A multi-centre randomised controlled trial of minimally invasive direct coronary bypass grafting versus percutaneous transluminal coronary angioplasty with stenting for proximal stenosis of the left anterior descending coronary artery. Local versus general anaesthesia in carotid surgery. A prospective, randomised study. The role of radiography in primary care patients with low back pain of at least 6 weeks duration: a randomised (unblinded) controlled trial. Quality of life and survival in patients with advanced non-small cell lung cancer receiving supportive care plus chemotherapy with carboplatin and etoposide or supportive care only. A multicentre randomised phase III trial. Joint Lung Cancer Study Group. Treatment of benign esophageal stricture by Eder-Puestow or balloon dilators: a comparison between randomized and prospective nonrandomized trials. Random versus nonrandom assignment in the evaluation of treatment for cocaine abusers. Cognitive therapy by allocation versus cognitive therapy by preference in the treatment of panic disorder. Ceruletide-assisted cholecystography: a clinical assessment. Nitrous oxide for colonoscopy: a randomized controlled study. Efficacy of adenoidectomy for recurrent otitis media in children previously treated with tympanostomy-tube placement. Results of parallel randomized and nonrandomized trials. Mortality in participants and non-participants of a multifactorial prevention study of cardiovascular diseases: a 28 year follow up of the Helsinki Businessmen Study. A randomised trial comparing local versus general anaesthesia for microwave endometrial ablation. The effect of nitrous oxide on in vitro fertilization success rate. Comparison of eligible randomized patients with two groups of ineligible patients: can the results of the VA Total Parenteral Nutrition clinical trial be generalized? Assessing effectiveness of treatment of depression in primary care. Partially randomised preference trial. A population based strategy to prevent insulin-dependent diabetes using nicotinamide. Theophylline for irreversible chronic airflow limitation: a randomized study comparing n of 1 trials to standard practice. Does cranial irradiation reduce the risk for bone marrow relapse in acute myelogenous leukemia? Unexpected results of the Childhood Acute Myelogenous Leukemia Study BFM-87. Randomised study of n of 1 trials versus standard practice. Integrating patient preferences in clinical trials: a pilot study of acupuncture versus midazolam for gastroscopy. Evaluation of anxiolysis and pain associated with combined peri- and retrobulbar eye block for cataract surgery. Long-term clinical outcome in the Bypass Angioplasty Revascularization Investigation Registry: comparison with the randomized trial. BARI Investigators. Admission-discharge policies for hysteroscopic surgery: a randomised comparison of day case with in-patient admission. Comparison of chorionic villus sampling and amniocentesis for fetal karyotyping at 10-13 weeks' gestation. Does informed consent influence therapeutic outcome? A clinical trial of the hypnotic activity of placebo in patients admitted to hospital. Results from a prospective, randomized, controlled study evaluating the acceptability and effects of routine pre-IVF counselling. Design of the multicenter Australian study of epidural anesthesia and analgesia in major surgery: the MASTER trial. Randomized and non-randomized patients in clinical trials: experiences with comprehensive cohort studies. Assessing clinical generalizability in sedation studies of upper GI endoscopy. Intergroup Hodgkin's disease in children study of stages I and II: a preliminary report. Use of intravenously administered immune globulin to prevent nosocomial sepsis in low birth weight infants: report of a pilot study. Patient-controlled versus nurse-administered sedation with propofol during colonoscopy. A prospective randomized trial. Hormonal replacement therapy reduces forearm fracture incidence in recent postmenopausal women - results of the Danish Osteoporosis Prevention Study. Forced-air warming is no more effective than conventional methods for raising postoperative core temperature after cardiac surgery. Antidepressant drugs and generic counselling for treatment of major depression in primary care: randomised trial with patient preference arms. Clinical experimental randomized study of 2.6-cis-diphenylhexamethylcyclotetrasiloxane and estramustine-17-phosphate in the treatment of prostatic carcinoma. Medical versus surgical abortion: comparing satisfaction and potential confounders in a partly randomized study. Asymptomatic cervical bruit and abnormal ocular pneumoplethysmography: a prospective study comparing two approaches to management. The impact of CytoGam on cardiac transplant recipients with moderate hypogammaglobulinemia: a randomized single-center study. Amniocentesis before 14 completed weeks as an alternative to transabdominal chorionic villus sampling: a controlled trial with infant follow-up. Is the wish to participate in a cancer rehabilitation program an indicator of the need? Comparisons of participants and non-participants in a randomized study. Nonattendance in the Stockholm mammography screening trial: relative mortality and reasons for nonattendance. A randomized evaluation of early revascularization to treat shock complicating acute myocardial infarction. The (Swiss) Multicenter Trial of Angioplasty for Shock-(S)MASH. Adjuvant chemotherapy of high-grade osteosarcoma of the extremity. Updated results of the Multi-Institutional Osteosarcoma Study. Randomised controlled trial of non-directive counselling, cognitive-behaviour therapy and usual general practitioner care in the management of depression as well as mixed anxiety and depression in primary care. Asymptomatic carotid endarterectomy. Patient and surgeon selection. Generalizability of trial results based on randomized versus nonrandomized allocation of OME infants to ventilation tubes or watchful waiting. Congenital nasolacrimal duct obstruction in the second year of life: a multicentre trial of management. Pregnancy outcome among non-participants in a trial on ultrasound screening. School-based intervention for adolescent obesity: analysis of treatment, randomly selected control, and self-selected control subjects. Participants in prospective, randomized clinical trials for resected non-small cell lung cancer have improved survival compared with nonparticipants in such trials. Comparison of medical abortion with surgical vacuum aspiration: women's preferences and acceptability of treatment. Balloon angioplasty versus bypass grafting in the era of coronary stenting. A comparison of buprenorphine and lofexidine for community opiate detoxification: results from a randomized controlled trial. Pragmatic randomized trial evaluating the clinical and economic effectiveness of acupuncture for chronic low back pain. Randomised trial of growth hormone in short normal girls. Acupuncture for patients with chronic neck pain. CAPD bag changing with integrated disconnect system gives lower incidence of peritonitis than with UV-box system. Amitriptyline in the treatment of anorexia nervosa: a double-blind, placebo-controlled study. Prophylactic intrapartum amnioinfusion for patients with oligohydramnios. A prospective randomized study. Combined 5-fluorouracil and radiation therapy as a surgical adjuvant for poor prognosis gastric carcinoma. Psychological sequelae of medical and surgical abortion at 10-13 weeks gestation. Evaluation of two educative models in a primary care hypertension programme. Efficacy of tonsillectomy for recurrent throat infection in severely affected children. Results of parallel randomized and nonrandomized clinical trials. Intratumoral and parametrial infusion of metronidazole in the radiotherapy of uterine cervix cancer: preliminary report. The impact of using a partially randomised patient preference design when evaluating alternative managements for heavy menstrual bleeding. Electrohydraulic high-energy shock-wave treatment for chronic plantar fasciitis. Nitrous oxide (Entonox) inhalation and tolerance of transrectal ultrasound guided prostate biopsy: a double-blind randomized controlled study. A randomised clinical trial of the effect of informed consent on the analgesic activity of placebo and naproxen in cancer pain. The need for delivery room intubation of thin meconium in the low-risk newborn: a clinical trial. Selection bias in clinical trials.
To compare the clinical- and cost-effectiveness of minimally invasive direct coronary artery bypass grafting (MIDCAB) and percutaneous transluminal coronary angioplasty (PTCA) with or without stenting in patients with single-vessel disease of the left anterior descending coronary artery (LAD).
                Multi-centre randomised trial without blinding. The computer-generated sequence of randomised assignments was stratified by centre, allocated participants in blocks and was concealed using a centralised telephone facility.
                Four tertiary cardiothoracic surgery centres in England.
                Patients with ischaemic heart disease with at least 50% proximal stenosis of the LAD, suitable for either PTCA or MIDCAB, and with no significant disease in another vessel.
                Patients randomised to PTCA had local anaesthetic and underwent PTCA according to the method preferred by the operator carrying out the procedure. Patients randomised to MIDCAB had general anaesthetic. The chest was opened through an 8-10-cm left anterior thoracotomy. The ribs were retracted and the left internal thoracic artery (LITA) harvested. The pericardium was opened in the line of the LAD to confirm the feasibility of operation. The distal LITA was anastomosed end-to-side to an arteriotomy in the LAD. All operators were experienced in carrying out MIDCAB.
                The primary outcome measure was survival free from cardiac-related events. Relevant events were death, myocardial infarction, repeat coronary revascularisation and recurrence of symptomatic angina or clinical signs of ischaemia during an exercise tolerance test at annual follow-up. Secondary outcome measures were complications, functional outcome, disease-specific and generic quality of life, health and social services resource use and their costs.
                A total of 12,828 consecutive patients undergoing an angiogram were logged at participating centres from November 1999 to December 2001. Of the 1091 patients with proximal stenosis of the LAD, 127 were eligible and consented to take part; 100 were randomised and the remaining 27 consented to follow-up. All randomised participants were included in an intention-to-treat analysis of survival free from cardiac-related events, which found a non-significant benefit from MIDCAB. Cumulative hazard rates at 12 months were estimated to be 7.1 and 9.2% for MIDCAB and PTCA, respectively. There were no important differences between MIDCAB and PTCA with respect to angina symptoms or disease-specific or generic quality of life. The total NHS procedure costs were 1648 British pounds and 946 British pounds for MIDCAB and PTCA, respectively. The costs of resources used during 1 year of follow-up were 1033 British pounds and 843 British pounds, respectively.
                The study found no evidence that MIDCAB was more effective than PTCA. The procedure costs of MIDCAB were observed to be considerably higher than those of PTCA. Given these findings, it is unlikely that MIDCAB represents a cost-effective use of resources in the reference population. Recent advances in cardiac surgery mean that surgeons now tend to carry out off-pump bypass grafting via a sternotomy instead of MIDCAB. At the same time, cardiologists are treating more patients with multi-vessel disease by PTCA. Future primary research should focus on this comparison. Other small trials of PTCA versus MIDCAB have now finished and a more conclusive answer to the original objective could be provided by a systematic review. A randomised, prospective study was performed to compare local (LA) and general anaesthesia (GA) in carotid surgery with special emphasis on complications and the need for intra-operative shunting. Fifty-six patients were randomised to LA and 55 to GA. Eight patients in the LA group required a GA for various reasons. During the same period 14 patients were not randomised. Seven perioperative neurological deficits occurred (5.6%), four in the LA group, two in the GA group, and one in the non-randomised group (NS). Selective shunting was used, in the Ga group according to stump pressure or in cases with a previous stroke and in the LA group according to the appearance of neurological symptoms. In the GA group 25 patients were shunted and in the LA group five patients (P less than 0.001) needed a shunt. If strict pressure criteria for shunting had been used in the LA patients, ten would have been shunted and three of the patients who developed symptoms during clamping would not have been shunted. During surgery the highest recorded systolic pressure was significantly higher in the LA group (210 mmHg versus 173 mmHg, P less than 0.001). LA for carotid endarterectomy is comparable with general anaesthesia regarding peroperative complications but produces significantly higher blood pressures than general anaesthesia. On the other hand it allows the possibility of neurologic monitoring of the patient and leads to significantly less use of an intra-operative shunt. To test the hypotheses that: (1) Lumbar spine radiography in primary care patients with low back pain is not associated with improved patient outcomes, including pain, disability, health status, sickness absence, reassurance, and patient satisfaction or belief in the value of radiography. (2) Lumbar spine radiography in primary care patients with low back pain is not associated with changes in patient management, including medication use, and the use of primary and secondary care services, physical therapies and complementary therapies. (3) Participants choosing their treatment group (i.e. radiography or no radiography) do not have better outcomes than those randomised to a treatment group. (4) Lumbar spine radiography is not cost-effective compared with usual care without lumbar spine radiography.
                A randomised unblinded controlled trial.
                Seventy-three general practices in Nottingham, North Nottinghamshire, Southern Derbyshire, North Lincolnshire and North Leicestershire. Fifty-two practices recruited participants to the trial.
                Randomised arm: 421 participants with low back pain, with median duration of 10 weeks. Patient preference arm: 55 participants with low back pain, with median duration of 11 weeks.
                Lumbar spine radiography and usual care versus usual care without radiography.
                Roland adaptation of the Sickness Impact Profile, visual analogue pain scale, health status scale, EuroQol, use of primary and secondary care services, and physical and complementary therapies, sickness absence, medication use, patient satisfaction, reassurance and belief in value of radiography at 3 and 9 months post-randomisation.
                Participants randomised to receive an X-ray were more likely to report low back pain at 3 months (odds ratio (OR) = 1.56; 95% confidence interval (CI), 1.02 to 2.40) and had a lower overall health status score (p = 0.02). There were no differences in health or functional status at 9 months. A higher proportion of participants consulted the general practitioner (GP) in the 3 months following an X-ray (OR = 2.72; 95% CI, 1.80 to 4.10). There were no differences in use of any other services, medication use or sickness absence at 3 or 9 months. No serious spinal pathology was identified in either group. The commonest X-ray reports were of discovertebral degeneration and normal findings. Many patients did not perceive their information needs were met within the consultation. Satisfaction with care was greater in the group receiving radiography at 9 months. Participants randomised to receive an X-ray were not less worried, or more reassured about serious disease causing their low back pain. Satisfaction was associated with meeting participants' information needs and reduced belief in the necessity for investigations for low back pain, including X-rays and blood tests. In both groups, at 3 and 9 months 80% of participants would choose to have an X-ray if the choice was available. Participants in the patient preference group achieved marginally better outcomes than those randomised to a treatment group, but the clinical significance of these differences is unclear. Lumbar spine radiography was associated with a net economic loss at 3 and 9 months.
                Lumbar spine radiography in primary care patients with low back pain of at least 6 weeks duration is not associated with improved functioning, severity of pain or overall health status, and is associated with an increase in GP workload. Participants receiving X-rays are more satisfied with their care, but are not less worried or more reassured about serious disease causing their low back pain. CONCLUSIONS - RECOMMENDATIONS FOR FURTHER RESEARCH: Further work is required to develop and test an educational package that educates patients and GPs about the utility of radiography and provides strategies for identifying and meeting the information needs of patients, and the needs of patients and GPs to be reassured about missing serious disease. Guidelines on the management of low back pain in primary care should be consistent about not recommending lumbar spine radiography in patients with low back pain in the absence of red flags for serious spinal pathology, even if the pain has persisted for at least 6 weeks. The aim of the present trial was to evaluate the effects of chemotherapy on the quality of life and survival of patients with advanced non-small cell lung cancer (NSCLC) (stage IIIB or IV). In a controlled multicentre trial, patients were randomised to receive supportive care only or supportive care plus chemotherapy. Chemotherapy consisted of intravenous (i.v.) carboplatin 300 mg/m2 on day 1 and etoposide 120 mg/m2 orally on days 1-5 every 4 weeks for a maximum of eight courses. Quality of life was measured at randomisation and prior to each treatment course and at corresponding 4-week intervals in the control arm, using the EORTC QLQ-C30 + LC13 questionnaire. 48 patients were randomised (supportive care 26, chemotherapy 22), being eligible for comparative analyses. Another 102 patients, 97 of which received chemotherapy, were subsequently included in the study on an individual treatment preference basis. Data from these patients were used for confirmative purposes. Patients in the chemotherapy group reported better overall physical functioning and symptom control compared with the supportive care group. Group differences were smaller within the psychosocial domain, although trends were seen in favour of the chemotherapy group. No significant differences were seen in favour of the supportive care group, except for hair loss. Median survival times were 29 weeks in the chemotherapy group versus 11 weeks in the supportive care group, and 1-year survival rates were 28% versus 8%. Quality of life and survival outcomes were similar in the randomised and non-randomised patients receiving chemotherapy. No treatment-related deaths occurred. In conclusion, treatment with carboplatin and etoposide can improve both the quality of life and the survival of patients with advanced NSCLC. To determine whether the natural history of strictures is affected by the type of dilator used to treat newly diagnosed peptic strictures, we designed a prospective randomized trial to compare the results after Eder-Puestow or Medi-Tech balloon dilation. We entered 31 patients into the trial. We also prospectively followed up all 92 nonrandomized patients who underwent their first dilation for a benign stricture during the same period as the prospective randomized trial. The nonrandomized patients also underwent dilation with either the Eder-Puestow or the balloon technique at the discretion of the gastroenterologist performing the endoscopy. We found no statistically significant differences in the immediate or long-term results of the two methods among the randomized, nonrandomized, and overall combined groups. All but 1 of the 123 patients had immediate relief of dysphagia. Within each group of patients, the probability of remaining free of dysphagia 1 year after the initial dilation was approximately 20%, and the probability of not requiring a second dilation was approximately 65% with either technique. Major (esophageal rupture) and minor (bleeding or chest pain) complications occurred in 1% and 5% of the patients and 0.4% and 3% of the total dilation procedures, respectively. The esophageal rupture and four of six minor complications occurred after repeated dilations. Five of the six minor complications occurred with use of the Eder-Puestow dilators. We conclude that Eder-Puestow and balloon dilations of benign esophageal strictures are associated with similar outcomes, but repeated dilations and the Eder-Puestow technique may be associated with an increased risk of complications. Cocaine-abusing patients randomly assigned to day-hospital or inpatient rehabilitation were compared with patients who self-selected these treatment settings to examine differences in substance use and psychosocial outcomes under experimental and nonexperimental designs. There was little evidence of setting or assignment effects or Setting x Assignment interactions over the 12-month follow-up period. However, Assignment x Time interactions were obtained with 2 measures of cocaine use and measures of family-social and psychiatric problem severity. These interactions indicated greater problem severity at intake among the randomized patients coupled with greater improvements by the 3-month follow-up relative to the nonrandomized patients. Findings suggest that randomized studies of treatment for cocaine abuse may produce somewhat larger estimates of improvement than what is observed in more typical treatment situations. Little is known about the influence of preference for a given therapy or preference against a modality of treatment on the outcome of that treatment. Results so far have been conflicting. The primary aim of this study was to investigate possible differences in outcome between panic disorder patients treated with preferred cognitive therapy and patients treated by randomization with the same intervention.
                A 12-week study comparing 35 patients treated by allocation with 31 patients treated by preference.
                There were no differences at pretest between the two conditions on demographic or outcome measures. Outcome was assessed with measurements rating the panic frequency and severity of agoraphobia, general anxiety and depression. Both conditions improved significantly on nearly all ratings. There were no significant differences demonstrable between the two conditions on any of the outcome measures.
                Preference for a given therapy is not a powerful moderator of effect in the psychological treatment of panic disorder.
                Copyright 2000 S. Karger AG, Basel The cholecystokinetic effect of ceruletide, a synthetic decapeptide similar in action to cholecystokinin, was examined in both a randomized and nonrandomized study in 81 patients scheduled for routine oral cholecystograms. Intramuscular injection of ceruletide in a dose of 0.3 microgram/kg resulted in a mean maximum contraction of the gallbladder of 68% and a mean time until maximum contraction of 28 minutes. Visualization of the cystic duct occurred in 57 patients (70%); the common duct was seen in 67 (83%). Ceruletide demonstrated superior gallbladder contraction when compared to fatty meals and demonstrated no interference with a subsequent upper gastrointestinal series. Intravenous sedation/analgesia for colonoscopy is accompanied with certain risks and postprocedure drowsiness. We sought to determine whether inhaled nitrous oxide (Entonox: 50% nitrous oxide, 50% oxygen) provides adequate analgesia for colonoscopy and the impact of this agent on recovery.
                All patients undergoing outpatient colonoscopy were considered for the study (n = 248) except those with previous colonic resection. Data for patients unsuitable for randomization (n = 58) and those who declined to participate (n = 88) were also analyzed.
                One hundred two patients were randomized to receive inhaled Entonox alone (n = 56) or intravenous midazolam and meperidine (n = 46). Forty-nine (88%) patients randomized to Entonox underwent complete colonoscopy without conversion to intravenous medications. Entonox patients reported more pain (p < 0.0001), tolerated colonoscopy less well (p < 0.0001), were less satisfied (p = 0.01), and less willing to undergo colonoscopy again under the same circumstances (p = 0.04). Of patients receiving intravenous medication, 91% found colonoscopy less unpleasant and 9% as unpleasant as anticipated; this compares with 52% and 21% Entonox patients, respectively, and an additional 27% Entonox patients who found colonoscopy more unpleasant than anticipated. Recovery was faster among Entonox patients (median 30 versus 60 minutes, p < 0.0001).
                Entonox is less effective than midazolam with meperidine for colonoscopy but is acceptable in many patients and allows faster recovery. We studied the efficacy of adenoidectomy in 213 children who had received tympanostomy-tube placement because of persistent and/or recurrent otitis media and had again developed otitis media after tubal extrusion. Ninety-nine of the children were assigned randomly to either an adenoidectomy group or a control group; in a separate trial, 114 children whose parents withheld consent for randomization were assigned according to parental preference. In both trials, control group outcomes appeared to have been biased favorably by the withdrawal of certain severely affected subjects from control status to receive adenoidectomy. Nonetheless, in both trials, adenoidectomy group outcomes were more favorable than control group outcomes during the first 2 follow-up years. Statistically significant differences were found mainly in the randomized trial, where during the first and second years, respectively, adenoidectomy subjects had 47% and 37% less time with otitis media than control subjects and 28% and 35% fewer suppurative (acute) episodes than control subjects. We conclude that adenoidectomy is warranted on an individualized basis for children who develop recurrent otitis media after extrusion of tympanostomy tubes. To investigate pretrial risk factors and long term mortality (1964-1992) in participants and non-participants of a multifactorial primary prevention trial.
                A prospective study among 3313 initially healthy businessmen. During the 1960s (1964 onwards), 3490 healthy male business executives born between 1919 and 1934 participated in voluntary health checks at the Institute of Occupational Health in Helsinki. From that period cardiovascular disease (CVD) risk factors were available in 3313 men. In the beginning of the 1970s these men were invited to join a multifactorial primary prevention trial of CVD. Six groups were formed: (I) healthy participants in a high risk intervention group (n = 612), and (II) their randomised control group (n = 610); (III) a non-participant low risk group (n = 593); (IV) an excluded group with signs of CVD (n = 563); (V) a refused group (n = 867); and (VI) dead (n = 68). Groups I and II participated in the five year prevention trial which started in 1974. Other groups were followed up through registers, with no personal contact.
                Cardiovascular risk factors during the 1960s. Mortality follow up using national registers up to 31 December, 1992.
                Baseline risk factors were lowest in the low risk group, highest in the excluded group, intermediate and comparable in other groups. Eighteen-year (1974-1992) mortality (per 1000) was 79.3, 106.6, 155.2, 179.9, and 259.3 in the low risk, control, intervention, refused, and excluded groups, respectively (P < 0.001). In the whole population of 3313 men, the 28-year (1964-1992) total (n = 577) and coronary deaths (n = 199) were significantly predicted by smoking, blood pressure, and cholesterol; cancer deaths (n = 163) by smoking only; and violent deaths (n = 83) by none of the risk factors. One-hour postload glucose was significantly associated with total mortality in the intervention group only. When the intervention and control groups were included in the same model, the effect of group on total mortality tended to be dependent on the 1 h blood glucose value (P = 0.06 for the group by 1 h glucose interaction term).
                The traditional risk factors (smoking, blood pressure, and cholesterol) are significantly associated with 28-year mortality in this high social class population with previous health education. Conversely, a "clustering" of low risk factors predicted low total, coronary, and cancer mortality. The findings on 1 h blood glucose suggest that factors related to glucose tolerance explain in part the excess mortality in the intervention group compared with the control group. To compare the acceptability of microwave endometrial ablation using a local anaesthesia/sedation regime or general anaesthesia. To compare recovery following treatment with each type of anaesthetic.
                Prospective randomised controlled trial with follow up of women who declined randomisation.
                The gynaecology department of a large teaching hospital in the UK.
                All women referred for microwave endometrial ablation at the Aberdeen Royal Infirmary between July 1999 and September 2000 without a medical reason to favour one or other type of anaesthetic.
                191 women were equally randomised to undergo microwave endometrial ablation under general or local anaesthesia. Details were also collected for women not randomised because of an anaesthetic preference. All procedures were undertaken in an operating theatre.
                Data collected by questionnaire including the woman's view of treatment acceptability, operative details and post-operative recovery.
                Sixty-nine percent of eligible women would consider treatment under local anaesthesia. Ninety-one percent of microwave endometrial ablation procedures that started under local anaesthesia were completed without conversion to general anaesthesia. Anaesthetic type and allocation by randomisation or preference made no significant difference to the proportion of women describing treatment as totally or generally acceptable at two weeks. Neither parity nor cavity size predicted acceptability. Women allocated general anaesthesia were more likely to describe the procedure as totally acceptable and to choose the same anaesthetic again. There was no significant difference between anaesthetic groups regarding post-operative pain, nausea or recovery time.
                Microwave endometrial ablation under local anaesthesia was acceptable to the majority of women referred for treatment. There was no recovery advantage from local anaesthesia and almost 1 in 10 women who starting treatment under local anaesthesia needed a general anaesthetic because of discomfort. The incidence of post-operative pain and nausea means that treatment with this local anaesthetic/sedation regime remains a day case rather than an outpatient procedure. The authors studied the effect of nitrous oxide on success rates for in vitro fertilization and pregnancy in women undergoing laparoscopy for oocyte retrieval. Ninety-eight patients in an in vitro fertilization program were randomly assigned to an anesthetic regimen including either 0.7% (end-tidal) isoflurane with 60% nitrous oxide in oxygen, or 1.4% (end-tidal) isoflurane in oxygen. Success rates for fertilization and pregnancy in 44 additional patients who declined randomization were also studied. Among the 51 randomized patients who did not receive nitrous oxide, 192 oocytes were obtained and 122 fertilized (63.5%), resulting in eight pregnancies (16.3%). From the 47 randomized patients given nitrous oxide, 168 oocytes were retrieved and 114 fertilized (67.9%), resulting in nine pregnancies (19.1%). No significant differences between rates of fertilization or pregnancy emerged between groups. Such differences would have been found with an 80% probability had nitrous oxide had a 20% effect on oocyte fertilization. The recently reported VA Cooperative Study "A Randomized Clinical Trial of Total Parenteral Nutrition (TPN) in Malnourished Surgical Patients" randomized 395 pre-operative patients to TPN treatment or control. The study concluded that the use of perioperative TPN should be limited to the most severely malnourished patients. The study also followed 233 patients eligible for the study who refused to give informed consent for randomization (Eligible Refusers) as well as 1220 patients who were ineligible because they were not sufficiently malnourished (Index Group). Patients in the Index Group were determined to be significantly healthier than those in the two eligible groups of patients. Those in the Eligible Refuser group were shown to be slightly less malnourished than the Randomized Patients. The 395 patients randomized to the study (Randomized Patients) showed the highest rate of septic complications at 30 days and at 90 days (10% and 13% respectively) with rates for the Eligible Refusers slightly lower (8% and 9%) and Index Group rates still lower (4% and 4%). Nonseptic complication rates showed the same pattern (19% and 22% for the Randomized group, 12% and 12% for Eligible Refusers, and 10% and 10% for the Index Group). Because (a) the beneficial effect of TPN is attained only in severely malnourished patients, (b) there is increased risk of septic complications with TPN use in patients not severely malnourished, (c) Index Group patients, and presumably the population of patients from which they are drawn, are not severely malnourished, it follows that unless specifically indicated, TPN should not be used in nonseverely malnourished patients. There is a mismatch between the wish of a patient with depression to have counselling and the prescription of antidepressants by the doctor.
                To determine whether counselling is as effective as antidepressants for depression in primary care and whether allowing patients to choose their treatment affects their response.
                A partially randomised preference trial, with patients randomised to either antidepressants or counselling or given their choice of either treatment. The treatment and follow-up were identical in the randomised and patient preference arms.
                There were 103 randomised and 220 preference patients in the trial. We found: no differences in the baseline characteristics of the randomised and preference groups; that the two treatments were equally effective at 8 weeks, both for the randomised group and when the randomised and patient preference groups for a particular treatment were combined; and that expressing a preference for either treatment conferred no additional benefit on outcome.
                These data challenge several assumptions about the most appropriate treatment for depression in a primary care setting. It has been postulated that treatment with nicotinamide may prevent or delay the onset of insulin dependent diabetes mellitus. We report the findings of a population based diabetes prevention trial which tests this hypothesis. 33,658 school children aged 5-7.9 years were randomly selected (by school) from a total population of 81,993 of such children in the Auckland (New Zealand) region. They were offered testing for islet cell antibodies. 20,195 (60%) consented to testing. Of these 185 had islet cell antibodies and met the criteria for treatment with nicotinamide. 173 received this treatment. The study population has an average follow up time of 7.1 years. The diabetes incidence of the untested controls was: 16.07 (12.4-20.5 95% CI) /100,000 person years at risk; in the group who were tested and treated when deemed appropriate: 7.14 (3.1-14.1 95% CI); and in the group offered testing but who did not consent ("refusers'): 18.48 (10.1-31.0 95% CI). The tested group had a rate of diabetes of 41% (20-85 95% CI) of the other groups combined after an age adjustment, which is significant (p = 0.008). The tested group combined with the "refuser' group (i.e. "intention to treat') also has a lower incidence than the control group (p = 0.12). Nicotinamide has a protective effect against the development of insulin dependent diabetes in this setting but the size of the effect has a wide confidence interval. Further follow up may define the magnitude of the protective effect within narrower limits. To compare quality of life and exercise capacity (primary aim), and drug usage (secondary aim), between groups of patients with irreversible chronic airflow limitation (CAL) who were undergoing theophylline Theo-Dur; Key Pharmaceuticals; Kenilworth, NJ) therapy guided by n of 1 trials or standard practice.
                Randomized study of n of 1 trials vs standard practice.
                Outpatient departments in two tertiary care centers.
                Sixty-eight patients with irreversible CAL who were symptomatic despite the use of inhaled bronchodilators, and who were unsure whether theophylline was helping them following open treatment, were randomized into n of 1 trials (N=34) or standard practice.
                The n of 1 trials (single-patient, randomized, double-blind, multiple crossover comparisons of the effect on dyspnea of theophylline vs a placebo) followed published guidelines. Standard practice patients stopped taking theophylline but resumed it if their dyspnea worsened. If their dyspnea then improved, theophylline was continued. In both groups, a decision about continuing or stopping the use of theophylline was made within 3 months of randomization.
                The primary outcomes (the chronic respiratory disease questionnaire [CRQ] and 6-min walk) were measured at baseline, 6 months, and 12 months by personnel blinded to treatment group allocation. No between-group differences (n of 1 minus standard practice) were seen in within-group changes over time (1 year minus baseline) in the CRQ Physical Function score (point estimate on the difference, -2.8; 95% confidence limits [CLs], -8.2, 2.5), CRQ Emotional Function score (point estimate on the difference, 0.5; 95% CLs, -4.7, 5.7), or 6-min walk (point estimate on the difference, 8 m; 95% CLs, -26, 44 m). No differences between groups were seen in the secondary outcome of the proportion of patients taking theophylline at 6 and 12 months. In 7 of 34 n of 1 trial patients (21%), dyspnea improved during theophylline treatment compared with placebo treatment.
                Using n of 1 trials to guide theophylline therapy in patients with irreversible CAL did not improve their quality of life or exercise capacity, or reduce drug usa e, over 1 year compared to standard practice. Under the objective conditions of an n of 1 trial, 21% of patients with CAL responded to theophylline. There remains a rationale for considering theophylline in patients with irreversible CAL who remain symptomatic despite the use of inhaled bronchodilators, but the use of n of 1 trials to guide this decision did not yield clinically important advantages over standard practice. One of the goals of study AMA-BFM-87 was to test prospectively in acute myelogenous leukemia (AML) patients if cranial irradiation could be replaced by late intensification therapy with high-dose cytarabine (Ara-C) and etoposide (VP-16).
                Patients with a low risk of CNS relapses (ie, no initial CNS disease, WBC count at diagnosis < or = 70.000/microL) were randomized for irradiation (group A, 31 patients). In 25 patients (group B), randomization was refused. As interim results showed no increase of CNS relapses in nonirradiated patients, prophylactic irradiation was discontinued after 2 1/2 years to prevent unnecessary CNS toxicity. Forty-four patients (group C) entered the study after randomization had been stopped.
                In all patients with a low risk of CNS recurrences (n = 100), a significantly higher probability of relapse-free interval (pRFI) of 5 years was found in irradiated patients (pRFI = .78) compared with nonirradiated patients (pRFI = .41) (P = .007). Moreover, a slightly higher incidence of CNS relapses was observed in nonirradiated patients. Due to the small number of patients, this was not observed when randomized patients only were analyzed. In accordance with these findings, the favorable outcome of low-risk patients in the preceding study, AML-BFM-83 (pRFI > .80), could only be reproduced in study AML-BFM-87 in patients who had received cranial irradiation.
                These results indicate that cranial irradiation should be an integral part of the treatment of all AML patients not undergoing bone marrow transplantation. Residual blasts in the CNS may escape systemic chemotherapy and lead to recurrence of the initial disease not only in the CNS, but also in the bone marrow. To compare outcomes between groups of patients with irreversible chronic airflow limitation given theophylline by n of 1 trials or standard practice.
                Randomised controlled study of n of 1 trials versus standard practice.
                Tertiary care center outpatient department.
                31 patients with irreversible chronic airflow limitation who were unsure that theophylline was helpful after an open trial.
                n Of 1 trials (single patient randomised multiple crossover comparisons of theophylline against placebo) followed published guidelines. For standard practice patients theophylline was stopped and resumed if their dyspnoea worsened; if their dyspnoea then improved theophylline was continued. For both groups a decision to continue or stop the drug was made within three months of randomisation.
                Exercise capacity as measured by six minute walking distance, quality of life as measured by the chronic respiratory disease questionnaire at baseline and six months after randomisation, and proportions of patients taking theophylline at six months.
                26 patients completed follow up. 47% fewer n of 1 trial patients than standard practice patients were taking theophylline at six months (5/14 versus 10/12; 95% confidence interval of difference 14% to 80%) without differences in exercise capacity or quality of life.
                n Of 1 trials led to less theophylline use without adverse effects on exercise capacity or quality of life in patients with irreversible chronic airflow limitation. These data directly support the presence of a clinically important bias towards unnecessary treatment during open prescription of theophylline for irreversible chronic airflow limitation. Confirmation in a larger study and similar studies for other problems appropriate for n of 1 trials are needed before widespread use of n of 1 trials can be advocated in routine clinical practice. Patient preferences play an important role when choosing between different treatment options and may have an influence on outcome. We performed a study to investigate (1) to what extent patients make use of the offer to receive acupuncture as a pretreatment for gastroscopy, (2) whether this is perceived as being as effective as sedation, and (3) whether characteristics and outcomes differ between patients giving consent to random allocation and patients choosing their pretreatment.
                Partially randomized patient preference trial. Patients who gave consent to randomization were allocated randomly while patients who had a preference received the treatment of their choice.
                One hundred and six (106) inpatients of a district hospital in southern Germany undergoing gastroscopy for diagnostic purposes.
                Pretreatment with a sedative (midazolam) or acupuncture.
                Patient's overall assessment on a visual analogue scale (VAS).
                Twenty-eight (28) patients (26%) agreed to be randomized, 21 (20%) chose acupuncture, 51 (47%) midazolam, and 8 (7%) did not want pretreatment. Patients receiving midazolam rated the examination as slightly less troublesome than those receiving acupuncture. Oxygen saturation, blood pressure, and heart rate were significantly lower in patients receiving midazolam. Characteristics and outcomes of randomized and nonrandomized patients did not differ significantly.
                Because of the low number of patients giving consent to random allocation conclusions on effectiveness are difficult to draw. The partially randomized patient preference design is recommended for use in future trials of acupuncture for gastroscopy. Such trials should be performed in an outpatient setting. To evaluate five different preoperative anxiolytic regimens in cataract surgery performed under regional anesthesia; to quantify the pain associated with combined peri- and retrobulbar injection (PRBI) of local anesthetic drugs; and to describe a technique of painless eye block.
                Randomized, double blind, placebo-controlled study.
                Private clinic.
                376 ASA I and II patients presenting for cataract surgery.
                Patients were extensively briefed by the nursing staff on the various procedures. Of the 376 study patients, 136 preferred to have no anxiolytic drug. The remaining 240 patients were randomly allocated to one of six groups to receive either 3 mg of bromazepam, 6 mg of bromazepam, 0.5 mg of alprazolam, 1 mg of alprazolam, 5 mg of diazepam, or a placebo on a double-blind protocol. All patients received a standard combined peri- and retrobulbar eye block (PRBB) before surgery.
                Anxiety at various stages of the procedure and PRBB were measured on visual analog scale (0-10). PRBB pain was compared with pain of intravenous (i.v.) cannula placement. On admission, anxiety of the 136 patients who preferred no anxiolytic premedication was significantly less than that of the 240 patients assigned to one of the six treatment groups (p < 0.05). There was no difference between the six treatment groups in reported anxiety before surgery (p > 0.05) except for Group 1 (3 mg bromazepam), where anxiety increased before and during PRBB administration (p < 0.05). In all six treatment groups, anxiety decreased significantly 30 minutes after medication was administered (p < 0.05). For the total group, 61.18% of patients reported more or equal pain associated with the placement of the 20-gauge i.v. cannula than by the PRBB. Of the patients who received medication, 94% stated that, should they require another eye operation, they would like the same anxiolytic treatment. No patient requested general anesthesia for their next operation or to be rendered unconscious for PRBB.
                1. There was interpersonal variation in the level of preoperative anxiety. 2. In patients who were anxious, the anxiolytic drugs and placebo decreasedanxiety although the level of anxiety did not differ between the anxiolytic drugs or between placebo and the anxiolytic drugs. The only difference was in Group 1 patients (3 mg promazepam), who reported slightly increased anxiety before and during PRBB administration (p < 0.05). 3. Placement of the PRBB is less painful than the insertion of a 20 g i.v. cannula. The Bypass Angioplasty Revascularization Investigation (BARI) included 4039 patients with multivessel coronary artery disease; 1829 consented to randomization, and 2010 did not but were followed up in a registry. Thus, we can evaluate the outcome of physician-guided versus random assignment of percutaneous transluminal coronary angioplasty (PTCA) versus coronary artery bypass graft surgery (CABG).
                We compared the baseline features and outcomes for PTCA and CABG in the overall registry and its predesignated subgroups. We assessed the impact of treatment by choice versus random assignment by comparing the results in the registry with those of the randomized trial. Statistical adjustments for differences in baseline characteristics were made. Within the registry, nearly twice as many patients were selected for PTCA (1189) as CABG (625); mortality at 7 years was similar for PTCA (13.9%) and CABG (14.2%) (P=0.66) before and after adjustment for baseline differences between patients selected for PTCA versus CABG (adjusted RR, 1.02; P=0.86). In contrast to the randomized trial, the 7-year mortality rate of treated diabetics in the registry was equally high (26%) with PTCA or CABG. Seven-year mortality was higher for patients undergoing PTCA in the randomized trial than in the registry (19.1% versus 13.9%, P<0.01) but not for those undergoing CABG (15.6% versus 14.2%, P=0.57). The adjusted relative mortality risk for PTCA in the randomized versus registry population was 1.17 (P=0.16).
                BARI physicians were able to select PTCA rather than CABG for 65% of registry patients who underwent revascularization without compromising long-term survival either in the overall population or in treated diabetics. To study the effectiveness and acceptability of day case hysteroscopic surgery.
                Prospective randomised controlled trial.
                Aberdeen Royal Infirmary.
                One hundred and ninety four consecutive women who underwent hysteroscopic endometrial ablation.
                Seventy three women were allocated to day case surgery and 37 to inpatient admission; 84 women though otherwise fit for day case surgery were scheduled for in-patient admission as they lived more than 20 miles away. All women completed a questionnaire 24 h after their operations. Readmission rates were obtained from case notes. Satisfaction rates 12 months after the operation were recorded by means of a follow-up questionnaire.
                Post-operative pain was absent or slight in 48 (75%) of the women in the day case group 27 (84%) of women in the in-patient group, and 55 (82%) in the non-randomised in-patient group. Post-operative analgesia was necessary in 34 (52%) women in the day case group, 24 (75%) women in the in-patient group and 36 (53%) women in the non-randomised in-patient group. Hospital costs were significantly less in the day case group. Satisfaction with stay 92% in the day case group, and 100% in the other two groups.
                In this setting, day care is a safe acceptable and less expensive alternative to in-patient care for hysteroscopic endometrial ablation. We did a prospective study of women with singleton viable pregnancies at 10-13 weeks' gestation who requested first-trimester fetal karyotyping because of advanced maternal age, parental anxiety, or family history of chromosomal abnormality. Women were counselled as to the available options of non-invasive screening or invasive testing by mid-trimester amniocentesis, early amniocentesis (EA), or chorionic villus sampling (CVS), or randomisation to EA or CVS at 10-13 weeks. EA was done in 731 patients (493 by choice and 238 by randomisation) and CVS in 570 (320 by choice and 250 by randomisation). Both procedures were done by transabdominal ultrasound-guided insertion of a 20-gauge needle. The rate of successful sampling was the same for both procedures (97.5%). Spontaneous loss (intrauterine or neonatal death) was significantly higher after EA (total group mean = 5.3%, 95% CI 3.8-7.2; randomised subgroup mean = 5.9%, 3.3-9.7) than after CVS (total group: mean = 2.3%, 1.2-3.9; randomised subgroup: mean = 1.2%, 0.3-3.5). The gestation at delivery and birthweight of the infants after EA and CVS were similar. In the EA group the incidence of talipes equinovarus (1.63%), was higher than in the CVS group (0.56%), but this difference was not significant. To examine whether written informed consent might influence the results of clinical trials the effect of placebo when given with or without informed consent to patients suffering from insomnia was studied. The study was a single blind observer blinded trial, and patients were paired according to sex, age, and hospital environment. Randomisation assigned the first patient of each pair to the control group (without informed consent) or the group to give informed consent. Of the 56 patients, 26 refused to give informed consent, and the age and sex distribution of these differed significantly (p less than 0.02) from the 30 pairs of patients ultimately enrolled into the study. In this "biased" sample, the hypnotic activity of placebo was significantly higher in the control group (p less than 0.05). It is concluded that the informed consent procedure biases the results of clinical trials and might affect their general applicability. The aim of this study was to evaluate a model of routine pre-IVF counselling focusing on the narrative capacities of couples. The acceptability of counselling, the effects on emotional factors and the participants' assessments were considered.
                The study included 141 consecutive childless couples preparing for their first IVF. Randomization was carried out through sealed envelopes attributing participants to counselled and non-counselled groups and was accepted by 100 couples. Another 12 couples refused randomization because they wanted counselling and 29 because they did not. Questionnaires including the State-Trait Anxiety Inventory, the Beck Depression Inventory and assessments of help were mailed to couples before IVF and counselling, and after the IVF outcome.
                Counselling was accepted by 79% (112/141) of couples. There was no significant effect of counselling on anxiety and depression scores which were within normal ranges at both times. Counselling provided help for 86% (75/87) of initially non-demanding subjects and 96% (25/26) of those initially requesting a session. Help was noted in areas of psychological assistance, technical explanations and discussing relationships.
                This model of routine counselling centred on the narrative provides an acceptable form of psychological assistance for pre-IVF couples. The Multicenter Australian Study of Epidural Anesthesia and Analgesia in Major Surgery (The MASTER Trial) was designed to evaluate the possible benefit of epidural block in improving outcome in high-risk patients. The trial began in 1995 and is scheduled to reach the planned sample size of 900 during 2001. This paper describes the trial design and presents data comparing 455 patients randomized in 21 institutions in Australia, Hong Kong, and Malaysia, with 237 patients from the same hospitals who were eligible but not randomized. Nine categories of high-risk patients were defined as entry criteria for the trial. Protocols for ethical review, informed consent, randomization, clinical anesthesia and analgesia, and perioperative management were determined following extensive consultation with anesthesiologists throughout Australia. Clinical and research information was collected in participating hospitals by research staff who may not have been blind to allocation. Decisions about the presence or absence of endpoints were made primarily by a computer algorithm, supplemented by blinded clinical experts. Without unblinding the trial, comparison of eligibility criteria and incidence of endpoints between randomized and nonrandomized patients showed only small differences. We conclude that there is no strong evidence of important demographic or clinical differences between randomized and nonrandomized patients eligible for the MASTER Trial. Thus, the trial results are likely to be broadly generalizable. In clinical research, randomized trials are widely accepted as the definitive method of evaluating the efficacy of therapies. Random assignment of patients to treatment ensures internal validity of the comparison of new treatments with controls. An assessment of external validity can best be achieved by comparing the randomized study sample to the population of patients who met the eligibility criteria but did not consent to randomization. The Comprehensive Cohort Study (CCS) is designed to recruit all patients fulfilling the clinical eligibility criteria regardless of their consent to randomization. The CCS concept was adopted in the major clinical trials of the German Breast Cancer Study Group (GBSG) conducted between 1983 and 1989. In this period 124 centres recruited 2084 patients in three clinical trials. 734 (35 per cent) of these patients accepted being randomized, while 1350 (65 per cent) chose one of the treatments under study; the randomization rates differed remarkably between trials. In this paper we examine the representativeness of the randomized patients in the three trials. Based on a median follow-up of about 5 years we present results on the external validity of the treatment effects estimated in the randomized patients by means of Cox's proportional hazards model and compare them between trials. We discuss advantages and disadvantages of the CCS design and conclude that its use is only justified under extraordinary circumstances. Prior endoscopic studies evaluating conscious sedation have recruited only a small proportion of the patients actually approached. The generalizability of such results to an unselected adult ambulatory care population is thus questionable. The objectives of this study were to determine the characteristics of patients who refused inclusion in a randomized controlled trial of sedation and to compare these characteristics to those of patients who agreed to participate.
                Patients who refused participation in a randomized controlled trial of sedation completed standardized questionnaires addressing demographic data and possible confounding variables, and they also completed a validated anxiety questionnaire. Characteristics associated with refusal to participate in the randomized controlled trial were assessed by using uni- and multivariate analysis. Exploratory comparisons of outcomes between both groups included self-reported satisfaction with level of comfort and technical adequacy.
                Of 302 patients screened, 203 refused to participate in the randomized controlled trial. The most common reason for refusal was the request for no sedation (135/203). A total of 163 were enrolled in this synchronous study. Patients who refused to participate exhibited 3 distinguishing characteristics: prior treatment for an anxiety disorder (risk difference 9.4%: 95% CI[3%, 17%]), use of analgesic medication (risk difference 10.4%: 95% CI[2%, 19%]), and prior experience with EGD (risk difference 17.9: 95% CI[5%, 30%]). Only upper endoscopy experience was predictive of refusal to participate in the randomized controlled trial. No differences in outcomes existed between patients randomized to sedation and those refusing the randomized controlled trial who chose to receive sedative medication. Patients who refused participation in the randomized controlled trial and who underwent upper endoscopy without sedation were more satisfied than patients randomized to placebo (1.33 vs. 2.58; risk difference -1.25: 95% CI[-0.38, -2.1]). Moreover, the procedure in these patients was more adequate technically (4.86 vs. 4.18; risk difference 0.68: 95% CI[0.21, 1.13]).
                Characteristics of patients accepting and refusing randomization were highly similar, differing only with regard to upper endoscopy experience. An exploratory analysis of outcomes suggests that randomized controlled trial results may be biased in a direction that may underestimate the benefits of not administering sedative medication in a real-life setting. The intergroup study of involved-field (IF) radiotherapy, IF radiotherapy plus MOPP chemotherapy, and extended-field (EF) radiotherapy for treatment of Hodgkin's disease in children has assessed 305 patients. Of these, 279 were "not ineligible" (no mediate cause for disqualification). Among 223 randomized patients, 144 were evaluable, 131 had documentation of complete or partial remission, 20 of the remitters relapsed, and two died. Among 62 nonrandomized patients with favorable presentations (unilateral upper neck, unilateral inguinal, or massive mediastinal disease), 29 had documented remission, two relapsed, and none died. Length of initial disease control (LIDC) was used to measure duration of response. LIDC was best in patients given IF plus MOPP, and 95% are disease free. EF was better than IF radiotherapy (P = 0.004). Of the disease characteristics prognostic for response (stage, histologic subtype, and presence of symptoms), only the last factor had a statistically significant effect on LIDC (P = 0.004). Ninety-six percent of the patients survive. Using criteria developed by the committee, 23% of the staging procedures reviewed were nonevaluable and 28% of the radiotherapy treatments were nonevaluable. The necessity for criteria for evaluation of staging and treatment is certain. Length of followup is too short for correlations of treatment with significant late effects and for relevant therapeutic recommendations. To evaluate the use of intravenously administered immune globulin (IVIG) for prevention of sepsis in preterm infants, we administered IVIG in a protocol designed to maintain a therapeutic serum "target level" of 700 mg/dl. The 200 patients who were eligible for the study (600 to 2000 gm birth weight) were monitored throughout their initial hospitalization. Of these, 115 patients were randomly assigned in a double-blind, controlled trial to treatment and placebo groups. The remaining 85 infants were not randomly assigned to a group, by parental request, but were followed and analyzed separately. In one patient who received IVIG, transient tachycardia and a decrease in blood pressure developed during an infusion; resolution occurred promptly after the infusion was discontinued. No persistent hepatic or renal abnormalities were noted in either the IVIG- or the placebo-treated group. There were seven episodes of sepsis in the placebo group and nine in the group whose parents refused consent to the study. No infant who received IVIG acquired nosocomial sepsis (p less than 0.01). All patients in the placebo group in whom sepsis developed had serum IgG levels less than 400 mg/dl at the time sepsis developed. Serum IgG levels were maintained near 700 mg/dl in patients who received IVIG. These data indicate that administration of sufficient IVIG to maintain target serum IgG levels throughout hospitalization may decrease the incidence of nosocomial sepsis in preterm infants. Patient-controlled sedation (PCS) with propofol, is well tolerated and reduces recovery time and staff required during endoscopic interventions. "Who" administers the drug proves economically crucial. With the aim of maintaining safety, medical quality, and patient satisfaction, this study investigates PCS versus nurse-administered propofol sedation (NAPS) in a cohort of consecutive patients.
                One hundred and fourteen patients, aged 22-90 yr, undergoing only colonoscopy participated in this prospective randomized trial. Patients were randomly assigned to either PCS or NAPS. If patients declined randomization for different reasons of reluctance to PCS they were assigned to a standard nurse-sedated control group. All patients received pethidine presedation for analgesia. Visual analogue scales followed patient anxiety level, tolerability, pain, and satisfaction, and endoscopist's assessment of the procedure.
                Given the choice, 35% of the patients who were rather younger and more anxious declined randomization to PCS. The mean total dose of propofol needed in this group was higher, but the patients had a tendency to rate the global tolerance and the pain of the examination as less comfortable compared to the two randomized groups. Self-administration of propofol created a significantly different drug profile and higher medication costs. With regard to the safety parameters there was no difference between PCS and NAPS. In their global assessments, the patients and endoscopists tended to prefer NAPS.
                Individual patient characteristics and attitudes toward self-control are crucial for PCS. While being a viable option for patients who are able and willing to handle, this technique is not applicable in a considerable portion of everyday patients. To study the fracture reducing potential of hormonal replacement therapy (HRT) in recent postmenopausal women in a primary preventive scenario.
                Prospective controlled comprehensive cohort trial: 2016 healthy women aged 45-58 years, from three to 24 months past last menstrual bleeding were recruited from a random sample of the background population. Mean age was 50. 8+/-2.8 years, and the number of person years followed was 9335.3. There were two main study arms: a randomised arm (randomised to HRT; n=502, or not; n=504) and a non-randomised arm (on HRT; n=221, or not; n=789 by own choice). First line HRT was oral sequential oestradiol/norethisterone in women with intact uterus and oral continuous oestradiol in hysterectomised women.
                After five years, a total of 156 fractures were sustained by 140 women. There were 51 forearm fractures in 51 women. By intention-to-treat analysis (n=2016), overall fracture risk was borderline statistically significantly reduced (RR=0.73, 95% CI: 0.50-1.05), and forearm fracture risk was significantly reduced (RR=0.45, 95% CI: 0.22-0.90) with HRT. Restricting the analysis to women who had adhered to their initial allocation of either HRT (n=395) or no HRT (n=977) showed a significant reduction in both the overall fracture risk (RR=0.61, 95% CI: 0.39-0.97) and the risk of forearm fractures (RR=0.24, 95% CI: 0.09-0.69). Compliance with HRT was 65% after five years.
                It is possible to reduce the number of forearm fractures and possibly the total number of fractures in recent postmenopausal women by use of HRT as primary prevention. To determine whether postoperative forced-air warming of cardiac bypass patients in the intensive care unit (ICU) results in faster rate of warming and improved outcomes compared with more conventional ICU warming methods.
                Prospective randomized effectiveness study.
                Three hundred fifty-bed university-affiliated hospital.
                Sixty consenting randomized patients from a consecutive series of 84 patients undergoing routine adult cardiac surgery.
                One group of patients received usual patient care, which includes warm blankets and overhead heat lamps. Patients in the other group were placed under forced-air warming devices on arrival in the ICU. Sixty consenting patients (30 in each group) were randomly assigned to one or the other method of warming. The remaining 24 patients refused randomization and self-selected a treatment group.
                Results are presented for the randomized groups. Core temperature, measured by pulmonary artery catheter thermistor, increased in both groups at the rate of 0.25 degree C per hour. No statistically or clinically significant differences were found between the group for whom the warming device was used and the standard care group in the incidence of postoperative cardiac arrhythmia, duration of time in the ICU, or any other clinical variable.
                There is no evidence from this study to warrant use of forced-air warming devices for the care of postoperative cardiac surgical patients in the ICU. To compare the efficacy of antidepressant drugs and generic counselling for treating mild to moderate depression in general practice. To determine whether the outcomes were similar for patients with randomly allocated treatment and those expressing a treatment preference.
                Randomised controlled trial, with patient preference arms. Follow up at 8 weeks and 12 months and abstraction of GP case notes.
                31 general practices in Trent region.
                Patients aged 18-70 who met research diagnostic criteria for major depression; 103 patients were randomised and 220 patients were recruited to the preference arms.
                Difference in mean Beck depression inventory score; time to remission; global outcome assessed by a psychiatrist using all data sources; and research diagnostic criteria.
                At 12 months there was no difference between the mean Beck scores in the randomised arms. Combining the randomised and patient preference groups, the difference in Beck scores was 0.4 (95% confidence interval -2.7 to 3.5). Patients choosing counselling did better than those randomised to it (mean difference in Beck score 4.6, 0.0 to 9.2). There was no difference in the psychiatrist's overall assessment of outcome between any of the groups. 221/265 (83%) of participants with a known outcome had a remission. Median time to remission was shorter in the group randomised to antidepressants than the other three groups (2 months v 3 months). 33/221 (15%) patients had a relapse.
                Generic counselling seems to be as effective as antidepressant treatment for mild to moderate depressive illness, although patients receiving antidepressants may recover more quickly. General practitioners should allow patients to have their preferred treatment. Patients with poorly differentiated prostatic carcinoma and skeletal metastases were randomized to treatment with 2.6-cis-diphenylhexamethylcyclotetrasiloxane (2.6-cis) and estramustine-17-phosphate (estramustine). Parallel with the clinical study a group of non-randomized patients were treated with 2.6-cis. Cytological regression of the tumor could be registered in half of the estramustine group but not in the 2.6-cis group. There were no drug-related changes in blood chemistry, kidney function tests, hematology or liver enzymes. There was in increase in acid and alkaline phosphatase in both groups but more pronounced in the 2.6-cis group. In both groups follicle-stimulating and luteinizing hormone values were depressed. Testicular and penis atrophy was observed in the 2.6-cis group. Relief of pain and marked improvement of conditions occurred in the majority of the cases in both groups. In general, no tumor regression was observed during administration of 300 mg. 2.6-cis daily for at least 3 months. Some tumor regression was noted during 600 mg. estramustine therapy daily. The aim of the study was to compare satisfaction with medical and surgical abortion and to identify potential confounders affecting satisfaction.
                1033 women with gestational age (GA) < or = 63 days had either a medical (600 mg mifepristone followed by 1 mg gemeprost) or a surgical abortion (vacuum aspiration in general anaesthesia). The procedure was determined either by randomization (n = 111) or by choice (n = 922). Data on satisfaction, side effects and expectations were collected from questionnaires 2 and 8 weeks after termination.
                More women were very satisfied or satisfied after a surgical than a medical abortion both after choosing method (92% vs 82%, P < 0.0001), and after randomization (94% vs 68%, P < 0.001). Satisfaction was higher after choosing a medical procedure than after randomization to the same procedure; 82% and 68%, respectively, P < 0.05. Satisfaction with the medical procedure was inversely correlated with GA and the intensity of pain, nausea, vomiting and dizziness, while satisfaction with the surgical procedure was unaffected by these side effects. Fewer women with a failed medical than a failed surgical abortion were satisfied (17% vs 62%), P < 0.05.
                Satisfaction with both medical and surgical abortions is high, although higher with the surgical than the medical procedure, and higher after choosing method than after randomization. Fifty-seven patients with cervical bruits and abnormal ocular pneumoplethysmography but without symptoms were followed prospectively. Mean follow-up was 32 months and all patients were followed for at least 1 year. Twenty-nine patients consented to join a randomized study comparing treatment with aspirin, close follow-up, and no intervention unless symptoms developed [( NI: ASA] n = 14) versus intervention with arteriography and prophylactic surgery [( I: A/S] n = 15). Among patients who refused randomization, 14 were treated with NI: ASA and 14 with I: A/S. Endpoints for analysis included all unfavorable outcomes related to both management plans and included stroke, death of stroke, major angiographic and perioperative complications, asymptomatic carotid occlusion, and recurrent carotid artery stenosis. In both the randomized and nonrandomized portions of the study unfavorable outcomes were more frequent in patients treated with I: A/S, and by combining the results of both studies a significant difference was observed (N: ASA - 3.6% versus I: A/S - 31%; X:2 = 4.78; p less than 0.05). Among patients treated with NI: ASA, a single minor stroke occurred without warning. In patients from all groups who underwent arteriography, advanced carotid stenosis was found in 78% (mean percent diameter stenosis = 72% +/- 2%; mean residual lumen = 1.3 +/- 0.1 mm). We conclude that, despite the probability of underlying severe carotid stenosis, most patients with cervical bruit and abnormal ocular pneumoplethysmography but without symptoms are appropriately managed without intervention unless symptoms develop. We have previously shown that the preemptive use of cytomegalovirus (CMV) immunoglobulin (Ig) replacement (CytoGam) decreases the incidence of opportunistic infections in cardiac transplant recipients with severe hypogammaglobulinemia. However, the impact of Ig replacement in moderately hypogammaglobulinemic patients is unknown.
                Periodic monitoring of the IgG levels was done in 300 heart transplant recipients. Moderate hypogammaglobulinemia (IgG, 350-500 mg/dl) developed in 56 patients (18.6%). Thirty-three patients declined randomization but agreed to have their IgG levels monitored. Twenty-three patients were randomized to placebo (n = 10) or CytoGam (n = 13) at 105 +/- 63 days after transplantation.
                The baseline characteristics were similar. A significant reduction in CMV infection was noted in the CytoGam Group compared with the Placebo Group (15.4% [2/13] vs 60% [6/10], p = .039). Among patients who declined randomization, CMV infection developed in 13 (39.4%) of 33, and 6 (46.1%) of the 13 progressed to severe hypogammaglobulinemia. A trend for reduction in the average episodes of > or =grade 2 rejection during the 6-month period after randomization was noted in the CytoGam group (0.4 +/- 0.6 vs 1.4 +/- 1.3, p = 0.065).
                The preemptive use of CytoGam decreases the incidence of CMV infection in patients with moderate hypogammaglobulinemia. A larger randomized study is needed to substantiate these results. A (semi-) randomized controlled study with long-term follow-up was conducted to compare the effects of transabdominal chorionic villus sampling and early amniocentesis on fetal mortality and child morbidity. Women requesting early prenatal diagnosis for advanced maternal age were allocated to early amniocentesis or transabdominal chorionic villus sampling either by randomization or, if they declined randomization, by their own choice. Of the 212 women who entered the study, 117 were randomized, 70 chose early amniocentesis and 25 chose transabdominal chorionic villus sampling. Overall, 130 women underwent early amniocentesis and 74 underwent transabdominal chorionic villus sampling at a median gestation of 12 weeks. Two women were excluded because of fetal death before the procedure. Mosaic karyotypes were found in 5.4 per cent of the early amniocenteses and in none of the chorionic villus samples. All unintended fetal losses occurred after early amniocentesis with a frequency of 6.2 per cent (95 per cent confidence interval: 2.7 per cent to 11.8 per cent). Talipes equinovarus was only observed after early amniocentesis with a frequency of 3.1 per cent (95 per cent confidence interval: 0.8 per cent to 7.7 per cent). We conclude that chorionic villus sampling remains the method of choice if prenatal diagnosis is needed in the first trimester of pregnancy. In parallel with a randomized study of the 'starting again' rehabilitation program for cancer patients, a group of 73 non-participants were monitored (another 20 patients declined monitoring). In comparison with participants (intervention + control), gender, diagnosis, and 10 out of 18 dependent measures differed significantly at baseline. The non-participants group included more men, mostly with cancer of the prostate and irrespective of gender, they showed lower problem levels than participants throughout. Thus, the wish to participate seems to be an indicator of the need for assistance in the rehabilitation process. Social validation of effects was performed by comparing the non-participants with the intervention group. The rationale for this comparison is that non-participants presumably felt so well that they were in no need of rehabilitation. Effects on three variables were socially validated: patients' appraisal of having received sufficient information, physical strength and fighting spirit. No negative effects on outcome variables resulting from being randomized to the control condition (resentful demoralization) were detected when non-participants were compared with controls over one year. Further analysis showed that although a few patients in the control group may have experienced resentful demoralization, this did not significantly affect the outcome variables. The first objective of this study was to analyze the survival rate in a group of 69 breast cancers detected among nonattenders in a randomized mammographic screening trial in relation to 142 clinically detected cancers in a nonscreened control population. By analyzing the cancers of the nonattenders we identified two subgroups, one (A) had actively avoided mammography, had cancers in more advanced stages on diagnosis, and had significantly higher mortality from breast cancer than the control group (p = 0.003). The second subgroup (B) had mammography done outside the screening program. This subgroup had a nonsignificant, slightly better survival (p = 0.19) compared to the control group. Concerning stage the cancers in group B were similar to the cancers by the screening program. The second objective was to analyze women's reasons for nonattendance in the screening program. We interviewed 200 randomly selected nonattenders; 33% stated that they never could imaging having mammography (definite nonattenders), 29.5% that they for various reasons had missed the mammography but could imagine having it next time (possible future attenders), and 32% had been examined outside the program. Reasons for nonattendance included disinterest, medical problems, and fear of X-rays. From this interview investigation we believe that the subgroup of definite nonattenders (33%) is difficult to influence. The second subgroup classified as possible future attenders (29.5%) we believe can be influenced by more information and a new opportunity to receive mammography, i.e., a reminder letter. The third subgroup, those examined outside the screening program (32%) were aware of the benefit of mammography, taking action on their own.(ABSTRACT TRUNCATED AT 250 WORDS) To test whether emergency revascularization improves survival in patients with acute myocardial infarction and shock.
                Patients with acute myocardial infarction and early shock were randomized either to undergo emergency angiography, followed immediately by revascularization when indicated, or to receive initial medical management. In five of the nine participating centres, patients with shock but not randomized were entered in a registry. Only 55 patients could be randomized. Of the 32 patients in the invasive group, 30 (94%) underwent early angiography, 27 (84%) PTCA, and one (4%) CABG. Twenty-two (69%) died within 30 days in the invasive group vs 18/23 (78%) in the medically managed group (ns, RR=0.88, 95% confidence interval 0.6-1.2). Among the registry patients, 24/51 were excluded from randomization solely because of patient or physician preference for the invasive approach: 23 (96%) of them underwent emergency angiography, 21 (88%) PTCA, and 12 (50%) died within 30 days. Among the remaining registry patients (n=27) only nine (33%) underwent early angiography, nine (33%) PTCA and 20 (74%) died.
                We failed to demonstrate that emergency PTCA significantly improves survival in patients with acute myocardial infarction and early cardiogenic shock. Because the study was stopped prematurely, due to an insufficient patient inclusion rate, a clinically meaningful benefit of early reperfusion may have been missed.
                Copyright 1999 The European Society of Cardiology. The Multi-Institutional Osteosarcoma Study (MIOS) was designed to determine whether intensive multiagent adjuvant chemotherapy improves the outcome of patients with nonmetastatic high-grade osteosarcoma of the extremity as compared with concurrent controls. After definitive surgery of the primary tumor, patients were randomly assigned to immediate adjuvant chemotherapy or to observation without adjuvant treatment. Updated results of this trial indicate that the projected six-year event-free survival for the control group is 11% compared to 61% for the chemotherapy group (p less than 0.001). Similar results were observed in patients who declined randomization but who were followed according to the treatment arms of the protocol. When randomized and nonrandomized patients are pooled according to assigned treatment, a survival advantage favoring those patients treated with immediate adjuvant chemotherapy is apparent. An analysis of prognostic factors among patients receiving immediate adjuvant chemotherapy reveals that elevation of the serum lactic dehydrogenase at diagnosis is the factor most predictive of adverse outcome. Location of the primary site in the tibia confers a favorable prognosis. The authors conclude that the natural history of high-grade osteosarcoma of the extremity has not changed over the past two decades. The administration of immediate adjuvant chemotherapy has a significant favorable impact on event-free survival and should be recommended for all such patients. The aim of this study was to determine both the clinical and cost-effectiveness of usual general practitioner (GP) care compared with two types of brief psychological therapy (non-directive counselling and cognitive-behaviour therapy) in the management of depression as well as mixed anxiety and depression in the primary care setting.
                The design was principally a pragmatic randomised controlled trial, but was accompanied by two additional allocation methods allowing patient preference: the option of a specific choice of treatment (preference allocation) and the option to be randomised between the psychological therapies only. Of the 464 patients allocated to the three treatments, 197 were randomised between the three treatments, 137 chose a specific treatment, and 130 were randomised between the psychological therapies only. The patients underwent follow-up assessments at 4 and 12 months.
                The study was conducted in 24 general practices in Greater Manchester and London.
                A total of 464 eligible patients, aged 18 years and over, were referred by 73 GPs and allocated to one of the psychological therapies or usual GP care for depressive symptoms.
                The interventions consisted of brief psychological therapy (12 sessions maximum) or usual GP care. Non-directive counselling was provided by counsellors who were qualified for accreditation by the British Association for Counselling. Cognitive-behaviour therapy was provided by clinical psychologists who were qualified for accreditation by the British Association for Behavioural and Cognitive Psychotherapies. Usual GP care included discussions with patients and the prescription of medication, but GPs were asked to refrain from referring patients for psychological intervention for at least 4 months. Most therapy sessions took place on a weekly basis in the general practices. By the 12-month follow-up, GP care in some cases did include referral to mental healthcare specialists.
                The clinical outcomes included depressive symptoms, general psychiatric symptoms, social function and patient satisfaction. The economic outcomes included direct and indirect costs and quality of life. Assessments were carried out at baseline during face-to-face interviews as well as at 4 and 12 months in person or by post.
                At 4 months, both psychological therapies had reduced depressive symptoms to a significantly greater extent than usual GP care. Patients in the psychological therapy groups exhibited mean scores on the Beck Depression Inventory that were 4-5 points lower than the mean score of patients in the usual GP care group, a difference that was also clinically significant. These differences did not generalize to other measures of outcome. There was no significant difference in outcome between the two psychological therapies when they were compared directly using all 260 patients randomised to a psychological therapy by either randomised allocation method. At 12 months, the patients in all three groups had improved to the same extent. The lack of a significant difference between the treatment groups at this point resulted from greater improvement of the patients in the GP care group between the 4- and 12-month follow-ups. At 4 months, patients in both psychological therapy groups were more satisfied with their treatment than those in the usual GP care group. However, by 12 months, patients who had received non-directive counselling were more satisfied than those in either of the other two groups. There were few differences in the baseline characteristics of patients who were randomised or expressed a treatment preference, and no differences in outcome between these patients. Similar outcomes were found for patients who chose either psychological therapy. Again, there were no significant differences between the two groups at 4 or 12 months. Patients who chose counselling were more satisfied with treatment than those who chose c The applicability of prospective carotid endarterectomy protocols to the general population has been questioned. Outcomes for asymptomatic patients undergoing carotid endarterectomy were compared with the results of the Asymptomatic Carotid Atherosclerosis Study (ACAS) patients treated concurrently at our institution.
                Asymptomatic patients undergoing carotid endarterectomies (n = 277) from 1987 to 1993 (ACAS enrollment period) were reviewed. Primary end points were mortality, myocardial infarction, and stroke. Five subgroups were studied: (1) ACAS surgical patients; (2) ACAS-eligible patients not enrolled and ACAS surgeons; (3) ACAS-eligible patients not enrolled and non-ACAS surgeons; (4) ACAS-ineligible patients and ACAS surgeons; and (5) ACAS-ineligible patients and non-ACAS surgeons.
                ACAS-eligible patients were younger (P = .014), had more severe carotid stenosis (P = .001), and had lower incidences of pulmonary (P = .015) and renal (P = .008) diseases compared with ineligible patients. Patient selection (ACAS eligibility) significantly improved outcomes for mortality (P = .014) and myocardial infarction (P = .006). Length of stay favored ACAS-eligible patients (P = .004). ACAS surgeons operated on more severely stenotic carotid lesions (P = .005) and on patients with a lower incidence of coronary artery disease (P = .007). There was no difference in outcomes between ACAS and non-ACAS surgeons.
                Patient selection was a significant factor in determining outcome. With strict adherence to ACAS enrollment guidelines, the conclusions of ACAS appear applicable to patients seen at our institution with asymptomatic carotid stenosis. The objective was to study the generalizability of trial results by comparing randomized patients to eligible but nonrandomized patients who received the same management. Implementation of trial results is only justifiable when the results can be generalized to the total domain population. The design was a multicentre randomized controlled trial on the effect of early screening and treatment with ventilation tubes on infants with otitis media with effusion. Randomized (n = 187) and nonrandomized eligible patients (n = 133) were followed up. The study population comprised children who were detected by auditory screening at the age of 9-12 months and who were subsequently diagnosed with persistent bilateral otitis media with effusion for 4-6 months. A significant difference was found in the distribution of some prognostic factors: more randomized children had older siblings, did not attend day care and had mothers with a lower educational level than the nonrandomized children. These factors, however, did not modify the outcome. No differences were found in mean hearing levels between the randomized and nonrandomized children: in both the randomized and nonrandomized children ventilation tubes improved the hearing level, especially after 6 months. However, in the long term (12 months), the hearing levels were equal again. The results of the randomized and nonrandomized patients were comparable. The results of this trial appear to be generalizable to the total domain population. The procedure of following up both randomized and nonrandomized patients is recommended when there is concern about selective participation and reduced generalizability. We studied spontaneous resolution of congenital nasolacrimal duct obstruction in the second year of life and compared this with the cure rate after probings undertaken between the ages of 11 and 15 months. Of the 111 eyes of 95 patients studied, 26 eyes were included in a randomised prospective comparison of probing with spontaneous resolution. A further 63 eyes followed a similar management plan to the randomised group and are reported as an observational study. Thirty of the 50 eyes followed up without treatment resolved spontaneously before the age of 2 years, of which 24 resolved before 18 months. The overall cure rate for probing was 74% compared with 60% for spontaneous resolution. At 15 months of age the randomised study confirmed that probing at 12-14 months is an effective intervention compared with spontaneous resolution (p = 0.04). At 24 months of age probing was superior in both randomised and non-randomised studies, but with increased numbers in the spontaneous resolution groups the difference was no longer statistically significant. Up to 18 months of age the frequency of spontaneous resolution makes delay in probing a viable management option to be discussed with the parents. It will also lead to an overestimate of the cure rate in any study of interventional treatment unless controls are included. Our objective was to characterize and evaluate pregnancy outcome in women who declined participation in a trial on ultrasound screening in the second trimester. Between 1985 and 1987, 8768 women were recruited for a trial on ultrasound screening. By randomization, 4997 women were assigned to either a screening or a non-screening group. Of the 1414 excluded women, data were retrieved from 1211 (86%). Participation was declined by 526 of these 1211 women, either because of anxiety regarding harmful effects of ultrasound or because they could see no benefits of ultrasound scanning. Non-participants and participants were compared. The non-participants were older, had a higher birth/pregnancy ratio, were less often smokers, and had fewer ultrasound examinations than the participants. There was a longer mean pregnancy length, an increased number of post-term deliveries, more suspicions of small-for-gestational-age fetuses and later detections of multiple pregnancies among non-participants as compared with the screening group. No differences in neonatal morbidity were found except for a greater number of mild respiratory disorders in the non-participant group. The non-participant women were more obstetrically experienced and showed indications of a healthier lifestyle in comparison with participants. The differences found in pregnancy outcome could be explained by the ultrasound screening procedure. There were no major differences in neonatal morbidity between the groups. nan The survival of 78 patients with resected non-small cell lung cancer entered in prospective, randomized investigational trials is compared to that of a population-based group of control patients not included in such trials. The survival of trial patients is significantly better than that of controls (P less than 0.001). This survival advantage for trial participants is most apparent among late Stage I patients, and is observed after matching for known prognostic factors (i.e., primary tumor size, nodal status, tumor histology) and after adjusting in the analysis for age, sex, and the administration of radiation therapy. Several explanations for the improved outcome for trial patients are explored, including differences in preoperative evaluation, staging, surgical technique, placebo effects, and patient motivation. These results suggest the possibility that inclusion in these controlled cancer trials may have had an inherent advantage for all participants. To assess women's preferences for, and the acceptability of, medical abortion and vacuum aspiration in the early first trimester.
                Patient centred, partially randomised trial. Medical abortion was performed with mifepristone 600 mg followed 48 hours later by gemeprost 1 mg vaginal pessary. Vacuum aspiration was performed under general anaesthesia.
                Teaching hospital in Scotland.
                363 women undergoing legal induced abortion at less than nine weeks' gestation.
                Women's preferences for method of abortion before abortion; acceptability judged two weeks after abortion by recording the method women would opt to undergo in future and by semantic differential rating technique.
                73 (20%) women preferred to undergo medical abortion, and 95 (26%) vacuum aspiration; 195 (54%) were willing to undergo either method, and were allocated at random. Both procedures were highly acceptable to women with preferences. Gestation had a definite effect on acceptability in randomised women; at less than 50 days there were no differences, but between 50 and 63 days vacuum aspiration was significantly more acceptable.
                Women who wish to use a particular method should be allowed their choice, regardless of gestation. Women of 50-63 days' gestation without preferences for a particular method are likely to find vacuum aspiration more acceptable. A patient centred, partially randomised trial design may be a useful tool in pragmatic research. Patients with multivessel coronary artery disease are candidates for either angioplasty and stenting or coronary artery bypass grafting. A prospective randomized study designed to compare the both methods included only a minority of the eligible patients.
                To compare coronary artery bypass grafting to angioplasty plus stenting in patients with multivessel disease who declined randomization to a multicenter study (the ARTS).
                During 1997-98 we prospectively followed 96 consecutive patients who were eligible according to the ARTS criteria but refused randomization. Of these patients, 50 underwent angioplasty + stenting and 46 underwent coronary bypass surgery. We compared the incidence of major adverse cardiac and cerebral events, chest pain recurrence, quality of life and procedural cost during the first 6 months.
                All procedures were completed successfully without mortality or cerebral events. The rate of Q-wave myocardial infarction was 2% in the AS group vs. 0% in the CABG group (not significant). Minor complications occurred in 7 patients (14%) in the AS group and in 21 patients (45%) in the CABG group (P < 0.01). At 6 months follow-up the incidence of major cardiac and cerebral events was similar in both groups (11% and 4% in the AS and CABG groups respectively, P = NS). Seventeen patients (36%) in the AS group required repeat revascularization compared to only 3 (7%) in the CABG group (P = 0.002). Nevertheless, quality of life was better, hospitalization was shorter and the cost was lower during the first 6 months after angioplasty.
                Angioplasty with stenting compared to coronary bypass surgery in patients with multivessel disease resulted in similar short-term major complications. However, 36% of patients undergoing angioplasty may need further revascularization procedures during the first 6 months. To investigate whether a buprenorphine opiate detoxification regimen can be considered to be at least as clinically effective as a lofexidine regimen.
                An open-label randomized controlled trial (RCT) using a non-inferiority approach. Non-inferiority is demonstrated if, within a 95% confidence interval, buprenorphine performs within a preset tolerance limit of clinically acceptable difference in outcomes and completion rates between the two treatments.
                Individuals ready for heroin detoxification were given information about the trial and invited to participate. Consenting participants (n = 210) were then randomized to one of the two treatments. Detoxification was undertaken in a specialist out-patient clinic according to predefined protocols. The primary outcome was whether or not an individual completed the detoxification. Abstinence at 1-month follow-up was used as a secondary outcome measure. Additional secondary outcome measures were substance use, dependence, psychological health, social satisfaction, and treatment satisfaction. Data were also collected for individuals who declined randomization and instead chose their treatment (n = 271).
                A total of 46% of those on lofexidine and 65% of those on buprenorphine completed detoxification. Of these, 35.7% of the lofexidine and 45.9% of the buprenorphine groups reported abstinence at 1 month. Of those not completing detoxification abstinence was reported at 27.5% and 29.0%, respectively; 271 individuals who opted not to be allocated randomly and instead chose one of the two treatments produced similar results
                Buprenorphine is at least as effective as lofexidine detoxification treatment. Whether or not individuals were randomized to, or chose, a treatment appeared not to affect the study's outcome. In a randomized controlled trial plus a nonrandomized cohort, the authors investigated the effectiveness and costs of acupuncture in addition to routine care in the treatment of chronic low back pain and assessed whether the effects of acupuncture differed in randomized and nonrandomized patients. In 2001, German patients with chronic low back pain were allocated to an acupuncture group or a no-acupuncture control group. Persons who did not consent to randomization were included in a nonrandomized acupuncture group. All patients were allowed to receive routine medical care in addition to study treatment. Back function (Hannover Functional Ability Questionnaire), pain, and quality of life were assessed at baseline and after 3 and 6 months, and cost-effectiveness was analyzed. Of 11,630 patients (mean age=52.9 years (standard deviation, 13.7); 59% female), 1,549 were randomized to the acupuncture group and 1,544 to the control group; 8,537 were included in the nonrandomized acupuncture group. At 3 months, back function improved by 12.1 (standard error (SE), 0.4) to 74.5 (SE, 0.4) points in the acupuncture group and by 2.7 (SE, 0.4) to 65.1 (SE, 0.4) points among controls (difference=9.4 points (95% confidence interval 8.3, 10.5); p<0.001). Nonrandomized patients had more severe symptoms at baseline and showed improvements in back function similar to those seen in randomized patients. The incremental cost-effectiveness ratio was euro10,526 (euros) per quality-adjusted life year. Acupuncture plus routine care was associated with marked clinical improvements in these patients and was relatively cost-effective. There are few data on the long-term outcome of growth-hormone treatment in short normal children. We assessed the impact of growth-hormone treatment on pubertal development and near-final height in girls.
                In a randomised controlled trial, we studied ten girls, with a mean age of 8.07 years and height 2 SDs or more below the mean for their age, and eight short untreated controls matched for age, and 20 short untreated girls who did not give consent for randomisation. The girls received either 30 IU/m2 somatropin per week as daily subcutaneous injections or no treatment. We assessed pubertal staging and height gain every 6 months.
                Eight treated girls completed a mean of 6.2 years' therapy. By a mean age of 16.4 years, their mean height SD score had changed significantly from -2.42 to -1.14 (p=0.008) and they were, on average, 7.5 cm taller than the girls in the control group (height SD scores did not change significantly from -2.55) and 6.0 cm taller than the non-consent group. The timing of each pubertal stage, and the age and amplitude of peak height velocity were similar for all groups.
                Growth-hormone therapy effectively increased height SD score among short normal girls started on treatment in early to mid childhood, with no untoward effect on pubertal progression. Acupuncture is widely used by patients with neck pain, but there is a lack of information about its effectiveness in routine medical care. The aim was to investigate the effectiveness of acupuncture in addition to routine care in patients with chronic neck pain compared to treatment with routine care alone. We performed a randomized controlled multicentre trial plus non-randomized cohort in general practices in Germany. 14,161 patients with chronic neck pain (duration >6 months). Patients were randomly allocated to an acupuncture group or a control group receiving no acupuncture. Patients in the acupuncture group received up to 15 acupuncture sessions over three months. Patients who did not consent to randomization received acupuncture treatment. All subjects were allowed to receive usual medical care in addition to study treatment. Neck pain and disability (NPAD Scale by Wheeler) after three months. Of 14,161 patients (mean age 50.9+/-13.1 years, 68% female) 1880 were randomized to acupuncture and 1886 to control, and 10,395 included into the non-randomized acupuncture group. At three months, neck pain and disability improved by 16.2 (SE: 0.4) to 38.3 (SE: 0.4); and by 3.9 (SE: 0.4) to 50.5 (SE: 0.4), difference 12.3 (p<0.001) in the acupuncture and control group, respectively. Treatment success was essentially maintained through six months. Non-randomized patients had more severe symptoms at baseline and showed higher neck pain and disability improvement compared to randomized patients. Treatment with acupuncture added to routine care in patients with chronic neck pain was associated with improvements in neck pain and disability compared to treatment with routine care alone. The use of a UV-box disconnect system reduces the incidence of peritonitis as compared with manual exchanges. An integrated disconnect system (IDS) also gives good results. See Figure 1. From 1988-1991, we prospectively compared two groups of patients using either a UV-box disconnect system (Baxter, n = 18, mean age 64, range 28-75 yrs) or an IDS (Baxter, n = 25, mean age 53, range 30-78). The Tenckhoff catheter had been inserted by the same technique in all patients, and the training program and nursing care were also identical. Since many younger patients preferred IDS and refused randomization, age was significantly lower in the IDS group. All peritonitis episodes (PER) were registered. Excluded from calculations of PER were episodes most probably not due to failure in connective device: PER after incidental penetration of the dialysis bags, deep penetrating tunnel infections and in the direct course of abdominal surgery. Results: There were significantly fewer months with PER (one month = 1 PER; Chi-2 = 6.45, p < 0.05) in patients using the IDS (3 PER/269 months) compared with those using the UV-box system (15 PER/355 months). The IDS was requested mainly by younger patients, while some older patients found it to be too complicated. Conclusion: The integrated disconnect system is especially acceptable by younger patients, and patients using the IDS show a low incidence of peritonitis. The tricyclic antidepressant drug amitriptyline was evaluated as a short-term treatment of anorexia nervosa patients. In a 5-week double-blind, placebo-controlled study 11 patients were given amitriptyline and 14 received placebo. In addition, 18 patients who refused to participate in the drug trial and received only psychosocial treatment were used as an additional comparison group. Overall, patients in the three groups showed little improvement. No statistically significant differences favoring amitriptyline were found in any of the outcome variables. Plasma levels varied widely among patients receiving similar doses. No association was found between plasma levels and improvement in either psychiatric symptomatology or weight. Amitriptyline patients did not manifest any tendency for a reduction of depressive symptomatology. In addition, amitriptyline treatment was associated with substantial discomfort and adverse affects. This prospective study evaluated whether prophylactic saline amnioinfusion among patients with amniotic fluid index (AFI) < or = 5.0 cm decreases the incidence of adverse fetal outcomes. Randomization of 53 patients with decreased AFI at term, resulted in 21 patients' receiving prophylactic saline amnioinfusion early in labor, prior to development of an abnormal fetal heart rate tracing. For the treatment group the mean AFI on admission was 3.0 cm, and the postamnioinfusion AFI was 8.9 cm. For 32 comparison (noninfusion) patients, the mean AFI was 2.9 cm; the group consisted of 17 patients randomized to receive no amnioinfusion (control group) and 15 patients who refused to participate in the study. There was no statistically significant difference between the amnioinfused and nonamnioinfused patients with regard to age, parity, gestational age, AFI at admission or duration of first or second stage of labor. Amnioinfusion resulted in no statistically significant reduction in the incidence of recurrent variable decelerations/bradycardia (26.3% vs. 46.6%), intrapartum resuscitation with terbutaline (5.2% vs. 10.0%), cesarean section for fetal distress (9.5% vs. 9.3%), fetal-acidosis (10.5% vs. 12.0%) or Apgar scores < 7 at five minutes (5.2% vs. 0%) in patients with oligohydramnios. Sixty-two patients with resectable but poor-prognosis gastric carcinoma were randomized to either no surgical adjuvant therapy or treatment with 5-fluorouracil (15 mg/kg by rapid intravenous injection X 3) plus radiation (3,750 rad in 24 fractions) initiated 3 1/2 to six weeks postoperatively. Informed consent was obtained after randomization and only from the 39 randomized to treatment. Ten patients refused their treatment assignment. The five-year survival rate for patients randomized to treatment was 23%, and for those randomized to no treatment, 4% (P less than .05). Both the survival distributions and the alive-without-recurrence distributions were significantly different for the two groups (P = .024) and favored treatment assignment. When the treatment assignment group was broken down to those patients actually receiving treatment and those refusing, five-year survival rates were: treated, 20%; treatment refusal, 30%; controls, 4%; the three survival distributions were not significantly different. Thirty-nine percent of patients actually treated had a local-regional component of first clinical recurrence compared with 54% of those who received no treatment. This study does not establish 5-fluorouracil plus radiation as effective surgical adjuvant therapy for gastric cancer but suggests this approach as a possible fruitful area for continued research. This study also illustrates the potential problems that may be encountered in interpreting results when patients are randomized to a study before consent is obtained. Although not much research comparing the emotional distress following medical and surgical abortion is available, few studies have compared psychological sequelae following both methods of abortion early in the first trimester of pregnancy. The aim of this review was to assess the psychological sequelae and emotional distress following medical and surgical abortion at 10-13 weeks gestation.
                Partially randomized patient preference trial in a Scottish Teaching Hospital was conducted. The hospital anxiety and depression scales were used to assess emotional distress. Anxiety levels were also assessed using visual analog scales while semantic differential rating scales were used to measure self-esteem. A total of 368 women were randomized, while 77 entered the preference cohort.
                There were no significant differences in hospital anxiety and depression scales scores for anxiety or depression between the groups. Visual analog scales showed higher anxiety levels in women randomized to surgery prior to abortion (P < 0.0001), while women randomized to surgical treatment were less anxious after abortion (P < 0.0001). Semantic differential rating scores showed a fall in self-esteem in the randomized medical group compared to those undergoing surgery (P = 0.02).
                Medical abortion at 10-13 weeks is effective and does not increase psychological morbidity compared to surgical vacuum aspiration and hence should be made available to all women undergoing abortion at these gestations. This study was planned in the context of a regional high blood pressure programme, to compare the efficacy of two educative methods. The group of 722 hypertensive patients (58.8% women), mean age 61 years, was randomly selected from 19 primary care centres. Initial assessment was based on a patient interview including 22 questions on high blood pressure, its consequences and treatment. Patients agreeing to participate in an active education team programme were distributed into three groups: individual education, team education and a control group. Those who declined to participate formed two groups: individual education and controls. Team education consisted of two audiovisual sessions attended by groups of 8-12 patients and conducted by treating physicians and nurses. Individual education included comments related to the 22 questions. Follow-up assessment was made after two months. An increase in the level of hypertension control was observed only in the accepting group, in which educative action was followed by increased knowledge. Results were similarly favourable for both the individual and team education groups and suggested the need to consider educational factors together with those influencing patient attitude towards an active educational programme. We studied the efficacy of tonsillectomy, or tonsillectomy with adenoidectomy, in 187 children severely affected with recurrent throat infection. Ninety-one of the children were assigned randomly to either surgical or nonsurgical treatment groups, and 96 were assigned according to parental preference. In both the randomized and nonrandomized trials, the effects of tonsillectomy and of tonsillectomy with adenoidectomy were similar. By various measures, the incidence of throat infection during the first two years of follow-up was significantly lower (P less than or equal to 0.05) in the surgical groups than in the corresponding nonsurgical groups. Third-year differences, although in most cases not significant, also consistently favored the surgical groups. On the other hand, in each follow-up year many subjects in the nonsurgical groups had fewer than three episodes of infection, and most episodes among subjects in the nonsurgical groups were mild. Of the 95 subjects treated with surgery, 13 (14 per cent) had surgery-related complications, all of which were readily managed or self-limited. These results warrant the election of tonsillectomy for children meeting the trials' stringent eligibility criteria, but also provide support for nonsurgical management. Treatment for such children must therefore be individualized. In a recently started clinical trial, the short-term effects of radiotherapy of cervix cancer Stage IIb and III in combination with topical infusion of metronidazole solution were evaluated by determining the local clearance rate and cytologic damage in randomized and non-randomized cases. In regard to the short term effects the combined treatment was found to be superior to treatment without metronidazole. To identify the advantages and disadvantages of using a partially randomised patient preference design rather than a conventional randomised controlled design when evaluating alternative managements for heavy menstrual bleeding.
                Randomised controlled comparison of two clinical trial designs with subsequent follow up of the cohorts of women generated.
                Women attending a general gynaecology clinic for the first time because of heavy menstrual bleeding.
                Partially randomised patient preference clinical trial design and conventional randomised controlled design.
                Overall participation; participation in randomised clinical trial of medical management compared with transcervical surgical resection of the endometrium; prognostic characteristics (socio-demographic and Short Form 36) of clinical trial groups; outcomes (clinical and Short Form 36) of clinical trial groups.
                Overall, more women participated in the partially randomised patient preference design (130/135 vs 97/138; difference 27%, 95% CI 18% to 34%) but there was no difference in the numbers who agreed to be randomised (90/135 vs 97/138; difference-3%, 95% CI-15% to 7%). Women who chose medical management tended to have better general health, to be less restricted by their menstrual problems, with fewer having been previously treated by their general practitioner. Those who chose transcervical resection of the endometrium had all tried medical management and had higher bleeding scores. Follow up satisfactions and acceptability rates, and Short Form 36 scores were highest after transcervical resection of the endometrium, whether chosen or randomised. Acceptability and a desire to continue the same treatment was greater among those who chose medical management than those randomly allocated it.
                Use of the partially randomised patient preference design did not affect recruitment to the randomised controlled trial suggesting that a conventionally designed trial would not be biased by motivational factors in this context. Data from the preference groups informed the generalisability of the results but did tend to confirm conclusions that anyway reasonably followed from the randomised controlled trial. The extra resource implications of using the partially randomised patient preference design were significant reflecting the additional 40% who participated and the extra analyses entailed. Plantar fasciitis is a common foot disorder that may be resistant to nonoperative treatment. This study evaluated the use of electrohydraulic high-energy shock waves in patients who failed to respond to a minimum of six months of antecedent nonoperative treatment.
                A randomized, placebo-controlled, multiply blinded, crossover study was conducted. Phase 1 consisted of twenty patients who were nonrandomized to treatment with extracorporeal shock waves to assess the phase-2 study protocol. In phase 2, 293 patients were randomized and an additional seventy-one patients were nonrandomized. Following ankle-block anesthesia, each patient received 100 graded shocks starting at 0.12 to 0.22 mJ/mm(2), followed by 1400 shocks at 0.22 mJ/mm(2) with use of a high-energy electrohydraulic shock-wave device. Patients in the placebo group received minimal subcutaneous anesthetic injections and nontransmitted shock waves by the same protocol. Three months later, patients were given the opportunity to continue without further treatment or have an additional treatment. This allowed a patient in the active treatment arm to receive a second treatment and a patient who received the placebo to cross over to the active treatment arm. Patients were followed at least one year after the final treatment.
                Treatment was successful in seventeen of the twenty phase-1 patients at three months. This improved to nineteen (95%) of twenty patients at one year and was maintained at five years. In phase 2, three months after treatment, sixty-seven (47%) of the 144 actively treated patients had a completely successful result compared with forty-two (30%) of the 141 placebo-treated patients (p = 0.008). At one year, sixty-five of the sixty-seven actively treated, randomized patients maintained a successful result. Thirty-six (71%) of the remaining fifty-one nonrandomized patients had a successful result at three months. For all 289 patients who had one or more actual treatments, 222 (76.8%) had a good or excellent result. No patient was made worse by the procedure.
                The application of electrohydraulic high-energy shock waves to the heel is a safe and effective noninvasive method to treat chronic plantar fasciitis, lasting up to and beyond one year. We performed a randomized, placebo controlled double-blind trial to evaluate the effectiveness of Entonox (BOC Gases, Manchester, United Kingdom), that is 50% nitrous oxide and oxygen, as analgesia during transrectal ultrasound guided prostate biopsy.
                Patients referred for transrectal ultrasound guided prostate biopsy for the first time as an outpatient procedure were recruited subject to exclusion criteria and randomized to breathe Entonox or air via similar breath activated devices. At the end of the procedure patients completed a visual pain analog scale. Patients who refused study participation also completed the visual analog pain scale to assess the placebo effect of receiving gas through a mask.
                A total of 110 patients were studied. Statistical analysis using 1-way analysis of variance showed a highly significant difference in pain perception among the 3 groups (F [2,107] = 73.348, p <0.001). This significant decrease in pain was noted in the Entonox versus air and Entonox versus placebo groups. There was no significant difference in the air and placebo groups. Seven of the 51 patients receiving Entonox complained of feeling drowsy during the procedure, which resolved at completion of the procedure. In this group 49 patients would undergo this procedure again if needed. In 2 of the 45 patients in the group receiving air the procedure was abandoned due to pain, while another 19 would prefer more analgesia and 2 would prefer general anesthesia if the procedure was to be repeated.
                Our study shows that Entonox is a safe, rapidly acting and effective form of analgesia for the pain of prostate biopsy. We believe that it should be the analgesia of choice for this procedure. To determine whether informed consent in a therapeutic trial modifies the analgesic effect of naproxen and placebo, we conducted a prospective, randomised, single dose, placebo-controlled trial. Patients were randomly selected to receive or not information concerning the study. All patients included were then given a single dose of naproxen and placebo according to a crossover, double-blind design. Forty-nine patients with mild or moderate cancer pain which did not need narcotic analgesics entered the study. Twenty-five received both treatments without any information and constituted the uninformed group. Twenty-four had a complete information about the trial; six refused to participate. The 18 others constituted the informed-consent group. Visual analogue scales of pain before and 30, 60, 120 and 180 min after the intake of naproxen and placebo were recorded. As an analgesic, naproxen was more effective than placebo in both groups of patients (p = 0.001). For naproxen as well as for placebo, the analgesic effect was better in the informed-consent group compared to the uninformed group (p = 0.012). The difference in therapeutic activity between naproxen and placebo was moderately higher in the uninformed patients (p = 0.08). We concluded that, in contrast with parallel studies, giving information in a crossover, placebo-controlled trial may increase the apparent efficacy of both the tested agent and the placebo, and decrease the perceived difference the two. The delivery room management of meconium-stained amniotic fluid remains controversial. We attempted to determine if intubation of the low-risk newborn with thin meconium affects the incidence of respiratory symptoms. Exclusion criterion included moderate or thick meconium, fetal distress, neonatal depression, or prematurity. Eligible infants were randomized to either an intubation (group I) or to a nonintubation group (group II). The outcome was the presence of respiratory symptoms. Patients were studied from May 1994 to June 1997. There were 8967 births during this period: 7.9% (708/8967) were delivered through meconium. Thin meconium was noted in 50.3% (356/708) of all births. 24/356 infants with thin meconium were excluded for medical criterion. One hundred sixty-three infants were medically eligible but could not be randomized due to lack of consent, late arrival of the team, or obstetrician request. These were placed into intubation (group I B) and nonintubation (group II B) groups. Seventy-seven infants were randomized into group I and 92 infants into group II. From the intubation groups I and I B, one required supplemental oxygen and was weaned to room air in 7 hr. From the nonintubation groups II and II B, two infants required oxygen, weaning to room air in 11 and 46 hr. Comparing birth weight, gestational age, sex, mode of delivery and 5-min Apgar, there were no significant differences. However, the intubation groups had significantly lower 1-min Apgar scores. There was no airway morbidity reported in the intubation groups. In the infant with thin meconium and an otherwise low-risk pregnancy, we were unable to demonstrate a difference in respiratory symptoms with intubation and intratracheal suctioning. Of 90 patients with intermediate or high-grade sarcoma eligible for a randomized trial of adjuvant doxorubicin (Adriamycin, Adria Laboratories, Columbus, Ohio), 48 were not entered: 24 (27%) by physician's choice and 24 refused randomization. Sixty-five percent of lower stage patients were randomized compared with 37% of those with higher stage (P = .02). Patients with extremity lesions were more frequently offered participation in the study (P = .07). Patients with lower stage lesions accepted randomization more readily than those with higher stage lesions (P = .01). As predicted by the higher stage and percentage of central lesions, the disease-free survival of nonrandomized patients was inferior to that of randomized patients (P = .15). Thus, patients at high risk appeared to avoid randomization and adjuvant doxorubicin in this trial, resulting in an inferior disease-free survival for the nonrandomized control group. Important questions generally require randomized trials that reliably determine relative treatment differences. If, however, the patients in a clinical trial are not representative of the entire patient population because of patient and physician selection biases, the generalizability of the results to the entire patient population may be compromised. For example, the prognosis of the general population cannot necessarily be inferred from the selected group in the study. In this study, the randomized and nonrandomized series yielded differing conclusions regarding treatment efficacy, even when an adjustment was made for known prognostic facts.
This review indicates that participation in RCTs is associated with similar outcomes to receiving the same treatment outside RCTs. These results challenge the assertion that the results of RCTs are not applicable to usual practice.