroenteritis through 1 rotavirus season after vaccination and for adverse events postvaccination.\n Three doses of pentavalent rotavirus vaccine at the end of shelf life demonstrated efficacy against rotavirus gastroenteritis caused by human G-serotypes included in the vaccine (G1-G4). Efficacy against severe rotavirus gastroenteritis was 100%, and efficacy against any rotavirus gastroenteritis regardless of severity was 72.5%. A threefold rise in G1 serum neutralizing was observed in 57% and in anti-rotavirus immunoglobulin A in 96% of pentavalent rotavirus vaccine recipients. No statistically significant increase in vomiting, diarrhea, or irritability was observed among pentavalent rotavirus vaccine recipients compared with placebo recipients within the 7-day period from each dose. A statistically significant increase in fevers (> or = 100.5 degrees F, rectal equivalent) was observed among pentavalent rotavirus vaccine recipients compared with placebo recipients after dose 1.\n This pentavalent human-bovine rotavirus vaccine was generally well tolerated, efficacious, and immunogenic at the end of shelf life.", "Rotavirus vaccine has proved effective for prevention of severe rotavirus gastroenteritis in infants in developed countries, but no efficacy studies have been done in developing countries in Asia. We assessed the clinical efficacy of live oral pentavalent rotavirus vaccine for prevention of severe rotavirus gastroenteritis in infants in Bangladesh and Vietnam.\n In this multicentre, double-blind, placebo-controlled trial, undertaken in rural Matlab, Bangladesh, and urban and periurban Nha Trang, Vietnam, infants aged 4-12 weeks without symptoms of gastrointestinal disorders were randomly assigned (1:1) to receive three oral doses of pentavalent rotavirus vaccine 2 mL or placebo at around 6 weeks, 10 weeks, and 14 weeks of age, in conjunction with routine infant vaccines including oral poliovirus vaccine. Randomisation was done by computer-generated randomisation sequence in blocks of six. Episodes of gastroenteritis in infants who presented to study medical facilities were reported by clinical staff and from parent recollection. The primary endpoint was severe rotavirus gastroenteritis (Vesikari score >or=11) arising 14 days or more after the third dose of placebo or vaccine to end of study (March 31, 2009; around 21 months of age). Analysis was per protocol; infants who received scheduled doses of vaccine or placebo without intervening laboratory-confirmed naturally occurring rotavirus disease earlier than 14 days after the third dose and had complete clinical and laboratory results were included in the analysis. This study is registered with ClinicalTrials.gov, number NCT00362648.\n 2036 infants were randomly assigned to receive pentavalent rotavirus vaccine (n=1018) or placebo (n=1018). 991 infants assigned to pentavalent rotavirus vaccine and 978 assigned to placebo were included in the per-protocol analysis. Median follow up from 14 days after the third dose of placebo or vaccine until final disposition was 498 days (IQR 480-575). 38 cases of severe rotavirus gastroenteritis (Vesikari score >or=11) were reported during more than 1197 person-years of follow up in the vaccine group, compared with 71 cases in more than 1156 person years in the placebo group, resulting in a vaccine efficacy of 48.3% (95% CI 22.3-66.1) against severe disease (p=0.0005 for efficacy >0%) during nearly 2 years of follow-up. 25 (2.5%) of 1017 infants assigned to receive vaccine and 20 (2.0%) of 1018 assigned to receive placebo had a serious adverse event within 14 days of any dose. The most frequent serious adverse event was pneumonia (vaccine 12 [1.2%]; placebo 15 [1.5%]).\n In infants in developing countries in Asia, pentavalent rotavirus vaccine is safe and efficacious against severe rotavirus gastroenteritis, and our results support expanded WHO recommendations to promote its global use.\n PATH (GAVI Alliance grant) and Merck.\n Copyright 2010 Elsevier Ltd. All rights reserved.", "Rotavirus is the most common cause of severe gastroenteritis among young children worldwide. Data are needed to assess the efficacy of the rotavirus vaccine in African children.\n We conducted a randomized, placebo-controlled, multicenter trial in South Africa (3166 infants; 64.1% of the total) and Malawi (1773 infants; 35.9% of the total) to evaluate the efficacy of a live, oral rotavirus vaccine in preventing severe rotavirus gastroenteritis. Healthy infants were randomly assigned in a 1:1:1 ratio to receive two doses of vaccine (in addition to one dose of placebo) or three doses of vaccine--the pooled vaccine group--or three doses of placebo at 6, 10, and 14 weeks of age. Episodes of gastroenteritis caused by wild-type rotavirus during the first year of life were assessed through active follow-up surveillance and were graded with the use of the Vesikari scale.\n A total of 4939 infants were enrolled and randomly assigned to one of the three groups; 1647 infants received two doses of the vaccine, 1651 infants received three doses of the vaccine, and 1641 received placebo. Of the 4417 infants included in the per-protocol efficacy analysis, severe rotavirus gastroenteritis occurred in 4.9% of the infants in the placebo group and in 1.9% of those in the pooled vaccine group (vaccine efficacy, 61.2%; 95% confidence interval, 44.0 to 73.2). Vaccine efficacy was lower in Malawi than in South Africa (49.4% vs. 76.9%); however, the number of episodes of severe rotavirus gastroenteritis that were prevented was greater in Malawi than in South Africa (6.7 vs. 4.2 cases prevented per 100 infants vaccinated per year). Efficacy against all-cause severe gastroenteritis was 30.2%. At least one serious adverse event was reported in 9.7% of the infants in the pooled vaccine group and in 11.5% of the infants in the placebo group.\n Human rotavirus vaccine significantly reduced the incidence of severe rotavirus gastroenteritis among African infants during the first year of life. (ClinicalTrials.gov number, NCT00241644.)\n 2010 Massachusetts Medical Society", "A refrigerator-stable rotavirus (RV) vaccine that withstands gastric acid is anticipated to permit more widespread use of RV vaccine.\n We investigated for the first time in infants an oral, liquid formulation of G1 and G2 human bovine reassortant rotavirus vaccine (HRRV) with a new stabilizer/buffer (S/B) containing sucrose, sodium phosphate and sodium citrate.\n During 1997 through 1998, 731 healthy infants approximately 2 to 4 months of age were enrolled at 19 US sites to receive 3 HRRV or placebo doses approximately 6 to 8 weeks apart in a partially double blinded study. Infants were randomized to: (1) HRRV with no S/B but with prefeeding; (2) HRRV plus 1 of 3 different concentrations/volumes of S/B; or (3) placebo.\n No serious vaccine-related adverse experiences or intussusception cases were reported. No statistically significant differences were observed between vaccine and placebo recipients for fever (> or =38.1 degrees C) 0 to 7 days after any dose, irritability, vomiting or diarrhea incidence 0 to 42 days after any dose. Vaccine virus shedding among vaccine recipients was uncommon. Among S/B vaccine groups, proportions of infants with a > or =3-fold titer rise from baseline to Postdose 3 for G1 serum-neutralizing antibody (SNA), G2 SNA, WC3 SNA, serum anti-RV IgA, serum anti-RV IgG and stool anti-RV IgA were generally similar to those of the prefed non-S/B group.\n HRRV with a new S/B was generally well-tolerated; immunogenicity was generally similar to the prefed non-S/B group. No intussusception cases were reported, but the small sample size precluded a definitive conclusion. A large international clinical study is under way to address safety and efficacy of an S/B formulation of a pentavalent version of HRRV.", "Rotavirus is a major cause of gastroenteritis in children worldwide and is estimated to be responsible for more than 500,000 physician visits, 50,000 hospitalizations and 20 deaths in the United States each year.\n To compare the safety and immunogenicity of 2 dosages of a live attenuated oral monovalent G1 human rotavirus (HRV) vaccine in healthy infants.\n In this randomized, double blind trial conducted in the United States and Canada, 529 healthy infants 5-15 weeks of age received HRV vaccine containing either 10 or 10 focus-forming units or placebo. Two doses were administered orally at a 2-month interval concomitantly with routine childhood vaccines. Symptoms of fever, irritability/fussiness, diarrhea, vomiting, loss of appetite and cough/runny nose were solicited for 15 days postvaccination, nonserious adverse events for 43 days postvaccination and serious adverse events throughout the study. Vaccine take was defined as appearance of serum antirotavirus IgA in postimmunization sera at a titer of > or =20 units/mL or vaccine virus shedding in any stool sample collected between the first dose and 2 months after the second dose.\n No serious adverse events considered related to vaccine were reported. The incidence of solicited symptoms was similar among treatment groups during the 15-day postvaccination surveillance periods. No significant difference in vaccine take after 2 doses (88.0% in high dose group and 81.5% in low dose group) was seen between vaccine groups (P = 0.153).\n Two doses of either dosage level of HRV vaccine administered concurrently with routine childhood vaccines to healthy infants 5-15 weeks of age were well-tolerated and were highly immunogenic.", "Rotavirus gastroenteritis causes many deaths in infants in sub-Saharan Africa. Because rotavirus vaccines have proven effective in developed countries but had not been tested in developing countries, we assessed efficacy of a pentavalent rotavirus vaccine against severe disease in Ghana, Kenya, and Mali between April, 2007, and March, 2009.\n In our multicentre, double-blind, placebo-controlled trial, undertaken in rural areas of Ghana and Kenya and an urban area of Mali, we randomly assigned infants aged 4-12 weeks without symptoms of gastrointestinal disorders in a 1:1 ratio to receive three oral doses of pentavalent rotavirus vaccine 2 mL or placebo at around 6 weeks, 10 weeks, and 14 weeks of age. Infants with HIV infection were not excluded. Randomisation was done by computer-generated randomisation sequence in blocks of six. We obtained data for gastrointestinal symptoms from parents on presentation to health-care facilities and clinical data were obtained prospectively by clinicians. The primary endpoint was severe rotavirus gastroenteritis (Vesikari score >or=11), detected by enzyme immunoassay, arising 14 days or more after the third dose of placebo or vaccine to end of study (March 31, 2009; around 21 months of age). Analysis was per protocol; infants who received scheduled doses of vaccine or placebo without intervening laboratory-confirmed naturally occurring rotavirus disease earlier than 14 days after the third dose and had complete clinical and laboratory results were included in the analysis. This study is registered with ClinicalTrials.gov, number NCT00362648.\n 5468 infants were randomly assigned to receive pentavalent rotavirus vaccine (n=2733) or placebo (n=2735). 2357 infants assigned to vaccine and 2348 assigned to placebo were included in the per-protocol analysis. 79 cases of severe rotavirus gastroenteritis were reported in 2610.6 person-years in the vaccine group, compared with 129 cases in 2585.9 person-years in the placebo group, resulting in a vaccine efficacy against severe rotavirus gastroenteritis of 39.3% (95% CI 19.1-54.7, p=0.0003 for efficacy >0%). Median follow-up in both groups was 527 days starting 14 days after the third dose of vaccine or placebo was given. 42 (1.5%) of 2723 infants assigned to receive vaccine and 45 (1.7%) of 2724 infants assigned to receive placebo had a serious adverse event within 14 days of any dose. The most frequent serious adverse event was gastroenteritis (vaccine 17 [0.6%]; placebo 17 [0.6%]).\n Pentavalent rotavirus vaccine is effective against severe rotavirus gastroenteritis in the first 2 years of life in African countries with high mortality in infants younger than 5 years. We support WHO's recommendation for adoption of rotavirus vaccine into national expanded programmes on immunisation in Africa.\n PATH (GAVI Alliance grant) and Merck.\n Copyright 2010 Elsevier Ltd. All rights reserved.", "We evaluated the reactogenicity and antigenicity of a quadrivalent rotavirus vaccine composed of serotype 3 rhesus rotavirus (RRV) and three single-gene-substitution reassortants of RRV and human strain D (D x RRV, serotype 1), DS1 (DS1 x RRV, serotype 2), or ST3 (ST3 x RRV, serotype 4) in a double-masked study with 302 infants in Caracas, Venezuela. Three doses of the quadrivalent vaccine composed of either 10(5) PFU (low titer) or 10(6) PFU (high titer) of each component were administered to 99 and 101 infants, respectively, at 4-week intervals starting at the second month of age; 102 infants received a placebo. Postvaccination reactions were monitored by home visits every other day during the week postvaccination. The vaccine was associated with the occurrence of mild, short-lived febrile episodes in 26 and 23% of the recipients after the first doses of high- or low-titer vaccine, respectively, in comparison with 13% of the infants receiving the placebo. Febrile reactions occurred less frequently in vaccinees after the second or third dose than after the initial dose. The vaccine was not significantly associated with diarrhea or any additional symptom or sign. Serum specimens obtained shortly before the first, 4 weeks after the first, and 4 weeks after the third dose of vaccine or placebo were tested by an immunoglobulin A enzyme-linked immunosorbent assay and by neutralization assays. Seroresponses occurred significantly more often after 3 doses than after a single dose of either vaccine. Immunoglobulin A responses were observed in 80 and 79% of the infants after 3 doses of high- or low-titer vaccine, respectively. Most of the infants tested developed a neutralization response to RRV after 3 doses of the high- (90%) or low-(88%) titer vaccine. Neutralization response rates to human rotavirus serotypes 1 to 4 after 3 doses were similar in both vaccine and 87 of 90 receiving the high-titer vaccine developed seroresponses, as detected by any of the assays employed. The study indicates that 3 doses of quadrivalent vaccine at a titer of 10(6) PFU of each component offered no advantage over the lower-titer preparation for use in efficacy trials.", "We vaccinated 244 newborn infants orally with RIT 4237 bovine rotavirus vaccine or placebo and followed them serologically and clinically for 16 months. Initially 39 of the 119 (33%) vaccine recipients compared with 1 of the 120 placebo recipients seroconverted by enzyme-linked immunosorbent assay-immunoglobulin M. After the first winter rotavirus season, at 7 months of age 55% of the vaccinated infants and 37% of the unvaccinated infants were rotavirus-seropositive by enzyme-linked immunosorbent assay-immunoglobulin G (P less than 0.01, chi square test). At 12 months of age, after a low rotavirus prevalence season, 34% of the vaccinated children and 23% of the unvaccinated children remained seropositive. There were 14 confirmed episodes of rotavirus gastroenteritis in the vaccine group and 10 episodes in the placebo group during the first 16 months. However, only 1 of the episodes in the vaccine group was severe, 4 were moderately severe and 9 were mild, whereas 7 episodes in the placebo group were severe and 3 were moderately severe (P less than 0.001 between groups, Fisher's exact test). There was no clear correlation between vaccine-induced clinical protection and initial serologic response (enzyme-linked immunosorbent assay-immunoglobulin M) to vaccination, but during follow-up severe rotavirus gastroenteritis was more likely to occur in children with no serum rotavirus immunoglobulin G antibody at the time of infection. We conclude at the present stage that neonatal rotavirus vaccination with RIT 4237 vaccine gives no protection against rotavirus infection but appears to modify the severity of gastroenteritis.", "Rotavirus is the most common cause of severe, dehydrating diarrhoea in infants worldwide. We assessed the safety, immunogenicity, and efficacy of a live, oral human rotavirus vaccine, 89-12, in US children in a randomised, placebo-controlled, double-blind multicentre trial.\n 215 healthy infants were enrolled, of whom 213 were given two doses of 89-12 (containing 1x10(5) plaque-forming units) or placebo, and 213 were followed up through one rotavirus season. The frequency of side-effects was compared for 7 days after each dose of vaccine. Immune responses to rotavirus were assessed by serum and stool IgA, and by serum 89-12 neutralising titres. The primary outcome variable (protection from rotavirus disease) was evaluated by comparing the frequencies of rotavirus gastroenteritis in an intention-to-treat analysis.\n Adverse reactions were mild. Low-grade fever (> or = 38.1 degrees C) after the first dose was the only side-effect significantly more common in the vaccine group than in the placebo group (21 [19%] vs 5 [5%], p=0.001). An immune response to vaccine was detected in 94.4% of vaccinees. Rotavirus disease occurred in 18 of 107 placebo recipients and two of 108 vaccine recipients (vaccine efficacy 89.0% [95% CI 65.4-94.5]). Ten infants in the placebo group but none in the vaccine group were presented for medical care.\n The 89-12 rotavirus vaccine was safe and immunogenic and provided a high degree of protection against rotavirus disease. Further investigations of this vaccine are needed to confirm these findings in other settings.", "The reactogenicity and antigenicity of the rhesus rotavirus vaccine, strain MMU18006, developed at the Laboratory of Infectious Diseases (National Institute of Allergy and Infectious Diseases, National Institutes of Health) were examined in a double blind, placebo-controlled study of 40 newborn infants in Caracas, Venezuela. The children were observed for the first few days after birth in the hospital nursery and by home visits for 10 days after vaccination to detect any adverse reactions. No reactions could be attributed to the vaccine. Serologic responses to the vaccine were evaluated in paired sera obtained at birth (cord blood) and 4 weeks after vaccination. Serologic responses to the vaccine were not observed by complement fixation, neutralization or a rhesus rotavirus VP7 epitope-specific competition assay. However, such responses were found in 9 of 14 tested infants by an immunoglobulin A-specific enzyme-linked immunosorbent assay. Seventeen of the 20 vaccinees also shed rhesus rotavirus vaccine in stool during the postvaccination period.", "To assess safety and immunogenicity, 213 healthy infants aged 6 weeks to 4 months were randomized to receive a single dose of placebo, a 10(4) or 10(5) p.f.u. dose of rhesus rotavirus (RRV) serotype 3, human-RRV reassortant (VP-7 serotypes 1, 2 or 4) or a 10(4) or 10(5) p.f.u. dose of tetravalent rotavirus vaccine (containing equal parts of serotype 1, 2, 3 and 4 strains). The infants were fed ad libitum before and after vaccination; no buffer was used. For 7 days after vaccination, potential vaccine side effects were monitored, and no significant differences were noted for any symptom evaluated among the single serotype, tetravalent or placebo groups. Sera, obtained before and 28 days after vaccination, were measured for antibody to rotavirus by IgG, IgA and IgM enzyme-linked immunosorbent assay in all subjects, and by neutralizing antibody to the individual serotypes by plaque reduction in placebo and tetravalent vaccinees. The serological response rates for serotypes 1, 2, 3, 4 and the tetravalent vaccine were 25, 12, 19, 11 and 22%, respectively, at 10(4) p.f.u.; 47, 50, 35, 29 and 61%, respectively, at 10(5) p.f.u.; and 37% for placebo. The tetravalent vaccine was more immunogenic at 10(5) than at 10(4) p.f.u. (p = 0.04). Grouped together, the vaccines at 10(5) p.f.u. (single serotype and tetravalent) were more immunogenic than the vaccines at 10(4) p.f.u. (38 of 85 versus 17 of 94 seroresponders; p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)", "Transmission of excreted vaccine-derived infectious virus from vaccinated to unvaccinated individuals is possible within close contacts. This randomized (1:1), double-blind study evaluated the potential for transmission of human rotavirus vaccine strain, HRV (Rotarix™) from vaccine recipients to unvaccinated close contacts (twins). 100 pairs of healthy twins aged 6-14 weeks at the time of Dose 1 of HRV vaccine/placebo were enrolled and one randomly selected twin from each pair received two vaccine doses and the other received placebo doses (at 2 and 4 months of age). Presence of vaccine strain in the stool samples of placebo recipients was an indicator of transmission. Serial stool samples were tested for rotavirus using ELISA at pre-determined time points; rotavirus positive stool samples were tested with RT-PCR and reverse hybridization assay to identify G1P[8] vaccine strain. If G1P[8] vaccine strain was detected, the complete genome was sequenced to assess the similarity between viral isolates. Immunogenicity and safety of HRV vaccine in transmission cases was assessed. 15 transmission cases were reported in 80 evaluable twins who received placebo and the transmission rate was 18.8% (95% CI: 10.9-29.0%). None of the transmission cases was associated with gastroenteritis symptoms. Anti-rotavirus IgA seroconversion was 62.5% (95% CI: 51.0-73.1%) (HRV) and 21.3% (95% CI: 12.9-31.8%) (placebo) 7-weeks post-Dose 2; seroconversion in transmission cases was 26.7% (95% CI: 7.8-55.1%). Genetic variations or amino acid substitutions in transmission cases were similar to that seen in corresponding vaccine recipients. Transmission of HRV vaccine strain to unvaccinated twins living in close contact occurred, however, they were not associated with increased of gastroenteritis. Whether transmission leads to indirect protection among unvaccinated individuals remains unknown at this stage.\n Copyright © 2011. Published by Elsevier Ltd.", "The efficacy of the pentavalent rotavirus vaccine (PRV), RotaTeq(®), was evaluated in a double-blind, placebo-controlled, multicenter Phase III clinical trial conducted (April 2007-March 2009) in 3 low-income countries in Africa: Ghana, Kenya, and Mali. In total, 5468 infants were randomized 1:1 to receive 3 doses of PRV/placebo at approximately 6, 10, and 14 weeks of age; concomitant administration with routine EPI vaccines, including OPV, was allowed. HIV-infected infants were not excluded. The primary endpoint, vaccine efficacy (VE) against severe-rotavirus gastroenteritis (RVGE), as measured by Vesikari scoring system (VSS, score ≥11), from ≥14 days following Dose 3 through a follow-up period of nearly 2 years in the combined 3 African countries, and secondary endpoints by total follow-up period have been previously reported. In this study, we report post hoc subgroup analyses on secondary endpoints of public health importance. VE against RVGE of any severity was 49.2% (95%CI: 29.9, 63.5) through the first year of life and 30.5% (95%CI: 16.7, 42.2) through the complete follow-up period. VE against severe-gastroenteritis of any etiology was 21.5% (95%CI: <0, 38.4) through the first year of life and 10.6% (95%CI: <0, 24.9) through the complete follow-up period. Through the complete follow-up period, VE against severe-RVGE caused by (i) vaccine-contained G and P types (G1-G4, P1A[8]), (ii) non-vaccine G types (G8, G9, G10), and (iii) non-vaccine P types (P1B[4], P2A[6]) was 34.0% (95%CI:11.2, 51.2), 81.8% (95%CI:16.5, 98.0) and 40.7% (95%CI:8.4, 62.1), respectively. There was a trend towards higher VE with higher disease severity, although in some cases the numbers were small. In African countries with high under-5 mortality rates, PRV significantly reduced RVGE through nearly 2 years of follow-up; more modest reductions were observed against gastroenteritis of any etiology. PRV provides protection against severe-RVGE caused by diverse rotavirus genotypes, including those not contained in the vaccine.\n Copyright © 2012 Elsevier Ltd. All rights reserved.", "Rotavirus gastroenteritis is a major cause of morbidity and mortality among African infants and young children. A phase III, placebo-controlled, multi-centre clinical trial of a live, oral G1P[8] human rotavirus vaccine (RIX4414) undertaken in Malawi and South Africa significantly reduced the incidence of severe rotavirus gastroenteritis in the first year of life. We now report on vaccine efficacy in the Malawi cohort of children who were followed into the second year of life. A total of 1773 healthy infants were enrolled in Blantyre, Malawi into three groups. Two groups received three doses of RIX4414 or placebo at age 6, 10, and 14 weeks and the third group received placebo at 6 weeks and RIX4414 at age 10 and 14 weeks. Subjects were followed by weekly home visits for episodes of gastroenteritis until 1 year of age, and were then re-consented for further follow-up to 18-24 months of age. Severity of gastroenteritis episodes was graded according to the Vesikari scoring system. Seroconversion for anti-rotavirus IgA was determined on a subset of children by using ELISA on pre- and post-vaccine blood samples. Rotavirus VP7 (G) and VP4 (P) genotypes were determined by RT-PCR. A total of 70/1030 (6.8%, 95% CI 5.3-8.5) subjects in the pooled (2 dose plus 3 dose) RIX4414 group compared with 53/483 (11.0%, 8.3-14.1) subjects in the placebo group developed severe rotavirus gastroenteritis in the entire follow-up period (vaccine efficacy 38.1% (9.8-57.3)). The point estimate of efficacy in the second year of life (17.6%; -59.2 to 56.0) was lower than in the first year of life (49.4%; 19.2-68.3). There were non-significant trends towards a higher efficacy in the second year of life among children who received the three-dose schedule compared with the two-dose schedule, and a higher anti-rotavirus IgA seroresponse rate in the three-dose RIX4414 group. Rotavirus strains detected included genotype G12 (31%); G9 (23%); and G8 (18%); only 18% of strains belonged to the G1P[8] genotype. While the optimal dosing schedule of RIX4414 in African infants requires further investigation, vaccination with RIX4414 significantly reduced the incidence of severe gastroenteritis caused by diverse rotavirus strains in an impoverished African population with high rotavirus disease burden in the first two years of life.\n Copyright © 2011 Elsevier Ltd. All rights reserved.", "Three phase I trials of the rhesus rotavirus (RRV)-based quadrivalent vaccine [composed of serotype 3 (RRV), and serotypes 1 (D x RRV), 2 (DS1 x RRV), and 4 (ST3 x RRV) human rotavirus x RRV reassortants] and the M37 (nursery strain) rotavirus vaccine candidates were conducted in an attempt to find a safe and optimally antigenic formulation. Infants 10-20 weeks old received, in trial I, 1) the quadrivalent vaccine as two separate bivalent doses (1 x 10(4) PFU each of D x RRV and RRV, followed 4 weeks later by 1 x 10(4) PFU each of DS1 x RRV and ST3 x RRV) or 2) placebo; in trial II, 1) one dose of quadrivalent vaccine (10(4) PFU of each component), or 2) two doses of quadrivalent vaccine, or 3) a 10(4) PFU dose of M37 vaccine, or 4) M37 vaccine followed by the quadrivalent vaccine, or 5) placebo; in trial III, 1) a dose of a higher-titered quadrivalent vaccine (10(5) PFU of each component), or 2) two doses of higher titered quadrivalent vaccine, or 3) a dose of higher titered M37 vaccine (10(5) PFU) or 4) two doses of M37 vaccine (10(5) PFU), or 5) M37 vaccine (10(5) PFU) followed by the higher titered quadrivalent vaccine, or 6) placebo. A mild, transient fever during the first week postvaccination was associated with the bivalent or quadrivalent vaccines but not with the M37 vaccine. Fourfold or greater serum IgA ELISA responses to rotavirus were observed in 48-92% of the infants receiving quadrivalent vaccine and in 32-50% of those receiving M37 vaccine.(ABSTRACT TRUNCATED AT 250 WORDS)", "Rotavirus gastroenteritis (RVGE) is a leading cause of death in African children. The efficacy of pentavalent rotavirus vaccine (PRV) against severe RVGE evaluated in Ghana, Kenya, and Mali in a randomized, double-blind, placebo-controlled trial, showed a combined regional efficacy of 39.3% (95% confidence interval [CI]: 19.1,54.7) in nearly 2 years of follow-up. This report concentrates on the Kenya findings.\n Infants received 3 doses of PRV/placebo at approximately 6-, 10-, and 14-weeks of age. HIV testing was offered to all participants. Data on illness symptoms and signs were collected upon presentation to healthcare facilities, where stools were collected, and analyzed by rotavirus-specific enzyme-linked immunosorbent assay. The primary endpoint was severe RVGE (Vesikari score ≥ 11), occurring ≥ 14 days following the third dose. At monthly home visits, symptoms of illnesses during the past 2 weeks were solicited and limited physical exams were performed; dehydration was defined by WHO's Integrated Management of Childhood Illness.\n Vaccine efficacy (VE) against severe RVGE through nearly 2 years of follow-up among 1308 Kenyan children was 63.9% (95% CI: -5.9,89.8). Through the first year of life, VE against severe RVGE was 83.4% (95% CI: 25.5,98.2). From home visits, VE against all-cause gastroenteritis with severe dehydration was 34.4% (95% CI: 5.3,54.6) through the first year and 29.7% (95% CI: 2.5,49.3) through the entire follow-up period. The reduction in incidence of gastroenteritis with severe dehydration in the community during the first year of life (19.0 cases/100 person-years) was almost six times greater than the reduction in severe RVGE presenting to the clinic (3.3/100 person-years). Oral rehydration solution use was lower among PRV recipients (VE 23.1%, 95% CI: 8.8,35.1). An estimated 41% of gastroenteritis with severe dehydration in the first year reported at home was rotavirus-related.\n PRV significantly reduced severe RVGE in Kenya. The impact of PRV might be greatest in rural Africa in protecting the many children who develop severe gastroenteritis and cannot access health facilities.\n Copyright © 2012. Published by Elsevier Ltd.", "We aimed to assess the efficacy of the oral live attenuated human rotavirus vaccine Rotarix (RIX4414) for prevention of rotavirus gastroenteritis in European infants during their first 2 years of life.\n 3994 study participants were enrolled from six countries and were randomly assigned two oral doses of either RIX4414 (n=2646) or placebo (n=1348), which were coadministered with the first two doses of specific childhood vaccinations. Follow-up for gastroenteritis episodes was undertaken from 2 weeks post-dose two through the two consecutive rotavirus seasons following vaccinations (combined efficacy follow-up period; mean duration 17 months [SD 1.6]). Our primary endpoint was vaccine efficacy against rotavirus gastroenteritis of any severity during the first efficacy follow-up period (2 weeks post-dose two to the end of the first rotavirus season). Stool specimens obtained during gastroenteritis episodes were tested for rotavirus by ELISA and typed by RT-PCR. Episodes scoring 11 or greater on the 20-point Vesikari scale were classified as severe. Analysis was according to protocol. This study is registered with ClinicalTrials.gov, number NCT00140686 (eTrack102247).\n 120 infants were excluded from the according-to-protocol analysis. During the first efficacy follow-up period (mean duration 5.7 months [SD 1.2]), 24 of 2572 infants allocated RIX4414 versus 94 of 1302 given placebo had rotavirus gastroenteritis episodes of any severity, resulting in a vaccine efficacy of 87.1% (95% CI 79.6-92.1; p<0.0001). For the combined efficacy follow-up period, vaccine efficacy against severe rotavirus gastroenteritis was 90.4% (85.1-94.1; p<0.0001), for admission owing to rotavirus gastroenteritis 96.0% (83.8-99.5; p<0.0001), and for rotavirus-related medical attention 83.8% (76.8-88.9; p<0.0001), and significant protection against severe rotavirus gastroenteritis by circulating G1, G2, G3, G4, and G9 rotavirus types was shown.\n In a European setting, two doses of RIX4414 coadministered with childhood vaccines provided high protection against any and severe rotavirus gastroenteritis, with an overall reduction of admissions for gastroenteritis over two consecutive rotavirus epidemic seasons.", "The oral, pentavalent rotavirus vaccine (PRV), RotaTeq was assessed for prevention of severe rotavirus gastroenteritis (RVGE) in young children in two multi-site, randomized, placebo-controlled field trials; one in Asia (Vietnam and Bangladesh) and the other in sub-Saharan Africa (Ghana, Kenya and Mali). The efficacy results for the Mali site of the multi-country trial are presented here. We randomly assigned infants in a 1:1 ratio to receive 3 doses of PRV/placebo at approximately 6, 10, and 14 weeks of age. Gastroenteritis episodes were captured passively at the local health centers and by home visits. The primary study outcome was severe RVGE, as defined by a score of ≥ 11 using the Vesikari Clinical Scoring System occurring ≥ 14 days after the third dose until the end of the study. Other efficacy analyses included efficacy against severe RVGE through the first year and during the second years of life, as well as efficacy after receiving at least one dose of vaccine. In total, 1960 infants were enrolled in the trial at the Mali site and sera were collected on a subset of infants (approximately 150) for immunogenicity testing. In the first year of follow-up, largely due to cultural practices to visit traditional healers as the first point of care, the point estimate of efficacy was unreliable: the per protocol vaccine efficacy against severe RVGE was 1% (95% confidence interval [CI]: -431.7, 81.6); the intention-to-treat vaccine efficacy was 42.9% (95% CI: -125.7, 87.7). During the second year of follow-up, after the surveillance system was modified to adapt to local customs and health care seeking practices, the point estimate of per-protocol vaccine efficacy was 19.2% (95% CI: -23.1,47.3%). 82.5% of Malian infants (95% CI: 70.1,91.3%) who received PRV mounted a seroresponse (≥ 3-fold rise from baseline (prevaccination) to post-dose 3 vaccination) of anti-rotavirus immunoglobulin A antibody, with a post third-dose geometric mean titer (GMT) of 31.3 units/mL. By contrast, only 20.0% of placebo recipients (95% CI: 10.0, 33.7%) developed a seroresponse and the post-third dose GMT was 3.2 units/mL. None of the serious clinical adverse events observed were considered to be vaccine-related.\n Copyright © 2011 Elsevier Ltd. All rights reserved.", "Orally administered rhesus rotavirus vaccine was evaluated in a placebo-controlled study in young children and infants (ages, eight months to 61 months). Thirteen children received the rotavirus vaccine, and ten children served as the control group. The vaccine was well tolerated. There were no significant differences between the vaccine recipients and the control group in the number of child-days with temperatures greater than or equal to 37.8 C, vomiting, diarrhea, or cough. There were significantly more child-days of rhinorrhea among the vaccine recipients than there were among the control group. The vaccine recipients under two years of age passed a larger number of stools than did the children in the control group, and vaccine recipients had significantly more semiformed and unformed stools than did the children receiving the placebo. All twelve of the children tested were positive for viral shedding. Peak viral shedding occurred on days three and five postvaccination. On day eight, over one-half of the children from whom a stool specimen was obtained were still shedding rotavirus. Children less than two years old shed more rotavirus in their stool than did children more than two years old. All 13 vaccine recipients had a fourfold or greater rise in titer of antibody as measured by plaque reduction, tube neutralization, complement fixation, and/or immune adherence hemagglutination.", "This study evaluates the safety and efficacy against severe rotavirus gastroenteritis of the oral live attenuated human rotavirus vaccine RIX4414 (Rotarix) during the first 2 years of life in Asian infants from high-income countries. Healthy infants were enrolled to receive 2 doses of RIX4414 (N=5,359) or placebo (N=5,349). From 2 weeks post-dose 2 to 2 years of age, vaccine efficacy was 96.1% (95%CI:85.1%; 99.5%) against severe rotavirus gastroenteritis, 100% (95%CI:80.8%; 100%) against wild-type G1P[8] and 93.6% (95%CI:74.7%; 99.3%) against circulating non-G1 rotavirus types. No intussusception cases were reported within 31 days post-vaccination. RIX4414 shows a good safety profile and offers high protection during the first 2 years of life with potentially significant public health impact in this population.", "90 Venezuelan infants aged 10-20 weeks were randomly allocated to four groups which received one of the following: the M37 vaccine (1 x 10(4) pfu [plaque-forming units]); quadrivalent rotavirus vaccine (1 x 10(4) pfu each of serotype 3 rhesus rotavirus [RRV] and human rotavirus-RRV reassortants of serotypes 1, 2, and 4); balanced quadrivalent vaccine consisting of 1 x 10(4) pfu of serotype 1 and 3 components but 5 x 10(4) pfu of serotype 2 and 4 components; or placebo. The frequencies of transient febrile responses in these four groups were 20%, 27%, 30%, and 9%. 50% of 22 infants tested who received M37 vaccine showed a serum rotavirus IgA antibody response, compared with 74% of the 23 quadrivalent and 86% of the 22 balanced-quadrivalent recipients. 64% of the M37 recipients showed a neutralising antibody response to M37; 27% showed such responses to human serotype 1 Wa strain and 27% to serotype 4 neonatal strain ST3. 17-39% of the quadrivalent recipients and 27-41% of the balanced-quadrivalent recipients showed neutralising antibody responses to serotypes 1-4. 70-73% of the quadrivalent and balanced quadrivalent groups also showed neutralising antibody responses to RRV.", "A randomized placebo-controlled double-blind field trial of RIT 4237 attenuated rotavirus vaccine in Lima, Peru, evaluated the protection against diarrheal illness by one, two, or three doses of vaccine. There were 391 children, 2-18 months old, studied for the occurrence of diarrhea during the 18 months after vaccination. Three doses of the vaccine provided 40% protection against any diarrheal illness associated with rotavirus alone but 58%-75%; protection against the more severe rotaviral illnesses. The vaccine appeared to be more efficacious when it was administered to children in the first year of life. Three doses provided up to 89% efficacy against more severe diseases due to serotype 1 rotavirus, and one dose also afforded significant protection. The protection was lower, even with three doses, against serotype 2 rotavirus. This vaccine trial has provided important insights on how such trials should be conducted and on the serotype-specificity of protection from rotavirus infection. Future vaccines should be able to protect against severe disease caused by all rotavirus serotypes and must work in developing countries where rotavirus is the most important cause of diarrheal mortality.", "Between January and November 1989, we studied 174 infants aged 6 to 16 weeks in a randomized clinical trial to (1) determine the immunogenicity of a single dose of tetravalent rhesus rotavirus vaccine (RRV-TV) when administered with three different buffer regimens: no antacid buffer and small-volume (2.5-mL) and large-volume (30-mL) antacid buffer; and (2) examine the potential interference of RRV-TV on the immune response to oral polio vaccine. Immunogenicity of RRV-TV, measured as a fourfold rise in antibody titers to rotavirus, was similar in the groups receiving small- and large-dose buffer (45% and 49%, respectively) and significantly less in the group that received RRV-TV alone (23%). Administration of RRV-TV with oral polio vaccine did not significantly interfere with the neutralization response of oral polio vaccine poliovirus serotypes 1, 2, or 3, and overall, 29%, 87%, and 24% of the infants had a fourfold rise in titer to each serotype, respectively.", "Candidate oral bovine rotavirus vaccine RIT 4237 or placebo was given to 252 Finnish infants at birth and at 7 months of age. No vaccine-associated reactions were observed. Primary rotavirus ELISA IgM responses were detected in 36% of the infants after the first vaccination; after the second dose 68% of the vaccinees were seropositive for rotavirus ELISA IgG antibody. The infants remained in clinical follow-up over two rotavirus epidemic seasons (total 28 months). Counted from child years in follow-up the overall vaccine protection rate was 43%. The clinical severity of rotavirus episodes was assessed using a numerical score 0-20. Vaccine protection rate for cases with a score greater than or equal to 7 was 57% and for cases with a score greater than or equal to 11 it was 89%. It is concluded that vaccination with a bovine rotavirus vaccine at birth and at 7 months of age, with the second dose given shortly before rotavirus epidemic season, protects infants against moderately severe and severe rotavirus diarrhoea in the first 2 years of life." ]	Current evidence shows that rhesus rotavirus vaccines (particularly RRV-TV) and the human rotavirus vaccine 89-12 are efficacious in preventing diarrhoea caused by rotavirus and all-cause diarrhoea. Evidence about safety, and about mortality or prevention of severe outcomes, is scarce and inconclusive. Bovine rotavirus vaccines were also efficacious, but safety data are not available. Trials of new rotavirus vaccines will hopefully improve the evidence base. Randomized controlled trials should be performed simultaneously in high-, middle-, and low-income countries. 2010 Editor's Note: Several of the vaccines investigated in this review are no longer in routine clinical use (for example, live attenuated rhesus-human reassortant tetravalent vaccine) and further new vaccines have been tested and approved for use since this review was written in 2004. For an up-to-date assessment of rotavirus vaccines currently approved for use, please see : Soares-Weiser K, MacLehose H, Ben-Aharon I, Goldberg E, Pitan F, Cunliffe N. Vaccines for preventing rotavirus diarrhoea: vaccines in use. Cochrane Database of Systematic Reviews 2010, Issue 5. Art. No.: CD008521. DOI: 10.1002/14651858.CD008521.
CD004514	[ "16359741", "16895884", "17600848", "12967058", "18653121", "12823643", "12042457" ]	[ "Effects of folic acid supplementation on psychomotor performance and hemorheology in healthy elderly subjects.", "Effect of oral vitamin B-12 with or without folic acid on cognitive function in older people with mild vitamin B-12 deficiency: a randomized, placebo-controlled trial.", "A randomised double-blind placebo-controlled trial of folic acid supplementation of cholinesterase inhibitors in Alzheimer's disease.", "Folic acid supplementation in dementia: a preliminary report.", "Low folate levels in the cognitive decline of elderly patients and the efficacy of folate as a treatment for improving memory deficits.", "Effect of vitamins and aspirin on markers of platelet activation, oxidative stress and homocysteine in people at high risk of dementia.", "Short-term folate, vitamin B-12 or vitamin B-6 supplementation slightly affects memory performance but not mood in women of various ages." ]	[ "Cognitive impairment is associated with increased blood concentrations of homocysteine and high blood viscosity. Previous studies have shown that vitamin B supplementation reduces homocysteine and enhances cognitive function in patients with mild dementia and low serum folic acid. However, whether folic acid enhances cognitive function in elderly subjects without dementia and normal serum folic acid is unknown. Twenty-four healthy elderly subjects (age 73.0+/-5.6 years, mean+/-S.D.) with normal serum folic acid (6.3+/-2.4 microg/l) and Mini Mental State Examination (MMSE) >27/30 were randomized to 4-week treatment with folic acid 5mg/day or placebo in a randomized, placebo-controlled, parallel-group study. Continuous Attention Test (CAT), Four-Choice Reaction Time (FCRT), Digit-Symbol Substitution (DSS), Scanning Memory Sets (SMS), and blood viscosity for different shear rates were measured before and after treatment. Folic acid supplementation induced a significant increase in serum folic acid levels (+13.8 versus +1.6 microg/l, p<0.001) and fall in homocysteine levels (-1.91 versus -0.41 micromol/l, p=0.05) compared to placebo. However, there was no significant change in CAT, FCRT, DSS, SMS, and blood viscosity between the two groups. Short-term folic acid supplementation does not enhance psychomotor performance or reduce blood viscosity in healthy elderly subjects with normal serum folic acid levels and preserved cognitive function.", "Vitamin B-12 deficiency is associated with cognitive impairment in older people. However, evidence from randomized trials of the effects of vitamin B-12 supplementation on cognitive function is limited and inconclusive.\n The objective was to investigate whether daily supplementation with high doses of oral vitamin B-12 alone or in combination with folic acid has any beneficial effects on cognitive function in persons aged >/=70 y with mild vitamin B-12 deficiency.\n In a double-blind, placebo-controlled trial, 195 subjects were randomly assigned to receive 1000 microg vitamin B-12, 1000 microg vitamin B-12 + 400 microg folic acid, or placebo for 24 wk. Vitamin B-12 status was assessed on the basis of methylmalonic acid, total homocysteine (tHcy), and holotranscobalamin (holoTC) concentrations before and after 12 and 24 wk of treatment. Cognitive function was assessed before and after 24 wk of treatment with the use of an extensive neuropsychologic test battery that included the domains of attention, construction, sensomotor speed, memory, and executive function.\n Vitamin B-12 status did not change significantly after treatment in the placebo group; however, oral vitamin B-12 supplementation corrected mild vitamin B-12 deficiency. Vitamin B-12 + folic acid supplementation increased red blood cell folate concentrations and decreased tHcy concentrations by 36%. Improvement in memory function was greater in the placebo group than in the group who received vitamin B-12 alone (P = 0.0036). Neither supplementation with vitamin B-12 alone nor that in combination with folic acid was accompanied by any improvement in other cognitive domains.\n Oral supplementation with vitamin B-12 alone or in combination with folic acid for 24 wk does not improve cognitive function.", "(1) to assess the effect of 1 mg folic acid supplementation of cholinesterase inhibitors (ChI) in a 6 month double-blind placebo-controlled study of patients with Alzheimer's Disease (AD) and (2) to assess whether outcome measures were affected by changes in homocysteine levels.\n Fifty-seven consecutive outpatients with probable AD were treated concurrently with a ChI and either folic acid or placebo. None had conditions or medication known to interfere with folate metabolism. Fasting folate and homocysteine levels were measured prior to commencing ChI and 6 months later. Response was categorised using criteria of the National Institute of Clinical Excellence (NICE).\n Twelve males and 29 females completed treatment (mean age 76.27 SD 6.23 years, Mini-Mental State Examination (MMSE) 23.49 SD 3.53, baseline homocysteine 18.39 SD 4.62 micromoles per litre). 23 received folic acid and 18 placebo. There were no significant baseline differences or use of individual ChI between the two arms. After 6 months a significant difference was seen in the change from baseline in combined Instrumental Activities of Daily Living and Social Behaviour scores between arms (folate+1.50 (SD 5.32) vs placebo -2.29 (SD 6.16) (p=0.03) but not change in MMSE scores. Sixteen of 23 subjects receiving folic acid and 7/18 placebo subjects were classified as NICE responders (p=0.05).\n This pilot double blind study suggests that response to ChI in patients with AD may be improved by the use of folic acid. The relationship between any change in homocysteine levels and response to treatment is discussed.\n Copyright (c) 2007 John Wiley & Sons, Ltd.", "Recent work on high plasma homocysteine levels in patients at risk for developing Alzheimer's disease has led to the hypothesis that folic acid supplementation might reduce risk in such patients. The authors report on the effects of folic acid 10 mg/day versus placebo on 11 patients (only 7 completers) with dementia and low-normal folic acid levels. This is the first study evaluating folic acid or placebo in patients with dementia. Subjects had low-normal baseline folic acid levels. The magnitude of change between baseline and second testing was not statistically significant between the 2 groups. However, there was a trend for the folate group to perform worse on two specific cognitive measures, suggesting a possible trend toward worsening of some cognitive abilities after the folic acid. The folic acid in very high doses was well tolerated. Larger studies are necessary before empirically administering folic acid to patients already suffering from dementia.", "The relevance of low folate levels as determinants of cognitive deficits and the usefulness of folate supplementation in the treatment of cognitive deficits was reviewed from the literature. Over 40 papers and book chapters published in English, French, German, Italian and Spanish were examined. This represents those papers published in the international literature in the last 10 years which were identified by various key words including folate, cognition and aging (or ageing). Among these papers, only 13 articles specifically addressed issues relevant to the criteria adopted for this review. The remaining papers were principally concerned with depression and or with other pathologies of the aged associated with folate deficiency. Although the specific role of low folate levels in the physiopathology of dementia is still under debate, a growing consensus is emerging in the literature where low folate as well as cobalamin levels in aged patients with cognitive deficits are being considered as a sign of functional problems in the absorption and utilization of vitamins, and not merely as a sign of bad eating habits. In studies where folate compounds were evaluated for treatment effects, the results of a majority of investigations indicated that folate treatment was effective in lessening cognitive deficits. Treatment efficacy, however, has not yet been sufficiently demonstrated by these results because there were no controlled studies and the methodology was heterogeneous for the evaluation of cognitive characteristics. An ad hoc double-blind, controlled versus placebo pilot study was undertaken to evaluate the efficacy of folic acid in 30 aged patients with abnormal cognitive decline and folate level below 3 ng/ml to better understand the value of this type of intervention. Our results from this preliminary study demonstrated that patients treated with folic acid for 60 days showed a significant improvement on both memory and attention efficiency when compared with a placebo group. The intensity of memory improvement was positively correlated with initial severity of folate deficiency. On the contrary, the severity of initial cognitive decline was unrelated to the degree of folate deficiency.", "To examine the association of cognitive impairment with platelet activation and reactive oxygen species and total homocysteine levels; and to assess the biochemical efficacy of treatment with aspirin and vitamin supplements in people at high risk of dementia.\n People with dementia or mild cognitive impairment.\n In a 2 x 2 x 2 factorial design trial, 149 people at high-risk of dementia were randomized to receive either low-dose aspirin (81 mg) or placebo; and folic acid (2 mg) plus vitamin B12 (1 mg) or placebo; and vitamins E (500 mg) plus C (200 mg) or placebo. Participants were seen twice before and once after 12 weeks of treatment.\n At each visit, participants had their cognitive function assessed and had blood collected for homocysteine, folate and vitamin B12 determination and urine collected for markers of platelet activation (11-dehydro-thromboxane B2) and reactive oxygen species (8-epi-PGF2 alpha).\n Prior to treatment, cognitive function was inversely related with homocysteine and with urinary thromboxane and isoprostane, and these associations were independent of age. Aspirin was associated with a median reduction in 11-dehydrothromboxane B2 of 73% (P < 0.001). B-vitamins lowered plasma homocysteine concentration by 30% (P < 0.0001) and antioxidant vitamins lowered isoprostane excretion by 26% (P < 0.1). No effect of treatment on cognitive function was detected.\n Aspirin and B-vitamins were effective in reducing biochemical factors associated with cognitive impairment in people at risk of dementia. Large-scale trials are now required to assess the relevance of aspirin and B-vitamins for the maintenance of cognitive function in people at risk of dementia.", "Based on research demonstrating associations between folate, B-12 and B-6 vitamins and cognition and mood, we investigated the effects of short-term supplementation in 211 healthy younger, middle-aged and older women who took either 750 microg of folate, 15 microg of vitamin B-12, 75 mg of vitamin B-6 or a placebo daily for 35 d. In addition, we examined associations between dietary intake of these vitamins and cognition and mood. Usual dietary intake status was estimated using a retrospective, self-report, quantified food frequency questionnaire. Participants completed alternate forms of standardized tests of cognitive processing resources, memory, executive function, verbal ability and self-report mood measures before and after supplementation. Supplementation had a significant positive effect on some measures of memory performance only, and no effect on mood. Dietary intake status was associated with speed of processing, recall and recognition and verbal ability." ]	The small number of studies which have been done provide no consistent evidence either way that folic acid, with or without vitamin B12, has a beneficial effect on cognitive function of unselected healthy or cognitively impaired older people. In a preliminary study, folic acid was associated with improvement in the response of people with Alzheimer's disease to cholinesterase inhibitors. In another, long-term use appeared to improve the cognitive function of healthy older people with high homocysteine levels. More studies are needed on this important issue.
CD004696	[ "1575558", "11328958", "17158417", "15493734", "21402642", "11335744", "11533340", "19739491", "12242586", "10363538", "15208209" ]	[ "Randomised trial of nutrition for preterm infants after discharge.", "Feeding preterm infants after hospital discharge: growth and development at 18 months of age.", "Posthospital discharge feeding for preterm infants: effects of standard compared with enriched milk formula on growth, bone mass, and body composition.", "Feeding with premature or infant formula in premature infants after discharge: comparison of growth and nutrition status.", "Nutrient enrichment of mother's milk and growth of very preterm infants after hospital discharge.", "Growth of preterm infants fed nutrient-enriched or term formula after hospital discharge.", "Randomized trial of nutrient-enriched formula versus standard formula for postdischarge preterm infants.", "[Quality of post-discharge growth in small for gestational age preterm infants: an explorative study].", "Body composition in preterm infants fed standard term or enriched formula after hospital discharge.", "Transitioning preterm infants with nasogastric tube supplementation: increased likelihood of breastfeeding.", "Effect of bottles, cups, and dummies on breast feeding in preterm infants: a randomised controlled trial." ]	[ "In a randomised double blind trial, the effect on growth and clinical status of a nutrient enriched 'post-discharge' milk formula versus a standard term formula, was compared in 32 exclusively bottle fed preterm infants. The formulas were used as the sole milk intake up to a postnatal age of 9 months. Significant increases in linear growth and weight gain were observed in the infants who received the enriched diet. There were no differences in vomiting, posseting, or bowel habit between the groups. Formula volumes ingested were similar between diet groups, indicating that the difference in formula composition did not affect the infants' regulation of intake. These preliminary data suggest that there is a role for specially designed formulas for preterm infants after discharge from hospital.", "We have shown that preterm infants fed a preterm formula grow better than those fed a standard term infant formula after hospital discharge. The purpose of this follow-up study was to determine whether improved early growth was associated with later growth and development. Preterm infants (< or =1750 g birth weight, < or =34 wk gestation) were randomized to be fed either a preterm infant formula (discharge to 6 mo corrected age), or a term formula (discharge to 6 mo), or the preterm (discharge to term) and the term formula (term to 6 mo). Anthropometry was performed at 12 wk and 6, 12, and 18 mo. Mental and psychomotor development were assessed using the Bayley Scales of Infant Development II at 18 mo. Differences in growth observed at 12 wk were maintained at 18 mo. At 18 mo, boys fed the preterm formula were 1.0 kg heavier, 2 cm longer, and had a 1.0 cm greater occipitofrontal circumference than boys fed the term formula. Boys fed the preterm formula were also 600 g heavier and 2 cm longer than girls fed the preterm formula. However, no differences were noted in MDI or PDI between boys fed the preterm formula and boys fed the term formula or between the boys fed preterm formula and girls fed the preterm formula. Overall, boys had significantly lower MDI than girls (mean difference, 6.0; p < 0.01), primarily reflecting lower scores in boys fed the term formula. Thus, early diet has long-term effects on growth but not development at 18 mo of age. Sex remains an important confounding variable when assessing growth and developmental outcome in these high-risk infants.", "Despite the theoretical benefits of nutrient-enriched formula given to preterm infants after hospital discharge, its role in reversing growth deficits after hospital discharge remains poorly defined.\n The aim was to determine the effect of different formulas on the growth, bone mass, and body composition of preterm infants after hospital discharge.\n This was a randomized, double blind comparison of a nutrient-enriched formula (EF) and a formula for term infants (TF) given for 1 y after hospital discharge. Compared with the TF, the EF had a higher energy density and higher contents of protein, calcium, and phosphorus (by 10%, 21%, 44%, and 11%, respectively) and higher contents of almost all other nutrients (by >or=10%).\n Birth weights of the infants were 630-1620 g (median: 1250 g) and gestational ages were 24-34 wk (median: 29 wk). TF resulted in significantly greater weight, length, head circumference measurements, and their respective z scores on the basis of age- and sex-specific norms. At the end of the study, the mean z scores for the corrected age of infants in the TF group were -0.37 for weight, 0.001 for length, and 0.50 for head circumference. The TF group also had significantly greater dual-energy X-ray absorptiometry measured bone and lean and fat mass than did the EF group (P < 0.05 for all comparisons).\n The use of EF for preterm infants after hospital discharge shows no advantage over TF in growth, bone mineralization, and body composition. More studies are needed to determine the optimal postdischarge nutrition support for preterm infants.", "We designed this prospective randomized controlled study to evaluate the effects of premature and standard term formula on growth, nutrient intake and biochemical response in premature infants from hospital discharge to 6 months of corrected age. Premature infants with a gestational age of < or =35 weeks and a birth weight < or =1850 gm were assigned to receive premature infant formula (n = 19) or a standard term infant formula (n = 15). No differences were found between the two groups in weight, length, or head circumference at baseline or on follow-up. Infants fed premature formula had higher blood urea nitrogen and phosphorus at 3 months of corrected age. Those on the premature formula also had higher energy intake at 1 month of corrected age. We suggest that premature infants, especially very low birth weight infants, fed preterm infant formula after discharge until 6 months of corrected age tolerate the formula well and may benefit over those standard term formula.", "To determine if the addition of a multinutrient human milk fortifier to mother's milk while breastfeeding very preterm infants after hospital discharge is possible and whether it influences first-year growth.\n Of a cohort of 320 infants (gestational age: 24-32 weeks; birth weight: 535-2255 g), breastfed infants (65% [n = 207]) were randomly assigned shortly before hospital discharge to receive either unfortified (n = 102, group A) or fortified (n = 105, group B) mother's milk until 4 months' corrected age (CA). The remaining infants were bottle-fed with a preterm formula (group C). Follow-up was performed at term and at 2, 4, 6, and 12 months' CA.\n Mean duration of breastfeeding after term was not significantly different between groups A and B (11.8 and 10.6 weeks, respectively). Weight, length, and head circumference were not significantly different between groups A and B at 12 months' CA. Compared with groups A and B, infants in group C had a higher increase in weight z score until term and in length z score until 6 months' CA. At 12 months' CA, boys in group C were significantly longer and heavier compared with those in groups A and B, whereas girls in group C were longer and heavier compared with those in group A only. A higher protein intake was related to a higher serum urea nitrogen level and growth.\n Fortification of mother's milk after hospital discharge while breastfeeding very preterm infants was possible without influencing breastfeeding duration but did not significantly influence growth parameters at 1 year of age compared with unfortified mother's milk.", "At hospital discharge, preterm infants may have low body stores of nutrients, deficient bone mineralization, and an accumulated energy deficit. This double-blind, randomized study evaluated the growth of premature infants with birth weights <1800 g who were fed a 22 kcal/fl oz nutrient-enriched postdischarge formula (PDF) or a 20 kcal/fl oz term-infant formula (TF) from hospital discharge to 12 months' corrected age (CA).\n Infants were randomized to PDF or TF a few days before hospital discharge with stratification by gender and birth weight (<1250 g or >/=1250 g). The formulas were fed to 12 months' CA. Growth was evaluated using analysis of variance controlling for site, feeding, gender, and birth weight group. Interaction effects were also assessed. Secondary analyses included a repeated measures analysis and growth modeling.\n One hundred twenty-five infants were randomized; 74 completed to 6 months' CA and 53 to 12 months' CA. PDF-fed infants weighed more than TF-fed infants at 1 and 2 months' CA, gained more weight from study day 1 to 1 and 2 months' CA, and were longer at 3 months' CA. There were significant interactions between feeding and birth weight group-among infants with birth weights <1250 g, those fed PDF weighed more at 6 months' CA, were longer at 6 months' CA, had larger head circumferences at term 1, 3, 6, and 12 months' CA, and gained more in head circumference from study day 1 to term and to 1 month CA. The repeated measures and growth modeling analyses confirmed the analysis of variance results. The PDF formula seemed to be of particular benefit for the growth of male infants. Infants fed the PDF consumed less formula and had higher protein intakes at several time points. Energy intakes, however, were not different.\n Growth was improved in preterm infants fed a nutrient-enriched postdischarge formula after hospital discharge to 12 months' CA. Beneficial effects were most evident among infants with birth weights <1250 g, particularly for head circumference measurements.", "Preterm infants are frequently discharged from the hospital growth retarded and show reduced growth throughout childhood. In a large efficacy and safety trial, we tested the hypothesis that nutritional intervention in the first 9 months postterm would reverse postdischarge growth deficits and improve neurodevelopment without adverse safety outcomes.\n Two hundred eighty-four infants (mean gestation: 30.9 weeks) were studied; 229 were randomly assigned a protein, energy, mineral, and micronutrient-enriched postdischarge formula (PDF; N = 113) or standard term formula (TF; N = 116) from discharge (mean 36.5 weeks' postmenstrual age). A reference group (N = 65) was breastfed until at least 6 weeks' postterm. Outcome measures. Anthropometry was performed at 6 weeks and 3, 6, 9, and 18 months. Development was measured at 9 months (Knobloch, Passamanick, and Sherrard's developmental screening inventory) and 18 months (Bayley Scales of Infant Development II; primary outcome) postterm.\n At 9 months, compared with the TF group, those fed PDF were heavier (difference 370 g; 95% confidence interval [CI]: 84-660) and longer (difference 1.1 cm; 95% CI: 0.3-1.9); the difference in length persisted at 18 months (difference 0.82 cm; 95% CI: -0.04-1.7). There was no effect on head circumference. The effect of diet was greatest in males; at 9 months length deficit with TF was 1.5cm (95% CI: 0.3-2.7), and this remained at 18 months (1.5cm [95% CI: 0.3-2.7]). There was no significant difference in developmental scores at 9 or 18 months, although PDF infants had a 2.8 (-1.3-6.8) point advantage in Bayley motor score scales. At 6 weeks' postterm, exclusively breastfed infants were already 513 g (95% CI: 310-715) lighter and 1.6cm (95% CI: 0.8-2.3) shorter than the PDF group, and they remained smaller up to 9 months' postterm.\n 1) Improving postdischarge nutrition in the first 9 months may \"reset\" subsequent growth-at least until 18 months for body length. We intend to follow-up the children at older ages. The observed efficacy of PDF was not associated with adverse safety outcomes. 2) We cannot reject the hypothesis that postdischarge nutrition benefits motor development and this requires additional study. 3) Our data raise the possibility that breastfed postdischarge preterm infants may require nutritional supplementation, currently under investigation.", "The Preterm newborns, especially if born small for gestational age (SGA), appear to be at risk for developing post-natal growth failure and an altered body composition. Nutrition-related growth during a critical window in infancy may affect the development of metabolic syndrome in adult life. Aim of the present study was to test the hypothesis that the post-discharge period is critical for programming the catch up growth and the later development of metabolic syndrome in small for gestational-age infants fed either standard or enriched formula.\n A clinic randomized explorative study was conducted. Twenty-seven preterm SGA infants (gestational age < or = 33 weeks; birth weight < or = 1500 g) underwent assessment of growth and body composition by means of an air displacement system at 36 weeks, 15 days and 1 months adjusted age. SGA infants were randomized to receive standard formula (Kcal: 67/100 ml, proteins: 1,4 g/100 ml) or enriched formula (Kcal: 75/100 ml, proteins: 2 g/100 ml) after discharge.\n No differences in weight, fat mass, length and head circumference were found in SGA infants fed standard formula as compared to those fed enriched formula at 15 day or 1 months adjusted age.\n This explorative study suggests that in SGA infants growth, both in terms of quantity and quality, is not influenced by different nutritional management during the early post-discharge period.", "Most preterm infants are still preterm and have a low birth weight when they are discharged from the hospital. An important issue is whether the long-term consequences of early growth restriction can be diminished by nutritional intervention in preterm infants after discharge from the hospital.\n To evaluate differences in growth and in weight gain composition of preterm infants fed standard term formula (SF) or enriched formula (PDF) after discharge from hospital during the first 2 months of life.\n Thirty-three healthy preterm infants, birth weight < 1750 g at gestational age < 35 weeks, were randomised to SF or PDF at the time of discharge from hospital. Anthropometric variables were studied longitudinally and body composition was measured using dual energy x-ray absorptiometry (DEXA) twice, before hospital discharge and two months later. Weight gain composition was calculated as the difference between the two determinations.\n Seventeen infants were fed SF and 16 PDF. Anthropometric variables and whole body composition were similar at birth, at the start of the nutritional study (mean age 45 days), and at the end of the study 2 months later. Over the whole study period, weight gain and weight gain composition were similar in the two groups. Sex did not appear to influence weight gain and weight gain composition. In infants with growth restriction at discharge there was a significant reduction of weight gain, fat mass gain, and bone mineral content deposition independently of the formula provided.\n There is no immediate effect on preterm infants of a nutrient enriched formula compared with a standard formula on growth, weight gain, or weight gain composition.", "To compare nasogastric tube and bottle supplementation as two means of transitioning preterm infants to breastfeeding within an established breastfeeding support program.\n Prospective, randomized controlled trial; mothers and health care providers, who were not blinded.\n Metropolitan private regional perinatal center; 40-bed intensive-care nursery.\n Eighty-four preterm breastfed infants whose birth weight was 1,000-2,500 g.\n Rates of exclusive and partial breastfeeding at discharge from the intensive-care nursery, and at 3 days, 3 months, and 6 months after discharge.\n Compared with infants receiving bottle supplements, infants receiving nasogastric tube supplements were more likely to be breastfeeding at discharge and at 3 days, 3 months and 6 months, after adjusting for confounding variables. Odds ratios (confidence intervals = 95%) showed that the group receiving nasogastric supplements was 4.5 times (1.4 to 15) more likely to be breastfed at discharge and 9.4 times more likely to be fully breastfed (3.1 to 28.4). There were significantly fewer apnea and bradycardia episodes in the group receiving nasogastric supplements, although they had more episodes that required stimulation for resolution. Groups were not different with respect to length of hospitalization and infant weight at discharge.\n Using nasogastric tube supplementation during transition to oral feedings increases the likelihood of breastfeeding at discharge, 3 days, 3 months, and 6 months. This intervention requires a program with skilled personnel and an environment that allows the mother and infant to be in close physical proximity. Further study should investigate differences in the effects on maternal confidence, imprinting, and suck mechanism when preterm infants are bottle fed and breastfed.", "To determine the effect of artificial teats (bottle and dummy) and cups on breast feeding in preterm infants.\n Randomised controlled trial.\n Two large tertiary hospitals, 54 peripheral hospitals.\n 319 preterm infants (born at 23-33 weeks' gestation) randomly assigned to one of four groups: cup/no dummy (n = 89), cup/dummy (n = 72), bottle/no dummy (n = 73), bottle/dummy (n = 85). Women with singleton or twin infants < 34 weeks' gestation who wanted to breastfeed were eligible to participate.\n Cup or bottle feeding occurred when the mother was unable to be present to breast feed. Infants randomised to the dummy groups received a dummy on entry into the trial.\n Full breast feeding (compared with partial and none) and any breast feeding (compared with none) on discharge home. Secondary outcomes: prevalence of breast feeding at three and six months after discharge and length of hospital stay.\n 303 infants (and 278 mothers) were included in the intention to treat analysis. There were no significant differences for any of the study outcomes according to use of a dummy. Infants randomised to cup feeds were more likely to be fully breast fed on discharge home (odds ratio 1.73, 95% confidence interval 1.04 to 2.88, P = 0.03), but had a longer length of stay (hazard ratio 0.71, 0.55 to 0.92, P = 0.01).\n Dummies do not affect breast feeding in preterm infants. Cup feeding significantly increases the likelihood that the baby will be fully breast fed at discharge home, but has no effect on any breast feeding and increases the length of hospital stay." ]	Current recommendations to prescribe "post-discharge formula" for preterm infants following hospital discharge are not supported by the available evidence. Some limited evidence exists that feeding preterm infants following hospital discharge with "preterm formula" (which is generally only available for in-hospital use) may increase growth rates up to 18 months corrected age.
CD010078	[ "17888856", "15967546", "22375972", "18568115", "12775857" ]	[ "Nicotine replacement and behavioral therapy for smoking cessation in pregnancy.", "Case studies of three pregnant smokers and their use of nicotine replacement therapy.", "A randomized trial of nicotine-replacement therapy patches in pregnancy.", "Extended use of nicotine replacement therapy to maintain smoking cessation in persons with schizophrenia.", "Clinical trial comparing nicotine replacement therapy (NRT) plus brief counselling, brief counselling alone, and minimal intervention on smoking cessation in hospital inpatients." ]	[ "This study examines whether adding nicotine replacement therapy (NRT) to cognitive-behavioral therapy (CBT) for pregnant smokers increases rates of smoking cessation.\n An open-label randomized trial (Baby Steps, n=181) of CBT-only versus CBT+NRT (choice of patch, gum, or lozenge; 1:2 randomization) was used. Data were collected from 2003 through 2005; analyses were conducted in 2006 and 2007. Outcomes were biochemically validated self-reported smoking status at 7 weeks post-randomization, 38 weeks gestation, and 3 months postpartum.\n Women in the CBT+NRT arm were almost three times more likely than women in the CBT-only arm to have biochemically validated cessation at both pregnancy time points (after 7 weeks: 24% vs 8%, p=0.02; at 38 weeks gestation: 18% vs 7%, p=0.04), but not at 3 months postpartum (20% vs 14%, p=0.55). Recruitment was suspended early by an Independent Data and Safety Monitoring Board when an interim analysis found a higher rate of negative birth outcomes in the CBT+NRT arm than in the CBT-only arm. In the final analysis, the difference between the arms in rate of negative birth outcomes was 0.09 (p=0.26), when adjusted for previous history of preterm birth.\n The addition of NRT to CBT promoted smoking cessation in pregnant women. This effect did not persist postpartum. More data are needed to determine safety parameters and to confirm the efficacy of NRT use during pregnancy.", "To examine the barriers encountered by pregnant women who attempt to stop smoking by highlighting three women who used nicotine patches.\n A randomised-controlled trial of nicotine-replacement therapy (NRT) in the form of patches to test its acceptability for pregnant women. Ethics approval was granted despite NRT being contraindicated in Australia for pregnant women and having a low safety rating (category D) (Australian Drug Evaluation Committee, 1999). Salivary cotinine levels were used to assess nicotine exposure and provide some indicator of NRT safety. All participants were given pregnancy-specific cessation counselling, and the 20 women in the treatment arm were offered nicotine patches (15 mg/16 hr), with the option of weaning to lower strength patches if desired.\n The Women's and Children's Hospital, Adelaide, a public tertiary teaching hospital in South Australia, with almost 4000 births annually.\n 40 'high-risk' pregnant smokers who expressed interest in stopping smoking.\n As has been found in the general population, 'quit' rates with NRT use were low. Only three of the participants in this study, who became abstinent with patch use during pregnancy, were still abstinent at birth. The circumstances of two of these women, and a third woman who used patches to 'control' her smoking despite researcher advice, are detailed here. Only one of the two women 'abstinent at delivery' was still abstinent 3 months after birth, the last contact point of the study.\n Although health providers intuitively regard pregnancy as an appropriate time for women to stop smoking, the stressors during pregnancy seem to militate against cessation. This study does not indicate that use of NRT will provide an easier solution. It may be more fruitful to institute a concerted lifestyle approach with both the woman and her partner (or significant household members), and continue this support and education postnatally if cessation has not been achieved. Health professionals should also support better-targeted public health campaigns and tobacco-control initiatives generally, because, undoubtedly, the social environment is a major determinant of initiation and continuation of smoking.", "Nicotine-replacement therapy is effective for smoking cessation outside pregnancy and its use is widely recommended during pregnancy. We investigated the efficacy and safety of nicotine patches during pregnancy.\n We recruited participants from seven hospitals in England who were 16 to 50 years of age with pregnancies of 12 to 24 weeks' gestation and who smoked five or more cigarettes per day. Participants received behavioral cessation support and were randomly assigned to 8 weeks of treatment with active nicotine patches (15 mg per 16 hours) or matched placebo patches. The primary outcome was abstinence from the date of smoking cessation until delivery, as validated by measurement of exhaled carbon monoxide or salivary cotinine. Safety was assessed by monitoring for adverse pregnancy and birth outcomes.\n Of 1050 participants, 521 were randomly assigned to nicotine-replacement therapy and 529 to placebo. There was no significant difference in the rate of abstinence from the quit date until delivery between the nicotine-replacement and placebo groups (9.4% and 7.6%, respectively; unadjusted odds ratio with nicotine-replacement therapy, 1.26; 95% confidence interval, 0.82 to 1.96), although the rate was higher at 1 month in the nicotine-replacement group than in the placebo group (21.3% vs. 11.7%). Compliance was low; only 7.2% of women assigned to nicotine-replacement therapy and 2.8% assigned to placebo used patches for more than 1 month. Rates of adverse pregnancy and birth outcomes were similar in the two groups.\n Adding a nicotine patch (15 mg per 16 hours) to behavioral cessation support for women who smoked during pregnancy did not significantly increase the rate of abstinence from smoking until delivery or the risk of adverse pregnancy or birth outcomes. However, low compliance rates substantially limited the assessment of safety. (Funded by the National Institute for Health Research Health Technology Assessment Programme; Current Controlled Trials number, ISRCTN07249128.).", "This study was designed to determine the feasibility and efficacy of long-term nicotine replacement therapy (NRT) in helping persons with schizophrenia remain tobacco-free. Fifty smokers with a diagnosis of schizophrenia or schizo-affective disorder and whose symptoms had been stable for at least two months were enrolled in a program providing group support and NRT (patches) in individually adjusted doses set to maintain baseline nicotine intake. All participants attended weekly group support/motivation sessions. Smoking activity was determined by measuring carbon monoxide levels in expired air. Participants who quit tobacco use completely during the first three months were entered into a single-blind phase in which they received either placebo or active nicotine patches for up to six additional months, along with biweekly group sessions. Sixty days into the open-label phase, 66% of the subjects had reduced their use of tobacco by at least 75%. After 90 days of open-label treatment, 18 subjects (36%) were tobacco-free and qualified to enter the six-month, single-blind phase, eight on placebo and nine on active patches. A significantly greater proportion of those on placebo (8 of 8) compared with those on active patches (3 of 9) relapsed prior to completion of the 6-month period. This difference is statistically significant at the p = 0.009 level. The results of this study indicate that long-term use of NRT is feasible and effective for sustained tobacco-free success and may be an important strategy for reducing health risks due to tobacco use in this special population.", "Guidelines recommend that smoking cessation interventions are offered in all clinical settings to all smokers willing to make a quit attempt. Since the effectiveness of routine provision of behavioural counselling and nicotine replacement therapy (NRT) to smokers admitted to hospital has not been established, a randomised controlled trial of these interventions given together compared with counselling alone or minimal intervention was performed in hospital inpatients.\n Medical and surgical inpatients who were current smokers at the time of admission were randomised to receive either usual care (no additional advice at admission), counselling alone (20 minute intervention with written materials), or NRT plus counselling (counselling intervention with a 6 week course of NRT). Continuous and point prevalence abstinence from smoking (validated by exhaled carbon monoxide <10 ppm) was measured at discharge from hospital and at 3 and 12 months, and self-reported reduction in cigarette consumption in smokers was assessed at 3 and 12 months.\n 274 inpatient smokers were enrolled. Abstinence was higher in the NRT plus counselling group (n=91) than in the counselling alone (n=91) or usual care (n=92) groups. The difference between the groups was significant for validated point prevalence abstinence at discharge (55%, 43%, 37% respectively, p=0.045) and at 12 months (17%, 6%, 8%, p=0.03). The respective differences in continuous validated abstinence at 12 months were 11%, 4%, 8% (p=0.25). There was no significant difference between counselling alone and usual care, or in reduction in cigarette consumption between the treatment groups.\n NRT given with brief counselling to hospital inpatients is an effective routine smoking cessation intervention." ]	Nicotine replacement therapy is the only pharmacotherapy for smoking cessation that has been tested in RCTs conducted in pregnancy. There is insufficient evidence to determine whether or not NRT is effective or safe when used to promote smoking cessation in pregnancy or to determine whether or not using NRT has positive or negative impacts on birth outcomes. Further research evidence of efficacy and safety is needed, ideally from placebo-controlled RCTs that investigate higher doses of NRT than were tested in the included studies.
CD005360	[ "19673597", "20575704", "2403697", "17236918", "3324594", "10873356", "15843938", "7480237", "7648148" ]	[ "Does preoperative core needle biopsy increase surgical site infections in breast cancer surgery? Randomized study of antibiotic prophylaxis.", "Role of prophylactic antibiotics in laparoscopic cholecystectomy and risk factors for surgical site infection: a randomized controlled trial.", "A prospective, randomized double-blind study of the use of antibiotics at the time of mastectomy.", "Does prophylactic administration of systemic antibiotics prevent postoperative inflammatory complications after third molar surgery?", "Single-dose v. short-term antibiotic therapy for prevention of wound infection in general surgery. A prospective, randomized double-blind trial.", "Antibiotic prophylaxis for post-operative wound infection in clean elective breast surgery.", "Prospective, randomised study on antibiotic prophylaxis in colorectal surgery. Is it really necessary to use oral antibiotics?", "A prospective, double-blind, placebo-controlled trial of a single dose of azithromycin on postoperative wound infections in plastic surgery.", "Value of oral antibiotic prophylaxis in colorectal surgery." ]	[ "Preoperative core needle biopsies may increase the risk of surgical site infection (SSI) in breast cancer surgery. The purpose of this randomized trial was to determine whether a prophylactic antibiotic would prevent SSI under these conditions.\n Imaging-guided multiple core needle biopsies were performed one to two weeks prior to surgery to obtain confirmation of the presence of breast cancer. Then the patients were randomized to receive either a single intravenous dose of 1.0 g of dicloxacillin (n = 144) or placebo infusion of saline (n = 148) 30 min prior to operation. After breast surgery, incisional morbidity was monitored for 30 days. The number of SSIs was compared with that in 672 patients treated before the implementation of core needle biopsies.\n The patient characteristics and risk factors for SSI were similar in the antibiotic prophylaxis and placebo groups. The incidence of SSI was 7.2% (21/292) in the prospective trial compared with 6.8% (46/672) in the retrospective cohort (p = 0.890). The incidence of postoperative SSIs was 5.6% (8/144) in the dicloxacillin group and 8.8% (13/148) in the placebo group (p = 0.371). For the first two weeks, there was a non-significant trend to fewer SSIs in the antibiotic group (n = 1) than the placebo group (n = 4). Body mass index, smoking, or previous illness did not affect the likelihood of SSI.\n Core needle biopsy did not increase the incidence of SSI. Antibiotic prophylaxis did not prevent SSI, probably because so few infections occurred.", "The aim of this clinical trial was to determine whether prophylactic antibiotics could prevent surgical site infection (SSI) after laparoscopic cholecystectomy and to identify any risk factors for infection.\n The study included 100 patients undergoing laparoscopic cholecystectomy. They were randomized to receive either a single dose of ceftriaxone (Group A; n = 50) or physiologic saline as placebo (Group B; n = 50) after the induction of anesthesia. Patient demographics and clinical and surgical outcomes were recorded.\n The incidence of SSI was similar in the two groups: 2 patients in group A and 4 patients in group B (chi(2) = 0.71; p = 0.40). None of the factors studied was associated with surgical site infection statistically, as shown by binary logistic regression analysis.\n A single dose of prophylactic antibiotic failed to decrease the likelihood of SSI after laparoscopic cholecystectomy.", "The ability of perioperative cefazolin to reduce the incidence of postoperative wound infection in patients undergoing ablative surgical treatment for carcinoma of the breast was tested in this prospective, randomized, double-blinded study. From May 1983 until December 1985, 118 women were divided into two groups at random. Group 1 consisted of 59 patients and received cefazolin and group 2 was made up of 59 patients who received a placebo. The groups were similar with respect to age, operative procedure, operative time and time to discharge after operation. Three infections occurred among those in group 1 and five among those in group 2 (p = 0.72). The time to onset of infection was delayed in the patients in group 1 versus those in group 2 (17.7 days versus 9.6 days, p = 0.04). Six of eight infections occurred in patients in whom an interval between biopsy and definitive surgical treatment was present. Prophylactic antibiotics in mammary operations did not reduce postoperative wound infections in this study.", "To estimate and compare the frequencies of inflammatory complications after third molar (M3) surgery in subjects receiving intravenous prophylactic antibiotics or saline placebo.\n Using a placebo-controlled, double-blind, randomized clinical trial, the investigators enrolled a sample composed of subjects who required extraction of at least 1 impacted M3 and requested intravenous sedation or general anesthesia. The predictor variable was treatment group classified as active treatment (penicillin or clindamycin for penicillin-allergic subjects) or placebo (0.9% saline). Study medications were randomly assigned. Both surgeon and subject were blinded to treatment assignment. The medication was administered intravenously prior to any incision. The outcome variable was postoperative inflammatory complication classified as present or absent and included alveolar osteitis (AO) or surgical site infection (SSI). Other variables were demographic, anatomic, or operative. Descriptive and bivariate statistics were computed. Statistical significance was set at P < or = .05, single-tailed test of hypothesis.\n The sample was composed of 118 subjects (n = 59 per study group). In the active treatment group, there were no postoperative inflammatory complications. In the placebo group, 5 subjects (8.5%) were diagnosed with SSI, (P = .03). No subject met the case definition for AO. All SSIs were associated with the removal of partial bony or full bony impacted mandibular M3s.\n In the setting of third molar removal, these results suggest that the use of intravenous antibiotics administered prophylactically decrease the frequency of SSIs. The authors cannot comment on the efficacy of intravenous antibiotics in comparison to other antibacterial treatment regimens, eg chlorhexidine mouthrinse or intrasocket antibiotics.", "To investigate the effectiveness of a single-dose antibiotic regimen for preventing postoperative wound infection, a prospective, randomized double-blind trial was carried out in patients undergoing \"clean-contaminated\", \"contaminated\" or \"clean\" (vascular) surgery. Both elective and emergency operations were included. Single-dose (preoperative) prophylaxis was compared with short-term prophylaxis (1 dose preoperatively and 2 doses postoperatively). The antibiotics were penicillin, tobramycin and metronidazole in various combinations, and comparisons between single-dose and short-term prophylaxis were made with all the regimens. The incidence of wound infection was 5/277 (1.8%) in the short-term group and 9/287 (3.1%) in the single-dose group. The difference was not statistically significant. Nor was statistically significant difference found when the type of operation and the degree of contamination were considered. Single-dose antibiotic prophylaxis thus gave a low incidence of postoperative wound infection, even in \"clean-contaminated\" or \"contaminated\" cases.", "Antibiotic prophylaxis has been used to good effect in the prevention of post-operative wound infections in patients undergoing gastrointestinal operations. We have assessed the use of a single dose of intravenous antibiotic (Augmentin 1.2 g), given with induction of anaesthesia as prophylaxis, against post-operative wound infection in women undergoing clean, elective breast surgery. Three hundred and thirty-four patients were recruited. Of the 164 receiving antibiotic prophylaxis 29 (17.7%) had wound infections compared with 32 (18.8%) in the placebo group (P=0.79). There were no significant differences in any other post-operative infective complications. Antibiotic prophylaxis is probably not required in clean, elective breast surgery.\n Copyright 2000 Harcourt Publishers Ltd.", "The use of prophylactic antibiotics in addition to mechanical cleansing is the current standard of care prior to colonic surgery. The question of whether the antibiotics should be administered intravenously or orally, or by both routes, remains controversial. Our aim was to compare three methods of prophylactic antibiotic administration in elective colorectal surgery.\n Three hundred consecutive elective colorectal resections were studied. All patients had preoperative mechanical colon cleansing with oral sodium phosphate and intravenous antibiotic prophylaxis with cefoxitin (one dose before skin incision and two postoperative doses). Patients were randomised to one of the following three groups: group A: three doses of oral antibiotic (neomycin and metronidazole) at the time of mechanical colon cleansing; group B: one dose of oral antibiotic; group C: no oral antibiotics. All patients were followed during their hospital stay and at 7, 14 and 30 days post-surgery.\n Vomiting occurred in 31%, 11% and 9% of the studied patients (groups A, B and C, respectively) (p<0.001). Nausea was present in 44%, 18% and 13% of patients (p<0.001). Abdominal pain was recorded in 13%, 10% and 4% of patients (p: 0.077). Wound infection was present in 7%, 8% and 6% and suture dehiscence occurred in 2%, 2% and 3% of the patients in the three groups (no differences among them). Neither were differences found among the three groups in terms of urinary infections, pneumonia, postoperative ileus or intra-abdominal abscess.\n The addition of three doses of oral antibiotics to intravenous antibiotic prophylaxis is associated with lower patient tolerance in terms of increased nausea, vomiting and abdominal pain, and has shown no advantages in the prevention of postoperative septic complications. Therefore, we recommend that oral antibiotics should not be used prior to colorectal surgery.", "Over a 9-month period from September of 1991 to May of 1992, 339 patients were included in a randomized, double-blind, placebo-controlled study using azithromycin as the prophylactic agent to determine whether it effects a clinically meaningful reduction in postoperative surgical infections in plastic surgery. Azithromycin was given as prophylaxis in 171 patients and placebo in 168 patients. The study medication was a single oral dose taken at 8 P.M. the day before surgery. The patients were followed up for a minimum of 4 weeks after surgery. The patients who received wound infection prophylaxis had 5.1 percent infections compared with 20.5 percent in the placebo group (p = 0.00009). Eighty percent of all wound infections were first seen after discharge, explaining why plastic surgeons might overlook their infectious complications. There was a significant reduction in postoperative complications (p = 0.04) and in the additional use of antibiotics postoperatively (p = 0.007) in the prophylaxis group. Subgroup analysis showed a significant reduction in surgical infections in breast surgery (p < 0.05) and reconstructive surgery with flaps (p < 0.05). No effect of the prophylactic regime was demonstrated in patients undergoing secondary surgery for cleft lip and palate disease.", "A total of 169 patients undergoing colorectal surgery were randomly allocated to receive either gentamicin plus metronidazole or oral ciprofloxacin plus metronidazole as prophylaxis; they were also allocated to receive cover for 1 or 3 days. Twenty-eight patients (17 per cent) developed postoperative wound infections. The proportion of patients with wound infections and other infective complications was significantly less (P < 0.02) in those receiving oral ciprofloxacin. Cover for 3 days was no better than that for only 1 day. Oral ciprofloxacin for prophylaxis may offer advantages in efficacy and ease of administration compared with parenteral antibiotics." ]	Prophylactic antibiotics administered preoperatively reduce the risk of SSI in patients undergoing surgery for breast cancer. Further studies involving patients undergoing immediate breast reconstruction are needed as studies have identified this group as being at higher risk of infection than those who do not undergo immediate breast reconstruction.

Subsets and Splits

No community queries yet

The top public SQL queries from the community will appear here once available.