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MS213700 | ***TASK*** the task is to summarize an input biomedical literature in six sentences
***INPUT*** the input is a biomedical literature
***OUTPUT*** the output is the summary of an input biomedical literature in six sentences
***DOCUMENTATION***
***EXAMPLES***
Input: All 68,308 inhabitants of Göteborg born between 1918 and 1931 were r and omly divided into a test and a control group . The subjects in the test group were invited to perform Hemoccult II fecal occult blood testing on 3 days and to repeat the test after 16 to 24 months . In the prevalence screening 21,347 ( 63 % ) performed the test , and in the rescreening 19,991 ( 60 % ) . Investigation of the 942 ( 4.4 % ) with positive tests in the prevalence screening showed 47 cancers and 129 subjects with adenomas > or = 1.0 cm . In the rescreening 5.1 % had a positive test , and 34 cancers and 122 subjects with adenomas ( > or = 1.0 cm ) were found among those . Cancer had also been diagnosed in 19 subjects in the interval between the two screening occasions and in 15 subjects among the non-responders . Forty-four cancers had been diagnosed in the control group during the same period . Cancers detected by screening were at a less advanced stage than in the control group . It is too early to show any effect of screening on mortality from colorectal cancer To which groups of patients can the results of clinical trials be applied ? This question is often inappropriately answered by reference to the trial entry criteria . Instead , the benefit and harm ( adverse events , discomfort of treatment , etc ) of treatment could be assessed separately for individual patients . Patients at greatest risk of a disease will have the greatest net benefit as benefit to patients usually increases with risk while harm remains comparatively fixed . To assess net benefit , the relative risks should come from ( a meta- analysis of ) r and omised trials ; the risk in individual patients should come from multivariate risk equations derived from cohort studies . However , before making firm conclusions , the assumptions of fixed adverse effects and constant reduction in relative risk need to be checked BACKGROUND Although tests for occult blood in the feces are widely used to screen for colorectal cancers , there is no conclusive evidence that they reduce mortality from this cause . We evaluated a fecal occult-blood test in a r and omized trial and documented its effectiveness . METHODS We r and omly assigned 46,551 participants 50 to 80 years of age to screening for colorectal cancer once a year , to screening every two years , or to a control group . Participants who were screened su bmi tted six guaiac-impregnated paper slides with two smears from each of three consecutive stools . About 83 percent of the slides were rehydrated . Participants who tested positive underwent a diagnostic evaluation that included colonoscopy . Vital status was ascertained for all study participants during 13 years of follow-up . A committee determined causes of death . A single pathologist determined the stage of each tissue specimen . Differences in mortality from colorectal cancer , the primary study end point , were monitored with the sequential log-rank statistic . RESULTS The 13-year cumulative mortality per 1000 from colorectal cancer was 5.88 in the annually screened group ( 95 percent confidence interval , 4.61 to 7.15 ) , 8.33 in the biennially screened group ( 95 percent confidence interval , 6.82 to 9.84 ) , and 8.83 in the control group ( 95 percent confidence interval , 7.26 to 10.40 ) . The rate in the annually screened group , but not in the biennially screened group , was significantly lower than that in the control group . Reduced mortality in the annually screened group was accompanied by improved survival in those with colorectal cancer and a shift to detection at an earlier stage of cancer . CONCLUSIONS Annual fecal occult-blood testing with rehydration of the sample s decreased the 13-year cumulative mortality from colorectal cancer by 33 percent BACKGROUND : It has recently been suggested that all-cause mortality is a more appropriate end point than disease specific mortality in cancer screening trials , and that disease specific mortality is biased in favour of screening . This suggestion is based partly on supposed inconsistencies between all-cause mortality results and disease specific results in cancer screening trials , and alleged increases in deaths from causes other than breast cancer among breast cancer cases diagnosed among women invited to screening . METHODS : We used data from the Swedish Two-County Trial of mammographic screening for breast cancer , in which 77 080 women were r and omised to an invitation to screening and 55 985 to no invitation . We estimated relative risks ( RRs ) ( invited v control ) of death from breast cancer , death from other causes within the breast cancer cases , and death from all causes within the breast cancer cases . RRs were adjusted for age and took account of the longer follow up of breast cancer cases in the invited group due to lead time . RESULTS : There was a significant 31 % reduction in breast cancer mortality in the invited group ( RR 0.69 , 95 % confidence interval ( CI ) 0.58–0.80 ; p<0.001 ) . There was no significant increase in deaths from other causes among breast cancer cases in the invited group ( RR 1.12 , 95 % CI 0.96–1.31 ; p=0.14 ) . A significant 19 % reduction in deaths from all causes was observed among breast cancer cases in the group invited to screening ( RR 0.81 , 95 % CI 0.72–0.90 ; p<0.001 ) . A more conservative estimation gave a significant 13 % reduction ( RR 0.87 , 95 % CI 0.78–0.97 ; p=0.01 ) . These findings are consistent with the magnitude of the reduction in breast cancer mortality . CONCLUSIONS : Invitation to screening was associated with a reduction in deaths from all causes among breast cancer cases , consistent with high participation rates in screening . There is no significant evidence of bias in cause of death classification in the Two-County Trial , and as breast cancer mortality is the targeted clinical outcome in breast cancer screening , it is the appropriate end point in a breast cancer screening trial . All-cause mortality is a poor and inefficient surrogate for breast cancer mortality BACKGROUND There is growing evidence that faecal-occult-blood ( FOB ) screening may reduce colorectal cancer ( CRC ) mortality , but this reduction in CRC mortality has not been shown in an unselected population -based r and omised controlled trial . The aim of this study was to assess the effect of FOB screening on CRC mortality in such a setting . METHODS Between February , 1981 , and January , 1991 , 152,850 people aged 45 - 74 years who lived in the Nottingham area of the UK were recruited to our study . Participants were r and omly allocated FOB screening ( 76,466 ) or no screening ( controls ; 76,384 ) . Controls were not told about the study and received no intervention . Screening-group participants were sent a Haemoccult FOB test kit with instructions from their family doctor . FOB tests were not rehydrated and dietary restrictions were imposed only for retesting borderline results . Individuals with negative FOB tests at the first screening , together with those who tested positive but in whom no neoplasia was found on colonoscopy , were invited to take part in further screening every 2 years . Screening was stopped in February , 1995 , by which time screening-group participants had been offered FOB tests between three and six times . Screening-group participants who had a positive test were offered full colonoscopy . All participants were followed up until June , 1995 . The primary outcome measure was CRC mortality . FINDINGS Of the 152,850 individuals recruited to the study , 2599 could not be traced or had emigrated and were excluded from the analysis . Thus , there were 75,253 participants in the screening group and 74,998 controls . 44,838 ( 59.6 % ) screening-group participants completed at least one screening . 28,720 ( 38.2 % ) of these individuals completed all the FOB tests they were offered and 16,118 ( 21.4 % ) completed at least one screening but not all the tests they were offered . 30,415 ( 40.4 % ) did not complete any test . Of 893 cancers ( 20 % stage A ) diagnosed in screening-group participants ( CRC incidence of 1.49 per 1000 person-years ) , 236 ( 26.4 % ) were detected by FOB screening , 249 ( 27.9 % ) presented after a negative FOB test or investigation , and 400 ( 44.8 % ) presented in non-responders . The incidence of cancer in the control group ( 856 cases , 11 % stage A ) was 1.44 per 1000 person-years . Median follow-up was 7.8 years ( range 4.5 - 14.5 ) . 360 people died from CRC in the screening group compared with 420 in the control group-a 15 % reduction in cumulative CRC mortality in the screening group ( odds ratio=0.85 [ 95 % ; CI 0.74 - 0.98 ] , p = 0.026 ) . INTERPRETATION Our findings together with evidence from other trials suggest that consideration should be given to a national programme of FOB screening to reduce CRC mortality in the general population BACKGROUND In 1993 , a r and omized controlled trial in Minnesota showed , after 13 years of follow-up , that annual fecal occult blood testing was effective in reducing colorectal cancer mortality by at least 33 % . Biennial screening ( i.e. , every 2 years ) result ed in only a 6 % mortality reduction . Two European trials ( in Engl and and in Denmark ) subsequently showed statistically significant 15 % and 18 % mortality reductions with biennial screening . Herein , we provide up date d results -through 18 years of follow-up -- from the Minnesota trial that address the apparent inconsistent findings among the trials regarding biennial screening . METHODS From 1976 through 1977 , a total of 46551 study subjects , aged 50 - 80 years , were recruited and r and omly assigned to an annual screen , a biennial screen , or a control group . A screen consisted of six guaiac-impregnated fecal occult blood tests ( Hemoccult ) prepared in pairs from each of three consecutive fecal sample s. Participants with at least one of the six tests that were positive were invited for a diagnostic examination that included colonoscopy . All participants were followed annually to ascertain incident colorectal cancers and deaths . RESULTS The numbers of deaths from all causes were similar among the three study groups . Cumulative 18-year colorectal cancer mortality was 33 % lower in the annual group than in the control group ( rate ratio , 0.67 ; 95 % confidence interval [ CI ] = 0.51 - 0.83 ) . The biennial group had a 21 % lower colorectal cancer mortality rate than the control group ( rate ratio , 0.79 ; 95 % CI = 0.62 - 0.97 ) . A marked reduction was also noted in the incidence of Dukes ' stage D cancers in both screened groups in comparison with the control group . CONCLUSION The results from this study , together with the other two published r and omized trials of fecal occult blood screening , are consistent in demonstrating a substantial , statistically significant reduction in colorectal cancer mortality from biennial screening Background : Three large r and omised trials have shown that screening for colorectal cancer using faecal occult blood ( FOB ) tests can reduce the mortality from this disease . Two national pilot studies have recently been launched in the UK to investigate the feasibility of population screening for colorectal cancer in the National Health Service . The largest of the r and omised trials was conducted in Nottingham and r and omised 152 850 individuals between the ages of 45 and 74 years to receive biennial Haemoccult ( FOB ) test kit ( intervention group ) or to a control group . Aims : We have compared the mortality in the intervention group compared with the control group . Methods : The 152 850 r and omised individuals were followed up through local health records and central flagging ( Office for National Statistics ) over a median follow up period of 11 years . Results : At a median follow up of 11 years there was a 13 % reduction in colorectal cancer mortality ( 95 % confidence interval 3–22 % ) in the intervention group despite an uptake at first invitation of only approximately 50 % . The mortality reduction for those accepting screening was 27 % . The reduction in mortality was independent of sex and site of tumour . There was no significant difference in mortality from causes other than colorectal cancer between the intervention and control groups . Conclusions : Although the reduction in colorectal cancer mortality was sustained , further follow up of this population is required to determine whether a significant reduction in the incidence of colorectal cancer will be achieved BACKGROUND The most widely accepted end point in r and omized cancer screening trials is disease-specific mortality . The validity of this end point , however , rests on the assumption that cause of death can be determined accurately . An alternative end point is all-cause mortality , which depends only on the accurate ascertainment of deaths and when they occur . We compared disease-specific and all-cause mortality in published r and omized cancer-screening trials to indirectly assess the validity of the disease-specific mortality end point . METHODS We examined all 12 published r and omized trials of cancer screening for which both end points
Output:
| This review confirms previous research demonstrating that FOBT screening reduces the risk of CRC mortality .
The results also indicate that there is no difference in all-cause mortality between the screened and nonscreened population |
MS213701 | ***TASK*** the task is to summarize an input biomedical literature in six sentences
***INPUT*** the input is a biomedical literature
***OUTPUT*** the output is the summary of an input biomedical literature in six sentences
***DOCUMENTATION***
***EXAMPLES***
Input: In an 11 month period , 95 patients with acute upper gastrointestinal hemorrhage underwent early fiberoptic endoscopy . Patients were r and omized into two groups before endoscopy depending on whether the results of the procedure were revealed immediately or after 4 days . No attempt was made to influence the treatment or diagnostic plan . The groups were comparable with respect to historical features surrounding the bleeding episode and the anatomic site of hemorrhage . There were no significant differences in any aspect of patient management or outcome between groups . Important changes in diagnostic or treatment plan were made after learning the results of endoscopy in only 12 % of the patients , half of whom were bleeding briskly at the time of endoscopy . It is concluded that the natural history of acute upper gastrointestinal hemorrhage ( for example , the spontaneous cessation of bleeding ) precludes endoscopy from having a significant effect on patient management BACKGROUND Time to treatment with thrombolytic therapy is a critical determinant of mortality in acute myocardial infa rct ion . Little is known about the relationship between the time to treatment with direct coronary angioplasty and clinical outcome . The objectives of this study were to determine both the time required to perform direct coronary angioplasty in the Global Use of Strategies to Open Occluded Arteries in Acute Coronary Syndromes ( GUSTO-IIb ) trial and its relationship to clinical outcome . METHODS AND RESULTS Patients r and omized to direct coronary angioplasty ( n=565 ) were divided into groups based on the time between study enrollment and first balloon inflation . Patients r and omized to angioplasty who did not undergo the procedure were also analyzed . The median time from study enrollment to first balloon inflation was 76 minutes ; 19 % of patients assigned to angioplasty did not undergo an angioplasty procedure . The 30-day mortality rate of patients who underwent balloon inflation < /=60 minutes after study enrollment was 1.0 % ; 61 to 75 minutes after enrollment , 3.7 % ; 76 to 90 minutes after enrollment , 4.0 % ; and > /=91 minutes after enrollment , 6.4 % . The mortality rate of patients assigned to angioplasty who never underwent the procedure was 14.1 % ( P=0.001 ) . Logistic regression analysis revealed that the time from enrollment to first balloon inflation was a significant predictor of mortality within 30 days ; after adjustment for differences in baseline characteristics , the odds of death increased 1.6 times ( P=0.008 ) for a movement from each time interval to the next . CONCLUSIONS The time to treatment with direct PTCA , as with thrombolytic therapy , is a critical determinant of mortality CONTEXT Upper gastrointestinal tract hemorrhage ( UGIH ) is a common and potentially life-threatening disorder . Re source utilization can vary without adverse effect on patient outcome . Clinical practice guidelines are a potential solution to reduce variation in practice while improving patient outcomes . OBJECTIVE To vali date prospect ively the safety , acceptability , and impact of a clinical practice guideline defining the medically appropriate length of stay ( LOS ) for patients hospitalized with UGIH . DESIGN Prospect i ve , controlled time-series study with an alternate-month design . Outcome surveyors and patients were blinded to study group allocation . GUIDELINE : A retrospectively vali date d scoring system using 4 independent variables : hemodynamics , time from bleeding , comorbidity , and esophagogastroduodenoscopy ( EGD ) findings to predict risk of adverse events . The quantitative risk for the low-risk subset was 0.6 % ( 95 % confidence interval [ CI ] , 0.0%-2.0 % ) for subsequent complications and 0 % ( 95 % CI , 0.0%-0.9 % ) for life-threatening complications from this retrospective evaluation . SETTING A 1000-bed , not-for-profit , university-affiliated teaching hospital . PATIENTS Consecutive adult patients hospitalized for acute UGIH . INTERVENTION Concurrent feedback of guideline recommendation ( same-day hospital discharge ) to physicians caring for patients at low risk for complication . No risk information was provided during control months . RESULTS Seventy percent ( 209/299 ) of UGIH patients achieved low-risk status according to the guideline and were therefore potentially suitable for early discharge from the hospital . Providing real-time quantitative risk information ( intervention group only ) was associated with an increase in guideline compliance from 30 % to 70 % ( P<.001 ) and a decrease in mean ( SD ) LOS from 4.6 ( 3.5 ) days to 2.9 ( 1.3 ) days ( mean reduction of 1.7 days per patient ; P<.001 ) . No differences in complications , patient health status , or patient satisfaction were found when measured 1 month after discharge . An independent variable predicting decreased hospital LOS for low-risk UGIH patients was early EGD . CONCLUSIONS Implementation of the clinical practice guideline safely reduced hospital LOS for selected low-risk patients with acute UGIH . Further prospect i ve validation in other setting s is warranted A prospect i ve study was conducted to see whether emergent esophagogastroduodenoscopy ( EGD ) in patients with active upper gastrointestinal ( GI ) bleeding is associated with more oxygen desaturation than nonemergent EGD . Emergent EGD was performed in the study patients with active upper GI bleeding . Nonemergent EGD was performed in the control patients . Determination of oxygen saturation ( Sao2 ) was measured by pulse oximeter . A decrease in Sao2 of > 4 % was more frequent in the study patients ( 26 % , 13 of 50 ) than in controls ( 6 % , 3 of 50 ) ( P < .01 ) . During EGD , mean oxygen saturation decreased significantly in both groups of patients . After EGD , mean oxygen saturation did not recover toward the pre-endoscopy insertion level in the study group ( P < .01 ) . A linear association was found that oxygen desaturation = 5.46 + 0.15 ( status ) -0.06 ( baseline oxygen saturation ) . Emergent EGD for active upper GI bleeding in the emergency department tends to be associated with more frequent significant oxygen desaturation than nonemergent EGD . Continuous oxygen supplementation and oxygen saturation monitoring may be used during emergent nonse date d EGD in the emergency department BACKGROUND From January 1993 to December 1994 , we conducted a prospect i ve study to investigate the evolutionary change of rebleeding risk in bleeding peptic ulcers . To obviate possible confounding factors that would influence decision making for discharge of patients , subjects with coexistent acute illnesses , systemic bleeding disorders , alcoholism , and use of nonsteroidal anti-inflammatory drugs were excluded . METHODS Emergency endoscopies were performed in patients with hematemesis or a melena within 24 hours of admission . Ulcer lesions were divided into six categories according to endoscopic findings . The residual risks of rebleeding of each type of ulcers were calculated for 10 days , and the critical point of acceptable rebleeding risk after discharge was set at 3 % . RESULTS Three hundred ninety-two patients with bleeding peptic ulcers completed the study . The ulcers , characterized by clean bases , red or black spots , adherent clots , nonbleeding visible vessels without local therapy , nonbleeding visible vessels with local therapy , and bleeding visible vessels with local therapy took 0 , 3 , 3 , 4 , 4 , and 3 days , respectively , to decrease rebleeding risk to below the critical point . All episodes of fatal rebleeding ( n = 4 ) occurred within 24 hours after admission . CONCLUSIONS Patients with clean-based ulcers can be discharged in the first day of admission . The optimal duration required for hospitalization of patients with ulcers characterized by nonbleeding visible vessels at initial endoscopy is 4 days . The remaining patients with ulcers marked by other bleeding stigmata may be discharged after a 3-day observation BACKGROUND The impact of upper endoscopy in patients with upper gastrointestinal hemorrhage treated in community practice is unknown . Thus we examined the effectiveness of endoscopy performed within 24 hours of admission ( early endoscopy ) . METHODS Medical records of 909 consecutive hospitalized patients with upper gastrointestinal hemorrhage who underwent endoscopy at 13 hospitals in a large metropolitan area were review ed . We evaluated unadjusted and severity-adjusted associations of early endoscopy with recurrent bleeding or surgery to control hemorrhage , length of hospital stay , and associations of endoscopic therapy in patients with bleeding ulcers or varices . RESULTS Early endoscopy was performed in 64 % of patients and compared with delayed endoscopy and was associated with clinical ly significant reductions in adjusted risk of recurrent bleeding or surgery ( odds ratio [ OR ] 0.70 : 95 % CI [ 0.44 , 1.13 ] ) and a 31 % decrease in adjusted length of stay ( 95 % CI : [ 24 % , 37 % ] ) . In patients at high risk for recurrent bleeding , the use of early endoscopic therapy to control hemorrhage was associated with reductions in recurrent bleeding or surgery ( OR 0.21 : 95 % CI [ 0.10 , 0.47 ] ) and length of stay ( -31 % : 95 % CI [ -44 % , -14 % ) . CONCLUSION In this study of community-based practice , the routine use of endoscopy , and in selected cases endoscopic therapy , performed early in the clinical course of patients with upper gastrointestinal hemorrhage was associated with reductions in length of stay and , possibly , the risk of recurrent bleeding and surgery OBJECTIVES Patients with an ulcer and active bleeding or a nonbleeding , visible vessel are high-risk for further bleeding and should receive aggressive therapy . In this study , we tried to identify clinical parameters that predict these high-risk groups . METHODS Over a 7-month period , 16 clinical parameters were analyzed prospect ively in 316 patients with bleeding peptic ulcer . A multivariate analysis was used to find the independent predictors for the high-risk patients . RESULTS A total of 114 patients ( 36 % ) was found to have a spurting hemorrhage ( eight patients ) , oozing hemorrhage ( 27 patients ) , or a nonbleeding visible vessel ( 79 patients ) . Using an univariate analysis , a statistically significant predictor was the appearance of coffee ground fluid or blood from the nasogastric tube . This predictor also emerged as an independent factor ( odds ratio , 0.4333 ; 95 % confidence interval , 0.263 - 0.714 ) . CONCLUSIONS Patients with bleeding peptic ulcer who have coffee ground fluid or blood from the nasogastric tube should receive an emergency endoscopy and aggressive treatment Aims —To assess changes in practice and outcome in acute upper gastrointestinal haemorrhage following the feedback of data , the reemphasis of national guidelines , and specific recommendations following an initial survey . Design —A prospect i ve , multicentre , audit cycle . Forty five hospitals from three health regions participed in two phases of the audit cycle . Patients —Phase I : 2332 patients with acute upper gastrointestinal haemorrhage ; phase II : 1625 patients with upper gastrointestinal haemorrhage . Methods — Patients were evaluated with respect to management ( with reference to the recommendations in the national guidelines ) , mortality , and length of hospital stay . Results —Following the distribution of data from the first phase of the National Audit and the formulation of specific recommendations for improving practice , the proportion of hospitals with local guidelines or protocol s for the management of upper gastrointestinal haemorrhage rose from 71 % ( 32/45 ) to 91 % ( 41/45 ) ; 12 of the 32 hospitals with guidelines during the first phase revised their guidelines following the initial survey . There was a small but significant increase in the proportion of all patients who underwent endoscopy ( from 81 % to 86 % ) , the proportion who underwent endoscopy within 24 hours of admission ( from 50 % to 56 % ) , and the use of central venous pressure monitoring in patients with organ failure requiring blood transfusion or those with profound shock ( from 30 % to 43 % ) . There was , however , no change in the use of high dependency beds or joint medical/surgical management in high risk cases . There was no significant change in crude or risk st and ardised mortality ( 13.4 % in the first phase and 14.4 % in the second phase ) . Conclusions —Although many of the participating hospitals have made efforts to improve practice by producing or updating guidelines or protocol s , there has been only a small demonstrable change in some areas of practice during the National Audit . The failure to detect any improvement in mortality may reflect this lack of change of practice , but may also reflect the fact that a large proportion of the deaths in this unselected study are not preventable ; only a very large study could hope to demonstrate a significant change out of the context of a clinical trial PURPOSE The outcome of patients with upper gastrointestinal hemorrhage is greatly influenced by recurrence of bleeding , but it may be possible to identify patients who have a low risk for rebleeding , and can be discharged after a short hospitalization . To examine the effect of an early discharge protocol ( length of hospital stay < or =3 days ) , we conducted a 2-year prospect i ve study in patients with upper gastrointestinal bleeding at low risk for
Output:
| Seven of the 8 studies examining the effect of early endoscopy on length of stay as a measure of re source utilization demonstrated a significant reduction compared with that of delayed endoscopy .
The overwhelming majority of existing data suggest that early endoscopy is safe and effective for all risk groups . |
MS213702 | ***TASK*** the task is to summarize an input biomedical literature in six sentences
***INPUT*** the input is a biomedical literature
***OUTPUT*** the output is the summary of an input biomedical literature in six sentences
***DOCUMENTATION***
***EXAMPLES***
Input: Genotype scores that predict relevant clinical outcomes may detect other disease features and help direct prevention efforts . We report data that vali date a previously established v1.0 smoking cessation quit success genotype score and describe striking differences in the score in individuals who display differing developmental trajectories of use of common addictive substances . In a cessation study , v1.0 genotype scores predicted ability to quit with P=0.00056 and area under receiver-operating characteristic curve 0.66 . About 43 % vs 13 % quit in the upper vs lower genotype score terciles . Latent class growth analyses of a developmentally assessed sample identified three latent classes based on substance use . Higher v1.0 scores were associated with ( a ) higher probabilities of participant membership in a latent class that displayed low use of common addictive substances during adolescence ( P=0.0004 ) and ( b ) lower probabilities of membership in a class that reported escalating use ( P=0.001 ) . These results indicate that : ( a ) we have identified genetic predictors of smoking cessation success , ( b ) genetic influences on quit success overlap with those that influence the rate at which addictive substance use is taken up during adolescence and ( c ) individuals at genetic risk for both escalating use of addictive substances and poor abilities to quit may provide especially urgent focus for prevention efforts Abstract Alcohol and nicotine dependence are common in schizophrenia . Varenicline is effective in smoking cessation and has also been shown to decrease alcohol consumption in smokers . The present pilot study assessed the safety and effectiveness of varenicline for treatment of concurrent nicotine and alcohol dependence in schizophrenia . Out patients with schizophrenia or schizoaffective disorder and concurrent alcohol and nicotine dependence were enrolled in this 8-week , double-blind , r and omized , placebo-controlled trial . Alcohol use and smoking were assessed using self-report ( Timeline Follow-Back ) and biological measures . Adverse events were recorded . Changes in the number of st and ard drinks per week and cigarettes per week were compared in the 2 groups . Because of safety concerns or loss to follow-up , of 55 patients enrolled , only 10 started study medication , 5 each on varenicline and placebo . Gastrointestinal adverse effects , such as severe abdominal pain , limited study completion to only 4 subjects . Number of st and ard alcoholic drinks consumed per week decreased by [ mean ( SD ) ] 16.6 ( 20.1 ) in the varenicline group and by 2.4 ( 27.4 ) in the placebo group . Mean ( SD ) number of cigarettes smoked per week decreased by 66 ( 65 ) in the varenicline group and by 47 ( 77 ) in the placebo group . Varenicline treatment of concurrent alcohol and nicotine dependence in schizophrenia may be problematic because of safety concerns limiting recruitment and poor tolerability ( gastrointestinal adverse effects ) limiting retention . There was no increased number of serious neuropsychiatric adverse events in the varenicline group . Based on this small sample , concurrent alcohol and nicotine dependence in schizophrenia may present special obstacles to successful treatment with varenicline INTRODUCTION Dianicline is a α4β2 nicotinic acetylcholine receptor partial agonist , a class of drugs that includes varenicline and cytisine . Varenicline is efficacious for smoking cessation , while cytisine has not been studied systematic ally . The efficacy of dianicline has not been previously tested in an adequately powered study . METHODS In a r and omized , double-blind , parallel group placebo-controlled trial , 602 generally healthy cigarette smokers were assigned to dianicline ( n = 300 ) or placebo ( n = 302 ) for 7 weeks followed by a 19-week off drug follow-up period . RESULTS Exhaled carbon monoxide and cotinine-confirmed continuous abstinence rates for Weeks 4 - 7 were 24.0 % for dianicline versus 20.5 % for placebo ( odds ratio 1.22 ; 95 % CI , 0.83 - 1.80 ; p = .307 ) . For Weeks 4 - 26 , the abstinence rates were 16.7 % for dianicline versus 13.9 % for placebo ( odds ratio 1.24 ; 95 % CI , 0.79 - 1.93 ; p = .366 ) . Craving for a cigarettes was reduced by dianicline compared with placebo after 7 weeks ( p = .0175 ) . Nicotine withdrawal symptoms measured by the Hughes and Hatsukami Minnesota Withdrawal Scale were lower for dianicline compared with placebo in the first 3 weeks of treatment during which time quit rates were also higher in the dianicline-treated group . CONCLUSIONS Dianicline did not increase cigarette smoking abstinence rates beyond the initial phase of treatment . However , self-reported craving and nicotine withdrawal symptoms were reduced BACKGROUND Varenicline is approved as an aid to smoking cessation in adults aged > or = 18 years . OBJECTIVE The goal of this study was to characterize the multiple-dose pharmacokinetics , safety , and tolerability of varenicline in adolescent smokers . METHODS This multicenter , r and omized , double-blind , placebo-controlled , parallel-group study enrolled healthy 12- to 16-year-old smokers ( > or =3 cigarettes daily ) into high-body-weight ( > 55 kg ) and low-body-weight ( < or = 55 kg ) groups . Subjects were r and omized to receive 14 days of treatment with a high dose of varenicline , a low dose of varenicline , or placebo . The varenicline doses in the high-body-weight group were 1 mg BID and 0.5 mg BID ; the varenicline doses in the low-body-weight group were 0.5 mg BID and 0.5 mg once daily . The apparent renal clearance ( CL/F ) and volume of distribution ( V/F ) of varenicline and the effect of body weight on these parameters were estimated using nonlinear mixed-effects modeling . RESULTS The high-body-weight group consisted of 35 subjects ( 65.7 % male ; 77.1 % white ; mean age , 15.2 years ) . The low-body-weight group consisted of 37 subjects ( 37.8 % male ; 48.6 % white ; mean age , 14.3 years ) . The pharmacokinetic parameters of varenicline were dose proportional over the dose range from 0.5 to 2 mg/d . The CL/F for a 70-kg adolescent was 10.4 L/h , comparable to that in a 70-kg adult . The estimated varenicline V/F was decreased in individuals of small body size , thus predicting a varenicline C(max ) approximately 30 % greater in low-body-weight subjects than in high-body-weight subjects . In high-body-weight subjects , steady-state varenicline exposure , as represented by the AUC(0 - 24 ) , was 197.0 ng . h/mL for varenicline 1 mg BID and 95.7 ng . h/mL for varenicline 0.5 mg BID , consistent with values reported previously in adult smokers at the equivalent doses . In low-body-weight subjects , varenicline exposure was 126.3 ng . h/mL for varenicline 0.5 mg BID and 60.1 ng . h/mL for varenicline 0.5 mg once daily , values at the lower end of the range observed previously in adults at doses of 1 mg BID and 0.5 mg BID , respectively . Among high-body-weight subjects , adverse events ( AEs ) were reported by 57.1 % of subjects in both the high- and low-dose varenicline groups and by 14.3 % of subjects in the placebo group ; among low-body-weight subjects , AEs were reported by 64.3 % , 73.3 % , and 12.5 % of subjects in the high-dose varenicline , low-dose varenicline , and placebo groups , respectively . The most common AEs were nausea , headache , vomiting , and dizziness . Psychiatric AEs that were considered treatment related included abnormal dreams in 2 subjects and mild , transient anger in 1 subject . Of the AEs reported by > or = 1 subject in any treatment group , > or = 92 % were mild in intensity . No subject discontinued the study because of an AE . CONCLUSIONS Varenicline steady-state exposure in study subjects weighing > 55 kg was similar to that observed previously in adults . The body-weight effect on varenicline pharmacokinetics , which result ed in higher exposure in individuals of smaller body size ( < or = 55 kg ) , was adequately offset by administration of half the varenicline dose recommended in adults . Varenicline was generally well tolerated during the 14-day treatment period . Clinical Trials Identification Number : NCT00463918 Background — Smoking cessation is a key component of secondary cardiovascular disease prevention . Varenicline , a partial & agr;4&bgr;2 nicotinic acetylcholine receptor agonist , is effective for smoking cessation in healthy smokers , but its efficacy and safety in smokers with cardiovascular disease are unknown . Methods and Results — A multicenter , r and omized , double-blind , placebo-controlled trial compared the efficacy and safety of varenicline with placebo for smoking cessation in 714 smokers with stable cardiovascular disease . Participants received varenicline ( 1 mg twice daily ) or placebo , along with smoking-cessation counseling , for 12 weeks . Follow-up lasted 52 weeks . The primary end point was carbon monoxide – confirmed continuous abstinence rate for weeks 9 through 12 ( last 4 weeks of treatment ) . The continuous abstinence rate was higher for varenicline than placebo during weeks 9 through 12 ( 47.0 % versus 13.9 % ; odds ratio , 6.11 ; 95 % confidence interval [ CI ] , 4.18 to 8.93 ) and weeks 9 through 52 ( 19.2 % versus 7.2 % ; odds ratio , 3.14 ; 95 % CI , 1.93 to 5.11 ) . The varenicline and placebo groups did not differ significantly in cardiovascular mortality ( 0.3 % versus 0.6 % ; difference , −0.3 % ; 95 % CI , −1.3 to 0.7 ) , all-cause mortality ( 0.6 % versus 1.4 % ; difference , −0.8 % ; 95 % CI , −2.3 to 0.6 ) , cardiovascular events ( 7.1 % versus 5.7 % ; difference , 1.4 % ; 95 % CI , −2.3 to 5.0 ) , or serious adverse events ( 6.5 % and 6.0 % ; difference , 0.5 % ; 95 % CI , −3.1 to 4.1 ) . As a result of adverse events , 9.6 % of varenicline and 4.3 % of placebo participants discontinued study drug . Conclusions — Varenicline is effective for smoking cessation in smokers with cardiovascular disease . It was well tolerated and did not increase cardiovascular events or mortality ; however , trial size and duration limit definitive conclusions about safety . Clinical Trial Registration Information— URL : http://www . clinical trials.gov/ct2/show/NCT00282984 . Unique identifier : NCT00282984 UNLABELLED There are few data concerning changes in lung function and respiratory symptoms in smokers with chronic obstructive pulmonary disease ( COPD ) weeks to months after quitting smoking . We examined serial changes in spirometry and Clinical COPD Question naire ( CCQ ) scores ( measuring respiratory symptoms and health-related quality of life ) in COPD participants by smoking status during a smoking cessation trial . In this r and omized , double-blind trial , smokers with mild-to-moderate COPD were treated with varenicline 1 mg b.i.d . or placebo for 12 weeks and followed to Week 52 . Primary endpoints of abstinence were previously reported . Secondary endpoints were mean changes from baseline in post-bronchodilator forced expired volume in 1 s ( FEV(1 ) ) and CCQ scores . Change from baseline in post-bronchodilator FEV(1 ) was significantly improved in continuous abstainers ( 121.8 mL ) vs. continuous smokers ( 37.9 mL ) at Week 12 ( P = 0.0069 ) , but not at Weeks 24 or 52 . Mean change from baseline at Week 12 in CCQ Total Score was significantly better in continuous abstainers ( -1.04 ) vs. continuous smokers ( -0.53 ; P < 0.0001 ) : this improvement was sustained at Weeks 24 and 52 . In a 1-year cessation trial of smokers with COPD , continuous abstinence compared with continuous smoking significantly improved post-bronchodilator FEV(1 ) at Week 12 ( although the difference narrowed subsequently ) and
Output:
| However , subsequent observational cohort studies and meta-analyses have not confirmed these fears , and the findings of the EAGLES trial do not support a causal link between varenicline and neuropsychiatric disorders , including suicidal ideation and suicidal behaviour .
The evidence is not conclusive , however , in people with past or current psychiatric disorders .
Lower dose regimens also conferred benefits for cessation , while reducing the incidence of adverse events .
Limited evidence suggests that varenicline may have a role to play in relapse prevention .
The most frequently recorded adverse effect of varenicline is nausea , but mostly at mild to moderate levels and tending to subside over time . |
MS213703 | ***TASK*** the task is to summarize an input biomedical literature in six sentences
***INPUT*** the input is a biomedical literature
***OUTPUT*** the output is the summary of an input biomedical literature in six sentences
***DOCUMENTATION***
***EXAMPLES***
Input: The objective was to identify subgroups of patients with hypertension and atherosclerotic renal artery stenosis who may benefit from immediate intervention . In the DRASTIC study , patients with hypertension , significant atherosclerotic renal artery stenosis , and a normal or mildly impaired renal function were r and omized between immediate balloon angioplasty ( PTRA ; n=56 ) and drug therapy followed by angioplasty after 3 months , if needed ( Med-PTRA ; n=50 ) . In this secondary analysis of the data , changes in the renal function and blood pressure after 1 year were studied by analysis of covariance in the following subgroups : patients with positive captopril – renin challenge test , abnormal captopril renogram , recently developed hypertension , bilateral stenosis , and severe stenosis . We found a benefit of immediate angioplasty only for patients with bilateral stenosis . Their creatinine clearance had decreased ( mean±s.d . : −4.2±13.5 ml/min ) in the Med-PTRA group , whereas it had improved substantially ( + 10.0±15.7 ml/min ) in the PTRA group ( P=0.02 ) . For patients with unilateral stenosis , the change in creatinine clearance did not differ between PTRA and Med-PTRA ( + 4.3±15.5 and + 1.3±12.5 ml/min , respectively ) . The patients with bilateral stenosis also seemed to benefit most from immediate intervention with regard to blood pressure control . None of the other subgroups had a clear benefit of immediate intervention regarding renal function or blood pressure control . In conclusion , intervention should not be postponed in patients with bilateral stenosis , even if renal function is normal . Other hypertensive patients with atherosclerotic renal artery disease could initially well be treated by aggressive multidrug therapy alone unless hypertension persists or renal function deteriorates Renal function and antihypertensive drug efficacy were determined in a prospect i ve , double-blind , multicenter study comparing enalapril plus hydrochlorothiazide with st and ard triple therapy ( hydrochlorothiazide , timolol , and hydralazine ) in 75 patients with documented renovascular hypertension . Both groups had significant mean decreases in systolic and diastolic blood pressures . Effective control of diastolic hypertension occurred in 96 percent of patients receiving enalapril compared with 82 percent of patients receiving the triple-drug regimen . Effective renal plasma flow was significantly increased by enalapril therapy . In contrast , the glomerular filtration rate had a bimodal response . In 80 percent of enalapril-treated patients , there was no significant change in the inulin clearance , although in 20 percent of patients ( 10 ) , there was a 28 percent decrease in the inulin clearance with a concomitant 12 percent increase in renal plasma flow . Seven of the 10 patients had unilateral renal artery stenosis , but in all 10 , it was high- grade stenosis ( more than 80 to 90 percent stenosis ) . Although a significant rise in the serum creatinine level occurred in one patient in association with diuretic therapy , volume repletion reversed this azotemia . No oliguric acute renal failure occurred in the enalapril-treated group . The cause of the decrease in glomerular filtration rate induced by enalapril plus hydrochlorothiazide in a minority of patients with renal artery stenosis appears to be quite complex . Although the abolishment of the autoregulation of glomerular filtration secondary to blockage of angiotensin II appears to be a primary cause , the roles of decreased arterial pressure , renal counterbalance , concurrent diuretic therapy , and other hemodynamic factors that may maintain glomerular ultrafiltration pressure must also be considered . The results of this study show that enalapril plus hydrochlorothiazide is effective in treating renovascular hypertension . Special care is needed for a small group of patients with renovascular hypertension in whom there is a decrease in the glomerular filtration rate with this therapy . This may identify a subset of patients with unilateral or bilateral high- grade renal artery stenosis in whom alternative therapy -- percutaneous angioplasty or surgical intervention -- may be considered ACUTE renal failure occasionally complicates therapy with the oral angiotensin-converting-enzyme inhibitor captopril.1 2 3 4 5 A variety of mechanisms have been postulated to account for captopril- OBJECTIVE The objective of our study was to evaluate the safety of CO(2 ) and gadodiamide angiography for diagnosing and percutaneously treating renal artery stenosis in patients with chronic renal insufficiency and presumed ischemic nephropathy . SUBJECTS AND METHODS One hundred forty-six consecutive patients with chronic renal insufficiency ( serum creatinine > 1.5 mg/dL ) were examined for renal artery stenosis using CO(2 ) and gadodiamide as the angiographic contrast agents . If renal artery stenosis was detected , percutaneous balloon angioplasty with or without stenting was performed . In patients for whom 48-hr creatinine levels were available , we performed an analysis to determine the incidence of contrast-involved nephropathy ( increase in serum creatinine of 0.5 mg/dL at 48 hr without identifiable cause ) . Major complications were reported up to 1 week , and mortality was reported up to 30 days after the procedure . RESULTS Ninety-five patients had serum creatinine levels available at 48 hr . An increase in creatinine of greater than 0.5 mg/dL at 48 hr occurred in three patients ( 3.2 % ) , presumably caused by CO(2 ) , by gadodiamide , or by both . Neither diabetes nor the degree of preexisting chronic renal insufficiency was a predictor of worsening renal function 48 hr after the procedure . The volumes of CO(2 ) and gadodiamide used for diagnostic studies alone versus the volume used for interventional studies was not significantly different ( for CO(2 ) , p = 0.09 ; for gadodiamide , p = 0.30 ) . Eleven major complications occurred in eight patients ( 5.5 % ) . Two deaths ( 1.4 % ) occurred within 30 days . One death was due to cholesterol embolization and the other was not believed to be related to the procedure . CONCLUSION Angiography and percutaneous treatment of renal artery stenosis in patients with chronic renal insufficiency and suspected ischemic nephropathy can be performed relatively safely using CO(2 ) and gadodiamide as angiographic contrast agents without an increased risk of complications . Contrast-induced nephropathy potentially occurred in 3.2 % of patients . Neither the degree of underlying renal insufficiency nor diabetes was a risk factor for predicting a greater likelihood of renal function worsening at 48 hr of follow-up . The volumes of CO(2 ) and gadodiamide used in this study did not result in an increased risk of contrast-involved nephropathy Data for the effects on blood pressure of renal artery balloon angioplasty are mostly from uncontrolled studies . The aim of this study was to document the efficacy and safety of angioplasty for lowering blood pressure in patients with atherosclerotic renal artery stenosis . Patients were r and omly assigned antihypertensive drug treatment ( control group , n = 26 ) or angioplasty ( n = 23 ) . Twenty-four-hour ambulatory blood pressure , the primary end point , was measured at baseline and at termination . Termination took place 6 months after r and omization or earlier in patients who developed refractory hypertension . In those allocated angioplasty , antihypertensive treatment was discontinued after the procedure but was subsequently resumed if hypertension persisted . Secondary end points were the treatment score and the incidence of complications . Two patients in the control group and 6 in the angioplasty group suffered procedural complications ( relative risk , 3.4 ; 95 % confidence interval , 0.8 to 15.1 ) . Early termination was required for refractory hypertension in 7 patients in the control group . Antihypertensive treatment was resumed in 17 patients in the angioplasty group . Mean ambulatory blood pressure at termination did not differ between control ( 141+/-15/84+/-11 mm Hg ) and angioplasty ( 140+/-15/81+/-9 mm Hg ) groups . Angioplasty reduced by 60 % the probability of having a treatment score of 2 or more at termination ( relative risk , 0.4 ; 95 % confidence interval , 0.2 to 0.7 ) . There was 1 case of dissection with segmental renal infa rct ion and 3 of restenosis in the angioplasty group . No patient suffered renal artery thrombosis . In unilateral atherosclerotic renal artery stenosis , angioplasty is a drug-sparing procedure that involves some morbidity . Previous uncontrolled and unblinded assessment s of angioplasty overestimated its potential for lowering blood pressure PURPOSE To compare the results of balloon percutaneous transluminal renal angioplasty ( PTRA ) and stent placement in atherosclerotic ostial , proximal , and isolated truncal stenoses . MATERIAL S AND METHODS Between January 1994 and April 1998 the authors prospect ively followed up 163 consecutive patients with 200 atherosclerotic renal arterial lesions after primary PTRA or primary stent placement . Duplex ultrasonography was performed 1 day and 3 , 6 , and 12 months later . RESULTS The primary 12-month PTRA patency rates were 34 % ( 21 of 33 atherosclerotic lesions ) for ostial stenoses , 65 % ( 20 of 60 ) for proximal stenoses , and 83 % ( five of 30 ) for truncal stenoses ( chi(2 ) value , 15.63 ; P < .001 ) . The corresponding stent patency rates were 80 % ( four of 21 ) , 72 % ( nine of 34 ) , and 66 % ( five of nine ) , respectively ( chi(2 ) value , 4.11 ; not significant ) . Significant stent-related reduction in risk of restenosis was limited to the ostial stenoses ( P = .002 ) . CONCLUSION Renal arterial stent placement considerably improves patency in ostial stenoses , but compared with the technically successful PTRA , it does not significantly improve primary patency in proximal and isolated truncal renal arterial stenoses The purpose s of this study were to determine the prevalence of angiographically significant renal artery stenosis in a patient population referred for diagnostic cardiac catheterization and to develop a model that predicts the highest-risk subset of patients who have significant renal artery narrowing . A prospect i ve validation cohort study was undertaken in a referral-based university hospital . After left ventriculography , abdominal aortography was performed to screen for the presence of renal artery disease . A convenience sample of 1,302 of 1,651 consecutive patients undergoing diagnostic cardiac catheterization were enrolled in the study . Of the 1,302 abdominal aortograms performed , 1,235 ( 95 % ) were deemed of adequate quality for the evaluation of renal artery anatomy . Renal artery disease was identified in 30 % of the patients . Insignificant renal artery stenosis was found in 187 ( 15 % ) and significant ( greater than or equal to 50 % diameter narrowing ) stenosis was found in 188 ( 15 % ) . Significant unilateral disease was present in 11 % , and bilateral disease was present in 4 % . By univariable and multivariable logistic regression analysis , the association of both clinical ly and catheterization-derived variables with renal artery disease was assessed . Multivariable predictors included age , severity of coronary artery disease , congestive heart failure , female gender , and peripheral vascular disease . Hypertension was not an associated variable . These data reveal the previously undetected high prevalence of renal artery disease in patients undergoing cardiac catheterization and provide clinical and angiographic features that assist in predicting its presence Purpose : To determine pretreatment variables that may predict 1-year clinical outcome of stent placement for renal artery stenosis . Methods : In a prospect i ve study , 40 consecutive patients ( 29 men ; mean age 60 ± 9.1 years ) with angiographically proven atherosclerotic renal artery stenosis were treated with stent placement because of drug resistant hypertension ( n=14 ) , renal function impairment ( n=14 ) , or both ( n=12 ) . Clinical success at 1 year was defined as a decrease of diastolic blood pressure ≥10 mmHg or a decrease in serum creatinine ≥20 % , depending on the indication for treatment . Regression analysis was performed using anatomical parameters from angiography and intravascular ultrasound , estimates of renal blood flow from renal scintigraphy , and single-kidney renal function measurements . Results : Patients treated for hypertension had better outcome than those treated for renal function impairment , with clinical success rates of 85 % and 35 % , respectively . Preserved renal function , with low serum creatinine and high 2-kidney glomerular filtration rate at baseline , was associated with clinical success in the entire patient group at follow-up ( p=0.0
Output:
| Some evidence suggested similar kidney outcomes but better blood pressure outcomes with angioplasty , particularly in patients with bilateral renal disease .
Weak evidence suggested no large differences in mortality or cardiovascular events between medical and revascularization treatments .
No evidence directly compared adverse event rates between treatments . |
MS213704 | ***TASK*** the task is to summarize an input biomedical literature in six sentences
***INPUT*** the input is a biomedical literature
***OUTPUT*** the output is the summary of an input biomedical literature in six sentences
***DOCUMENTATION***
***EXAMPLES***
Input: Objective : To assess whether forest therapy is effective for treating depression and anxiety in patients with chronic stroke by using several psychological tests . We measured reactive oxygen metabolite ( d-ROM ) levels and biological antioxidant potentials ( BAPs ) associated with psychological stress . Methods : Fifty-nine patients with chronic stroke were r and omly assigned to either a forest group ( staying at a recreational forest site ) or to an urban group ( staying in an urban hotel ) ; the duration and activities performed by both groups were the same . Scores on the Beck Depression Inventory ( BDI ) , Hamilton Depression Rating Scale ( HAM-D17 ) , Spielberger State-Trait Anxiety Inventory ( STAI ) , d-ROMs and BAPs were evaluated both before and after the treatment programs . Results : In the forest group , BDI , HAM-D17 and STAI scores were significantly lower following treatment , and BAPs were significantly higher than baseline . In the urban group , STAI scores were significantly higher following treatment . Moreover , BDI , HAM-D17 and STAI scores of the forest group were significantly lower , and BAPs were significantly higher following treatment ( ANCOVA , p < 0.05 ) . Conclusion : Forest therapy is beneficial for treating depression and anxiety symptoms in patients with chronic stroke , and may be particularly useful in patients who can not be treated with st and ard pharmacological or electroconvulsive therapies Major depressive disorder ( MDD ) is prevalent after traumatic brain injury ( TBI ) ; however , there is a lack of evidence regarding effective treatment approaches . We conducted a choice-stratified r and omized controlled trial in 100 adults with MDD within 10 years of complicated mild to severe TBI to test the effectiveness of brief cognitive behavioral therapy administered over the telephone ( CBT-T ) ( n = 40 ) or in-person ( CBT-IP ) ( n = 18 ) , compared with usual care ( UC ) ( n = 42 ) . Participants were recruited from clinical and community setting s throughout the United States . The main outcomes were change in depression severity on the clinician-rated 17 item Hamilton Depression Rating Scale ( HAMD-17 ) and the patient-reported Symptom Checklist-20 ( SCL-20 ) over 16 weeks . There was no significant difference between the combined CBT and UC groups over 16 weeks on the HAMD-17 ( treatment effect = 1.2 , 95 % CI : -1.5 - 4.0 ; p = 0.37 ) and a nonsignificant trend favoring CBT on the SCL-20 ( treatment effect = 0.28 , 95 % CI : -0.03 - 0.59 ; p = 0.074 ) . In follow-up comparisons , the CBT-T group had significantly more improvement on the SCL-20 than the UC group ( treatment effect = 0.36 , 95 % CI : 0.01 - 0.70 ; p = 0.043 ) and completers of eight or more CBT sessions had significantly improved SCL-20 scores compared with the UC group ( treatment effect = 0.43 , 95 % CI : 0.10 - 0.76 ; p = 0.011 ) . CBT participants reported significantly more symptom improvement ( p = 0.010 ) and greater satisfaction with depression care ( p < 0.001 ) , than did the UC group . In-person and telephone-administered CBT are acceptable and feasible in persons with TBI . Although further research is warranted , telephone CBT holds particular promise for enhancing access and adherence to effective depression treatment A method for assessing affect states among older people with Alzheimer 's disease was developed for use in a study design ed to evaluate a special care unit for such residents of a nursing home . The 6-item Philadelphia Geriatric Center Affect Rating Scale was design ed for the use of research and other staff in assessing positive affect ( pleasure , interest , contentment ) and negative affect ( sadness , worry/anxiety , and anger ) by direct observation of facial expression , body movement , and other cues that do not depend on self-report , among 253 demented and 43 nondemented residents . Each affect scale was highly reliable , expressed in estimated portions of a 10-minute observation period when the affect expression occurred . Validity estimates were affirmative in showing discriminant correlations between the positive states and various independent measures of social and other outwardly engaged behavior and between negative states and other measures of depression , anger , anxiety , and withdrawal . Limited support for the two-factor dimensionality of the affect ratings was obtained , although positive and negative affect were correlated , rather than independent . Some hope is offered that the preference and aversions of Alzheimer patients may be better understood by observations of their emotional behaviors and that such methods may lead to a better ability to judge institutional quality PURPOSE To assess the effects of horticultural therapy ( HT ) on mood state and heart rate ( HR ) in patients participating in an inpatient cardiac rehabilitation program . METHODS Cardiac rehabilitation in patients ( n = 107 ) participated in the study . The HT group consisted of 59 subjects ( 34 males , 25 females ) . The control group , which participated in patient education classes ( PECs ) , consisted of 48 subjects ( 31 males , 17 females ) . Both HT sessions and PEC are components of the inpatient rehabilitation program . Each group was evaluated before and after a class in their respective modality . Evaluation consisted of the completion of a Profile of Mood States ( POMS ) inventory , and an HR obtained by pulse oximetry . RESULTS Changes in the POMS total mood disturbance ( TMD ) score and HR between preintervention and postintervention were compared between groups . There was no presession difference in either TMD score ( 16 + /- 3.6 and 19.0 + /- 3.2 , PEC and HT , respectively ) or HR ( 73.5 + /- 2.5 and 79 + /- 1.8 , PEC and HT , respectively ) . Immediately following the intervention , the HT TMD was significantly reduced ( post-TMD = 1.6 + /- 3.2 , P < .001 ) , while PEC TMD was not significantly changed ( TMD = 17.0 + /- 28.5 ) . After intervention , HR fell in HT by 4 + /- 9.6 bpm ( P < .001 ) but was unchanged in PEC . CONCLUSION These findings indicate that HT improves mood state , suggesting that it may be a useful tool in reducing stress . Therefore , to the extent that stress contributes to coronary heart disease , these findings support the role of HT as an effective component of cardiac rehabilitation Objective : To evaluate the contribution of social communication abilities and affective/behavioral functioning to socialintegration outcomes for persons with traumatic brain injury ( TBI ) . Design : Prospect i ve cohort study . Participants : A total of 184 adults with TBI ( 72.8 % men ) evaluated at least 6 months postdischarge from acute care orinpatient rehabilitation hospitals and after living at least 3 months in the community postdischarge ( Mean = 7.84 monthspostinjury ) . Measures : La Trobe Communication Question naire ( LCQ ) , Assessment of Interpersonal Problem-Solving Skills(AIPSS ) , Affective Behavioral subscale From the Problem Checklist of the Head Injury Family Interview ( AB-HIFI ) , Craig H and icap Assessment and Reporting Technique – Short Form Social Integration subscale ( CHART-SF-SI ) , Community Integration Question naireSocial Integration subscale ( CIQ-SI ) . Results : Social communication measures ( LCQ , AIPSS ) and self-reported behavioralfunctioning ( AB-HIFI ) contributed significantly to concurrently measured social integration outcomes after controlling for demographic and injury-related variables . Separate hierarchical multiple regression analyses revealed that social communication and behavioralvariables accounted for 11.3 % of variance in CIQ-SI and 16.3 % of variance in CHART-SF-SI . Conclusions : Social communication abilities and affective/behavioral functioning make a substantial contribution to social integration outcomes after TBI . The implication s of such evidence for clinical assessment and intervention are discussed BACKGROUND Severe mitral regurgitation ( MR ) is associated with frequent alteration of psychoemotional status ( PES ) , with anxiety and stress symptoms related to health-related quality of life ( HR-QOL ) . Yet , it is unknown whether surgical correction of MR leads to improvement or deterioration in PES and HR-QOL . METHODS We prospect ively performed comprehensive MR assessment and administered question naires assessing PES and HR-QOL in 131 patients ( aged 60 years ; 75 % men ) before and 6 months after operation for organic MR and compared them to 62 patients who did not undergo operation for mitral disease and 36 normal controls of similar age assessed with the same methods . RESULTS Baseline PES was poorer preoperatively in patients undergoing mitral operation compared with patients who did not undergo mitral operation and normal controls ( anxiety and posttraumatic stress [ PTS ] ; both p < 0.01 ) with poorer physical HR-QOL ( p < 0.01 ) . Six months later , all these psychoemotional variables improved ( all p ≤ 0.02 ) in the patients who underwent mitral operation , whereas no change was observed in the other 2 groups ( all p > 0.1 ) . Improvement after mitral repair result ed in postoperative normalization of emotional and physical well-being , with similar scores among all groups ( all p ≥ 0.4 ) . At 6-month follow-up , no difference in improvement in PES and HR-QOL was noted according to the surgical approach ( robotic versus sternotomy , all p ≥ 0.2 ) . CONCLUSIONS Patients with severe organic MR present with frequent psychoemotional alterations and HR-QOL deterioration , in contrast to patients who do not undergo mitral operation and normal controls . After mitral operation , notable improvement results in normalization of emotional and physical well-being . Quantification of emotional and physical well-being provides important outcome measures in patients with organic MR and uncovers important benefits provided by surgical correction of MR
Output:
| Evidence suggests that engaging with gardens , and gardening , can favourably impact the emotional and social health of people with dementia and , an explanatory theoretical model is proposed . |
MS213705 | ***TASK*** the task is to summarize an input biomedical literature in six sentences
***INPUT*** the input is a biomedical literature
***OUTPUT*** the output is the summary of an input biomedical literature in six sentences
***DOCUMENTATION***
***EXAMPLES***
Input: Objective : To analyze the effect of an immune enhancing ( IE ) diet on infection and metabolic indices in children with severe head injury fed either an IE or a regular formula . Design : R and omized , blinded , controlled study . Setting : Pediatric intensive care unit in a university hospital . Patients : A total of 40 mechanically ventilated children with severe head injury . Interventions : Within 12 hrs of pediatric intensive care unit admission , patients were r and omized to receive a masked formula : either IE or regular formula . Feedings were advanced to a target volume of energy intake equal to 0.50 % , 100 % , 125 % , 150 % , and 150 % of the predicted basal metabolic rate on days 1–5 . Measurements and Main Results : Nutritional and metabolic indices ; interleukins-1β , -6 , and -8 ; tumor necrosis factor-α ; and outcome end points ( survival , length of stay , length of mechanical ventilation ) were compared between the two groups . Only interleukin-8 levels were lower in the IE group compared with the regular formula group by day 5 ( 23.6 ± 1.5 vs. 35.5 ± 4 pg/mL , p < .04 ) . In multivariate regression analysis , interleukin-8 was also independently negatively correlated with immunonutrition ( p < .04 ) . Nitrogen balance became positive in 30.8 % of patients in the regular formula group and in 69.2 % of patients in the IE group by day 5 ( p < .05 ) . Less gastric cultures were positive in the IE group compared with the regular formula group ( 26.7 % vs. 71.4 % , p < .02 ) . Nosocomial infections ( 15 % vs. 25 % ) , length of stay ( 16.7 vs. 12.2 days ) , length of mechanical ventilation ( 11 vs. 8 days ) , and survival ( 80 % vs. 95 % ) did not differ between groups . Conclusions : Although immunonutrition might decrease interleukin-8 and gastric colonization in children with severe head injury , it might not be associated with additional advantage over the one demonstrated by regular early enteral nutrition Introduction During pressure support ventilation ( PSV ) a part of the breathing pattern is controlled by the patient , and synchronization of respiratory muscle action and the result ing chest wall kinematics is a valid indicator of the patient 's adaptation to the ventilator . The aim of the present study was to analyze the effects of different PSV setting s on ventilatory pattern , total and compartmental chest wall kinematics and dynamics , muscle pressures and work of breathing in patients with acute lung injury . Method In nine patients four different levels of PSV ( 5 , 10 , 15 and 25 cmH2O ) were r and omly applied with the same level of positive end-expiratory pressure ( 10 cmH2O ) . Flow , airway opening , and oesophageal and gastric pressures were measured , and volume variations for the entire chest wall , the ribcage and abdominal compartments were recorded by opto-electronic plethysmography . The pressure and the work generated by the diaphragm , rib cage and abdominal muscles were determined using dynamic pressure-volume loops in the various phases of each respiratory cycle : pre-triggering , post-triggering with the patient 's effort combining with the action of the ventilator , pressurization and expiration . The complete breathing pattern was measured and correlated with chest wall kinematics and dynamics . Results At the various levels of pressure support applied , minute ventilation was constant , with large variations in breathing frequency/ tidal volume ratio . At pressure support levels below 15 cmH2O the following increased : the pressure developed by the inspiratory muscles , the contribution of the rib cage compartment to the total tidal volume , the phase shift between rib cage and abdominal compartments , the post-inspiratory action of the inspiratory rib cage muscles , and the expiratory muscle activity . Conclusion During PSV , the ventilatory pattern is very different at different levels of pressure support ; in patients with acute lung injury pressure support greater than 10 cmH2O permits homogeneous recruitment of respiratory muscles , with result ing synchronous thoraco-abdominal expansion BACKGROUND Multiple organ dysfunction syndrome ( MODS ) is a major cause of mortality in intensive care units . A breakdown in gut barrier function and immune dysfunction are associated with the onset of MODS . Probiotic bacteria have been shown to modulate intestinal barrier and immune function . OBJECTIVE This study assessed the efficacy of a probiotic compound in a viable and nonviable formulation in modulating intestinal permeability and immune function and preventing the onset of MODS in patients in the intensive care unit . DESIGN A double-blind , r and omized controlled trial was conducted in the intensive care unit of a tertiary care teaching hospital . Twenty-eight critically ill patients admitted to the intensive care unit were r and omly assigned to receive 1 of 3 treatments daily for 7 d : 1 ) placebo , 2 ) viable probiotics , or 3 ) equivalent probiotic sonicates . MODS scores and systemic concentrations of immunoglobulin ( Ig ) A and IgG were measured on days -1 , 4 , and 7 , and intestinal permeability measurements were taken daily . RESULTS The patients responded to viable probiotics with a significantly larger increase in systemic IgA and IgG concentrations than in the patients who received placebo or sonicates ( P < 0.05 ) . MODS scores were not significantly affected by probiotic treatment . Over the study period , intestinal permeability decreased in most patients . CONCLUSION Patients receiving viable probiotics show a greater enhancement in immune activity than do patients receiving either placebo or probiotic bacterial sonicates Objective : To assess the effect of isocaloric isonitrogenous parenteral glutamine supplementation on intestinal permeability and nitrogen loss in newborns and infants after major digestive-tract surgery . Summary Background Data : Glutamine supplementation in critically ill and surgical adults may normalize intestinal permeability , attenuate nitrogen loss , improve survival , and lower the incidence of nosocomial infections . Previous studies in critically ill children were limited to very-low-birthweight infants and had equivocal results . Methods : Eighty newborns and infants were included in a double-blind , r and omized trial comparing st and ard parenteral nutrition ( sPN ; n = 39 ) to glutamine-supplemented parenteral nutrition ( GlnPN ; glutamine target intake , 0.4 g kg−1 day−1 ; n = 41 ) , starting on day 2 after major digestive-tract surgery . Primary endpoints were intestinal permeability , as assessed by the urinary excretion ratio of lactulose and rhamnose ( weeks 1 through 4 ) ; nitrogen balance ( days 4 through 6 ) , and urinary 3-methylhistidine excretion ( day 5 ) . Secondary endpoints were mortality , length of stay in the ICU and the hospital , number of septic episodes , and usage of antibiotics and ICU re sources . Results : Glutamine intake plateaued at 90 % of the target on day 4 . No differences were found between patients assigned sPN and patients assigned GlnPN regarding any of the endpoints . Glutamine supplementation was not associated with adverse effects . Conclusions : In newborns and infants after major digestive-tract surgery , we did not identify beneficial effects of isonitrogenous , isocaloric glutamine supplementation of parenteral nutrition . Glutamine supplementation in these patients therefore is not warranted until further research proves otherwise The aim of the study was to analyse the effects of early enteral feeding on the prevention of enterogenic infection in severely burned patients . A total of 22 patients with severe burns were r and omly divided into an early enteral feeding group ( EF ) and a delayed enteral feeding group ( DF ) . The levels of serum endotoxin and TNF-alpha were dynamically detected in the members of both groups , and two unmetabolized sugars ( lactulose and mannitol ) were orally administered to these patients 1 , 3 and 5 days postburn . Intestinal permeability was evaluated by detecting the concentrations of lactulose and mannitol in the urine and the lactulose-mannitol ratio ( L/M ) ratio . The levels of serum endotoxin and TNF-alpha in severely burned patients were significantly higher than in normal subjects ( P<0.01 ) . The endotoxin level was positively related to the TNF-alpha level ( rEF=0.93 , P<0.01 ; rDF=0.80 , P<0.05 ) . The urinary lactulose levels in both groups were significantly higher than in normal ( P<0.01 ) , the urinary mannitol levels showed no obvious changes ( P>0.05 ) . The urinary L/M ratios in both groups were significantly higher than in normal subjects ( P<0.01 ) . The urinary L/M ratio was positively related to the serum endotoxin level ( r=0.95 , P<0.01 ) . The urinary lactulose levels and the urinary L/M ratios in the EF group were significantly lower than in the DF group ( P<0.01 ) . The levels of serum endotoxin and TNF-alpha in the EF group were significantly lower than in the DF group ( P<0.01 ) . It is suggested that intestinal permeability was markedly higher after burns than normal , and was positively related to the gut-derived endotoxemia . Early enteral feeding may decrease intestinal permeability , preserve the intestinal mucosal barrier and have a beneficial effect on the reduction of enterogenic infection BACKGROUND / PURPOSE Nutritional support of surgical patients has improved in recent years because of the possibility of modulating catabolism and anabolism , thus enhancing the immune response and repair processes . The objective of this study was to evaluate metabolic effects of early parenteral nutrition ( PN ) after major surgery . METHODS The authors studied 63 children aged 4 to 14 years with diffuse peritonitis caused by perforated-suppurative appendicitis . They were assigned r and omly to a study group ( SG , n = 31 ) , which received PN for 5 days , starting 24 to 48 hours after surgery or to a control group ( CG , n = 32 ) , that received st and ard treatment ( fluids ) . Weight , C-reactive protein ( CRP ) , albumin , prealbumin , glycemia , nitrogen balance ( NB ) , and insulinlike growth factor ( IGF-I ) , were evaluated on postoperative days 1 , 4 , and 6 . RESULTS Early nutritional support was associated with a significant improvement in NB and IGF-I ( Repeat measures analysis of variance IGF-I , P<.001 and NB P<.01 ) . CONCLUSIONS The authors conclude that early parenteral nutrition has a positive effect on the anabolic response as shown by improved NB and higher IGF-I levels in pediatric patients after major surgery Objective To compare the effect of early enteral feeding using immune-enhancing ( IE ) vs. non-immune-enhancing ( NIE ) formulas on cytokines in children with septic shock . Design and setting A single-center , r and omized , blinded controlled trial in a pediatric intensive care unit of a university hospital . Patients We r and omized 38 patients with septic shock to either IE or NIE . Feedings were advanced to a target volume of energy intake equal to 1/2 , 1 , 5/4 , 6/4 , and 6/4 of the predicted basal metabolic rate on days 1–5 , respectively . Measurements and results Interleukins ( IL ) 1β , 6 , and 8 , tumor necrosis factor α , C-reactive protein , Pediatric Risk of Mortality ( PRISM ) score , survival , secondary infections , length of stay , and mechanical ventilation were compared within and between the two groups . Actual mean energy and protein intakes did not differ between the two groups and the caloric-protein balance was not correlated to cytokine levels . On day 5 IL-6 levels were significantly lower ( 11.8±2.4 vs. 38.3±3.6 ) and IL-8 significantly higher in the IE than in the NIE group ( 65.4±17 vs. 21±2.5 ) . After 5 days of nutritional support a significant decrease in IL-6 levels was recorded only in group IE ( mean of paired differences 39.4±3 pg/ml ) . In multivariate regression analysis the variation in cytokines was independently correlated only to PRISM ( R2=−0.50 ) , but pediatric intensive care unit outcome endpoints did not differ between the two groups . Conclusions Early IE nutrition may modulate cytokines in children with septic shock , but there is no evidence that this immunomodulation has any impact on short-term outcome Objectives : To measure energy expenditure in critically ill children and compare it with the energy expenditure predicted by recommended formulas , and relate the measured energy expenditure to nutritional and clinical indices . Design : A prospect i ve , clinical study . Setting : Tertiary care pediatric intensive care unit in a university children 's hospital . Patients : A total of 37 patients with critical illness who were mechanically ventilated for ≥24 hrs were studied . Interventions : None . Measurements and Main Results : Chronic protein‐energy malnutrition ( CPEM ) and acute protein‐energy malnutrition were defined by the Waterlow 's stages and fat and protein stores were classified as defined by Frisancho , Ryan , and Martinez . Severity
Output:
| the mortality rate is different in children who are given enteral nutrition alone versus enteral and parenteral combined;4 .
the mortality rate is different in children who are given both enteral feeds and parenteral nutrition versus no nutrition .
No statistically significant differences were observed for mortality , sepsis , ventilator days , length of stay , unexpected adverse events , resting energy expenditure , nitrogen balance , or albumin levels . |
MS213706 | ***TASK*** the task is to summarize an input biomedical literature in six sentences
***INPUT*** the input is a biomedical literature
***OUTPUT*** the output is the summary of an input biomedical literature in six sentences
***DOCUMENTATION***
***EXAMPLES***
Input: To comprehend the results of a r and omised controlled trial ( RCT ) , readers must underst and its design , conduct , analysis , and interpretation . That goal can be achieved only through total transparency from authors . Despite several decades of educational efforts , the reporting of RCTs needs improvement . Investigators and editors developed the original CONSORT ( Consoli date d St and ards of Reporting Trials ) statement to help authors improve reporting by use of a checklist and flow diagram . The revised CONSORT statement presented here incorporates new evidence and addresses some criticisms of the original statement . The checklist items pertain to the content of the Title , Abstract , Introduction , Methods , Results , and Discussion . The revised checklist includes 22 items selected because empirical evidence indicates that not reporting this information is associated with biased estimates of treatment effect , or because the information is essential to judge the reliability or relevance of the findings . We intended the flow diagram to depict the passage of participants through an RCT . The revised flow diagram depicts information from four stages of a trial ( enrolment , intervention allocation , follow- up , and analysis ) . The diagram explicitly shows the number of participants , for each intervention group , included in the primary data analysis . Inclusion of these numbers allows the reader to judge whether the authors have done an intention- to-treat analysis . In sum , the CONSORT statement is intended to improve the reporting of an RCT , enabling readers to underst and a trial 's conduct and to assess the validity of its results A pilot study was conducted to investigate the effects of Healing Touch ( HT ) on agitation in persons with dementia . Because of the restricted availability of patients , the main purpose of the study was to investigate the effectiveness of HT on dementia patients who demonstrated similar high levels of agitation as measured by the Cohen-Mansfield Agitation Inventory . Results indicated that agitation levels were significantly lowered and that HT is worthy of further study & NA ; Pain intensity is frequently measured on an 11‐point pain intensity numerical rating scale ( PI‐NRS ) , where 0=no pain and 10=worst possible pain . However , it is difficult to interpret the clinical importance of changes from baseline on this scale ( such as a 1‐ or 2‐point change ) . To date , there are no data driven estimates for clinical ly important differences in pain intensity scales used for chronic pain studies . We have estimated a clinical ly important difference on this scale by relating it to global assessment s of change in multiple studies of chronic pain . Data on 2724 subjects from 10 recently completed placebo‐controlled clinical trials of pregabalin in diabetic neuropathy , postherpetic neuralgia , chronic low back pain , fibromyalgia , and osteoarthritis were used . The studies had similar design s and measurement instruments , including the PI‐NRS , collected in a daily diary , and the st and ard seven‐point patient global impression of change ( PGIC ) , collected at the endpoint . The changes in the PI‐NRS from baseline to the endpoint were compared to the PGIC for each subject . Categories of ‘ much improved ’ and ‘ very much improved ’ were used as determinants of a clinical ly important difference and the relationship to the PI‐NRS was explored using graphs , box plots , and sensitivity/specificity analyses . A consistent relationship between the change in PI‐NRS and the PGIC was demonstrated regardless of study , disease type , age , sex , study result , or treatment group . On average , a reduction of approximately two points or a reduction of approximately 30 % in the PI‐NRS represented a clinical ly important difference . The relationship between percent change and the PGIC was also consistent regardless of baseline pain , while higher baseline scores required larger raw changes to represent a clinical ly important difference . The application of these results to future studies may provide a st and ard definition of clinical ly important improvement in clinical trials of chronic pain therapies . Use of a st and ard outcome across chronic pain studies would greatly enhance the comparability , validity , and clinical applicability of these studies Pain , swelling , loss of function , and hyperthermia are acute postoperative sequelae of inflammation due to tissue injury during surgical procedures . Pharmacologic strategies for minimizing the clinical manifestations of surgical trauma are often directed toward blocking the formation or inhibiting the effects of the biochemical mediators of acute inflammation . This study compared two nonsteroidal anti-inflammatory drugs ( NSAIDs ) , flurbiprofen and ibuprofen , with a prototype glucocorticoid , methylprednisolone , in two replicate placebo-controlled studies for suppression of inflammation due to the surgical removal of impacted third molars . The results indicate that NSAIDs produce greater initial analgesia than do steroids , whereas steroids result in greater suppression of swelling and less loss of function . Examination of the pooled data from the two studies indicates that NSAID pretreatment results in a modest suppression of swelling in comparison with placebo . These data suggest that the acute analgesic effects of NSAIDs in the oral surgery model are due to suppression of a nociceptive process , presumably prostagl and in formation , rather than a generalized anti-inflammatory effect Reiki is one type of alternative therapy that is increasing in popularity . It is advocated by its practitioners as a precise method for connecting universal life energy with the body 's innate process of healing through h and s-on techniques . The cl aim of Reiki practitioners is that Reiki reduces a variety of physical problems and improves psychospiritual well-being . There are abundant anecdotal records that support the previous cl aim , and a few pioneer scientific studies are starting to emerge . Although the Reiki research in totality supports the anecdotal records , the absence of r and omized and placebo-controlled trials precludes the interpretation of the outcomes as result ing from specific effects as opposed to placebo effects plus natural history . Authorities in the field indicate that research ers interested in placebo-controlled studies should have the placebo treatment look exactly like the real intervention in every respect . Because no studies could be found in the literature that tested st and ardization procedures for real and placebo Reiki , the decision was made to conduct one . The purpose of this study was to test the st and ardization procedures developed by our research team for placebo Reiki , before going ahead and conducting our planned full-scale r and omized and placebo-controlled Reiki efficacy study . This study used a 4-round , crossover experimental design in which 20 blinded subjects ( 12 students , 4 breast cancer survivors , and 4 observers ) were exposed to a combination of 2 interventions ( Reiki plus Reiki , or placebo plus placebo , or Reiki plus placebo , or placebo plus Reiki ) ; and were then asked to evaluate the interventions using a self-administered question naire . The blinded observers were used in round number 4 . Two real Reiki practitioners in the Usui system were chosen first , then 2 placebo practitioners who closely resembled them were recruited . The placebo practitioners were trained in Reiki by the study Reiki Master and the principal investigator , but were not initiated . The belief in Reiki is that only practitioners that are initiated could give Reiki , thus making it possible to have a placebo arm in efficacy studies . The findings of the study indicate that the developed st and ardization procedures were successful because none of the final participants in round 4 ( 4 breast cancer patients and 4 observers ) could differentiate between the identity of placebo and Reiki practitioners . The qualitative comments expressed by the participants further con-firmed the quantitative data . It was concluded based on these findings that it is safe to go ahead and conduct the planned r and omized 3-arm Reiki efficacy clinical trial . It is recommended that scholars interested in Reiki research could incorporate our techniques to strengthen their design s by adding a placebo arm
Output:
| Results of trials conducted by more experienced practitioners appeared to yield greater effects in pain reduction .
Touch therapies may have a modest effect in pain relief . |
MS213707 | ***TASK*** the task is to summarize an input biomedical literature in six sentences
***INPUT*** the input is a biomedical literature
***OUTPUT*** the output is the summary of an input biomedical literature in six sentences
***DOCUMENTATION***
***EXAMPLES***
Input: Use of statins is hypothesized to reduce colorectal cancer risk but the evidence remains inconsistent . This may be partly explained by differential associations according to tumor location or molecular subtypes of colorectal cancer . We examined the association between statin use and colorectal cancer risk according to tumor location , KRAS mutation status , microsatellite instability ( MSI ) status , PTGS2 ( COX-2 ) expression , or CpG isl and methylator phenotype ( CIMP ) status in two large prospect i ve cohort studies , the Nurses ' Health Study and Health Professionals Follow-up Study . We applied Cox regression to a competing risks analysis . We identified 1,818 colorectal cancers during 1990 to 2006 . Compared with nonusers , current statin use was not associated with colorectal cancer [ relative risk ( RR ) = 0.99 , 95 % CI = 0.86–1.14 ] or colon cancer ( RR = 1.10 , 95 % CI = 0.94–1.29 ) but was inversely associated with rectal cancer ( RR = 0.59 , 95 % CI = 0.41–0.84 , Pheterogeneity < 0.001 ) . When we examined the association within strata of KRAS mutation status , we found no association with KRAS-mutated cancers ( RR = 1.20 , 95 % CI = 0.87–1.67 ) but did observe a possible inverse association among KRAS wild-type cancers ( RR = 0.80 , 95 % CI = 0.60–1.06 , Pheterogeneity = 0.06 ) . The association did not substantially differ by PTGS2 expression , MSI status , or CIMP status . Current statin use was not associated with risk of overall colorectal cancer . The possibility that statin use may be associated with lower risk of rectal cancer or KRAS wild-type colorectal cancer requires further confirmation . Cancer Prev Res ; 4(11 ) ; 1808–15 . © 2011 AACR The authors compared five methods of study ing survival bias associated with time-to-treatment initiation in a drug effectiveness study using medical administrative data bases ( 1996 - 2002 ) from Quebec , Canada . The first two methods illustrated how survival bias could be introduced . Three additional methods were considered to control for this bias . Methods were compared in the context of evaluating statins for secondary prevention in elderly patients post-acute myocardial infa rct ion who initiated statins within 90 days after discharge and those who did not . Method 1 that classified patients into users and nonusers at discharge result ed in an overestimation of the benefit ( 38 % relative risk reduction at 1 year ) . In method 2 , following users from the time of the first prescription and nonusers from a r and omly selected time between 0 and 90 days attenuated the effect toward the null ( 10 % relative risk reduction ) . Method 3 controlled for survival bias by following patients from the end of the 90-day time window ; however , it suffered a major loss of statistical efficiency and precision . Method 4 matched prescription time distribution between users and nonusers at cohort entry . Method 5 used a time-dependent variable for treatment initiation . Methods 4 and 5 better controlled for survival bias and yielded similar results , suggesting a 20 % risk reduction of recurrent myocardial infa rct ion or death events Epidemiologists are aware that the estimated effect of an exposure can be biased if the investigator fails to adjust for confounding factors when analyzing either a prospect i ve or retrospective etiologic study . St and ard texts warn , however , that intervening factors are an exception : one should not adjust for any factor which is intermediate on the causal pathway between the exposure and the disease . Other factors which are not on the causal pathway but are caused in part by the exposure are often adjusted for in epidemiologic studies . This paper illustrates that bias can result when adjustment is made for any factor which is caused in part by the exposure under study and is also correlated with the outcome under study . Intervening variables are only one example of this phenomenon . The misleading effects of this practice are illustrated with examples Background An association between tumor-specific HMG-CoA reductase ( HMGCR ) expression and good prognosis has previously been demonstrated in breast and ovarian cancer . In this study , the expression , clinicopathological correlates and prognostic value of HMGCR expression in colorectal cancer was examined . Findings Immunohistochemical expression of HMGCR was assessed in tissue microarrays with primary tumours from 557 incident cases of colorectal cancer in the Malmö Diet and Cancer Study . Pearson ’s Chi Square test was applied to explore the associations between HMGCR expression and clinicopathological factors and other investigative biomarkers . Kaplan Meier analysis and Cox proportional hazards modeling were used to assess the relationship between HMGCR expression and cancer-specific survival ( CSS ) according to negative vs positive HMGCR expression . A total number of 535 ( 96.0 % ) tumours were suitable for analysis , of which 61 ( 11.4 % ) were HMGCR negative . Positive cytoplasmic HMGCR expression was associated with distant metastasis-free disease at diagnosis ( p = 0.002 ) , lack of vascular invasion ( p = 0.043 ) , microsatellite-instability ( p = 0.033 ) , expression of cyclin D1 ( p = < 0.001 ) and p21 ( p = < 0.001 ) . Positive HMGCR expression was significantly associated with a prolonged CSS in unadjusted Cox regression analysis in the entire cohort ( HR = 1.79 ; 95 % CI 1.20 - 2.66 ) and in Stage III-IV disease ( HR = 1.71 ; 95 % CI 1.09 - 2.68 ) , but not after adjustment for established clinicopathological parameters . Conclusions Findings from this prospect i ve cohort study demonstrate that HMGCR is differentially expressed in colorectal cancer and that positive expression is associated with favourable tumour characteristics and a prolonged survival in unadjusted analysis . The utility of HMGCR as a predictor of response to neoadjuvant or adjuvant statin treatment in colorectal cancer merits further study .Virtual slidesThe virtual slides for this article can be found here : http://www.diagnosticpathology.diagnomx.eu/vs/2115647072103464 BACKGROUND The st and ard adjuvant treatment of colon cancer is fluorouracil plus leucovorin ( FL ) . Oxaliplatin improves the efficacy of this combination in patients with metastatic colorectal cancer . We evaluated the efficacy of treatment with FL plus oxaliplatin in the postoperative adjuvant setting . METHODS We r and omly assigned 2246 patients who had undergone curative resection for stage II or III colon cancer to receive FL alone or with oxaliplatin for six months . The primary end point was disease-free survival . RESULTS A total of 1123 patients were r and omly assigned to each group . After a median follow-up of 37.9 months , 237 patients in the group given FL plus oxaliplatin had had a cancer-related event , as compared with 293 patients in the FL group ( 21.1 percent vs. 26.1 percent ; hazard ratio for recurrence , 0.77 ; P=0.002 ) . The rate of disease-free survival at three years was 78.2 percent ( 95 percent confidence interval , 75.6 to 80.7 ) in the group given FL plus oxaliplatin and 72.9 percent ( 95 percent confidence interval , 70.2 to 75.7 ) in the FL group ( P=0.002 by the stratified log-rank test ) . In the group given FL plus oxaliplatin , the incidence of febrile neutropenia was 1.8 percent , the incidence of gastrointestinal adverse effects was low , and the incidence of grade 3 sensory neuropathy was 12.4 percent during treatment , decreasing to 1.1 percent at one year of follow-up . Six patients in each group died during treatment ( death rate , 0.5 percent ) . CONCLUSIONS Adding oxaliplatin to a regimen of fluorouracil and leucovorin improves the adjuvant treatment of colon cancer PURPOSE Aspirin and other nonsteroidal anti-inflammatory drugs ( NSAIDs ) protect against colorectal cancer ( CRC ) and are associated with reduced disease recurrence and improved outcome after primary treatment . However , toxicities of NSAIDs have limited their use as antineoplastic therapy . Recent data have suggested that the benefit of aspirin after CRC diagnosis is limited to patients with PIK3CA-mutant cancers . We sought to determine the predictive utility of PIK3CA mutation for benefit from both cyclooxygenase-2 inhibition and aspirin . METHODS We performed molecular analysis of tumors from 896 participants in the Vioxx in Colorectal Cancer Therapy : Definition of Optimal Regime ( VICTOR ) trial , a large r and omized trial comparing rofecoxib with placebo after primary CRC resection . We compared relapse-free survival and overall survival between rofecoxib therapy and placebo and between the use and nonuse of low-dose aspirin , according to tumor PIK3CA mutation status . RESULTS We found no evidence of a greater benefit from rofecoxib treatment compared with placebo in patients whose tumors had PIK3CA mutations ( multivariate adjusted hazard ratio [ HR ] , 1.2 ; 95 % CI , 0.53 to 2.72 ; P = .66 ; (P)INTERACTION = .47 ) compared with patients with PIK3CA wild-type cancers ( HR , 0.87 ; 95 % CI , 0.64 to 1.16 ; P = .34 ) . In contrast , regular aspirin use after CRC diagnosis was associated with a reduced rate of CRC recurrence in patients with PIK3CA-mutant cancers ( HR , 0.11 ; 95 % CI , 0.001 to 0.832 ; P = .027 ; (P)INTERACTION = .024 ) but not in patients lacking tumor PIK3CA mutation ( HR , 0.92 ; 95 % CI , 0.60 to 1.42 ; P = .71 ) . CONCLUSION Although tumor PIK3CA mutation does not predict benefit from rofecoxib treatment , it merits further evaluation as a predictive biomarker for aspirin therapy . Our findings are concordant with recent data and support the prospect i ve investigation of adjuvant aspirin in PIK3CA-mutant CRC BACKGROUND Although pre clinical and epidemiological data suggest that statins may have antineoplastic properties , the impact of statin use on patient survival after a curative resection of stage III colon cancer is unknown . METHODS We conducted a prospect i ve observational study of 842 patients with stage III colon cancer enrolled in a r and omized adjuvant chemotherapy trial from April 1999 to May 2001 to investigate the relationship between statin use and survival . Disease-free survival ( DFS ) , recurrence-free survival ( RFS ) , and overall survival ( OS ) were investigated by Kaplan-Meier curves and log-rank tests in the overall study population and in a subset of patients stratified by KRAS mutation status ( n = 394 ) , and Cox proportional hazards regression was used to assess the simultaneous impact of confounding variables . All statistical tests were two-sided . RESULTS Among 842 patients , 134 ( 15.9 % ) reported statin use after completing adjuvant chemotherapy . DFS among statin users and nonusers was similar ( hazard ratio [ HR ] of cancer recurrence or death = 1.04 , 95 % confidence interval [ CI ] = 0.73 to 1.49 ) . RFS and OS were also similar between statin users and nonusers ( adjusted HR of cancer recurrence = 1.14 , 95 % CI = 0.77 to 1.69 ; adjusted HR of death = 1.15 , 95 % CI = 0.77 to 1.71 ) . Survival outcomes were similar regardless of increasing duration of statin use before cancer diagnosis ( P(trend ) = .63 , .63 , and .59 for DFS , RFS , and OS , respectively ) . The impact of statin use did not differ by tumor KRAS mutation status , with similar DFS , RFS , and OS for statin use among mutant and wild-type subgroups ( P(interaction ) = .84 , .67 , and .98 for DFS , RFS , and OS , respectively ) . CONCLUSION Statin use during and after adjuvant chemotherapy was not associated with improved DFS , RFS , or OS in patients with stage III colon cancer , regardless of KRAS mutation status BACKGROUND : Achieving a pathologic complete response to neoadjuvant chemoradiation improves prognosis in rectal cancer . Statin therapy has been shown to enhance the impact of treatment in several malignancies , but little is known regarding the impact on rectal cancer response to neoadjuvant chemoradiation . OBJECTIVE : The purpose of this study was to determine whether statin use during neoadjuvant chemoradiation improves pathologic response in rectal cancer . DESIGN : This was a retrospective cohort study based on data from a prospect ively maintained colorectal cancer data base . The 2 cohorts were defined by statin use during neoadjuvant chemoradiation . SETTING : This study
Output:
| In a Scottish CRC cohort and up date d meta- analysis there was some evidence that statin use was associated with improved survival .
However , these associations were weak in magnitude and , particularly for post-diagnosis use , varied markedly between studies |
MS213708 | ***TASK*** the task is to summarize an input biomedical literature in six sentences
***INPUT*** the input is a biomedical literature
***OUTPUT*** the output is the summary of an input biomedical literature in six sentences
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Input: CONTEXT The generalized type of social phobia ( social anxiety disorder ) is a severe and often disabling form of social anxiety that affects approximately 5 % of the general population . Earlier research has shown monoamine oxidase inhibitors or benzodiazepines to be effective in treating this condition , but neither has achieved widespread use . OBJECTIVE To compare the efficacy of paroxetine , a selective serotonin reuptake inhibitor , with placebo in adults with generalized social phobia . DESIGN Twelve-week , multicenter , r and omized , double-blind trial . SETTING Thirteen centers across the United States and 1 in Canada . PARTICIPANTS Between April 13 , 1995 , and February 28 , 1996 , 187 persons meeting Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition criteria for generalized social phobia were r and omized ( and 183 returned for at least 1 efficacy assessment ) to treatment . INTERVENTION After a 1-week , single-blind , placebo , run-in period , patients received a double-blind , 11-week course of either paroxetine or matching-image placebo . The initial daily dosage of paroxetine ( or placebo ) was 20 mg with increases of 10 mg/d weekly ( flexible dosing to a maximum of 50 mg/d ) permitted after the second week of treatment . MAIN OUTCOME MEASURES Number of responders based on the Clinical Global Impression Global Improvement Item ( " much improved " or " very much improved " ) ; mean change from baseline on the Liebowitz Social Anxiety Scale total score . RESULTS Fifty ( 55.0 % ) of 91 persons taking paroxetine and 22 ( 23.9 % ) of 92 persons taking placebo were much improved or very much improved at the end of treatment ( odds ratio [ OR ] , 3.88 ; 95 % confidence interval [ CI ] , 2.81 - 5.36 ) . Mean Liebowitz Social Anxiety Scale total scores were reduced by 39.1 % ( the mean baseline score of 78.0 declined by a mean of 30.5 points at follow-up ) in the paroxetine group compared with 17.4 % ( the mean baseline score of 83.5 declined 14.5 points at follow-up ) in the placebo group , a difference of 21.7 % ( 95 % CI , 8.7%-34.7 % ) favoring paroxetine . CONCLUSIONS Paroxetine is an effective treatment for patients with generalized social phobia . Short-term ( ie , 11-week ) treatment results in substantial and clinical ly meaningful reductions in symptoms and disability . Future research should test whether these may be further reduced by extended treatment or supplementation with specific educational-cognitive-behavioral techniques Rationale Seasonal affective disorder ( SAD ) is a relatively common cyclical depressive illness characterized by seasonal depressions during winter . The disorder is commonly responsive to light therapy , but antidepressant drug efficacy has not been definitely established . Serotonin selective re-uptake inhibitors are potentially efficacious treatments for SAD . Objectives The objective of this study was to evaluate the efficacy , tolerability and safety of sertraline treatment for SAD . Methods One hundred and eighty seven out patients with seasonal pattern recurrent winter depression ( DSM-III-R defined ) and a minimum 29-item Hamilton depression scale ( SIGH-SAD version ) score of 22 were r and omized to 8 weeks treatment with either sertraline or placebo in a double-blind , multi-country , multi-center , parallel-group , flexible dose ( 50–200 mg once daily ) study . Efficacy was investigated using physician and patient-rated scales measuring depression , anxiety and symptoms characteristic of seasonal affective disorder . Results Sertraline produced a significantly greater response than placebo at endpoint as measured by changes in the 29-item and 21-item Hamilton depression scales , the clinical global impression ( CGI ) severity scale , the Hamilton anxiety scale , and the hospital anxiety and depression scale . The proportion of sertraline-treated subjects achieving a response on the CGI improvement rating ( ratings of 1 or 2 ) at endpoint ( last observation carried forward ) was significantly greater than that of the placebo group . Overall sertraline was well tolerated with the most frequent placebo adjusted adverse events , being nausea , diarrhea , insomnia and dry mouth . Adverse events were mostly mild to moderate and transient . Conclusions Sertraline pharmacotherapy has been demonstrated to be an effective and well-tolerated therapy for out patients with SAD . As such , sertraline offers an important pharmacological option in the clinical management of this condition The efficacy of paroxetine in the treatment of obsessive-compulsive disorder in Western population s is well established . The present study compares the efficacy and safety of paroxetine with placebo in the treatment of obsessive-compulsive disorder in Japanese patients . Patients aged 16 years or older who met Diagnostic and Statistical Manual of Mental Disorders ( 4th edn ; DSM-IV ) criteria for obsessive-compulsive disorder and had a Yale-Brown Obsessive-Compulsive Scale ( Y-BOCS ) score of > /=16 were r and omized to receive 12 weeks ' therapy in a double-blind manner . Paroxetine 20 - 50 mg/day or placebo was administered following a 1 week , placebo run-in phase . One hundred and ninety-one patients were r and omized to either paroxetine or placebo , 188 patients were assessed as the full analysis set ( FAS ) and 144 patients completed the 12 week study . After adjustment for the Y-BOCS total score at baseline , reductions in obsessive-compulsive total score at week 6 and at the end of therapy were significantly greater in the paroxetine group than the placebo group . Most of the adverse events that occurred during the study were of mild to moderate intensity . Paroxetine is effective and well tolerated in Japanese adult patients with obsessive-compulsive disorder The safety and efficacy of sertraline versus placebo were examined in a group of nondepressed out patients with obsessive-compulsive disorder ( OCD ) . Patients with moderate-to-severe OCD were recruited at 10 sites . After a 1-week placebo lead-in , patients were treated in a double-blind fashion for 12 weeks with sertraline or placebo . Sertraline was administered at a starting dose of 50 mg/day , with flexible titration up to 200 mg/day . The efficacy measures were the Yale-Brown Obsessive Compulsive Scale ( Y-BOCS ) , the National Institute of Mental Health Global Obsessive Compulsive Scale ( NIMH ) , and the Clinical Global Impression Scale ( CGI ) Severity of Illness and Improvement subscales . One hundred sixty-seven patients were r and omly assigned and received at least one dose of double-blind medication : 86 received sertraline and 81 received placebo . All efficacy measures showed significantly greater improvement in the sertraline group from the end of week 8 until the end of week 12 . Significantly greater improvement ( p < 0.05 ) in the sertraline group first became apparent by the end of week 3 on the Y-BOCS and the CGI Improvement scale , and by the end of weeks 6 and 8 , respectively , on the NIMH and CGI Severity scale . Sertraline was well tolerated , without serious adverse effects . In conclusion , sertraline was safe and effective in the treatment of patients with OCD One hundred and sixty patients with a primary diagnosis of obsessive compulsive disorder were enrolled in a multicentre , r and omized , double-blind , placebo-controlled study of fluvoxamine . After a placebo washout phase , patients were r and omized to treatment with placebo or fluvoxamine ( 100–300 mg/day ) for 10 weeks . Seventy-eight patients in each group were evaluable for efficacy . Fluvoxamine was significantly more effective than placebo as assessed by the Yale Brown Obsessive-Compulsive Scale ( Y-BOCS ) , the National Institute of Mental Health Obsessive Compulsive ( NIMH-OC ) scale and ( be Global Improvement item of the Clinical Global Impression ( CGI ) scale . The percentage of patients classified as “ responders ” ( much or very much improved according to the Global Improvement item ) was also significantly higher in the fluvoxamine group from Week 6 onwards , with 33.3 % of fluvoxamine-treated patients and 9.0 % of those given placebo classified as “ responders ” at : endpoint . The “ responders ” to fluvoxamine experienced a substantial clinical benefit as reflected in decreases in their Y-BOCS and NIMH-OC scores . Fluvoxamine was well tolerated with the majority of adverse events considered mild or moderate Selective serotonin reuptake inhibitors are the pharmacological treatment of choice for the treatment of social anxiety disorder ( SAD ) . The efficacy and tolerability of fixed doses of escitalopram were compared to those of placebo in the long‐term treatment of generalised SAD , using paroxetine as an active reference . Patients with a DSM‐IV diagnosis of SAD between 18–65 years of age were r and omised to 24 weeks of double‐blind treatment with placebo ( n = 166 ) , 5 mg escitalopram ( n = 167 ) , 10 mg escitalopram ( n = 167 ) , 20 mg escitalopram ( n = 170 ) , or 20 mg paroxetine ( n = 169 ) . Based on the primary efficacy parameter , Liebowitz Social Anxiety Scale ( LSAS ) total score at Week 12 ( LOCF ) , a significantly superior therapeutic effect compared to placebo was seen for 5 and 20 mg escitalopram and for all doses for the OC analyses . Further improvement in LSAS scores was seen at Week 24 ( OC and LOCF ) , with significant superiority over placebo for all doses of escitalopram , and 20 mg escitalopram was significantly superior to 20 mg paroxetine . Response to treatment ( assessed by a Clinical Global Impression‐Improvement score ≤2 ) was significantly higher for all active treatments than for placebo at Week 12 . Clinical relevance was supported by a significant decrease in all the Sheehan disability scores , and the good tolerability of escitalopram treatment . It is concluded that doses of 5–20 mg escitalopram are effective and well tolerated in the short‐ and long‐term treatment of generalised SAD . Depression and Anxiety 00:000–000 , 2004 . © 2004 Wiley‐Liss , BACKGROUND The serotonin selective reuptake inhibitors are increasingly being used for the treatment of panic disorder . We examined the efficacy and safety of the serotonin selective reuptake inhibitor sertraline hydrochloride in patients with panic disorder . METHODS One hundred seventy-six nondepressed out patients with panic disorder , with or without agoraphobia , from 10 sites followed identical protocol s that used a flexible-dose design . After 2 weeks of single-blind placebo , patients were r and omly assigned to 10 weeks of double-blind , flexible-dose treatment with either sertraline hydrochloride ( 50 - 200 mg/d ) or placebo . RESULTS Sertraline-treated patients exhibited significantly greater improvement ( P=.01 ) at end point than did patients treated with placebo for the primary outcome variable , panic attack frequency . Significant differences between groups were also evident for clinician and patient assessment s of improvement as measured by the Clinical Global Impression Improvement ( P=.01 ) and Severity ( P=.009 ) Scales , Panic Disorder Severity Scale ratings ( P=.03 ) , high end-state function assessment ( P=.03 ) , Patient Global Evaluation rating ( P=.01 ) , and quality of life scores ( P=.003 ) . Adverse events , generally characterized as either mild or moderate , were not significantly different in overall incidence between the sertraline and placebo groups . CONCLUSION Results support the safety and efficacy of sertraline for the short-term treatment of patients with panic disorder Background : Generalized social anxiety disorder is a highly prevalent anxiety disorder with deleterious effects on social and family relationships , as well as work performance . We report the results of a multicenter , r and omized , placebo-controlled trial comparing the efficacy , safety , and tolerability of fluvoxamine controlled release ( CR ) to placebo in patients with generalized social anxiety disorder . Methods : A total of 279 adult patients meeting all inclusion /exclusion criteria was recruited at 23 United States sites and r and omly assigned to receive either fluvoxamine CR ( 100 - 200 mg/d ) or placebo for 12 weeks . The dose could be increased , based on efficacy and tolerability , in increments of 50 mg/d at weekly intervals . The dosage remained constant during weeks 6 to 12 . Results : Treatment with fluvoxamine CR result ed in statistically and clinical ly significant improvements in symptoms associated with generalized social anxiety disorder as early as week 4 on the Liebowitz Social Anxiety Scale and the Clinical Global Impression Scale Global Improvement , and at week 6 on the Sheehan Disability Scale , Clinical Global Impression Scale Severity of Illness and the Patient Global Impression of Improvement Scale . The most frequent adverse events reported by
Output:
| Systematic assessment led to higher rates than less systematic assessment .
Conclusion : Adverse effect profiles reported in clinical trials are strongly influenced by expectations from investigators and patients .
This difference can not be attributed to ascertainment methods .
Adverse effect patterns of the drug group are closely related to adverse effects of the placebo group .
These results question the validity of the assumption that adverse effects in placebo groups reflect the ‘ drug-unspecific effects ’ |
MS213709 | ***TASK*** the task is to summarize an input biomedical literature in six sentences
***INPUT*** the input is a biomedical literature
***OUTPUT*** the output is the summary of an input biomedical literature in six sentences
***DOCUMENTATION***
***EXAMPLES***
Input: BACKGROUND Our objectives were to determine the incidence of acute and late toxicities and to estimate the 2-year overall survival for patients treated with reirradiation and chemotherapy for unresectable squamous cell carcinoma of the head and neck ( SCCHN ) . METHODS Patients with recurrent squamous cell carcinoma or a second primary arising in a previously irradiated field were eligible . Four weekly cycles of 5-fluorouracil 300 mg/m2 IV bolus and hydroxyurea 1.5 g by mouth were used with 60 Gy at 1.5 Gy twice-daily fractions . Toxicity was scored according to Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer ( RTOG/EORTC ) criteria . RESULTS Seventy-nine of the 86 patients enrolled were analyzable . The worst acute toxicity was grade 4 in 17.7 % and grade 5 in 7.6 % . Grade 3 and 4 late toxicities were found in 19.4 % and 3.0 % , respectively . The estimated cumulative incidence of grade 3 to 4 late effects occurring at > 1 year was 9.4 % ( 95 % confidence interval [ CI ] : 0 , 19.7 ) at 2 and 5 years . The 2- and 5-year cumulative incidence for grade 4 toxicity was 3.1 % ( 95 % CI : 0 , 9.3 ) . The estimated 2- and 5-year survival rates were 15.2 % ( 95 % CI : 7.3 , 23.1 ) and 3.8 % ( 95 % CI : 0.8 , 8.0 ) , respectively . Patients who entered the study at > 1 year from initial radiotherapy ( RT ) had better survival than did those who were < 1 year from prior RT ( median survival , 9.8 months vs 5.8 months ; p = .036 ) . No correlation was detected between dose received and overall survival . Three patients were alive at 5 years . CONCLUSION This is the first prospect i ve multi-institutional trial testing reirradiation plus chemotherapy for recurrent or second SCCHN . The approach is feasible with acceptable acute and late effects . The results serve as a benchmark for ongoing RTOG trials BACKGROUND The purpose of this study was to evaluate long-term outcomes after induction chemotherapy followed by " risk-based " local therapy for locally-advanced squamous cell carcinoma of the head and neck ( SCCHN ) . METHODS Forty-seven patients ( stage IV ; ≥N2b ) were enrolled in a phase II trial . Baseline and 24-month functional measures included modified barium swallow ( MBS ) studies , oropharyngeal swallow efficiency ( OPSE ) , and the MD And erson Dysphagia Inventory ( MDADI ) . Functional status was assessed at 5 years . RESULTS Five-year overall survival ( OS ) was 89 % ( 95 % confidence interval [ CI ] , 81 % to 99 % ) . A nonsignificant 13 % average reduction in swallowing efficiency ( OPSE ) was observed at 24 months relative to baseline ( p = .191 ) . MDADI scores approximated baseline at 24 months . Among 42 long-term survivors ( median , 5.9 years ) , 3 patients ( 7.1 % ) had chronic dysphagia . The rate of final gastrostomy dependence was 4.8 % ( 2 of 42 ) . CONCLUSION Sequential chemoradiotherapy achieved favorable outcomes among patients with locally advanced SCCHN , mainly of oropharyngeal origin . MBS and MDADI scores found modest swallowing deterioration at 2 years , and chronic aspiration was uncommon in long-term survivors BACKGROUND The purpose of this study was to analyse the results of salvage surgery after failure of irradiation to control the primary T1-T2 glottic cancer . MATERIAL S AND METHODS Ninety-eight patients with T1 and T2 squamous cell cancer of the glottic larynx were treated with curative intent by radiotherapy . The tumour recurred in 22 of the 98 ( 22 % ) patients . Surgical management consisted of total and frontolateral laryngectomy . Survival rates were calculated from the date of the salvage operation . RESULTS Two of the 22 patients refused to undergo salvage surgery and one patient had pulmonary metastasis . Of the 19 patients who underwent salvage surgery , 14 ( 74 % ) had total laryngectomy and 5 ( 26 % ) had frontolateral laryngectomy . The operations were curative in 15 ( 79 % ) of the 19 patients . The overall 5-year survival rate after surgery was 78 % . CONCLUSION Stringent follow-up of patients with irradiated T1 and T2 glottic laryngeal cancer is essential to permit a successful salvage OBJECTIVES To determine the incidence of local control in patients with " advanced " moderately to well-differentiated endolaryngeal invasive squamous cell carcinoma classified as T3 , treated with a supracricoid partial laryngectomy ; to identify any statistical relationship ; and to analyze the consequences of local recurrence . DESIGN Retrospective nonr and omized case series . SETTING A tertiary referral care center and university teaching hospital . PATIENTS An inception cohort of 118 patients . Tumor stage was T3 N0 M0 in 90 patients , T3 N1 M0 in 21 patients , T3 N2 M0 in 5 patients , and T3 N3 M0 in 2 patients . INTERVENTIONS All patients underwent supracricoid partial laryngectomy . A platin-based induction chemotherapy regimen was used in 100 patients . Postoperative radiotherapy was used for 24 patients . MAIN OUTCOME MEASURES Local recurrence , nodal recurrence , distant metastasis , and survival ; univariate and multivariate analysis of local recurrence . RESULTS Nine patients developed a local recurrence . The 1- , 3- , and 5-year actuarial local control estimates were 97.3 % , 93.5 % , and 91.4 % , respectively . In a stepwise regression model , the presence of positive margins of resection was the only variable that statistically increased the risk of local recurrence ( P = .008 ) . Local recurrence result ed in a significant increase in nodal recurrence ( P<.001 ) and distant metastasis ( P<.001 ) and a significant decrease in survival ( P = .03 ) . An overall 89.8 % laryngeal preservation rate and 98.3 % local control rate were achieved . CONCLUSION Supracricoid partial laryngectomies should be considered when an organ preservation strategy is discussed in patients with advanced endolaryngeal squamous cell carcinoma classified as T3 OBJECTIVES /HYPOTHESES Study 1 : To assess the oncologic outcome following supracricoid partial laryngectomy ( SCPL ) . Study 2 : To compare the quality of life ( QOL ) following SCPL to total laryngectomy ( TL ) with tracheoesophageal puncture ( TEP ) . Study 3 : To analyze whole organ TL sections to determine the percentage of lesions amenable to SCPL STUDY DESIGN : Study 1 : A retrospective review of patients who underwent SCPL . Study 2 : A non-r and omized , prospect i ve study using QOL instruments to compare patients who underwent either SCPL or TL Study 3 : A retrospective histopathologic study of TL specimens assessed for the possibility of performing an SCPL . METHODS Study 1 : Twenty-five patients with carcinoma of the larynx underwent SCPL between June 1992 and June 1999 . Various rates of oncologic outcome were calculated . Study 2 : Thirty-one patients participated in the QOL assessment . This included the SF-36 general health status measure , the University of Michigan Head and Neck Quality of Life ( HNQOL ) instrument , and the University of Michigan Voice-Related Quality of Life ( VRQOL ) instrument . Study 3 : Ninety surgical specimens were obtained and studied from the total laryngectomy cases in the Tucker Collection . Multiple sites were evaluated for the presence of carcinoma A computer program was written to classify whether the patient was amenable to SCPL . RESULTS Study 1 : The overall local control rate was 96 % ( 24/25 ) . The local control rate following SCPL with cricohyoidoepiglottopexy ( CHEP ) was 95 % ( 20/21 ) . The local control rate following SCPL with cricohyoidopexy ( CHP ) was 100 % ( 4/4 ) . Study 2 : The SCPL had significantly higher domain scores than TL and TEP in the following categories for the SF-36 : physical function , physical limitations , general health , vitality , social functioning , emotional limitations , and physical health summary . The significantly higher domains for the SCPL when compared with the TL and TEP for the HNQOL were eating and pain . Finally , when voice-related QOL was assessed with the V-RQOL , the domains of physical functioning and the total score were significantly better with SCPL when compared with TL and TEP . Study 3 : Forty of 90 ( 44 % ) laryngeal whole organ specimens were determined to be resectable by SCPL . In 16 ( 18 % ) specimens , the patients could have undergone SCPL with CHEP and in 24 ( 27 % ) specimens the patients could have undergone SCPL with CHP . Among the 40 ( 44 % ) specimens determined to be able to have undergone SCPL , 19 were glottic ( 1 T1 , 15 T2 , 3 T3 ) and 21 were supraglottic ( 9 T2 , 12 T3 ) . CONCLUSIONS 1 ) A review of the literature and an analysis of the data in this study indicate that excellent local control may be expected following SCPL . 2 ) The QOL following SCPL , as measured by three vali date d QOL instruments , is superior to TL with TEP . 3 ) A histologic assessment of whole organ sections of TL specimens indicates that many patients who have been subjected to TL may have been c and i date s for SCPL . 4 ) If the indications and contraindications are rigorously adhered to , SCPLs are reasonable alternatives to TL in selected cases
Output:
| We therefore hypothesised that careful assessment of tumour extension might be responsible for the high 5-year OS and 5-year DFS . |
MS213710 | ***TASK*** the task is to summarize an input biomedical literature in six sentences
***INPUT*** the input is a biomedical literature
***OUTPUT*** the output is the summary of an input biomedical literature in six sentences
***DOCUMENTATION***
***EXAMPLES***
Input: Clinical trials , systematic review s and guidelines compare beneficial and non-beneficial outcomes following interventions . Often , however , various studies on a particular topic do not address the same outcomes , making it difficult to draw clinical ly useful conclusions when a group of studies is looked at as a whole.1 This problem was recently thrown into sharp focus by a systematic review of interventions for preterm birth prevention , which found that among 103 r and omised trials , no fewer than 72 different outcomes were reported.2 There is a growing recognition among clinical research ers that this variability undermines consistent synthesis of the evidence , and that what is needed is an agreed st and ardised collection of outcomes – a “ core outcomes set ” – for all trials in a specific clinical area.1 Recognising that the current inconsistency is a serious hindrance to progress in our specialty , the editors of over 50 journals related to women 's health have come together to support The CROWN ( CoRe Outcomes in WomeN 's health ) Initiative ( Box 1 ) . ! [Graphic][1 ] Box 1 # # # Aims of The CROWN Initiative ( http://www.crown-initiative.org ) 1 . Form a consortium among all gynaecology-obstetrics and related journals to promote core outcome sets in all areas of our specialty . … [ 1 ] : OBJECTIVES : To compare the efficacy of letrozole and clomiphene citrate ( CC ) in patients of anovulatory polycystic ovarian syndrome ( PCOS ) with infertility . MATERIAL S AND METHODS : This prospect i ve r and omized clinical trial included 204 patients of PCOS . 98 patients ( 294 cycles ) received 2.5–5 mg of letrozole ; 106 patients ( 318 cycles ) received 50–100 mg of CC ( both orally from Days 3–7 of menstrual cycle ) . The treatment continued for three cycles in both the groups . Main outcome measures : ovulation rate , endometrial thickness , and pregnancy rate . Statistical analysis was done using SPSS 13 software . P value less than 0.05 was considered significant . RESULTS : The mean number of dominant follicles in letrozole groups and CC groups was 1.86±0.26 and 1.92±0.17 , respectively ( P=0.126 ) . Number of ovulatory cycle in letrozole group was 196 ( 66.6 % ) versus 216 ( 67.9 % ) in CC group ( P=0.712 ) . The mean mid-cycle endometrial thickness was 9.1±0.3 mm in letrozole group and 6.3±1.1 in CC group , which was statistically significant ( P=0.014 ) . The mean Estradiol [ E2 ] level in clomiphene citrate group was significantly higher in CC group ( 364.2±71.4 pg/mL ) than letrozole group ( 248.2± 42.2 pg/mL ) . 43 patients from the letrozole group ( 43.8 % ) and 28 patients from the CC group ( 26.4 % ) became pregnant . CONCLUSION : Letrozole and CC have comparable ovulation rate . The effect of letrozole showed a better endometrial response and pregnancy rate compared with CC BACKGROUND An RCT among newly diagnosed , therapy naive women with polycystic ovary syndrome ( PCOS ) showed no significant differences in ovulation rate , ongoing pregnancy rate or spontaneous abortion rate in favour of clomifene citrate plus metformin compared with clomifene citrate . We wanted to assess whether there are specific subgroups of women with PCOS in whom clomifene citrate plus metformin leads to higher pregnancy rates . METHODS Subgroup analysis based on clinical and biochemical parameters of 111 women r and omized to clomifene citrate plus metformin compared with 114 women r and omized to clomifene citrate plus placebo . The data for age , BMI , waist – hip ratio ( WHR ) and plasma testosterone were available in all women , 2 h glucose in 80 % of women and homeostatic model assessment for assessing insulin sensitivity ( HOMA ) in 50 % of women . RESULTS Of the women who were allocated to the metformin group , 44 women ( 40 % ) reached an ongoing pregnancy . In the placebo group , 52 women ( 46 % ) reached an ongoing pregnancy . There was a significantly different chance of an ongoing pregnancy for metformin versus placebo between subgroups based on age and WHR ( P = 0.014 ) . There was a positive effect of metformin versus placebo on pregnancy rate in older women ( ≥28 years ) with a high WHR , a negative effect of metformin versus placebo in young women ( < 28 years ) regardless of their WHR and no effect in older , not viscerally obese women . No significant differences in effect of treatment were found for groups based on BMI , 2 h glucose , HOMA or plasma testosterone . CONCLUSIONS Metformin may be an effective addition to clomifene citrate in infertile women with PCOS , especially in older and viscerally obese patients OBJECTIVE : To compare Letrozole ( 5 mg ) and clomiphene citrate ( 100 mg ) as first line ovulation induction drug in infertile PCOS women . STUDY DESIGN : Prospect i ve R and omised trial . SETTING : A Tertiary level infertility centre . Patients : 103 infertile PCOS women INTERVENTION(S ) : Treatment naïve infertile PCOS women were r and omised to treatment with 5 mg letrozole ( 51 patients ) or 100 mg clomiphene citrate ( 52 patients ) daily starting day 2 to day 6 of menstrual cycle . Timed intercourse or Intra Uterine Insemination ( IUI ) was advised 24 to 36 hours after Human Chorionic Gonadotropin ( HCG ) injection . MAIN OUTCOME MEASURES : Ovulation rate , mono or multi follicular rate , days to ovulation , endometrial thickness , serum progesterone , serum estrogen , pregnancy rate , miscarriage rate . RESULTS : The mean age , Body Mass Index ( BMI ) , duration of infertility in both Clomiphene Citrate ( CC ) and Letrozole groups were similar . Ovulation rate was 73.08 % in letrozole group and 60.78 % in CC , which was not statistically significant ( P=0.398 ) . There was no statistically significant difference between Endometrial thickness ( CC 7.61 ±1.96 , Let 7.65 ± 2.10 ) , Sr E2 on day of HCG ( CC 178.3 ± 94.15 , Let 162.09 ± 73.24 ) , Days to ovulation ( CC 14.2 ± 3.41 ; Let 13.13 ± 2.99 ) and Sr P4 on D21 ( CC 10.58 ± 6.65 ; Let 11.86 ± 6.51 ) . Monofolliculo genesis ( CC 54.84 , Let 79.49 % , P=0.027 ) and Pregnancy rate ( CC 7.84 % , Let 21.56 % P=0.0125 ) were statistically significantly higher in letrozole group . CONCLUSION : Our study shows that letrozole has excellent pregnancy rates compared to clomiphene citrate . Letrozole should be considered at par with clomiphene citrate as first line drug for ovulation induction in infertile PCOS women OBJECTIVE To report the baseline characteristics and racial differences in the polycystic ovary syndrome ( PCOS ) phenotype from a large multicenter clinical trial ( PPCOS ) . DESIGN Double-blind , r and omized trial of three treatment regimens ( with extended release metformin or clomiphene citrate ) . SETTING Academic medical centers . PATIENT(S ) Six hundred twenty-six infertile women with PCOS , aged 18 - 39 years , with elevated T levels and oligomenorrhea ( exclusion of secondary causes ) , seeking pregnancy , with > or = 1 patent fallopian tube , normal uterine cavity , and a partner with sperm concentration > or = 20 x 10(6)/mL in > or = 1 ejaculate . INTERVENTION(S ) Baseline characterization . MAIN OUTCOME MEASURE(S ) Historical , biometric , and biochemical measures of PCOS . RESULT ( S ) There were no significant differences in baseline variables between treatment groups . The overall mean ( + /-SD ) age of the subjects was 28.1 + /- 4.0 years , and the mean body mass index was 35.2 kg/m2 ( + /-8.7 ) . Polycystic ovaries ( PCOs ) were present in 90.3 % of the subjects , and the mean volume of each ovary was 10 cm3 or more . Of the subjects , 7 % had ovaries that were discordant for PCO morphology . At baseline , 18.3 % of the subjects had an abnormal fasting glucose level ( > 100 mg/dL ) . Asians tended to have a milder phenotype , and whites and African Americans were similar in these measures . CONCLUSION ( S ) The treatment groups were well matched for baseline parameters , and we have added further information to the PCOS phenotype OBJECTIVE Small intervention studies suggest that modest weight loss increases the chance of conception and may improve perinatal outcome , but large r and omized controlled trials ( RCT ) are lacking . Our objective was to investigate the effects of a lifestyle intervention in obese infertile women in a multicenter RCT . DESIGN We r and omly assigned infertile women with body mass index ≥ 29 k/m² to a six-month lifestyle intervention preceding infertility treatment or to prompt infertility treatment . The primary outcome was the vaginal birth of a healthy singleton at term within 2 years of r and omization . RESULTS Between June 2009-June 2102 we r and omly allocated 577 women to one of two treatment strategies : 290 to lifestyle intervention preceding infertility treatment ( intervention group ) and 287 to prompt infertility treatment ( control group ) . Three women withdrew informed consent , leaving 289 and 285 women for analysis . Discontinuation rate during the lifestyle intervention was 22 % . Mean weight loss in the intervention group was 4.4 kg and in the control group 1.1 kg ( p < 0.001 ) ; the primary outcome occurred in 76 women ( 27 % ) in the intervention group versus 100 ( 35 % ) in the control group ( RR : 0.77 , 95 % CI 0.60 to 0.99 ) . The number of natural conceptions leading to ongoing pregnancies was 73 ( 26 % ) versus 46 ( 16 % ) ( RR : 1.6 , 95 % CI 1.2 to 2.2 ) . Maternal pregnancy-related and labor-related complications and neonatal complications were comparable . CONCLUSION In obese infertile women lifestyle intervention preceding infertility treatment did not result in better rates of vaginal birth of healthy singletons at term as compared to prompt infertility treatment BACKGROUND The st and ard therapy for women with unexplained infertility is gonadotropin or clomiphene citrate . Ovarian stimulation with letrozole has been proposed to reduce multiple gestations while maintaining live birth rates . METHODS We enrolled couples with unexplained infertility in a multicenter , r and omized trial . Ovulatory women 18 to 40 years of age with at least one patent fallopian tube were r and omly assigned to ovarian stimulation ( up to four cycles ) with gonadotropin ( 301 women ) , clomiphene ( 300 ) , or letrozole ( 299 ) . The primary outcome was the rate of multiple gestations among women with clinical pregnancies . RESULTS After treatment with gonadotropin , clomiphene , or letrozole , clinical pregnancies occurred in 35.5 % , 28.3 % , and 22.4 % of cycles , and live birth in 32.2 % , 23.3 % , and 18.7 % , respectively ; pregnancy rates with letrozole were significantly lower than the rates with st and ard therapy ( gonadotropin or clomiphene ) ( P=0.003 ) or gonadotropin alone ( P<0.001 ) but not with clomiphene alone ( P=0.10 ) . Among ongoing pregnancies with fetal heart activity , the multiple gestation rate with letrozole ( 9 of 67 pregnancies , 13 % ) did not differ significantly from the rate with gonadotropin or clomiphene ( 42 of 192 , 22 % ; P=0.15 ) or clomiphene alone ( 8 of 85 , 9 % ; P=0.44 ) but was lower than the rate with gonadotropin alone ( 34 of 107 , 32 % ; P=0.006 ) . All multiple gestations in the clomiphene and letrozole groups were twins , whereas gonadotropin treatment result ed in 24 twin and 10 triplet gestations . There were no significant differences among groups in the frequencies of congenital anomalies or major fetal and neonatal complications . CONCLUSIONS
Output:
| Conclusions In women with WHO group II anovulation , letrozole and the combination of clomiphene and metformin are superior to clomiphene alone in terms of ovulation and pregnancy .
Compared with clomiphene alone , letrozole is the only treatment showing a significantly higher rate of live birth . |
MS213711 | ***TASK*** the task is to summarize an input biomedical literature in six sentences
***INPUT*** the input is a biomedical literature
***OUTPUT*** the output is the summary of an input biomedical literature in six sentences
***DOCUMENTATION***
***EXAMPLES***
Input: Financial and other competing interests have recently received increasing attention . In particular clinical research in plastic surgery attracts for-profit organizations , thus , explaining the increasing number of financial sponsorships . However , research articles often lack sufficient description of study design as well as disclosure of the source of funding . Furthermore , debate exists whether industry funding influences research findings and is leading to pro-industry results .A h and search was conducted identifying all r and omized controlled ( RCT ) and controlled clinical trials ( CCT ) in 4 plastic surgery journals ( Plastic and Reconstructive Surgery , British Journal of Plastic Surgery , Annals of Plastic Surgery , and AestheticPlastic Surgery ) between 1990 and 2005 . Subsequently , the influence of financial support on study outcome was analyzed . A total of 10,476 original articles were analyzed , result ing in the identification of 346 clinical trials which meet the Cochrane criteria for RCTs and CCTs . One hundred eighty-three trials and 163 studies were found to be RCTs and CCTs , respectively . Hereof , only 70 trials ( 20.2 % ) reported on grant support . Of these , 42 trials ( 60 % ) were supported by the industry . Depending on the topic addressed marked differences were detected regarding grant support . Studies with a focus on reconstructive plastic surgery were supported by the industry and by public institutions in almost equal shares ( 18 trials vs. 15 trials ) , whereas aesthetic surgical topics were predominantly funded by the industry ( 13 trials vs. 6 trials ) . Industry-funded trials reported more often statistically significant differences between treatment arms ( 28 trials vs. 16 trials ) . Authors ' conclusions were found to be positively associated with financial competing interests . However , trial funding is rarely declared in the plastic surgery literature . Thus , the quality of reporting needs to be improved to be able to investigate these relationships in greater detail and draw more representative conclusions The current report tests the hypotheses that commercial funding , country of origin , and presence of a coinvestigator with training in statistics are related to the likelihood of a published orthopaedic study arriving at a positive conclusion . All articles from the Journal of Bone and Joint Surgery ( American ) , the Journal of Arthroplasty , and the American Journal of Sports Medicine published in 1 year were review ed . The blinded review process classified each article as to study design and outcome ( positive or negative ) , according to previously published definitions . Commercial funding was significantly associated with a positive outcome ; 78.9 % of commercially funded studies concluded with a positive outcome , compared with 63.3 % of nonfunded studies . The presence of a statistician or epidemiologist as a coinvestigator , and the place of origin of the study were not associated with outcome . Only 21 % of published studies were prospect i ve , 3.5 % were r and omized , and 10.5 % stated an experimental hypothesis ; these factors were not associated with study outcome . Published studies that received funding from commercial parties were significantly more likely to report a positive outcome than studies that received no such funding . This does not imply the presence of a corrupting or causative influence of industry sponsorship on research outcomes ; additional research is needed to determine whether such nonscientific factors actually affect study outcome or likelihood of publication Compared with nonfunded or peer- review ed funded projects , industry-sponsored clinical trials have traditionally been associated with more positive results . This relationship has been extensively studied in the nonsurgical literature . Although a few authors have addressed specialties , little has been reported on orthopedic clinical trials and their association with funding , study outcome , and efforts to reduce bias after r and omization across journals of multiple subspecialties . For the study reported here , we selected 5 major orthopedic subspecialty journals : Journal of Bone and Joint Surgery ( American Volume ) , Spine , Journal of Arthroplasty , Journal of Orthopaedic Trauma , and American Journal of Sports Medicine . We chose a 2-year limit for investigation ( 2002 - 2004 ) ; included all original r and omized clinical trials reported in these 5 journals ; and examined these trials for their study design , funding source , outcome , bias potential , and conclusion reached . Support for the 100 eligible orthopedic clinical trials was stated as coming from industry ( 26 trials , 26 % ) , nonprofit sources ( 19 trials , 19 % ) , and mixed sources ( 5 trials , 5 % ) ; no support was stated in 46 trials ( 46 % ) , and support was not reported in 4 trials ( 4 % ) . Of the 26 trials reporting industry support , 22 ( 85 % ) were grade d as indicating an outcome favorable to the new treatment . The association between industry funding and favorable outcome was strong and significant ( P<.001 ) . In almost half of the studies reported in Journal of Bone and Joint Surgery and Spine , measures taken to reduce bias were not documented BACKGROUND AND OBJECTIVE To conduct a pilot study to compare the frequency of errors that accompany single vs. double data extraction , compare the estimate of treatment effect derived from these methods , and compare the time requirements for these methods . METHODS Review ers were r and omized to the role of data extractor or data verifier , and were blind to the study hypothesis . The frequency of errors associated with each method of data extraction was compared using the McNemar test . The data set for each method was used to calculate an efficacy estimate by each method , using st and ard meta-analytic techniques . The time requirement for each method was compared using a paired t-test . RESULTS Single data extraction result ed in more errors than double data extraction ( relative difference : 21.7 % , P = .019 ) . There was no substantial difference between methods in effect estimates for most outcomes . The average time spent for single data extraction was less than the average time for double data extraction ( relative difference : 36.1 % , P = .003 ) . CONCLUSION In the case that single data extraction is used in systematic review s , review ers and readers need to be mindful of the possibility for more errors and the potential impact these errors may have on effect estimates Objective To identify trends in r and omized controlled trials ( RCTs ) in leading otolaryngology journals . Study Design and Setting We review ed all RCTs of treatment efficacy from 2000 through 2005 in 4 major otolaryngology journals . Data included study quality , author 's conclusions , adverse events , and study support/ funding . Results Of 5467 total articles , 202 ( 3.7 % ) were RCTs of treatment efficacy . Slightly more than half of the trials were supported by for-profit organizations ( 25 % ) , not-for-profit groups ( 21 % ) , or both ( 7 % ) . Intent-to-treat analysis was used in 58 percent of trials , P values in 88 percent , and confidence intervals in 11 percent . Conclusions favoring the experimental group were unrelated to presence or absence of industry funding , and conclusions suggesting equivalence were unrelated to sample size . Conclusions RCTs are uncommon in otolaryngology journals , but they demonstrate frequent use of intent-to-treat analysis , no evidence of publication bias for funded studies , and no evidence of low power in studies suggesting equivalence . Significance This study has implication s for both the otolaryngology research er design ing studies and the practicing clinician interpreting them Objectives To investigate the degree to which Cochrane review s of drug interventions published in 2010 reported conflicts of interest from included trials and , among review s that reported this information , where it was located in the review documents . Design Cross sectional study . Data sources Cochrane Data base of Systematic Review s. Selection criteria Systematic review s of drug interventions published in 2010 in the Cochrane Data base of Systematic Review s , with review content classified as up to date in 2008 or later and with results from one or more r and omised controlled trials . Results Of 151 included Cochrane review s , 46 ( 30 % , 95 % confidence interval 24 % to 38 % ) reported information on the funding sources of included trials , including 30 ( 20 % , 14 % to 27 % ) that reported information on trial funding for all included trials and 16 ( 11 % , 7 % to 17 % ) that reported for some , but not all , trials . Only 16 of the 151 Cochrane review s ( 11 % , 7 % to 17 % ) provided any information on trial author-industry financial ties or trial author-industry employment . Information on trial funding and trial author-industry ties was reported in one to seven locations within each review , with no consistent reporting location observed . Conclusions Most Cochrane review s of drug trials published in 2010 did not provide information on trial funding sources or trial author-industry financial ties or employment . When this information was reported , location of reporting was inconsistent across review BACKGROUND Conflicting reports exist in the medical literature regarding the association between industry funding and published research findings . In this study , we examine the association between industry funding and the statistical significance of results in recently published medical and surgical trials . METHODS We examined a consecutive series of 332 r and omized trials published between January 1999 and June 2001 in 8 leading surgical journals and 5 medical journals . Each eligible study was independently review ed for method ological quality using a 21-point index with 5 domains : r and omization , outcomes , eligibility criteria , interventions and statistical issues . Our primary analysis included studies that explicitly identified the primary outcome and reported it as statistically significant . For studies that did not explicitly identify a primary outcome , we defined a " positive " study as one with at least 1 statistically significant outcome measure . We used multivariable regression analysis to determine whether there was an association between reported industry funding and trial results , while controlling for study quality and sample size . RESULTS Among the 332 r and omized trials , there were 158 drug trials , 87 surgical trials and 87 trials of other therapies . In 122 ( 37 % ) of the trials , authors declared industry funding . An unadjusted analysis of this sample of trials revealed that industry funding was associated with a statistically significant result in favour of the new industry product ( odds ratio [ OR ] 1.9 , 95 % confidence interval [ CI ] 1.3 - 3.5 ) . The association remained significant after adjustment for study quality and sample size ( adjusted OR 1.8 , 95 % CI 1.1 - 3.0 ) . There was a nonsignificant difference between surgical trials ( OR 8.0 , 95 % CI 1.1 - 53.2 ) and drug trials ( OR 1.6 , 95 % CI 1.1 - 2.8 ) , both of which were likely to have a pro-industry result ( relative OR 5.0 , 95 % CI 0.7 - 37.5 , p = 0.14 ) . INTERPRETATION Industry-funded trials are more likely to be associated with statistically significant pro-industry findings , both in medical trials and surgical interventions
Output:
| Discussion This study was design ed to clarify whether industry-sponsored trials report more positive outcomes than non-industry trials .
It will be the first study to evaluate this topic in general and abdominal surgery . |
MS213712 | ***TASK*** the task is to summarize an input biomedical literature in six sentences
***INPUT*** the input is a biomedical literature
***OUTPUT*** the output is the summary of an input biomedical literature in six sentences
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Input: The transition to college has been identified as a critical period for increases in overweight status . Overweight college students are at-risk of becoming obese adults , and , thus prevention efforts targeting college age individuals are key to reducing adult obesity rates . The current study evaluated an Internet intervention with first year college students ( N=170 ) r and omly assigned to one of four treatment conditions : 1 ) no treatment , 2 ) 6-week online intervention 3 ) 6-week weight and caloric feedback only ( via email ) , and 4 ) 6-week combined feedback and online intervention . The combined intervention group had lower BMI s at post-testing than the other three groups . This study demonstrated the effectiveness and feasibility of an online intervention to prevent weight gain among college students Background Epidemiologic data indicate most adolescents and adults experience multiple , simultaneous risk behaviors . Purpose The purpose of this study is to examine the efficacy of a brief image-based multiple-behavior intervention ( MBI ) for college students . Methods A total of 303 college students were r and omly assigned to : ( 1 ) a brief MBI or ( 2 ) a st and ard care control , with a 3-month postintervention follow-up . Results Omnibus treatment by time multivariate analysis of variance interactions were significant for three of six behavior groupings , with improvements for college students receiving the brief MBI on alcohol consumption behaviors , F(6 , 261 ) = 2.73 , p = 0.01 , marijuana-use behaviors , F(4 , 278 ) = 3.18 , p = 0.01 , and health-related quality of life , F(5 , 277 ) = 2.80 , p = 0.02 , but not cigarette use , exercise , and nutrition behaviors . Participants receiving the brief MBI also got more sleep , F(1 , 281 ) = 9.49 , p = 0.00 , than those in the st and ard care control . Conclusions A brief image-based multiple-behavior intervention may be useful in influencing a number of critical health habits and health-related quality -of-life indicators of college students Objective : The authors ' purpose in this study was to compare the effects of macronutrient intake on systemic glucose levels in previously sedentary participants who followed 1 of 4 diets that were either higher protein or high carbohydrate , while initiating an exercise program . Participants and Methods : The authors r and omly assigned 94 sedentary participants to 1 of 4 diet groups consisting of Diet 1 ( 55 % carbohydrate , 30 % fat , 15 % protein ) , Diet 2 ( 55 % carbohydrate , 30 % fat , 15 % protein and caloric restriction ) , Diet 3 ( 40 % carbohydrate , 30 % fat , 25 % protein ) , and Diet 4 ( 40 % carbohydrate , 30 % fat , 25 % protein and caloric restriction ) and followed recommended aerobic exercise prescriptions . Results : Repeated measures analyses of variance ( ANOVA ) revealed a significant time factor ( p = .021 ) but no significant differences between diet groups ( p = .207 ) . A trend was evident in the higher protein groups , with a 5.2 % decrease in glucose levels with Diet 3 and 5.0 % with Diet 4 . Although glucose levels changed over time with the greatest changes in the 2 higher protein diets , levels were not significantly different within participants . Conclusions : The results of the study indicate that systemic glucose availability was affected by higher protein consumption in Diet 3 participants , with the same trend in Diet 4 participants , although nonsignificant . These findings demonstrate that consuming a lower carbohydrate diet for 12 weeks can possibly change systemic glucose levels PURPOSE This study examined the effects of brief image-based interventions , including a multiple behavior health contract , a one-on-one tailored consultation , and a combined consultation plus contract intervention , for impacting multiple health behaviors of students in a university health clinic . METHODS A total of 155 college students attending a major southern university were recruited to participate in a study evaluating a health promotion program titled Project Fitness during the fall 2005 and spring 2006 . Participants were r and omly assigned to one of three treatments as they presented at the clinic : 1 ) a multiple behavior health contract , 2 ) a one-on-one tailored consultation , or 3 ) a combined consultation plus contract intervention . Baseline and 1-month post-intervention data were collected using computer-assisted question naires in a quiet office within the student health clinic . RESULTS Omnibus repeated- measures analyses of variance were significant for drinking driving behaviors , F(2,136 ) = 4.43 , p = .01 , exercise behaviors , F(5,140 ) = 6.12 , p = .00 , nutrition habits , F(3,143 ) = 5.37 , p = .00 , sleep habits , F(2,144 ) = 5.03 , p = .01 , and health quality of life , F(5,140 ) = 3.09 , p = .01 , with improvements on each behavior across time . Analysis of group-by-time interaction effects showed an increase in the use of techniques to manage stress , F(2,144 ) = 5.48 , p = .01 , and the number of health behavior goals set in the last 30 days , F(2,143 ) = 5.35 , p = .01 , but only among adolescents receiving the consultation , or consultation plus contract . Effect sizes were consistently larger across health behaviors , and medium in size , when both consult and contract were used together . CONCLUSIONS Brief interventions using a positive goal image of fitness , and addressing a number of health habits using a contract and consultation strategy alone , or in combination , have the potential to influence positive changes in multiple health behaviors of college students attending a university primary health care clinic BACKGROUND This study examined the effect of using physical activity homework on physical activity levels of college students . METHODS Students in r and omly assigned sections of a university health course were assigned 30 minutes of physical activity homework 3 days a week or no homework for 12 weeks . Participants completed self-reports of physical activity before the homework intervention and again at the conclusion of the 12 weeks of physical activity homework . RESULTS Participants in all course sections reported significant increases in the number of days per week of moderate and vigorous physical activity . Participants in homework sections additionally showed significant increases in the days they engaged in muscular strength/endurance training and activities to manage weight . Participants in sections without homework showed a significant increase in the number of days engaged in flexibility training . Comparison of gain scores showed statistically significant increases by the homework group in the days they participated in activities design ed to manage weight . CONCLUSION Physical activity homework was deemed to be an effective method of increasing college students ' levels of physical activity Purpose . Examine the impact of “ point of decision ” messages on fruit selection in a single dining hall setting . Setting . Competitive undergraduate liberal arts college in the southeastern United States . Intervention . “ Point of decision ” messages were compiled into a 35-slide multimedia PowerPoint presentation . Messages were displayed on a computer screen at a “ point of decision ” between the cookie and fruit stations during lunch for a total of 9 days . Measures . Baseline cookie and fruit consumption was measured 9 days prebaseline and 9 days postbaseline . A r and om sample of students completed surveys 1 week after the intervention . Analysis . t-tests were used to examine differences between prelevels of fruit consumption and levels measured simultaneously during “ point of decision ” messages . Descriptive statistics were used to examine perceptions of survey items 1 week postintervention . Results . A significant mean difference in daily fruit consumption was found following the slide presentation ( df-8 , t = − 2.800 ; p = .023 ) . Average daily fruit consumption at baseline was 408 ( SD = 73.43 ) . Postbaseline average daily fruit consumption significantly increased ( 533 ; SD = 102 ) . No significant prebaseline and postbaseline cookie differences were found ( p = .226 ) . Approximately 71 % of women and 68 % of men noticed the “ point of decision ” messages . Nineteen percent of women and 10 % of males reported modifying their food selection as a result of viewing the messages . Conclusion . The “ point of decision ” messaging significantly influenced fruit selection in a single dining hall setting . ( Am J Health Promot 2011;25[5]:298 - 300 . BACKGROUND Recent public health initiatives have promoted accumulating 10,000 steps per day . Little previous research has evaluated its effects in young adults . The aim of this study was to determine the effects of taking 10,000 steps per day on fitness and cardiovascular risk factors in sedentary university students . METHODS Healthy , sedentary students ( mean age 21.16 ± SD 6.17 ) were r and omly allocated to take 10,000 steps per day or to a control group who maintained their habitual activity . Members of the 10,000 step group wore a pedometer and reported daily step count in a diary . Outcome measurements ( 20-meter multistage shuttle run , BMI , and blood pressure ) were measured before and after 6 weeks . RESULTS There were no significant differences between the groups at baseline . After 6 weeks , the 10,000 steps group were taking significantly more steps ( 8824.1 ± SD 5379.3 vs. 12635.9 ± SD 6851.3 ; P = .03).No changes were observed in fitness , or BMI ( P > .05 ) . Significant reductions in blood pressure ( P = .04 ) in the 10,000 step group . CONCLUSIONS A daily target of 10,000 steps may be an appropriate intervention in sedentary university students to increase their physical activity levels . The positive health benefits of simple everyday physical activity should be promoted among health professionals Purpose . The purpose of this pilot study was to conduct an impact evaluation of a 10-week Web-based physical activity intervention . Design . Quasi-experimental , three-group pretest , posttest design . Setting . Large Midwestern university . Subjects . Participants ( N = 233 ) included college students registered for three courses . The study employed a convenience sample consisting of a Web-based group ( n = 108 ) , a physical activity group ( n = 64 ) , and a general health group ( n = 61 ) . Intervention . The Web-based group received a Social Cognitive Theory behavioral skill-building intervention and exercised 3 days per week in their leisure time . The physical activity group received exercise instruction and was required to attend three physical activity labs per week . The comparison group received health instruction . Measures . Outcome variables included moderate and vigorous physical activity , self-regulation , social support , self-efficacy , and outcome expectations and expectancies . Analysis . Differences between groups were assessed at pretest and posttest using multiple analyses of variance . Results . Vigorous physical activity , self-regulation , and outcome expectancy value changed significantly in the Web-based and physical activity course groups ( p < .01 ) . Conclusions . Even with consideration of limitations such as small sample size and lack of r and omization , the Web-based and traditional physical activity lecture and activity lab interventions were superior in eliciting changes in vigorous physical activity , self-regulation , and outcome expectancy value than a traditional health course . ( Am J Health Promot 2011;25[4]:227–230 . This study investigates the importance of peer effects in explaining weight gain among freshman college students . We exploit a natural experiment that takes place on most college campuses in the US -- r and omized roommate assignments . While previous studies suggest that having an obese spouse , friend , or sibling increases one 's likelihood of becoming obese , these social interactions are clearly non-r and om . We collect data from female students living on campus at a private Midwestern university at the beginning and end of their first year of college . Our findings suggest that the amount of weight gained during the freshman year is strongly and negatively correlated to the roommate 's initial weight . Further , our analysis of behaviors suggests that female students adopt some of their roommates ' weight-loss behaviors which cause them to gain less weight than they otherwise would have . In particular , we find evidence that this effect may be through influences in eating , exercise , and use of weight loss supplements BACKGROUND Research has shown that many college students do not meet recommended national guidelines for physical activity . The objective of this pilot study was to examine the short-term efficacy of a brief motivational intervention ( BMI ) design ed to increase physical activity . METHODS Participants were 70 college students who reported low physical activity ( 83 % women , 60 % African American ) . Participants were r and omly assigned to either the BMI condition or to an education-only ( EO ) condition . They completed measures of physical activity at baseline and 1-month follow-up . RESULTS Those in the BMI condition reported more vigorous-intensity physical activity at a 1-month follow-up than those in the EO condition . CONCLUSIONS The findings from this study provide preliminary support for the efficacy of a BMI design ed to increase physical activity among college students . Future studies should continue to examine and refine the intervention in an effort to improve health-related behaviors among this group Abstract Objective : To determine the impact of My Student Body (MSB)–Nutrition , an Internet-based obesity prevention program for college students . Participants : Three hundred and twenty ethnically diverse undergraduate students were r and omly assigned to 1 of 3 conditions : MSB-Nutrition program , an on-campus weight management course , and a comparison group . Methods : Students completed baseline and follow-up surveys regarding their nutrition and physical activity behaviors , self-efficacy , stress , attitudes , and body weight . Results : Compared with the on-campus course and a comparison group , the MSB-Nutrition program increased fruit and vegetable consumption
Output:
| This appears to be the first systematic review of physical activity , diet and weight loss interventions targeting university and college students . |
MS213713 | ***TASK*** the task is to summarize an input biomedical literature in six sentences
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Input: PURPOSE To evaluate intravitreal aflibercept injections ( IAI ; also called VEGF Trap-Eye ) for patients with macular edema secondary to central retinal vein occlusion ( CRVO ) . DESIGN R and omized controlled trial . METHODS This multicenter study r and omized 189 patients ( 1 eye/patient ) with macular edema secondary to CRVO to receive 6 monthly injections of either 2 mg intravitreal aflibercept ( IAI 2Q4 ) ( n = 115 ) or sham ( n = 74 ) . From week 24 to week 52 , all patients received 2 mg intravitreal aflibercept as needed ( IAI 2Q4 + PRN and sham + IAI PRN ) according to retreatment criteria . The primary endpoint was the proportion of patients who gained ≥15 ETDRS letters from baseline at week 24 . Additional endpoints included visual , anatomic , and quality -of-life NEI VFQ-25 outcomes at weeks 24 and 52 . RESULTS At week 24 , 56.1 % of IAI 2Q4 patients gained ≥15 letters from baseline compared with 12.3 % of sham patients ( P < .001 ) . At week 52 , 55.3 % of IAI 2Q4 + PRN patients gained ≥15 letters compared with 30.1 % of sham + IAI PRN patients ( P < .001 ) . At week 52 , IAI 2Q4 + PRN patients gained a mean of 16.2 letters of vision vs 3.8 letters for sham + IAI PRN ( P < .001 ) . The most common adverse events for both groups were conjunctival hemorrhage , eye pain , reduced visual acuity , and increased intraocular pressure . CONCLUSIONS Monthly injections of 2 mg intravitreal aflibercept for patients with macular edema secondary to CRVO result ed in a statistically significant improvement in visual acuity at week 24 , which was largely maintained through week 52 with intravitreal aflibercept PRN dosing . Intravitreal aflibercept injection was generally well tolerated Background : To compare the effectiveness of subthreshold grid laser treatment ( SGLT ) with infrared micropulse diode laser alone or in combination with intravitreal triamcinolone injection ( SGLT-IVTJ ) for the treatment of macular oedema ( MO ) secondary to branch retinal vein occlusion ( BRVO ) . Methods : Pilot r and omised clinical trial including 24 patients ( 24 eyes ) who were r and omised either to the SGLT ( 13 eyes ) or to SGLT-IVTJ ( 11 eyes ) . Complete ophthalmic examinations , including Early Treatment of Diabetic Retinopathy Study visual acuity , OCT and fluorescein angiography , were performed at the moment of the study entry and at 3-month intervals , with a planned follow-up of 12 months . Main outcome measures were the decrease in mean foveal thickness ( MFT ) on OCT , and the proportion of eyes that gained at least 10 letters ( approximately two or more lines of visual acuity gain ) at the 12-month examination . Secondary outcomes were the decrease in mean total macular volume on OCT , and the timing of MO resolution . Results : The change in MFT from the initial values was statistically significant for the SGLT-IVTJ from the 3-month examination and for the SGLP from the 6-month examination ( p<0.001 ) . At the 12-month evaluation , 10 patients of the SGLT-IVTJ group ( 91 % ) and eight of the SGLT group ( 62 % ) gained at least 10 letters ( two lines ) in visual acuity . The mean number of lines gained was 3.4 and 1.3 in the SGLT-IVTJ and in the SGLT group , respectively . Conclusions : The combined SGLT-IVT treatment of MO secondary to BRVO allows a significant visual acuity improvement , when compared with simple grid laser treatment OBJECTIVE To describe effects of ranibizumab and bevacizumab when administered monthly or as needed for 2 years and to describe the impact of switching to as-needed treatment after 1 year of monthly treatment . DESIGN Multicenter , r and omized clinical trial . PARTICIPANTS Patients ( n = 1107 ) who were followed up during year 2 among 1185 patients with neovascular age-related macular degeneration who were enrolled in the clinical trial . INTERVENTIONS At enrollment , patients were assigned to 4 treatment groups defined by drug ( ranibizumab or bevacizumab ) and dosing regimen ( monthly or as needed ) . At 1 year , patients initially assigned to monthly treatment were reassigned r and omly to monthly or as-needed treatment , without changing the drug assignment . MAIN OUTCOME MEASURES Mean change in visual acuity . RESULTS Among patients following the same regimen for 2 years , mean gain in visual acuity was similar for both drugs ( bevacizumab-ranibizumab difference , -1.4 letters ; 95 % confidence interval [ CI ] , -3.7 to 0.8 ; P = 0.21 ) . Mean gain was greater for monthly than for as-needed treatment ( difference , -2.4 letters ; 95 % CI , -4.8 to -0.1 ; P = 0.046 ) . The proportion without fluid ranged from 13.9 % in the bevacizumab-as-needed group to 45.5 % in the ranibizumab monthly group ( drug , P = 0.0003 ; regimen , P < 0.0001 ) . Switching from monthly to as-needed treatment result ed in greater mean decrease in vision during year 2 ( -2.2 letters ; P = 0.03 ) and a lower proportion without fluid ( -19 % ; P < 0.0001 ) . Rates of death and arteriothrombotic events were similar for both drugs ( P > 0.60 ) . The proportion of patients with 1 or more systemic serious adverse events was higher with bevacizumab than ranibizumab ( 39.9 % vs. 31.7 % ; adjusted risk ratio , 1.30 ; 95 % CI , 1.07 - 1.57 ; P = 0.009 ) . Most of the excess events have not been associated previously with systemic therapy targeting vascular endothelial growth factor ( VEGF ) . CONCLUSIONS Ranibizumab and bevacizumab had similar effects on visual acuity over a 2-year period . Treatment as needed result ed in less gain in visual acuity , whether instituted at enrollment or after 1 year of monthly treatment . There were no differences between drugs in rates of death or arteriothrombotic events . The interpretation of the persistence of higher rates of serious adverse events with bevacizumab is uncertain because of the lack of specificity to conditions associated with inhibition of VEGF PURPOSE Assess 12-month efficacy and safety of intraocular injections of 0.3 mg or 0.5 mg ranibizumab in patients with macular edema after branch retinal vein occlusion ( BRVO ) . DESIGN Prospect i ve , r and omized , sham injection-controlled , double-masked , multicenter trial . PARTICIPANTS A total of 397 patients with macular edema after BRVO . METHODS Eligible patients were r and omized 1:1:1 to 6 monthly injections of 0.3 mg or 0.5 mg ranibizumab or sham injections . After 6 months , all patients with study eye best-corrected visual acuity ( BCVA ) ≤20/40 or central subfield thickness ≥250 μm were to receive ranibizumab . Patients could receive rescue laser treatment once during the treatment period and once during the observation period if criteria were met . MAIN OUTCOME MEASURES The main efficacy outcome reported is mean change from baseline BCVA letter score at month 12 . Additional visual and anatomic parameters were assessed . RESULTS Mean ( 95 % confidence interval ) change from baseline BCVA letter score at month 12 was 16.4 ( 14.5 - 18.4 ) and 18.3 ( 15.8 - 20.9 ) in the 0.3 mg and 0.5 mg groups , respectively , and 12.1 ( 9.6 - 14.6 ) in the sham/0.5 mg group ( P<0.01 , each ranibizumab group vs. sham/0.5 mg ) . The percentage of patients who gained ≥15 letters from baseline BCVA at month 12 was 56.0 % and 60.3 % in the 0.3 mg and 0.5 mg groups , respectively , and 43.9 % in the sham/0.5 mg group . On average , there was a marked reduction in central foveal thickness ( CFT ) after the first as-needed injection of 0.5 mg ranibizumab in the sham/0.5 mg group , which was sustained through month 12 . No new ocular or nonocular safety events were identified . CONCLUSIONS At month 12 , treatment with ranibizumab as needed during months 6 - 11 maintained , on average , the benefits achieved by 6 monthly ranibizumab injections in patients with macular edema after BRVO , with low rates of ocular and nonocular safety events . In the sham/0.5 mg group , treatment with ranibizumab as needed for 6 months result ed in rapid reduction in CFT to a similar level as that in the 0.3 mg ranibizumab treatment group and an improvement in BCVA , but not to the extent of that in the 2 ranibizumab groups . Intraocular injections of ranibizumab provide an effective treatment for macular edema after BRVO . FINANCIAL DISCLOSURE(S ) Proprietary or commercial disclosure may be found after the references PURPOSE Assess the 12-month efficacy and safety of intraocular injections of 0.3 mg or 0.5 mg ranibizumab in patients with macular edema after central retinal vein occlusion ( CRVO ) . DESIGN Prospect i ve , r and omized , sham injection-controlled , double-masked , multicenter clinical trial . PARTICIPANTS We included 392 patients with macular edema after CRVO . METHODS Eligible patients were r and omized 1:1:1 to receive 6 monthly intraocular injections of 0.3 mg or 0.5 mg of ranibizumab or sham injections . After 6 months , all patients with BCVA ≤20/40 or central subfield thickness ≥250 μm could receive ranibizumab . MAIN OUTCOME MEASURES Mean change from baseline best-corrected visual acuity ( BCVA ) letter score at month 12 , additional parameters of visual function , central foveal thickness ( CFT ) , and other anatomic changes were assessed . RESULTS Mean ( 95 % confidence interval ) change from baseline BCVA letter score at month 12 was 13.9 ( 11.2 - 16.5 ) and 13.9 ( 11.5 - 16.4 ) in the 0.3 mg and 0.5 mg groups , respectively , and 7.3 ( 4.5 - 10.0 ) in the sham/0.5 mg group ( P<0.001 for each ranibizumab group vs. sham/0.5 mg ) . The percentage of patients who gained ≥15 letters from baseline BCVA at month 12 was 47.0 % and 50.8 % in the 0.3 mg and 0.5 mg groups , respectively , and 33.1 % in the sham/0.5 mg group . On average , there was a marked reduction in CFT after the first as-needed injection of 0.5 mg ranibizumab in the sham/0.5 mg group to the level of the ranibizumab groups , which was sustained through month 12 . No new ocular or nonocular safety events were identified . CONCLUSIONS On average , treatment with ranibizumab as needed during months 6 through 11 maintained the visual and anatomic benefits achieved by 6 monthly ranibizumab injections in patients with macular edema after CRVO , with low rates of ocular and nonocular safety events . After sham injections for 6 months , treatment with ranibizumab as needed for 6 months result ed in rapid reduction in CFT in the sham/0.5 mg group to a level similar to that in the 2 ranibizumab treatment groups and an improvement in BCVA , but not to the same level as that in the 2 ranibizumab groups . Intraocular injections of ranibizumab provide an effective treatment for macular edema after CRVO . FINANCIAL DISCLOSURE(S ) Proprietary or commercial disclosure may be found after the references Purpose To evaluate long-term efficacy of intravitreal bevacizumab ( IVB ) versus combined IVB and macular grid laser photocoagulation for the treatment of macular edema secondary to branch retinal vein occlusion ( BRVO ) . Methods In this prospect i ve study , 18 eyes were r and omized into 2 groups according to treatment : Group 1 ( 9 eyes ) underwent IVB at baseline , at month 1 , and at month 2 ; Group 2 ( 9 eyes ) underwent same IVB protocol combined with macular grid laser photocoagulation . Macular edema and visual acuity represented the endpoints of the study . IVB reinjections were performed in both groups if rec
Output:
| CONCLUSIONS Anti-VEGF agents result in a promising gain of visual acuity , but require a high injection frequency .
Dexamethasone implant might be an alternative , but comparison is impaired as the effect is temporary and it has not yet been tested in PRN regimen .
The ocular risk profile seems to be favorable for anti-VEGF agents in comparison to steroids . |
MS213714 | ***TASK*** the task is to summarize an input biomedical literature in six sentences
***INPUT*** the input is a biomedical literature
***OUTPUT*** the output is the summary of an input biomedical literature in six sentences
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Input: We determined the barriers to and facilitators of colorectal cancer ( CRC ) screening among two faith-based , inner city neighborhood health centers in Southwestern Pennsylvania . Data from a r and om sample of patients 50 years and older ( n=375 ) were used to estimate logistic regression equations to compare and contrast the predictors of four different CRC screening protocol s : ( 1 ) fecal occult blood test ( FOBT ) ≤ 2 years ago , ( 2 ) colonoscopy ≤ 10 years ago , ( 3 ) lower endoscopy ( colonoscopy or sigmoidoscopy ) ≤ 10 years ago , and ( 4 ) any of these screening measures . Racial differences ( between African Americans or Caucasians ) in type of colon cancer screening were not found . Controlling for covariates , logistic regression equations showed that a physician ’s support of colon cancer screening was positively associated with the receipt of colonoscopy ( OR : 19.47 , 95 CI : 5.45–69.54 ) , lower endoscopy ( OR : 10.96 , 95 CI : 3.77–31.88 ) and any colon cancer screening ( OR : 10.12 , 95 CI : 3.36–30.46 ) . Patients who see their physicians more frequently were also more likely to be screened for CRC . Unlike other studies , the faith-based environment in which these patients are treated may explain the lack of racial disparity specific to our measures of CRC screening Little is known about how minority groups react to public information that highlights racial disparities in cancer . This double-blind r and omized study compared emotional and behavioral reactions to four versions of the same colon cancer ( CRC ) information presented in mock news articles to a community sample of African-American adults ( n = 300 ) . Participants read one of four articles that varied in their framing and interpretation of race-specific CRC mortality data , emphasizing impact ( CRC is an important problem for African-Americans ) , two dimensions of disparity ( Blacks are doing worse than Whites and Blacks are improving , but less than Whites ) , or progress ( Blacks are improving over time ) . Participants exposed to disparity articles reported more negative emotional reactions to the information and were less likely to want to be screened for CRC than those in other groups ( both P < 0.001 ) . In contrast , progress articles elicited more positive emotional reactions and participants were more likely to want to be screened . Moreover , negative emotional reaction seemed to mediate the influence of message type on individuals wanting to be screened for CRC . Overall , these results suggest that the way in which disparity research is reported in the medium can influence public attitudes and intentions , with reports about progress yielding a more positive effect on intention . This seems especially important among those with high levels of medical mistrust who are least likely to use the health care system and are thus the primary target of health promotion advertising . ( Cancer Epidemiol Biomarkers Prev 2008;17(11):2946–53 Low-income minorities often face system-based and personal barriers to screening colonoscopy ( SC ) . Culturally targeted patient navigation ( CTPN ) programs employing professional navigators ( Pro-PNs ) or community-based peer navigators ( Peer-PNs ) can help overcome barriers but are not widely implemented . In East Harlem , NY , USA , where approximately half the residents participate in SC , 315 African American patients referred for SC at a primary care clinic with a Direct Endoscopic Referral System were recruited between May 2008 and May 2010 . After medical clearance , 240 were r and omized to receive CTPN delivered by a Pro-PN ( n = 106 ) or Peer-PN ( n = 134 ) . Successful navigation was measured by SC adherence rate , patient satisfaction and navigator trust . Study enrollment was 91.4 % with no significant differences in SC adherence rates between Pro-PN ( 80.0 % ) and Peer-PN ( 71.3 % ) ( P = 0.178 ) . Participants in both groups reported high levels of satisfaction and trust . These findings suggest that CTPN Pro-PN and Peer-PN programs are effective in this urban primary care setting . We detail how we recruited and trained navigators , how CTPN was implemented and provide a preliminary answer to our questions of the study aims : can peer navigators be as effective as professionals and what is the potential impact of patient navigation on screening adherence Purpose . Identify the influence of medical mistrust , fears , attitudes , and sociodemographic characteristics on unwillingness to participate in colorectal cancer ( CRC ) screening . Design . Cross-sectional , disproportionally allocated , stratified , r and om-digit-dial telephone question naire of noninstitutionalized households . Setting . New York City , New York ; Baltimore , Maryl and ; San Juan , Puerto Rico . Subjects . Ethnically diverse sample of 454 adults ≥50 years of age . Measures . Health status , cancer screening effectiveness , psychosocial factors ( e.g. , perceptions of pain , fear , trust ) , and CRC screening intentions using the Cancer Screening Question naire , which addresses a range of issues related to willingness of minorities to participate in cancer screening . Analysis . Multivariate logistic regression was used to model the probability of reporting unwillingness to participate in CRC screening . Results . Fear of embarrassment during screening ( odds ratio [ OR ] = 10.72 ; 95 % confidence interval [ CI ] , 2.15–53.39 ) , fear of getting AIDS ( OR = 8.75 ; 95 % CI , 2.48–30.86 ) , fear that exam might be painful ( OR = 3.43 ; 95 % CI , 1.03–11.35 ) , and older age ( OR = 1.10 ; 95 % CI , 1.04–1.17 ) were positively associated with unwillingness to participate in CRC screening . Fear of developing cancer ( OR = .12 ; 95 % CI , .03–.57 ) and medical mistrust ( OR = .19 ; 95 % CI , .06–.60 ) were negatively associated with unwillingness to screen . Conclusions . Findings suggest that CRC health initiatives should focus on increasing knowledge , addressing fears and mistrust , and normalizing CRC screening as a beneficial preventive practice , and should increase focus on older adults BACKGROUND Fecal occult blood testing ( FOBT ) can reduce colorectal cancer ( CRC ) mortality . Unfortunately , CRC screening is underutilized . Sociocultural mediators of FOBT adherence have not been extensively studied in lower income , minority population s. This study prospect ively studied FOBT return in a low-income , multiethnic population . METHODS Participants ( N = 298 ) , aged > or = 40 years , were surveyed and given FOBT kits with instructions . Those not returning kits within 30 days received a reminder telephone call . Bivariate and multivariate analyses assessed predictors of FOBT card return at 90 days . RESULTS Participants ( median age = 48 ) were predominately African American ( 69 % ) , without private insurance ( 88 % ) , and of low income . The largest group of participants preferred FOBT alone ( 46 % ) , followed by whatever my doctor recommends ( 19 % ) , endoscopy + annual FOBT ( 16 % ) , endoscopy alone ( 14 % ) , and no screening ( 5 % ) . In multivariate analyses , FOBT return was predicted by age ( OR = 1.05 ) and lack of reported FOBT barriers ( OR = 3.81 ) . Among those > or = 50 and not up-to- date with screening , FOBT return was predicted by cancer fatalism ( OR = 0.83 ) . FOBT barriers were associated with age ( OR = 0.96 ) , less than high school education ( OR = 2.05 ) , and less physician trust ( OR = 2.12 ) . Endoscopy barriers were associated with age ( OR = 0.93 ) , less physician trust ( OR = 1.95 ) , and female gender ( OR = 3.45 ) . CONCLUSIONS Younger individuals and those with less education , less trust in health care providers , and more fatalistic beliefs are at risk for CRC screening non-adherence . Strategies addressing common misconceptions should improve CRC screening rates in low-income , multiethnic population OBJECTIVE This study examined the effects ( affective reactions , cognitive reactions and processing , perceived benefits and barriers and intent to screen ) of targeted peripheral+evidential ( PE ) and peripheral+evidential+socio-cultural ( PE+SC ) colorectal cancer communications . METHODS This study was a two-arm r and omized control study of cancer communication effects on affective , cognitive processing , and behavioral outcomes over a 22-week intervention . There were 771 African American participants , 45 - 75 years , participating in the baseline survey related to CRC screening . Three follow-up interviews that assessed intervention effects on affective response to the publications , cognitive processing , and intent to obtain CRC screening were completed . RESULTS There were no statistically significant differences between PE and PE+SC intervention groups for affect , cognitive processing or intent to screen . However , there were significant interactions effects on outcome variables . CONCLUSIONS The advantages and disadvantages of PE+SC targeted cancer communications and implication s of sex differences are considered . PRACTICE IMPLICATION S While there do not appear to be significant differences in behavioral outcomes when using PE and PE+SC strategies , there appear to be subtle differences in affective and cognitive processing outcomes related to medical suspicion and ethnic identity , particularly as it relates to gender PURPOSE We report the validation of an instrument to measure mistrust of health care organizations and examine the relationship between mistrust and health care service underutilization . METHODS We conducted a telephone survey of a r and om sample of households in Baltimore City , MD . We surveyed 401 persons and followed up with 327 persons ( 81.5 percent ) 3 weeks after the baseline interview . We conducted tests of the validity and reliability of the Medical Mistrust Index ( MMI ) and then conducted multivariate modeling to examine the relationship between mistrust and five measures of underutilization of health services . RESULTS Using principle components analysis , we reduced the 17-item MMI to 7 items with a single dimension . Test-retest reliability was moderately strong , ranging from Pearson correlation of 0.346 - 0.697 . In multivariate modeling , the MMI was predictive of four of five measures of underutilization of health services : failure to take medical advice ( b=1.56 , p<.01 ) , failure to keep a follow-up appointment ( b=1.11 , p=.01 ) , postponing receiving needed care ( b=0.939 , p=.01 ) , and failure to fill a prescription ( b=1.48 , p=.002 ) . MMI was not significantly associated with failure to get needed medical care ( b=0.815 , p=.06 ) . CONCLUSIONS The MMI is a robust predictor of underutilization of health services . Greater attention should be devoted to building greater trust among patients BACKGROUND Colorectal cancer ( CRC ) screening is effective but underutilized . Although physician recommendation is an important predictor of screening , considerable variation in CRC screening completion remains . PURPOSE To characterize the influence of patient trust in care providers on CRC screening behavior . METHODS Data were collected as part of a cluster-r and omized CRC screening intervention trial performed in the San Francisco Community Health Network from March 2007 to January 2012 ( analysis , Spring 2012 ) . All study participants received a recommendation to complete CRC screening from their primary care provider ( PCP ) . Included participants were aged 50 - 79 years , not current with screening , and completed the Wake Forest Trust Scale ( WFTS ) measuring trust in PCPs and doctors in general . Primary outcome was CRC screening completion ( colonoscopy or fecal occult blood testing ) within 12 months following enrollment . Multivariable association adjusted for race/ethnicity , language , and other sociodemographics was estimated using generalized estimating equations with logit link and binomial distribution . RESULTS WFTS response was 70.3 % ( 701 ) . Most participants ( 83 % ) were Latino , Asian , or black . Most had income < $ 30,000 ( 96 % ) and public health insurance ( 86 % ) . Higher trust in PCP was associated with screening completion ( OR=1.11 , 95 % CI=1.03 , 1.17 ) , but trust in doctors was not ( OR=1.02 , 95 % CI=0.82 , 1.28 ) . Race , language , and other sociodemographic factors were not significant in multivariable analysis . CONCLUSIONS After controlling for traditional factors , trust in PCP remained the only significant driver of CRC screening completion in low-income patients . Interventions to promote CRC screening may be improved by including efforts to enhance patient trust in PCP
Output:
| Quantitative differences in mistrust and CRC screening by gender were mixed , but qualitative studies highlighted fear of experimentation and intrusiveness of screening methods as unique themes among African American men . |
MS213715 | ***TASK*** the task is to summarize an input biomedical literature in six sentences
***INPUT*** the input is a biomedical literature
***OUTPUT*** the output is the summary of an input biomedical literature in six sentences
***DOCUMENTATION***
***EXAMPLES***
Input: Background The success of a human intervention trial depends upon the ability to recruit eligible volunteers . Many trials fail because of unrealistic recruitment targets and flawed recruitment strategies . In order to predict recruitment rates accurately , research ers need information on the relative success of various recruitment strategies . Few published trials include such information and the number of participants screened or approached is not always cited . Methods This paper will describe in detail the recruitment strategies employed to identify older adults for recruitment to a 6-month r and omised controlled dietary intervention trial which aim ed to explore the relationship between diet and immune function ( The FIT study ) . The number of people approached and recruited , and the reasons for exclusion , will be discussed . Results Two hundred and seventeen participants were recruited to the trial . A total of 7,482 letters were sent to potential recruits using names and addresses that had been supplied by local Family ( General ) Practice s. Eight hundred and forty three potential recruits replied to all methods of recruitment ( 528 from GP letters and 315 from other methods ) . The eligibility of those who replied was determined using a screening telephone interview , 217 of whom were found to be suitable and agreed to take part in the study . Conclusion The study demonstrates the application of multiple recruitment methods to successfully recruit older people to a r and omised controlled trial . The most successful recruitment method was by contacting potential recruits by letter on NHS headed note paper using contacts provided from General Practice s. Ninety percent of recruitment was achieved using this method . Adequate recruitment is fundamental to the success of a research project , and appropriate strategies must therefore be adopted in order to identify eligible individuals and achieve recruitment targets . Trial registration numberIS RCT N45031464 Reports of cluster r and omised trials require additional information to allow readers to interpret them accurately The effective reporting of r and omised controlled trials has received useful attention in recent years . Many journals now require that reports conform to the guidelines in the Consoli date d St and ards of Reporting Trials ( CONSORT ) statement , first published in 1996 and revised in 2001 . The statement includes a checklist of items that should be included in the trial report . These items are evidence based whenever possible and are regularly review ed . The statement also recommends including a flow diagram to show the flow of participants from group assignment through to the final analysis . The CONSORT statement focused on reporting parallel group r and omised trials in which individual participants are r and omly assigned to study groups . However , in some situations it is preferable to r and omly assign groups of individuals ( such as families or medical practice s ) rather than individuals . Reasons include the threat of contamination of some interventions ( such as dietary interventions ) if individual r and omisation is used . 5 Also , in certain setting s r and omisation by group may be the only feasible method of conducting a trial . Trials with this design are variously known as field trials , community based trials , place based trials , or ( as in this paper ) cluster r and omised trials . In an earlier discussion paper we considered the implication s of the CONSORT statement for the reporting of cluster r and omised trials . Here we present up date d guidance , based on the 2001 revision of the CONSORT statement Background It is notoriously difficult to recruit patients to r and omised controlled trials in primary care . This is particularly true when the disease process under investigation occurs relatively infrequently and must be investigated during a brief time window . Bell 's palsy , an acute unilateral paralysis of the facial nerve is just such a relatively rare condition . In this case study we describe the organisational issues presented in setting up a large r and omised controlled trial of the management of Bell 's palsy across primary and secondary care in Scotl and and how we managed to successfully recruit and retain patients presenting in the community . Methods Where possible we used existing evidence on recruitment strategies to maximise recruitment and retention . We consider that the key issues in the success of this study were ; the fact that the research was seen as clinical ly important by the clinicians who had initial responsibility for recruitment ; employing an experienced trial co-ordinator and dedicated research ers willing to recruit participants seven days per week and to visit them at home at a time convenient to them , hence reducing missed patients and ensuring they were retained in the study ; national visibility and repeated publicity at a local level delivered by locally based principal investigators well known to their primary care community ; encouraging recruitment by payment to practice s and reducing the workload of the referring doctors by providing immediate access to specialist care ; good collaboration between primary and secondary care and basing local investigators in the otolarnygology trial centres Results Although the recruitment rate did not meet our initial expectations , enhanced retention meant that we exceeded our planned target of recruiting 550 patients within the planned time-scale . Conclusion While difficult , recruitment to and retention within multi-centre trials from primary care can be successfully achieved through the application of the best available evidence , establishing good relationships with practice s , minimising the workload of those involved in recruitment and offering enhanced care to all participants . Primary care trialists should describe their experiences of the methods used to persuade patients to participate in their trials when publishing their results Background Recruitment of patients by health professionals is reported as one of the most challenging steps when undertaking studies in primary care setting s. Numerous investigations of the barriers to patient recruitment in trials which recruit patients to receive an intervention have been published . However , we are not aware of any studies that have reported on the recruitment barriers as perceived by health professionals to recruiting patients into cluster r and omised trials where patients do not directly receive an intervention . This particular subtype of cluster trial is commonly termed a professional-cluster trial . The aim of this study was to investigate factors that contributed to general practitioners recruitment of patients in a professional-cluster trial which evaluated the effectiveness of an intervention to increase general practitioners adherence to a clinical practice guideline for acute low-back pain . Method General practitioners enrolled in the study were posted a question naire , consisting of quantitative items and an open-ended question , to assess possible reasons for poor patient recruitment . Descriptive statistics were used to summarise quantitative items and responses to the open-ended question were coded into categories . Results Seventy-nine general practitioners completed at least one item ( 79/94 = 84 % ) , representing 68 practice s ( 85 % practice response rate ) , and 44 provided a response to the open-ended question . General practitioners recalled inviting a median of two patients with acute low-back pain to participate in the trial over a seven-month period ; they reported that they intended to recruit patients , but forgot to approach patients to participate ; and they did not perceive that patients had a strong interest or disinterest in participating . Additional open-ended comments were generally consistent with the quantitative data . Conclusion A number of barriers to the recruitment of patients with acute low-back pain by general practitioners in a professional-cluster trial were identified . These barriers were similar to those that have been identified in the literature surrounding the recruitment of patients in individual patient r and omised trials . To advance the evidence base for patient recruitment strategies in primary care setting s , trialists undertaking professional-cluster trials need to develop and evaluate patient recruitment strategies that minimise the efforts required by practice staff to recruit patients , while also meeting privacy and ethical responsibilities and minimising the risk of selection bias . Trial registration Australian New Zeal and Clinical Trials Registry ACTRN012606000098538 ( date registered 14/03/2006 ) BACKGROUND Specialist National Health Service clinics for smoking cessation have increased in number , but most smokers prefer less intensive self-help and many smokers have no serious intentions to attempt to quit . Computer-tailored self-help material s can be adapted to provide advice to less motivated smokers , and can also take into account features such as level of education and socio-economic circumstance . OBJECTIVE To assess the feasibility of delivering tailored feedback to a large population by identifying smokers from general practice records , with the aim of informing a large-scale trial of effectiveness . METHOD Question naires were sent to a r and om sample of smokers ( n = 876 ) aged between 18 and 65 years , identified from records in four practice s. Smokers returning the question naire ( n = 78 ) were r and omized to receive st and ard information , or to receive st and ard information plus computer-tailored feedback reports . Follow-up question naires were sent 3 months after the return of the baseline question naire . RESULTS The recruitment strategy yielded a response rate of 8.9 % , and a 66.7 % follow-up rate . There were no significant differences in outcome between the two conditions , and no significant differences in outcome between practice s. In the Intervention group significantly more of those who remembered receiving the tailored advice letter had made a quit attempt ( 6[60%]/3[21.4 % ] , P < 0.05 ) . CONCLUSION This pilot study demonstrated the feasibility of carrying out such a trial to evaluate the effectiveness of delivering an intervention for smoking cessation in primary care , and highlighted issues that should be addressed in considering the design of a large-scale trial Background Financial incentives have been used for many years internationally to improve quality of care in general practice . The aim of this pilot study was to determine if offering general practitioners ( GP ) a small incentive payment per test would increase chlamydia testing in women aged 16 to 24 years , attending general practice . Methods General practice clinics ( n = 12 ) across Victoria , Australia , were cluster r and omized to receive either a $ AUD5 payment per chlamydia test or no payment for testing 16 to 24 year old women for chlamydia . Data were collected on the number of chlamydia tests and patient consultations undertaken by each GP over two time periods : 12 month pre-trial and 6 month trial period . The impact of the intervention was assessed using a mixed effects logistic regression model , accommodating for clustering at GP level . Results Testing increased from 6.2 % ( 95 % CI : 4.2 , 8.4 ) to 8.8 % ( 95 % CI : 4.8 , 13.0 ) ( p = 0.1 ) in the control group and from 11.5 % ( 95 % CI : 4.6 , 18.5 ) to 13.4 % ( 95 % CI : 9.5 , 17.5 ) ( p = 0.4 ) in the intervention group . Overall , the intervention did not result in a significant increase in chlamydia testing in general practice . The odds ratio for an increase in testing in the intervention group compared to the control group was 0.9 ( 95 % CI : 0.6 , 1.2 ) . Major barriers to increased chlamydia testing reported by GPs included a lack of time , difficulty in remembering to offer testing and a lack of patient awareness around testing . Conclusions A small financial incentive alone did not increase chlamydia testing among young women attending general practice . It is possible small incentive payments in conjunction with reminder and feedback systems may be effective , as may higher financial incentive payments . Further research is required to determine if financial incentives can increase testing in Australian general practice , the type and level of financial scheme required and whether incentives needs to be part of a multi-faceted package . Trial Registration Australian New Zeal and Clinical Trial Registry ACTRN12608000499381 BACKGROUND Recruiting adequate numbers of participants represents a major problem to the completion of r and omised clinical trials in primary care . Information on different recruitment strategies applied in one trial is scarce . AIM To evaluate the application of two recruitment strategies in one trial . DESIGN OF STUDY The study was performed within the framework of a r and omised clinical trial on the effectiveness of a behavioural treatment for patients with chronic shoulder complaints . SETTING Thirty-two general practice s in the Netherl and s. METHOD Patients recruited during a consultation with their GP for chronic shoulder complaints were compared with patients recruited by advertisement in a local newspaper as regards baseline characteristics , withdrawals ( drop-outs and losses to follow-up ) and post-treatment clinical outcomes . RESULTS Patients recruited by the GPs ( n = 83 ) were similar to those recruited by advertisement ( n = 83 ) in terms of demographic characteristics and clinical outcome measures at baseline , but differed slightly in disease characteristics and treatment preferences . Recruitment strategy was not related to reasons for or numbers of withdrawals . Improvements on outcome measures were greater in patients recruited by the GPs , irrespective of allocated treatment . Results on the clinical effectiveness of treatments at the end of the treatment period or during follow-up were neither modified by recruitment strategy , nor by differences between the two strategy groups in patient characteristics found at baseline . CONCLUSION Using two recruitment strategies did not influence the outcomes on clinical effectiveness in this trial . However , recruitment strategy should be considered as a putative modifying factor in the design of a study Recruitment methods heavily impact budget and outcomes in clinical trials . We conducted a post-hoc examination of the efficiency and cost of three different recruitment methods used in Journey for Control of Diabetes : the IDEA Study , a r and omized controlled trial evaluating outcomes of group and individual diabetes education in New Mexico and Minnesota . Electronic data bases were used to identify health plan members with diabetes and then one of the following three methods was used to recruit study participants : 1 . Minnesota Method 1 - -Mail only ( first half of recruitment period ) . Mailed invitations with return-response forms . 2 . Minnesota Method 2 - -Mail and selective phone calls ( second half of recruitment period ) . Mailed invitations with return-response forms and subsequent phone calls to nonresponders . 3 . New Mexico Method 3 - -Mail and non-selective phone calls ( full recruitment period ) : Mailed invitations with subsequent phone calls to all . The combined methods succeeded in meeting the recruitment goal of 623 subjects . There were 147 subjects recruited using Minnesota 's Method 1 , 190 using Minnesota 's Method 2 , and 286 using New Mexico 's Method 3
Output:
| The most effective recruitment in primary care research requires practitioner involvement .
The active participation of primary care practitioners in both the design and conduct of research helps to identify strategies that are congruent with the context in which patient care is delivered .
This is reported to be the optimal recruitment strategy |
MS213716 | ***TASK*** the task is to summarize an input biomedical literature in six sentences
***INPUT*** the input is a biomedical literature
***OUTPUT*** the output is the summary of an input biomedical literature in six sentences
***DOCUMENTATION***
***EXAMPLES***
Input: CONTEXT Diabetes is frequently diagnosed late , when the development of complications is almost inevitable , decreasing the quality of life of patients . However , early detection of affected individuals would allow the implementation of timely and effective therapies . OBJECTIVE Here we set to describe the profile of circulating microRNAs ( miRNAs ) in prediabetic patients with the intention of identifying novel diagnostic and therapeutic tools . DESIGN We used real-time RT-PCR to measure the abundance of 176 miRNAs in serum of a cohort of 92 control and prediabetic individuals with either impaired fasting glucose or impaired glucose tolerance , as well as newly diagnosed diabetic patients . We vali date d the results in a second cohort of control and prediabetic subjects undergoing a therapeutic exercise intervention , as well as in a mouse model of glucose intolerance . RESULTS We identified two miRNAs , miR-192 and miR-193b , whose abundance is significantly increased in the prediabetic state but not in diabetic patients . Strikingly , these miRNAs are also increased in plasma of glucose-intolerant mice . Moreover , circulating levels of miR-192 and miR-193b return to baseline in both prediabetic humans and glucose-intolerant mice undergoing a therapeutic intervention consisting in chronic exercise , which succeeded in normalizing metabolic parameters . CONCLUSIONS Our data show that the pattern of circulating miRNAs is modified by defects in glucose metabolism in a similar manner in mice and humans . This circulating miRNA signature for prediabetes could be used as a new diagnostic tool , as well as to monitor response to intervention Saturated fatty acids ( SFA ) and monounsaturated fatty acids ( MUFA ) show different effects on the development of insulin resistance . In this study , we compared the effect of dietary SFA and MUFA on the insulin signaling pathway in the skeletal muscle of a type 2 diabetic animal model . Twenty-nine-week-old male Otsuka Long-Evans Tokushima fatty ( OLETF ) rats were r and omly divided into three groups and fed one of the following diets for 3 weeks ; a normal chow diet , an SFA ( lard oil ) enriched or a MUFA ( olive oil ) enriched high-fat diet . The vastus lateralis muscle was used for analyses . Insulin tolerance test showed improved insulin sensitivity in rats fed the MUFA diet , as compared to those fed the SFA diet ( p < 0.001 ) . The SFA diet reduced IRS-1 expression and phosphorylated PI3 K levels in skeletal muscle , as compared with a chow diet ( p < 0.001 , respectively ) . On the contrary , muscle IRS-2 expression and phosphorylated ERK1/2 was significantly increased in rats fed the SFA diet ( p < 0.001 , respectively ) . Membrane translocation of glucose transporter type 4 decreased in the skeletal muscle of rats fed the SFA diet , as compared to those fed a chow diet ( p < 0.001 ) . These changes in insulin signaling pathway in skeletal muscle were not observed in rats fed the MUFA diet . In conclusion , the beneficial effect of dietary MUFA on insulin sensitivity is associated with a conserved IRS-1/PI3 K insulin signaling pathway which was altered by dietary SFA OBJECTIVE Fat intake , especially monounsaturated fatty acid ( MUFA ) , has been liberalized in diabetic diets to preserve HDL cholesterol and improve glycemic control , yet the exact sources have not been clearly defined . Therefore , we assessed the effect of mixed nut consumption as a source of vegetable fat on serum lipids and HbA1c in type 2 diabetes . RESEARCH DESIGN AND METHODS A total of 117 type 2 diabetic subjects were r and omized to one of three treatments for 3 months . Supplements were provided at 475 kcal per 2,000-kcal diet as mixed nuts ( 75 g/day ) , muffins , or half portions of both . The primary outcome was change in HbA1c . RESULTS The relative increase in MUFAs was 8.7 % energy on the full-nut dose compared with muffins . Using an intention-to-treat analysis ( n = 117 ) , full-nut dose ( mean intake 73 g/day ) reduced HbA1c ( −0.21 % absolute HbA1c units , 95 % CI −0.30 to −0.11 , P < 0.001 ) with no change after half-nut dose or muffin . Full-nut dose was significantly different from half-nut dose ( P = 0.004 ) and muffin ( P = 0.001 ) , but no difference was seen between half-nut dose and muffins . LDL cholesterol also decreased significantly after full-nut dose compared with muffin . The LDL cholesterol reduction after half-nut dose was intermediate and not significantly different from the other treatments . Apolipoprotein ( apo ) B and the apoB : apoA1 ratio behaved similarly . Nut intake related negatively to changes in HbA1c ( r = −0.20 , P = 0.033 ) and LDL cholesterol ( r = −0.24 , P = 0.011 ) . CONCLUSIONS Two ounces of nuts daily as a replacement for carbohydrate foods improved both glycemic control and serum lipids in type 2 diabetes Rationale : MicroRNAs ( miRNAs ) have been implicated in the epigenetic regulation of key metabolic , inflammatory , and antiangiogenic pathways in type 2 diabetes ( DM ) and may contribute to common disease complications . Objective : In this study , we explore plasma miRNA profiles in patients with DM . Methods and Results : Total RNA was extracted from plasma sample s of the prospect i ve population -based Bruneck study . A total of 13 c and i date miRNAs identified by microarray screening and miRNA network inference were quantified by quantitative PCR in all diabetic patients of the Bruneck study and age- and sex-matched controls ( 1995 evaluation , n=80 each ) . Quantitative PCR assessment revealed lower plasma levels of miR-20b , miR-21 , miR-24 , miR-15a , miR-126 , miR-191 , miR-197 , miR-223 , miR-320 , and miR-486 in prevalent DM , but a modest increase of miR-28 - 3p . Findings emerged as robust in multivariable analysis and were independent of the st and ardization procedure applied . For endothelial miR-126 , results were confirmed in the entire Bruneck cohort ( n=822 ) in univariate ( odds ratio [ 95 % confidence interval ] , 0.38 [ 0.26 to 0.55 ] ; P=2.72 × 10−7 ) and multivariate analyses ( 0.57 [ 0.37 to 0.86 ] ; P=0.0082 ) . Importantly , reduced miR-15a , miR-29b , miR-126 , miR-223 , and elevated miR-28 - 3p levels ante date d the manifestation of disease . Most differences in miRNA levels were replicated in plasma obtained from hyperglycemic Lepob mice . High glucose concentrations reduced the miR-126 content of endothelial apoptotic bodies . Similarly in patients with DM , the reduction of miR-126 was confined to circulating vesicles in plasma . Conclusions : We reveal a plasma miRNA signature for DM that includes loss of endothelial miR-126 . These findings might explain the impaired peripheral angiogenic signaling in patients with DM OBJECTIVE Recent studies have suggested that nuts have favorable effects beyond lipid lowering . We aim ed to investigate effect of the Antep pistachio ( Pistacia vera L. ) on blood glucose , lipid parameters , endothelial function , inflammation , and oxidation in healthy young men living in a controlled environment . METHODS A Mediterranean diet was administered to normolipidemic 32 healthy young men ( mean age 22 y , range 21 - 24 ) for 4 wk . After 4 wk , participants continued to receive the Mediterranean diet but pistachio was added for 4 wk by replacing the monounsaturated fat content constituting approximately 20 % of daily caloric intake . Fasting blood sample s and brachial endothelial function measurements were performed at baseline and after each diet . RESULTS Compared with the Mediterranean diet , the pistachio diet decreased glucose ( P<0.001 , -8.8+/-8.5 % ) , low-density lipoprotein ( P<0.001 , -23.2+/-11.9 % ) , total cholesterol ( P<0.001 , -21.2+/-9.9 % ) , and triacylglycerol ( P=0.008 , -13.8+/-33.8 % ) significantly and high-density lipoprotein ( P=0.069 , -3.1+/-11.7 % ) non-significantly . Total cholesterol/high-density lipoprotein and low-density lipoprotein/high-density lipoprotein ratios decreased significantly ( P<0.001 for both ) . The pistachio diet significantly improved endothelium-dependent vasodilation ( P=0.002 , 30 % relative increase ) , decreased serum interleukin-6 , total oxidant status , lipid hydroperoxide , and malondialdehyde and increased superoxide dismutase ( P<0.001 for all ) , whereas there was no significant change in C-reactive protein and tumor necrosis factor-alpha levels . CONCLUSION In this trial , we demonstrated that a pistachio diet improved blood glucose level , endothelial function , and some indices of inflammation and oxidative status in healthy young men . These findings are in accordance with the idea that nuts , in particular pistachio nuts , have favorable effects beyond lipid lowering that deserve to be evaluated with prospect i ve follow-up studies BACKGROUND AND AIMS Carotenoids may reduce diabetes risk , due to their antioxidant properties . However , the association between dietary carotenoids intake and type 2 diabetes risk is still unclear . Therefore , the objective of this study was to examine whether higher dietary carotenoid intakes associate with reduced type 2 diabetes risk . METHODS AND RESULTS Data from 37,846 participants of the European Prospect i ve Investigation into Cancer and Nutrition- Netherl and s study were analyzed . Dietary intakes of β-carotene , α-carotene , β-cryptoxanthin , lycopene , lutein & zeaxanthin and the sum of these carotenoids were assessed using a vali date d food frequency question naire . Incident type 2 diabetes was mainly self-reported , and verified against general practitioner information . Mean ±SD total carotenoid intake was 10 ± 4 mg/day . During a mean ±SD follow-up of 10 ± 2 years , 915 incident cases of type 2 diabetes were ascertained . After adjustment for age , sex , diabetes risk factors , dietary intake , waist circumference and BMI , higher β-carotene intakes associated inversely with diabetes risk [ Hazard Ratio quartile 4 versus quartile 1 ( HR(Q4 ) ) : 0.78 ( 95%CI:0.64,0.95 ) , P-linear trend 0.01 ] . For α-carotene , a borderline significant reduced risk was observed , with a HR(Q4 ) of 0.85 ( 95%CI:0.70,1.03 ) , and P-linear trend 0.05 . β-cryptoxanthin , lycopene , lutein & zeaxanthin , and the sum of all carotenoids did not associate with diabetes risk . CONCLUSIONS This study shows that diets high in β-carotene and α-carotene are associated with reduced type 2 diabetes in generally healthy men and women BACKGROUND Diabetes is a chronic , potentially debilitating , and often fatal disease . Dietary strategies to reduce postpr and ial glycemia are important in the prevention and treatment of diabetes . Nuts are rich in mono- and polyunsaturated fatty acids , which may reduce hyperglycemia and improve metabolism . OBJECTIVES To evaluate the effectiveness of pistachio nut supplementation on glycemic and inflammatory measures in patients with type 2 diabetes . METHODS In this double-blind , r and omized , placebo-controlled , crossover trial , 48 diabetic patients were equally assigned to groups A and B. Patients in group A received a snack of 25 g pistachio nuts twice a day for 12 weeks and group B received a control meal without nuts . After 12 weeks of intervention , the patients had an 8-week washout . Then the groups were displaced , and group B received the same amount of pistachios for 12 weeks . RESULTS With respect to the total change in variables over both phases , there was a marked decrease in Hb
Output:
| The synergism between PUFA , MUFA , polyphenols and carotenoids present in pistachios can modulate specific miRNA , increasing insulin sensitivity through the PI3K-AKT signaling pathway . |
MS213717 | ***TASK*** the task is to summarize an input biomedical literature in six sentences
***INPUT*** the input is a biomedical literature
***OUTPUT*** the output is the summary of an input biomedical literature in six sentences
***DOCUMENTATION***
***EXAMPLES***
Input: We performed a clinical study to identify biological markers useful for the treatment of resectable non-small-cell lung cancers ( NSCLCs ) . In all , 173 patients were studied . By immunohistochemistry , we evaluated the Ki-67 proliferation index , tumour vascularity , thymidylate synthase ( TS ) , vascular endothelial growth factor (VEGF)-A , VEGF-C , and E (epithelial)-cadherin . Concerning the survival of NSCLC patients , tumour vascularity ( P<0.01 ) , VEGF-A status ( P=0.03 ) , VEGF-C status ( P=0.03 ) , and E-cadherin status ( P=0.03 ) were significant prognostic factors in patients with stage I NSCLCs . The Ki-67 proliferation index ( P=0.02 ) and TS status ( P<0.01 ) were significant prognostic factors in patients with stage II – III NSCLCs . In patients with stage II – III NSCLCs , furthermore , the survival of UFT ( a combination of tegafur and uracil)-treated patients with TS-negative tumours was significantly better than those of any other patients . Biological markers associated with tumour angiogenesis or metastasis are useful for the detection of aggressive tumours among early-stage NSCLCs . Postoperative chemotherapy might be necessary in such tumours even in stage I. In contrast , tumour proliferation rate and TS status are useful markers for identifying less aggressive tumours in locally advanced NSCLCs . Thymidylate synthase expression is also a useful marker to evaluate responsiveness of UFT-based chemotherapy for these tumours PURPOSE This study attempted to determine the prognostic value for survival of various pretreatment characteristics in patients with nonresectable non-small-cell lung cancer in the context of more than 10 years of experience of a European Cooperative Group . PATIENTS AND METHODS We included in the analysis all eligible patients ( N = 1,052 ) with advanced non-small-cell lung cancer registered onto one of seven trials conducted by the European Lung Cancer Working Party ( ELCWP ) during one decade . The patients were treated by chemotherapy regimens based on platinum derivatives . We prospect ively collected 23 variables and analyzed them by univariate and multivariate methods . RESULTS The global estimated median survival time was 29 weeks , with a 95 % confidence interval of 27 to 30 weeks . After univariate analysis , we applied two multivariate statistical techniques . In a Cox regression model , the selected explanatory variables were disease extent , Karnofsky performance status , WBC and neutrophil counts , metastatic involvement of skin , serum calcium level , age , and sex . These results were confirmed by application of recursive partitioning and amalgamation algorithms ( RECPAM ) , which led to classification of the patients into four homogeneous subgroups . CONCLUSION We confirmed by our analysis the role of well-known independent prognostic factors for survival , but also identified the effect of the neutrophil count , rarely studied , with the use of two methods : a classical Cox regression model and a RECPAM analysis . The classification of patients into the four subgroups we obtained needs to be vali date d in other series BACKGROUND Bevacizumab , a monoclonal antibody against vascular endothelial growth factor , has been shown to benefit patients with a variety of cancers . METHODS Between July 2001 and April 2004 , the Eastern Cooperative Oncology Group ( ECOG ) conducted a r and omized study in which 878 patients with recurrent or advanced non-small-cell lung cancer ( stage IIIB or IV ) were assigned to chemotherapy with paclitaxel and carboplatin alone ( 444 ) or paclitaxel and carboplatin plus bevacizumab ( 434 ) . Chemotherapy was administered every 3 weeks for six cycles , and bevacizumab was administered every 3 weeks until disease progression was evident or toxic effects were intolerable . Patients with squamous-cell tumors , brain metastases , clinical ly significant hemoptysis , or inadequate organ function or performance status ( ECOG performance status , > 1 ) were excluded . The primary end point was overall survival . RESULTS The median survival was 12.3 months in the group assigned to chemotherapy plus bevacizumab , as compared with 10.3 months in the chemotherapy-alone group ( hazard ratio for death , 0.79 ; P=0.003 ) . The median progression-free survival in the two groups was 6.2 and 4.5 months , respectively ( hazard ratio for disease progression , 0.66 ; P<0.001 ) , with corresponding response rates of 35 % and 15 % ( P<0.001 ) . Rates of clinical ly significant bleeding were 4.4 % and 0.7 % , respectively ( P<0.001 ) . There were 15 treatment-related deaths in the chemotherapy-plus-bevacizumab group , including 5 from pulmonary hemorrhage . CONCLUSIONS The addition of bevacizumab to paclitaxel plus carboplatin in the treatment of selected patients with non-small-cell lung cancer has a significant survival benefit with the risk of increased treatment-related deaths . ( Clinical Trials.gov number , NCT00021060 . Vascular endothelial growth factor ( VEGF ) is an important regulator of angiogenesis and vascular permeability . Increased serum VEGF concentrations ( S-VEGF ) have been found in patients with various types of human cancer , including cancer of the lung . However , the clinical and prognostic significance of S-VEGF in cancer is unknown . We measured S-VEGF , using enzyme-linked immunosorbent assay , in sera taken from 68 untreated patients with small-cell lung cancer ( SCLC ) at the time of diagnosis . The patients were treated with 6 cycles of cisplatin and etoposide , and were r and omly assigned to receive recombinant interferon , leukocyte interferon or neither . S-VEGF ranged from 70 to 1738 pg/ml ( mean , 527 pg/ml ) . The patients who achieved partial or complete response to treatment had lower pre-treatment S-VEGF than the non-responding patients ( p = 0.0083 , Mann-Whitney test ) . High ( > 527 pg/ml ) S-VEGF was associated with poor survival ( p = 0.012 , Log Rank Test ) , and all 3-year survivors had lower than mean pre-treatment S-VEGF . In a multivariate analysis , S-VEGF and stage were the only independent prognostic factors , and the estimated 3-year survival of the patients with limited stage disease and low pretreatment S-VEGF ( n = 17 , 25 % of all patients ) was 41 % ( p = 0.0055 , log rank test ) . These data show that high pretreatment S-VEGF is associated with poor response to treatment and unfavourable survival in patients with SCLC treated with combination chemotherapy with or without interferon Long-term beta blockade for perhaps a year or so following discharge after an MI is now of proven value , and for many such patients mortality reductions of about 25 % can be achieved . No important differences are clearly apparent among the benefits of different beta blockers , although some are more convenient than others ( or have slightly fewer side effects ) , and it appears that those with appreciable intrinsic sympathomimetic activity may confer less benefit . If monitored , the side effects of long-term therapy are not a major problem , as when they occur they are easily reversible by changing the beta blocker or by discontinuation of treatment . By contrast , although very early IV short-term beta blockade can definitely limit infa rct size , more reliable information about the effects of such treatment on mortality will not be available until a large trial ( ISIS ) reports later this year , with data on some thous and s of patients entered within less than 4 hours of the onset of pain . Our aim has been not only to review the 65-odd r and omized beta blocker trials but also to demonstrate that when many r and omized trials have all applied one general approach to treatment , it is often not appropriate to base inference on individual trial results . Although there will usually be important differences from one trial to another ( in eligibility , treatment , end-point assessment , and so on ) , physicians who wish to decide whether to adopt a particular treatment policy should try to make their decision in the light of an overview of all these related r and omized trials and not just a few particular trial results . Although most trials are too small to be individually reliable , this defect of size may be rectified by an overview of many trials , as long as appropriate statistical methods are used . Fortunately , robust statistical methods exist -- based on direct , unweighted summation of one O-E value from each trial -- that are simple for physicians to use and underst and yet provide full statistical sensitivity . These methods allow combination of information from different trials while avoiding the unjustified direct comparison of patients in one trial with patients in another . ( Moreover , they can be extended of such data that there is no real need for the introduction of any more complex statistical methods that might be more difficult for physicians to trust . ) Their robustness , sensitivity , and avoidance of unnecessary complexity make these particular methods an important tool in trial overviews
Output:
| However , VEGFC and vascular endothelial growth factor receptor 3 (VEGFR3)/flt-1 overexpression did not significantly correlate with survival in patients with NSCLC .
The data collected were not sufficient to determine the prognostic value of VEGF in patients with squamous cell lung carcinomas .
CONCLUSION VEGF overexpression indicates a poor prognosis for patients with NSCLC and SCLC ; VEGFC and VEGFR3/flt-1 overexpression was not significantly correlated with survival for patients with NSCLC |
MS213718 | ***TASK*** the task is to summarize an input biomedical literature in six sentences
***INPUT*** the input is a biomedical literature
***OUTPUT*** the output is the summary of an input biomedical literature in six sentences
***DOCUMENTATION***
***EXAMPLES***
Input: Technological change in general orthopaedics and its multiple subspecialisations is continual . These changes are regulated , to varying degrees , by delegated authorities within appropriately m and ated concepts . One relatively recent technology , since approximately 1990 , has been the revision of treating relatively deep seated urolithiasis , whether in the renal parenchyma or the ureter , to more superficial musculoskeletal indications . Although originally conceived to dissipate calcifications in rotator cuff tendinopathy and to alter osseous biology , the technology rapidly spread to other common disorders that affect the musculoskeletal system . Unfortunately many of these applications were not tested through appropriate r and omised clinical trials or practical clinical trials , which could adequately assess clinical efficacy and significant modification of the natural history of a given musculoskeletal disorder . Such studies are obviously in dem and by clinicians and healthcare provider organisations to justify the application of both a given treatment modality and the efficiency of a new drug or device to accomplish an end result that is personally satisfactory to the patient and doctor and economically justifiable to the healthcare insurer/provider . Background Plantar heel pain is one of the most common musculoskeletal disorders of the foot and ankle . Treatment of the condition is usually conservative , however the effectiveness of many treatments frequently used in clinical practice , including stretching , has not been established . We performed a participant-blinded r and omised trial to assess the effectiveness of calf muscle stretching , a commonly used short-term treatment for plantar heel pain . Methods Ninety-two participants with plantar heel pain were recruited from the general public between April and June 2005 . Participants were r and omly allocated to an intervention group that were prescribed calf muscle stretches and sham ultrasound ( n = 46 ) or a control group who received sham ultrasound alone ( n = 46 ) . The intervention period was two weeks . No participants were lost to follow-up . Primary outcome measures were ' first-step ' pain ( measured on a 100 mm Visual Analogue Scale ) and the Foot Health Status Question naire domains of foot pain , foot function and general foot health . Results Both treatment groups improved over the two week period of follow-up but there were no statistically significant differences in improvement between groups for any of the measured outcomes . For example , the mean improvement for ' first-step ' pain ( 0–100 mm ) was -19.8 mm in the stretching group and -13.2 mm in the control group ( adjusted mean difference between groups -7.9 mm ; 95 % CI -18.3 to 2.6 ) . For foot function ( 0–100 scale ) , the stretching group improved 16.2 points and the control group improved 8.3 points ( adjusted mean difference between groups 7.3 ; 95 % CI -0.1 to 14.8 ) . Ten participants in the stretching group experienced an adverse event , however most events were mild to moderate and short-lived . Conclusion When used for the short-term treatment of plantar heel pain , a two-week stretching program provides no statistically significant benefit in ' first-step ' pain , foot pain , foot function or general foot health compared to not stretching Plantar fasciitis is one of the most common causes of foot pain in adults . In this prospect i ve study , the outcomes of local tenoxicam injection and corticosteroid therapy for the treatment of plantar fasciitis were compared . Patients were r and omly assigned to either the tenoxicam or corticosteroid group . The tenoxicam group ( n=31 ) was treated using a local injection of 1 mL of tenoxicam ( 20 mg/2 mL ) and 1 mL of 2 % lidocaine , whereas the steroid group ( n=30 ) was treated with a local 1-mL injection containing 40 mg of methylprednisolone acetate and 1 mL of 2 % lidocaine . Clinical evaluations , which were performed before the injection and 6 and 12 months after the injection , consisted of patient-assessed pain using a visual analog scale . In addition , patient satisfaction was measured using the Roles and Maudsley score . Comparison of pre- and posttreatment visual analog scale scores demonstrated a statistically significant difference in both groups ( P<.05 ) . Furthermore , no significant difference was found between the steroid and tenoxicam groups in terms of visual analog scale scores measured 12 months after injection ( P>.05 ) . The tenoxicam injection was not significantly more effective than the corticosteroid injection . However , both methods were effective and successful in treating patients with plantar fasciitis . Tenoxicam therapy appears to provide pain relief , but its effectiveness in the long term should be explored in additional studies Background Plantar heel pain is a commonly occurring foot complaint . Stretching is frequently utilised as a treatment , yet a systematic review focusing only on its effectiveness has not been published . This review aim ed to assess the effectiveness of stretching on pain and function in people with plantar heel pain . Methods Medline , EMBASE , CINAHL , AMED , and The Cochrane Library were search ed from inception to July 2010 . Studies fulfilling the inclusion criteria were independently assessed , and their quality evaluated using the modified PEDro scale . Results Six studies including 365 symptomatic participants were included . Two compared stretching with a control , one study compared stretching to an alternative intervention , one study compared stretching to both alternative and control interventions , and two compared different stretching techniques and duration s. Quality rating on the modified Pedro scale varied from two to eight out of a maximum of ten points . The method ologies and interventions varied significantly between studies , making meta- analysis inappropriate . Most participants improved over the course of the studies , but when stretching was compared to alternative or control interventions , the changes only reached statistical significance in one study that used a combination of calf muscle stretches and plantar fascia stretches in their stretching programme . Another study comparing different stretching techniques , showed a statistically significant reduction in some aspects of pain in favour of plantar fascia stretching over calf stretches in the short term . Conclusions There were too few studies to assess whether stretching is effective compared to control or other interventions , for either pain or function . However , there is some evidence that plantar fascia stretching may be more effective than Achilles tendon stretching alone in the short-term . Appropriately powered r and omised controlled trials , utilizing vali date d outcome measures , blinded assessors and long-term follow up are needed to assess the efficacy of stretching Plantar fasciitis is a common cause of heel pain . It is a disabling disease in its chronic form . It is a degenerative tissue condition of the plantar fascia rather than an inflammation . Various treatment options are available , including nonsteroidal anti-inflammatory drugs , corticosteroid injections , orthosis , and physiotherapy . This study compared the effects of local platelet-rich plasma , corticosteroid , and placebo injections in the treatment of chronic plantar fasciitis . In this double-blind study , patients were divided r and omly into 3 groups . Local injections of platelet-rich plasma , corticosteroid , or normal saline were given . Patients were assessed with the visual analog scale for pain and with the American Orthopaedic Foot and Ankle Society ( AOFAS ) Ankle and Hindfoot score before injection , at 3 weeks , and at 3-month follow-up . Mean visual analog scale score in the platelet-rich plasma and corticosteroid groups decreased from 7.44 and 7.72 preinjection to 2.52 and 3.64 at final follow-up , respectively . Mean AOFAS score in the platelet-rich plasma and corticosteroid groups improved from 51.56 and 55.72 preinjection to 88.24 and 81.32 at final follow-up , respectively . There was a significant improvement in visual analog scale score and AOFAS score in the platelet-rich plasma and corticosteroid groups at 3 weeks and at 3-month follow-up . There was no significant improvement in visual analog scale score or AOFAS score in the placebo group at any stage of the study . The authors concluded that local injection of platelet-rich plasma or corticosteroid is an effective treatment option for chronic plantar fasciitis . Platelet-rich plasma injection is as effective as or more effective than corticosteroid injection in treating chronic plantar fasciitis Dear Editor-in-ChiefThe treatment of Plantar Fasciitis ( PF ) is primarily conservative , initially with rest and icing to give pain relief . In about 10 % of the cases who do not respond to such treatments , surgical intervention is suggested . An alternative to the surgical treatment of PF is Extracorporeal Shockwave Therapy - ESWT ( 1 , 2 ) . The aim of the study was to compare analgesic effects of ESWT and P-ESWT in males with chronic PF.Thirty patients were included in the study from September 2012 to October 2014 . The study was conducted in Military Hospital in Busko-Zdroj . Exclusion criteria were local soft-tissue infection , skin ulcerations , malignant disease , pacemaker , epileptic disorders , local arthritis , rheumatoid arthritis , ankylosing spondylitis , and Reiter syndrome , previous operation on the heel , patients who had received local corticosteroid injection within 12 weeks , age under 18 years . Patients were r and omized into the ESWT or PESWT group . R and omization was done before the first treatment by means of a computer-generated r and omization list ( MedCalc 11.4.3.0 , Kielce ) . In the ESWT group , patients received either 1000 or 2000 shock waves per treatment of energy levels varying between 0.02 mJ/mm2 and 0.33 mJ/mm2 , pulse frequency gradually increased to 240 per minute . In the P-ESWT , treatment consisted of 100 shock waves per treatment , energy level of 0.02 mJ/mm2 , frequency 60 per minute . Both groups took a series of 5 ESWT . Apparatus used for the treatment was BTL-5000 SWT . The procedure was performed in the area of most intense pain - calcaneal tubercle . The basic method of research was to evaluate pain after normal daily activity according to VAS . The patients of the two groups were tested pretreatment , and 12 months post treatment . In various combinations , the value of the function t was observed . The statistical significant of differences in the intensity of pain assessed was noticed ( PCalculations were performed at the Department of Computer Science at Holy Cross College in Kielce with the use of MedCalc software - version 11.4.3.0 . The research project was authorized by the Bioethics Committee at Holy Cross College in Kielce - resolutions of 1/10/KB on 20.06.2012.In the ESWT group and P-ESWT group , a significant decrease of VAS was seen 12 months post treatment after normal daily activity ( Table 1 ) . The analgesic efficacy of ESWT was confirmed by the analysis of differences in the frequency of occurrence of pain intensity between groups 12 months post treatment ( Table 2).Metzner et al. ( 3 ) used ESWT in patients with chronic PF.Each patient received 1000 impulses of shock wave ; the density of energy stream was 0.35 mJ/mm2 . It turned out that pain was reduced in 81 % of patients after 6 weeks , in 88 % of patients - after 16 months , and in 96 % of patients - after 72 months post ESWT . Objective : To investigate the effectiveness of a physiotherapy-based exercise program versus dexamethasone injection for chronic plantar fasciopathy in workers st and ing for prolonged periods of time . Design : A parallel group nonblinded r and omized controlled trial with 12-week follow-up . Setting : An outpatient sports medicine clinic in Vancouver , British Columbia , Canada . Participants : Fifty-six workers required to st and for greater than 5 h/d with chronic plantar fasciopathy took part . Diagnosis from a physiotherapist must include signs of structural changes to the plantar fascia seen on ultrasound . Interventions : The PHYSIO group included 7 physiotherapy-led exercises performed daily over a 12-week period . The INJECTION group received 1 palpation-guided dexamethasone injection followed by a daily routine of calf stretching . Main Outcome Measures : The Foot and Ankle Disability Index ( FADI ) scores 12-weeks postintervention and ultrasound-based measures of ligament appearance . Results : At follow-up , both groups reported significant improvements in FADI and visual analog scales for pain at work and with activities of daily living at 6 and 12 weeks compared with baseline scores ( P < 0.001 ) . There were no significant between-group differences . There were no significant changes to plantar fascia thickness reported at the 6- and 12-week follow-up point . Both the number of cases with focal anechoic areas and the size of these anechoic areas improved significantly in the PHYSIO ( P = 0.003 ) and INJECTION ( P < 0.001 ) groups at 12-week follow-up . Conclusions : Workers st and ing for prolonged periods experienced the same short-term therapeutic effectiveness with a physiotherapy-led exercise program compared with an injection of corticosteroid with stretching OBJECTIVE To explore the effect of extracorporeal shock wave therapy in patients with chronic plantar faciitis . METHODS The prospect i ve study was conducted at Department of Orhopaedic , Regional Hospital , Limerick , Irel and from January to December 2004 and comprised 70 heels in 62 patients with chronic plantar fasciitis in whom conventional conservative treatment consisting of non-steroidal anti-inflammatory drugs , heel cup , orthoses and /or shoe modifications , local steroid injections had failed , and they were treated with low energy extracorporeal shock wave therapy . Patients were review ed at 6 , 12 and 24 weeks post treatment . RES
Output:
| There was no evidence of inconsistency detected between direct and indirect treatment comparisons in the networks , but sparse data led to frequently wide CIs .
Available evidence does not suggest that any of the commonly used treatments for the management of PHP are better than any other , although corticosteroid injections , alone or in combination with exercise , and ESWT were ranked most likely to be effective for the management of short-term , medium-term and long-term pain or function ; placebo/sham/control appeared least likely to be effective ; and exercise appeared to only be beneficial for long-term pain or function .
Conclusions Current evidence is equivocal regarding which treatment is the most effective for the management of PHP . |
MS213719 | ***TASK*** the task is to summarize an input biomedical literature in six sentences
***INPUT*** the input is a biomedical literature
***OUTPUT*** the output is the summary of an input biomedical literature in six sentences
***DOCUMENTATION***
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Input: Background Prevalence of type 2 diabetes ( T2D ) is increasing worldwide . T2D prevention by lifestyle intervention is effective . Pragmatic scalable interventions are needed , with evidence to efficiently target and monitor such interventions . We report pooled analyses of data from three European trial cohorts : to analyse T2D incidence , sustained weight loss and utility of risk predictors . Methods We analysed data on 749 adults with impaired glucose tolerance ( 278 men and 471 women , mean age 56 years , mean BMI 31 kgm−2 ) recruited between 1993 and 2003 , and r and omised to intensive lifestyle intervention ( I ) or lifestyle advice control ( C ) . The intervention aim ed to increase physical activity , modify diet , and promote weight loss≥5 % . Using Cox-regression survival analysis , we assessed T2D incidence and the impact on T2D incidence of sustained weight loss , and of baseline cut-point values of FINDRISC score , fasting plasma glucose ( FPG ) , and HbA1c . Results Mean follow-up duration was 3.1 years . T2D was diagnosed in 139 participants ( I = 45/379 , C = 94/370 ) . Cumulative T2D incidence was 57 % lower in the intervention compared with the control group ( HR 0.42 ( 95 % CI 0.29 to 0.60 ) P<0.001 ) . Participants with ≥5 % weight loss at one year had 65 % lower T2D incidence ( HR 0.35 ( 95 % CI 0.22 to 0.56 ) P<0.001 ) ; maintaining ≥5 % weight loss for two and three years further reduced T2D incidence . Recommended cut-points to identify those at high risk for T2D would have identified different proportions of European Diabetes Prevention Study ( EDIPS ) participants with similar hazard-ratios for intervention effect . Conclusions Pooled analysis of EDIPS trial data reinforces evidence for T2D prevention by lifestyle intervention . Analysis showed the preventive effect of ≥5 % weight loss , especially if maintained long term , which has utility for intervention monitoring . Analysis of proposed cut-points demonstrates difficulties in balancing risk and benefit , to efficiently target interventions and suggests evidence is needed to define clinical policy . Trial registration s The Finnish Diabetes Prevention study , Helsinki , Finl and : Clinical Trials.gov ; NCT00518167 The SLIM diabetes prevention study , Maastricht , The Netherl and s : Clinical Trials.gov ; NCT00381186 The EDIPS-Newcastle diabetes prevention study , Newcastle upon Tyne , UK : International St and ard R and omised Controlled Trial Number ; IS RCT N15670600 We examined self-determination theory ( SDT ) and weight loss , and hypothesized that the Diabetes Prevention Program ’s ( DPP ) intervention would result in an increase in autonomous regulation of motivation ( AR ) in participants . Further , that those with higher AR , and those who perceived educators as supporting SDT-defined needs , would lose more weight . Support , Health Information , Nutrition and Exercise ( SHINE ) Study data ( N = 257 ) were analyzed . SHINE was a r and omized , controlled DPP translation trial ( 2-years , telephonic , primary care staff ) . Autonomous motivation in males increased significantly , while females showed no change . Males with high AR , but not females , lost more weight . However , the significance of these relationships varied over time . Participants who perceived educators as more supportive of psychological needs lost more weight ( especially males ) . However , effect of support on weight loss was not mediated by AR change . Autonomous motivation and educator support are relevant to male weight loss . Future research might develop interventions to enhance autonomous motivation and educator support , and underst and change pathways Background The prevention of type 2 diabetes is a recognised health care priority globally . Within the United Kingdom , there is a lack of research investigating optimal methods of translating diabetes prevention programmes , based on the promotion of a healthy lifestyle , into routine primary care . This study aims to establish the behavioural and clinical effectiveness of a structured educational programme design ed to target perceptions and knowledge of diabetes risk and promote a healthily lifestyle , particularly increased walking activity , in a multi-ethnic population at a high risk of developing type 2 diabetes . Design Cluster r and omised controlled trial undertaken at the level of primary care practice s. Follow-up will be conducted at 12 , 24 and 36 months . The primary outcome is change in objective ly measured ambulatory activity . Secondary outcomes include progression to type 2 diabetes , biochemical variables ( including fasting glucose , 2-h glucose , HbA1c and lipids ) , anthropometric variables , quality of life and depression . Methods 10 primary care practice s will be recruited to the study ( 5 intervention , 5 control ) . Within each practice , individuals at high risk of impaired glucose regulation will be identified using an automated version of the Leicester Risk Assessment tool . Individuals scoring within the 90th percentile in each practice will be invited to take part in the study . Practice s will be assigned to either the control group ( advice leaflet ) or the intervention group , in which participants will be invited to attend a 3 hour structured educational programme design ed to promote physical activity and a healthy lifestyle . Participants in the intervention practice s will also be invited to attend annual group-based maintenance workshops and will receive telephone contact halfway between annual sessions . The study will run from 2010–2014 . Discussion This study will provide new evidence surrounding the long-term effectiveness of a diabetes prevention programme run within routine primary care in the United Kingdom . Trial Registration Clinical Trials . Gov identifier : Abstract Background Diabetes prevalence is increasing . The Finnish Diabetes Prevention Study ( DPS ) showed a 58 % reduction in Type 2 Diabetes ( T2D ) incidence in adults with impaired glucose tolerance ( IGT ) . The European Diabetes Prevention Study ( EDIPS ) extends the DPS to different European population s , using the same study design . In the Newcastle arm of this study ( EDIPS-Newcastle ) , we tested the hypothesis that T2D can be prevented by lifestyle intervention and explored secondary outcomes in relation to diabetes incidence . Methods We recruited 102 participants ( 42 men and 60 women , mean age 57 years , mean BMI 34 kgm-2 ) with IGT to EDIPS-Newcastle and r and omised to Intervention and usual care Control groups . The intervention included individual motivational interviewing aim ed at : weight reduction , increase in physical activity , fibre and carbohydrate intake and reduction of fat intake ( secondary outcomes ) . The primary outcome was diagnosis of T2D . Results Mean duration of follow-up was 3.1 years . T2D was diagnosed in 16 participants ( I = 5 , C = 11 ) . Absolute incidence of T2D was 32.7 per 1000 person-years in the Intervention-group and 67.1 per 1000 person-years in the Control-group . The overall incidence of diabetes was reduced by 55 % in the Intervention-group , compared with the Control-group : RR 0.45 ( 95%CI 0.2 to 1.2).Explanatory survival analysis of secondary outcomes showed that those who sustained beneficial changes for two or more years reduced their risk of developing T2D . Conclusion Our results are consistent with other diabetes prevention trials . This study was design ed as part of a larger study and although the sample size limits statistical significance , the results contribute to the evidence that T2D can be prevented by lifestyle changes in adults with IGT . In explanatory analysis small sustained beneficial changes in weight , physical activity or dietary factors were associated with reduction in T2D incidence . Trial Registration International St and ard R and omised Controlled Trial Number registry ( IS RCT N)Registry number : IS RCT N 15670600 http://www.controlled-trials.com/is rct n/ search .html?srch=15670600%26sort=3%26dir = OBJECTIVE —In participants of the Diabetes Prevention Program ( DPP ) r and omized to intensive lifestyle modification ( ILS ) , meeting ILS goals strongly correlated with prevention of diabetes in the group as a whole . Men met significantly more ILS goals than women but had a similar incidence of diabetes . Therefore , we explored sex differences in risk factors for diabetes and the effect of ILS on risk factors . RESEARCH DESIGN AND METHODS —Baseline risk factors for diabetes and percent change in risk factors over the first year in men versus women were compared using Wilcoxon 's rank-sum tests . RESULTS —At baseline , men were older and had a larger waist circumference ; higher fasting plasma glucose concentration , caloric intake , and blood pressure ; and lower HDL cholesterol and corrected insulin response than women , who were less physically active and had a higher BMI ( P < 0.01 for all comparisons ) . Over the first year of the DPP , no sex difference in risk factors for diabetes was observed for those who lost <3 % body weight . Weight loss of 3–7 % body weight yielded greater decreases in 2-h glucose ( P < 0.01 ) , insulin concentration ( P < 0.04 ) , and insulin resistance ( P < 0.03 ) in men than in women . Weight loss of > 7 % body weight result ed in greater decreases in 2-h glucose ( P < 0.01 ) , triglyceride level ( P < 0.01 ) , and A1C ( P < 0.03 ) in men than in women . CONCLUSIONS —Weight loss > 3 % body weight yielded greater reduction in risk factors for diabetes in men than in women . Despite the more favorable effects of ILS in men , baseline risk factors were more numerous in men and likely obscured any sex difference in incident diabetes Background Mobile technologies for health ( mHealth ) represent a promising strategy for reducing type 2 diabetes ( T2DM ) risk . The PROPELS trial investigates whether structured group-based education alone or supplemented with a follow-on support program combining self-monitoring with pedometers and tailored text-messaging is effective in promoting and maintaining physical activity among people at high risk of T2DM . Objective This paper describes the iterative development of the PROPELS follow-on support program and presents evidence on its acceptability and feasibility . Methods We used a modified mHealth development framework with four phases : ( 1 ) conceptualization of the follow-on support program using theory and evidence , ( 2 ) formative research including focus groups ( n=15 , ages 39 - 79 years ) , ( 3 ) pre-testing focus groups using a think aloud protocol ( n=20 , ages 52 - 78 years ) , and ( 4 ) piloting ( n=11 ) . Analysis was informed by the constant comparative approach , with findings from each phase informing subsequent phases . Results The first three phases informed the structure , nature , and content of the follow-on support program , including the frequency of text messages , the need for tailored content and two-way interaction , the importance of motivational messages based on encouragement and reinforcement of affective benefits ( eg , enjoyment ) with minimal messages about weight and T2DM risk , and the need for appropriate language . The refined program is personalized and tailored to the individual ’s perceived confidence , previous activity levels , and physical activity goals . The pilot phase indicated that the program appeared to fit well with everyday routines and was easy to use by older adults . Conclusions We developed a feasible and innovative text messaging and pedometer program based on evidence and behavior change theory and grounded in the experiences , views , and needs of people at high diabetes risk . A large scale trial is testing the effectiveness of this 4-year program over and above structured group education alone . Trial Registration International St and ard R and omized Controlled Trial Number ( IS RCT N ) : 83465245 ; http://www.controlled-trials.com/IS RCT N83465245/83465245 ( Archived by WebCite at http://www.webcitation.org/6dfSmrVAe Background Lifestyle modifications are considered the most effective means of delaying or preventing the development of type 2 diabetes ( T2DM ) . To contain the growing population of T2DM , it is critical to clarify effective and efficient setting s for intervention and modalities for intervention delivery with a wide population reach . The Japan Diabetes Outcome Intervention Trial-1 ( J-DOIT1 ) is a cluster r and omized controlled trial to test whether goal -focused lifestyle coaching delivered by telephone can prevent the development of T2DM in high-risk individuals in a real-world setting . This paper describes the study design and recruitment of the study subjects . Methods For the recruitment of study subjects and their follow-up annually over 3 years , we employed health checkups conducted annually at communities and worksites . Health care divisions recruited from communities and companies across Japan formed groups as a cluster r and omization unit . C and i date s for the study , aged 20 - 65 years with fasting plasma glucose ( FPG ) of 5.6 - 6.9 mmol/l , were recruited from each group using health checkups results in 2006 . Goal -focused lifestyle support is delivered by healthcare providers via telephone over a one-year period . Study subjects will be followed-up for three years by annual health checkups . Primary outcome is the development of diabetes defined as FPG≥7.0 mmol/l on annual health checkup or based on self-report , which is confirmed by referring to medical cards . Results Forty-three groups ( clusters ) , formed from 17 health care divisions , were r and om
Output:
| AUTHORS ' CONCLUSIONS There is no firm evidence that diet alone or physical activity alone compared to st and ard treatment influences the risk of T2DM and especially its associated complications in people at increased risk of developing T2DM .
However , diet plus physical activity reduces or delays the incidence of T2DM in people with IGT .
Data are lacking for the effect of diet plus physical activity for people with intermediate hyperglycaemia defined by other glycaemic variables . |
MS213720 | ***TASK*** the task is to summarize an input biomedical literature in six sentences
***INPUT*** the input is a biomedical literature
***OUTPUT*** the output is the summary of an input biomedical literature in six sentences
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Input: The CONSORT ( Consoli date d St and ards of Reporting Trials ) statement is used worldwide to improve the reporting of r and omized , controlled trials . Schulz and colleagues describe the latest version , CONSORT 2010 , which up date s the reporting guideline based on new method ological evidence and accumulating experience . Idiopathic thrombocytopenic purpura ( ITP ) is an autoimmune disorder characterized by persistent thrombocytopenia ( peripheral blood platelet count < 150 · 10 ⁄ l ) due to autoantibody binding to platelet antigen(s ) causing their premature destruction by the reticuloendothelial system , and in particular the spleen ( Woods et al , 1984a , b ) . Although the basic underlying pathophysiology of ITP has been known for 50 years ( Harrington et al , 1951 ) , the literature shows that the investigation and management of patients with thrombocytopenia vary widely , and is not evidence -based , due to a lack of clinical trials and quality research . Despite major advances in our underst and ing of the molecular basis of many blood disorders , the diagnosis of ITP remains one of exclusion ; there are currently no robust clinical or laboratory parameters that are able to establish the diagnosis of ITP with accuracy . This guideline aims to assess available diagnostic tests and therapies , and attempts to provide a rational approach to the diagnosis and treatment in adults , children and in pregnancy . Although natural history data are becoming available ( Cohen et al , 2000 ; Djulbegovic & Cohen , 2001 ; Portielje et al , 2001 ) , there are few r and omized trials in ITP and many of the recommendations , like those of the American Society of Hematology ( ASH ) Panel ( George et al , 1996 ) , are based on expert opinion Romiplostim is a thrombopoietin receptor agonist that increases platelet counts in patients with chronic immune thrombocytopenia ( ITP ) . Thrombopoietin receptor agonists are reported to increase the risk for reticulin fiber deposition within bone marrow . This report describes bone marrow findings from romiplostim-treated rats , a retrospective analysis of reticulin observed in romiplostim ITP clinical trials , and a prospect i ve clinical study of the effects of romiplostim on bone marrow morphology . In rats , romiplostim produced a dose-dependent increase in bone marrow fibrosis that resolved after treatment withdrawal . Of 271 ITP patients in romiplostim clinical trials , 10 were reported to have reticulin deposition ; reticulin grade was increased in 4 of 5 patients with both pretreatment and on-treatment bone marrow results . Reticulin grade often decreased soon after romiplostim discontinuation . In the prospect i ve study , reticulin grade during romiplostim treatment remained within the normal range for all patients and was increased in only 1 of 6 patients with pretreatment and on-treatment bone marrow results . This report suggests that romiplostim produces reversible , dose-dependent bone marrow changes in rats and produces modest increases in bone marrow reticulin in some ITP patients that decrease when therapy is discontinued . These studies were registered at www . clinical trials.gov as # NCT00102323 , # NCT00102336 , # NCT00861224 , and # NCT00116688 BACKGROUND Eltrombopag is an oral thrombopoietin receptor agonist for the treatment of thrombocytopenia . We aim ed to compare the response to once daily eltrombopag versus placebo in patients with chronic immune thrombocytopenia during a 6-month period . METHODS We undertook a phase 3 , double-blind , placebo-controlled study in adults with previously treated immune thrombocytopenia of more than 6 months ' duration who had baseline platelet counts lower than 30,000 per μL. Patients were r and omly allocated ( in a 2:1 ratio ) treatment with local st and ard of care plus 50 mg eltrombopag or matching placebo once daily for 6 months . R and omisation was done central ly with a computer-generated r and omisation schedule and was stratified by baseline platelet count ( ≤ 15,000 per μL ) , use of treatment for immune thrombocytopenia , and splenectomy status . Patients , investigators , and those assessing data were masked to allocation . Dose modifications were made on the basis of platelet response . Patients were assessed for response to treatment ( defined as a platelet count of 50,000 - 400,000 per μL ) weekly during the first 6 weeks and at least once every 4 weeks thereafter ; the primary endpoint was the odds of response to eltrombopag versus placebo . Analysis was by intention to treat . This study is registered at Clinical Trials.gov , number NCT00370331 . FINDINGS Between Nov 22 , 2006 , and July 31 , 2007 , 197 patients were r and omly allocated to treatment groups and were included in the intention-to-treat analysis ( 135 eltrombopag , 62 placebo ) . 106 ( 79 % ) patients in the eltrombopag group responded to treatment at least once during the study , compared with 17 ( 28 % ) patients in the placebo group . The odds of responding were greater in patients in the eltrombopag group compared with those in the placebo group throughout the 6-month treatment period ( odds ratio 8·2 , 99 % CI 3·59 - 18·73 ; p<0·0001 ) . 37 ( 59 % ) patients receiving eltrombopag reduced concomitant treatment versus ten ( 32 % ) patients receiving placebo ( p=0·016 ) . 24 ( 18 % ) patients receiving eltrombopag needed rescue treatment compared with 25 ( 40 % ) patients receiving placebo ( p=0·001 ) . Three ( 2 % ) patients receiving eltrombopag had thromboembolic events compared with none in patients on placebo . Nine ( 7 % ) eltrombopag-treated patients and two ( 3 % ) in the placebo group had mild increases in alanine aminotransferase concentration , and five ( 4 % ) eltrombopag-treated patients ( vs none allocated to placebo ) had increases in total bilirubin . Four ( 7 % ) patients taking placebo had serious bleeding events , compared with one ( < 1 % ) patient treated with eltrombopag . INTERPRETATION Eltrombopag is effective for management of chronic immune thrombocytopenia , and could be particularly beneficial for patients who have not responded to splenectomy or previous treatment . These benefits should be balanced with the potential risks associated with eltrombopag treatment . FUNDING GlaxoSmithKline Eltrombopag ( SB-497 115 ) is a first-in-class , oral , small-molecule , nonpeptide agonist of the thrombopoietin receptor ( TpoR ) , being developed as a treatment for thrombocytopenia of various etiologies . In this phase 1 placebo-controlled clinical trial in 73 healthy male subjects , eltrombopag was administered as once-daily oral capsules for 10 days at doses of 5 , 10 , 25 , 30 , 50 , and 75 mg . The pharmacokinetics of eltrombopag were dose dependent and linear , and eltrombopag increased platelet counts in a dose-dependent manner . There were no apparent differences in the incidence or severity of adverse events in subjects receiving active or placebo study medication . These observations indicate that eltrombopag is a once-daily , oral TpoR agonist with demonstrated thrombopoietic activity in human subjects , encouraging further studies in patients with thrombocytopenia BACKGROUND Most current treatments for chronic immune thrombocytopenic purpura ( ITP ) act by decreasing platelet destruction . In a phase 1 - 2 study , we administered a thrombopoiesis-stimulating protein , AMG 531 , to patients with ITP . METHODS In phase 1 , 24 patients who had received at least one treatment for ITP were assigned to escalating-dose cohorts of 4 patients each and given two identical doses of AMG 531 ( 0.2 to 10 microg per kilogram of body weight ) . In phase 2 , 21 patients were r and omly assigned to receive six weekly subcutaneous injections of AMG 531 ( 1 , 3 , or 6 microg per kilogram ) or placebo . The primary objective was to assess the safety of AMG 531 ; the secondary objective was to evaluate platelet counts during and after treatment . RESULTS No major adverse events that could be attributed directly to AMG 531 occurred during the treatment period ; 4 of 41 patients had transient post-treatment worsening of thrombocytopenia . In phase 1 , a platelet count that was within the targeted range ( 50,000 to 450,000 per cubic millimeter ) and at least twice the baseline count was achieved in 4 of 12 patients given 3 , 6 , or 10 mug of AMG 531 per kilogram . Overall , a platelet count of at least 50,000 per cubic millimeter was achieved in 7 of 12 patients , including 3 with counts exceeding 450,000 per cubic millimeter . Increases in the platelet count were dose-dependent ; mean peak counts were 163,000 , 309,000 , and 746,000 per cubic millimeter with 3 , 6 , and 10 microg of AMG 531 per kilogram [ corrected ] , respectively . In phase 2 , the targeted platelet range was achieved in 10 of 16 patients treated with 1 or 3 mug of AMG 531 per kilogram per week for 6 weeks . Mean peak counts were 135,000 , 241,000 , and 81,000 per cubic millimeter in the groups that received the 1-mug dose , the 3-mug dose , and placebo , respectively . CONCLUSIONS AMG 531 caused no major adverse events and increased platelet counts in patients with ITP . ( Clinical Trials.gov number , NCT00111475 [ Clinical Trials.gov ] . ) BACKGROUND Romiplostim , a thrombopoietin mimetic , increases platelet counts in patients with immune thrombocytopenia , with few adverse effects . METHODS In this open-label , 52-week study , we r and omly assigned 234 adult patients with immune thrombocytopenia , who had not undergone splenectomy , to receive the st and ard of care ( 77 patients ) or weekly subcutaneous injections of romiplostim ( 157 patients ) . Primary end points were incidences of treatment failure and splenectomy . Secondary end points included the rate of a platelet response ( a platelet count > 50 × 10(9 ) per liter at any scheduled visit ) , safety outcomes , and the quality of life . RESULTS The rate of a platelet response in the romiplostim group was 2.3 times that in the st and ard-of-care group ( 95 % confidence interval [ CI ] , 2.0 to 2.6 ; P<0.001 ) . Patients receiving romiplostim had a significantly lower incidence of treatment failure ( 18 of 157 patients [ 11 % ] ) than those receiving the st and ard of care ( 23 of 77 patients [ 30 % ] , P<0.001 ) ( odds ratio with romiplostim , 0.31 ; 95 % CI , 0.15 to 0.61 ) . Splenectomy also was performed less frequently in patients receiving romiplostim ( 14 of 157 patients [ 9 % ] ) than in those receiving the st and ard of care ( 28 of 77 patients [ 36 % ] , P<0.001 ) ( odds ratio , 0.17 ; 95 % CI , 0.08 to 0.35 ) . The romiplostim group had a lower rate of bleeding events , fewer blood transfusions , and greater improvements in the quality of life than the st and ard-of-care group . Serious adverse events occurred in 23 % of patients ( 35 of 154 ) receiving romiplostim and 37 % of patients ( 28 of 75 ) receiving the st and ard of care . CONCLUSIONS Patients treated with romiplostim had a higher rate of a platelet response , lower incidence of treatment failure and splenectomy , less bleeding and fewer blood transfusions , and a higher quality of life than patients treated with the st and ard of care . ( Clinical Trials.gov number , NCT00415532 . ) The objective of this study was to evaluate the tolerability , pharmacodynamics , and pharmacokinetics of AMG 531 , a novel thrombopoietin receptor lig and , after a single intravenous or subcutaneous injection in healthy subjects BACKGROUND Chronic immune thrombocytopenic purpura ( ITP ) is characterised by accelerated platelet destruction and decreased platelet production . Short-term administration of the thrombopoiesis-stimulating protein , romiplostim , has been shown to increase platelet counts in most
Output:
| There was currently no evidence to support that TPO receptor agonists are effective in chronic ITP .
Compared to placebo or SOC , despite significantly increased platelet response , there was no evidence to demonstrate that TPO receptor agonists did improve significant bleeding events in chronic ITP .
Although long-term studies are lacking , current data demonstrated adverse effects of TPO receptor agonists were similar to that of placebo and SOC |
MS213721 | ***TASK*** the task is to summarize an input biomedical literature in six sentences
***INPUT*** the input is a biomedical literature
***OUTPUT*** the output is the summary of an input biomedical literature in six sentences
***DOCUMENTATION***
***EXAMPLES***
Input: BACKGROUND Paracetamol is a recommended symptomatic treatment of osteoarthritis ( OA ) , but in clinical trials sample sizes have been relatively small and variable daily doses of paracetamol have been used . OBJECTIVES To determine the therapeutic efficacy of paracetamol in OA of the knee and identify predictive factors of clinical response to treatment . METHODS A double blind , parallel group , placebo controlled trial of analgesic efficacy and safety of paracetamol versus placebo including 779 patients with OA of the knee . Patients were r and omly assigned to receive paracetamol 4 g/day ( n = 405 ) or placebo ( n = 374 ) for 6 weeks . Symptomatic OA of the knee was required at inclusion with global pain intensity of the knee during physical activities for the past 24 hours of > or=30 mm on a 100 mm visual analogue scale . The primary end point was a 30 % decrease of global pain intensity of the knee . Intention to treat analyses were performed . RESULTS The percentage of responders did not differ significantly between groups : 52.6 % and 51.9 % in paracetamol and placebo groups , respectively ( p = 0.840 ) . In a subgroup of patients with chronic mechanical knee pain without signs of inflammation ( n = 123 ) , the mean change in pain intensity from baseline was 25.2 mm v 15.2 mm , in the paracetamol ( n = 63 ) and placebo ( n = 60 ) groups , respectively-mean difference 10.0 mm ; 95 % CI 1.0 to 19.0 ; p = 0.0294 . No serious adverse events were attributable to treatment . CONCLUSION A statistically significant symptomatic effect of oral paracetamol 4 g/day over placebo was not found , suggesting that paracetamol use in symptomatic OA of the knee should be further explored . The tolerability and safety of paracetamol , at the recommended maximum dose of 4 g/day , was confirmed over 6 weeks Abstract Variability in patients ' response to interventions in pain and other clinical setting s is large . Many explanations such as trial methods , environment or culture have been proposed , but this paper sets out to show that the main cause of the variability may be r and om chance , and that if trials are small their estimate of magnitude of effect may be incorrect , simply because of the r and om play of chance . This is highly relevant to the questions of ‘ How large do trials have to be for statistical accuracy ? ’ and ‘ How large do trials have to be for their results to be clinical ly valid ? ’ The true underlying control event rate ( CER ) and experimental event rate ( EER ) were determined from single‐dose acute pain analgesic trials in over 5000 patients . Trial group size required to obtain statistically significant and clinical ly relevant ( 0.95 probability of number‐needed‐to‐treat within ±0.5 of its true value ) results were computed using these values . Ten thous and trials using these CER and EER values were simulated using varying group sizes to investigate the variation due to r and om chance alone . Most common analgesics have EERs in the range 0.4–0.6 and CER of about 0.19 . With such efficacy , to have a 90 % chance of obtaining a statistically significant result in the correct direction requires group sizes in the range 30–60 . For clinical relevance nearly 500 patients are required in each group . Only with an extremely effective drug ( EER>0.8 ) will we be reasonably sure of obtaining a clinical ly relevant NNT with commonly used group sizes of around 40 patients per treatment arm . The simulated trials showed substantial variation in CER and EER , with the probability of obtaining the correct values improving as group size increased . We contend that much of the variability in control and experimental event rates is due to r and om chance alone . Single small trials are unlikely to be correct . If we want to be sure of getting correct ( clinical ly relevant ) results in clinical trials we must study more patients . Credible estimates of clinical efficacy are only likely to come from large trials or from pooling multiple trials of conventional ( small ) size SUMMARY Objectives : To compare patient and physician attitudes to osteoarthritis ( OA ) treatment with rofecoxib or traditional non-steroidal anti-inflammatory drugs ( tNSAIDs ) . Methods : A 6-month prospect i ve study involving 562 OA patients enrolled at 29 Spanish primary -care centres . Patients were continued on established tNSAID therapy for the first 3 months then switched to rofecoxib 12.5 or 25 mg/day . Results : Both patients and physicians were significantly more likely to be satisfied with rofecoxib treatment than with tNSAIDs ( p < 0.001 ) and assessment s of overall health status improved significantly during rofecoxib therapy ( p < 0.001 ) . Adherence to therapy was significantly better with rofecoxib than during tNSAID treatment ( p < 0.001 ) . Use of rofecoxib was associated with a significant reduction in the proportion of discontinuations attributed to lack of effectiveness ( p < 0.001 ) or gastrointestinal ( GI ) adverse events ( p < 0.001 compared with tNSAIDs ) . Rofecoxib was also associated with a > 60 % reduction in the proportion of patients experiencing a GI adverse event and a halving in the proportion of patients who received GI co-medications ; concomitant analgesic use decreased by one-third during rofecoxib therapy . Conclusions : Use of rofecoxib was associated with marked improvements in several indices of treatment effectiveness and tolerability , and in patient and physician satisfaction and perception of general health status compared with tNSAIDs . Rofecoxib is a valuable additional medication for relieving the symptoms of OA and its use in place of tNSAIDs may lead to a reduction in the prescription of concomitant medications BACKGROUND Chronic pain is recognised as an important problem in the community but our underst and ing of the epidemiology of chronic pain remains limited . We undertook a study design ed to quantify and describe the prevalence and distribution of chronic pain in the community . METHODS A r and om sample of 5036 patients , aged 25 and over , was drawn from 29 general practice s in the Grampian region of the UK and surveyed by a postal self-completion question naire . The question naire included case-screening questions , a question on the cause of the pain , the chronic pain grade question naire , the level of expressed needs question naire , and sociodemographic questions . FINDINGS 3605 question naires were returned completed . 1817 ( 50.4 % ) of patients self reported chronic pain , equivalent to 46.5 % of the general population . 576 reported back pain and 570 reported arthritis ; these were the most common complaints and accounted for a third of all complaints . Backward stepwise logistic-regression modelling identified age , sex , housing tenure , and employment status as significant predictors of the presence of chronic pain in the community . 703 ( 48.7 % ) individuals with chronic pain had the least severe grade of pain , and 228 ( 15.8 % ) the most severe grade . Of those who reported chronic pain , 312 ( 17.2 % ) reported no expressed need , and 509 ( 28.0 % ) reported the highest expressed need . INTERPRETATION Chronic pain is a major problem in the community and certain groups within the population are more likely to have chronic pain . A detailed underst and ing of the epidemiology of chronic pain is essential for efficient management of chronic pain in primary care CONTEXT Conventional nonsteroidal anti-inflammatory drugs ( NSAIDs ) are associated with a spectrum of toxic effects , notably gastrointestinal ( GI ) effects , because of inhibition of cyclooxygenase (COX)-1 . Whether COX-2-specific inhibitors are associated with fewer clinical GI toxic effects is unknown . OBJECTIVE To determine whether celecoxib , a COX-2-specific inhibitor , is associated with a lower incidence of significant upper GI toxic effects and other adverse effects compared with conventional NSAIDs . DESIGN The Celecoxib Long-term Arthritis Safety Study ( CLASS ) , a double-blind , r and omized controlled trial conducted from September 1998 to March 2000 . SETTING Three hundred eighty-six clinical sites in the United States and Canada . PARTICIPANTS A total of 8059 patients ( > /=18 years old ) with osteoarthritis ( OA ) or rheumatoid arthritis ( RA ) were enrolled in the study , and 7968 received at least 1 dose of study drug . A total of 4573 patients ( 57 % ) received treatment for 6 months . INTERVENTIONS Patients were r and omly assigned to receive celecoxib , 400 mg twice per day ( 2 and 4 times the maximum RA and OA dosages , respectively ; n = 3987 ) ; ibuprofen , 800 mg 3 times per day ( n = 1985 ) ; or diclofenac , 75 mg twice per day ( n = 1996 ) . Aspirin use for cardiovascular prophylaxis ( < /=325 mg/d ) was permitted . MAIN OUTCOME MEASURES Incidence of prospect ively defined symptomatic upper GI ulcers and ulcer complications ( bleeding , perforation , and obstruction ) and other adverse effects during the 6-month treatment period . RESULTS For all patients , the annualized incidence rates of upper GI ulcer complications alone and combined with symptomatic ulcers for celecoxib vs NSAIDs were 0.76 % vs 1.45 % ( P = .09 ) and 2 . 08 % vs 3.54 % ( P = .02 ) , respectively . For patients not taking aspirin , the annualized incidence rates of upper GI ulcer complications alone and combined with symptomatic ulcers for celecoxib vs NSAIDs were 0.44 % vs 1.27 % ( P = .04 ) and 1.40 % vs 2.91 % ( P = .02 ) . For patients taking aspirin , the annualized incidence rates of upper GI ulcer complications alone and combined with symptomatic ulcers for celecoxib vs NSAIDs were 2.01 % vs 2.12 % ( P = .92 ) and 4.70 % vs 6.00 % ( P = .49 ) . Fewer celecoxib-treated patients than NSAID-treated patients experienced chronic GI blood loss , GI intolerance , hepatotoxicity , or renal toxicity . No difference was noted in the incidence of cardiovascular events between celecoxib and NSAIDs , irrespective of aspirin use . CONCLUSIONS In this study , celecoxib , at dosages greater than those indicated clinical ly , was associated with a lower incidence of symptomatic ulcers and ulcer complications combined , as well as other clinical ly important toxic effects , compared with NSAIDs at st and ard dosages . The decrease in upper GI toxicity was strongest among patients not taking aspirin concomitantly . JAMA . 2000;284:1247 - Renal prostagl and in inhibition by nonsteroidal antiinflammatory drugs ( NSAIDs ) may decrease renal function , especially under conditions of low effective circulating volume . To evaluate the risk of important deterioration of renal function due to this effect , the authors performed a nested case-control study using Tennessee Medicaid enrollees aged > or = 65 years in 1987 - 1991 . Cases were patients who had been hospitalized with community-acquired acute renal failure ; they were selected on the basis of medical record review of Medicaid enrollees with selected discharge diagnoses . Information on the timing , duration , and dose of prescription NSAIDs used , demographic factors , and comorbidity was gathered from computerized Medicaid-Medicare data files . Of the 1,799 patients with acute renal failure ( 4.51 hospitalizations per 1,000 person-years ) , 18.1 % were current users of prescription NSAIDs as compared with 11.3 % of 9,899 r and omly selected population controls . After control for demographic factors and comorbidity , use of NSAIDs increased the risk of acute renal failure 58 % ( adjusted odds ratio = 1.58 ; 95 % confidence interval ( CI ) : 1.34 , 1.86 ) . For ibuprofen , which accounted for 35 % of NSAID use , odds ratios associated with dosages of < or = 1,200 mg/day , > 1,200-<2,400 mg/day , and > or = 2,400 mg/day were 0.94 ( 95 % CI : 0.58 , 1.51 ) , 1.89 ( 95 % CI : 1.34 , 2.67 ) , and 2.32 ( 95 % CI : 1.45 , 3.71 ) , respectively ( test for linear trend : p = 0.009 ) . Prescription NSAID use result ed in an estimated 25 excess hospitalizations associated with renal failure per 10,000 years of use . Thus , NSAIDs represent a relatively uncommon but avoidable cause of acute renal failure in frail elderly persons Abstract Objective : To compare rates of upper gastrointestinal haemorrhage among elderly patients given selective cyclo-oxygenase-2 ( COX 2 ) inhibitors and non-selective non-stero
Output:
| Compared with placebo , celecoxib had fewer discontinuations for any cause or for lack of efficacy , fewer serious adverse events , and less nausea .
It had more patients with dyspepsia , diarrhoea , oedema , more adverse events that were gastrointestinal or treatment related , and more patients experiencing an adverse event .
There were no differences for hypertension , gastrointestinal tolerability , or discontinuations for adverse events .
Compared with paracetamol , celecoxib had fewer discontinuations for any cause , for lack of efficacy , or diarrhoea , but no other differences .
Compared with rofecoxib , celecoxib had fewer patients with abdominal pain and oedema , but no other differences .
Compared with NSAIDs , celecoxib had fewer symptomatic ulcers and bleeds , endoscopically detected ulcers , and discontinuations for adverse events or gastrointestinal adverse events .
Fewer patients had any , or a gastrointestinal , or a treatment-related adverse event , or vomiting , abdominal pain , dyspepsia , or reduced haemoglobin or haematocrit .
Discontinuations for lack of efficacy were higher .
No differences were found for all-cause discontinuations , serious adverse events , hypertension , diarrhoea , nausea , oedema , myocardial infa rct ion , cardiac failure , or raised creatinine . |
MS213722 | ***TASK*** the task is to summarize an input biomedical literature in six sentences
***INPUT*** the input is a biomedical literature
***OUTPUT*** the output is the summary of an input biomedical literature in six sentences
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Input: BACKGROUND Mild perioperative hypothermia , which is common during major surgery , may promote surgical-wound infection by triggering thermoregulatory vasoconstriction , which decreases subcutaneous oxygen tension . Reduced levels of oxygen in tissue impair oxidative killing by neutrophils and decrease the strength of the healing wound by reducing the deposition of collagen . Hypothermia also directly impairs immune function . We tested the hypothesis that hypothermia both increases susceptibility to surgical-wound infection and lengthens hospitalization . METHODS Two hundred patients undergoing colorectal surgery were r and omly assigned to routine intraoperative thermal care ( the hypothermia group ) or additional warming ( the normothermia group ) . The patient 's anesthetic care was st and ardized , and they were all given cefam and ole and metronidazole . In a double-blind protocol , their wounds were evaluated daily until discharge from the hospital and in the clinic after two weeks ; wounds containing culture-positive pus were considered infected . The patients ' surgeons remained unaware of the patients ' group assignments . RESULTS The mean ( + /- SD ) final intraoperative core temperature was 34.7 + /- 0.6 degrees C in the hypothermia group and 36.6 + /- 0.5 degrees C in the normothermia group ( P < 0.001 ) Surgical-wound infections were found in 18 of 96 patients assigned to hypothermia ( 19 percent ) but in only 6 of 104 patients assigned to normothermia ( 6 percent , P = 0.009 ) . The sutures were removed one day later in the patients assigned to hypothermia than in those assigned to normothermia ( P = 0.002 ) , and the duration of hospitalization was prolonged by 2.6 days ( approximately 20 percent ) in hypothermia group ( P = 0.01 ) . CONCLUSIONS Hypothermia itself may delay healing and predispose patients to wound infections . Maintaining normothermia intraoperatively is likely to decrease the incidence of infectious complications in patients undergoing colorectal resection and to shorten their hospitalizations OBJECTIVE To compare the effectiveness for prevention of central venous and arterial catheter colonization of 3 skin antisepsis with 1 of 3 antiseptic solutions : 10 % aqueous povidone iodine ( aqueous PI ) , 2 % aqueous chlorhexidine gluconate ( aqueous CG ) , and 0.5 % alcoholic chlorhexidine gluconate ( alcoholic CG ) . DESIGN Prospect i ve , r and omized controlled trial . SETTING Intensive care unit in a teaching hospital . METHODS Patients were r and omly assigned to 1 of the 3 skin antisepsis groups . The distal tips of catheters were semiquantitatively cultured when the catheters were no longer necessary or if there was a suspicion of catheter-related infection . Rates of catheter colonization , catheter-related sepsis , and catheter-related bacteremia were compared among the 3 groups . RESULTS A total of 631 catheters were included in the study ( 194 from the aqueous PI group , 211 from the aqueous CG group , and 226 from the alcoholic CG group ) . The incidence of catheter colonization was significantly lower in the alcoholic CG than in the aqueous PI group ( 14.2 % vs 24.7 % ; relative risk , 0.5 [ 95 % confidence interval , 0.3 - 0.8 ; P < .01 ] ) ; it was also significantly lower in the aqueous CG group than in the aqueous PI group ( 16.1 % vs 24.7 % ; relative risk , 0.6 [ 95 % confidence interval , 0.4 - 0.9 ; P = .03 ] ) . There were no significant differences between the aqueous CG and the alcoholic CG groups . Incidences of catheter-related bacteremia were similar for all 3 groups . The aqueous and alcoholic CG solutions were superior to the aqueous PI solution in preventing catheter colonization due to gram-positive bacteria . CONCLUSIONS The aqueous and alcoholic CG solutions for cutaneous antisepsis were similarly effective in preventing colonization of central venous catheters and arterial catheters . Both had significantly lower incidences of colonization than did the aqueous PI solution ; this effect seems to be related to the CG solutions ' more efficacious prevention of colonization with gram-positive bacteria BACKGROUND Orthopedic surgical procedures involving the foot and ankle are associated with high rates of infection . The optimal method of preparing the skin and nails for foot and ankle surgery remains unknown . OBJECTIVE This study was conducted to compare the efficacy of 4 different methods of skin and nail preparation of the foot using various antiseptic solutions . METHODS In this prospect i ve , r and omized study , 4 methods of skin and nail preparation were compared in terms of their efficacy in eliminating bacteria from the hallux nailfold and first web space of the normal foot in 28 healthy adult volunteers . Efficacy was determined by evaluating the difference in the total bacterial load before and after skin preparation . The foot-preparation solutions evaluated were 4 % chlorhexidine gluconate , 70 % isopropyl alcohol , and 7.5 % to 10 % povidone-iodine . RESULTS The addition of alcohol to povidone-iodine was found to increase the efficacy of the preparation method . The nailfold remained contaminated after any of the preoperative skin- and nail-preparation methods studied . LIMITATIONS This study did not measure clinical ly relevant infections , and the results may not correlate with decreased rates of infection after surgery . CONCLUSION Incorporation of alcohol and povidone-iodine into the preoperative skin- and nail-preparation process may help reduce the bacterial load . Every effort should be made to lower the risk of contamination from the nail The effects of alcohol , chlorhexidine cream and iodophor cream on the infectious complications associated with intravenous catheters were studied . One hundred and fifty patients were r and omly allocated into each antiseptic group . Daily cleansing and disinfecting the cut down wounds were done with the above antiseptics . Minor surgical wound infections were found in one patient in the alcohol and iodophor group compared to five in the chlorhexidine group . Phlebitis complicated four patients , two in the iodophor group and one in each of the remaining groups . Only one patient in the chlorhexidine group had septicaemia due to A. antitratus . Thirty-four catheter tips ( 22.7 % ) yielded bacteria on culture . Incidence of positive tip cultures was significantly higher in the chlorhexidine group than in the other two . The rates of positive tip cultures correlated with duration of catheterization . It is concluded that alcohol is the antiseptic of choice for cut down wounds . Application of antiseptic cream to the wounds was less effective than alcohol and this practice should be discouraged The optimum duration of antimicrobial prophylaxis in elective gastric cancer surgery is still open to question . This multicentre r and omized clinical trial compared a single‐dose with a multiple‐dose regimen of antimicrobial prophylaxis for prevention of surgical‐site infection Estimating the cost of hospital infection has become a matter of increasing interest in terms of health economics . This study aim ed to assess the accuracy of economic studies on hospital infections , using surgical site infection ( SSI ) as an example . A search was performed for original articles reporting the cost of SSI , published in the English language between 1996 and 2005 . For the critical review , the period of cost tracking , classification of costs and cost counting methods were noted . Fifteen articles met the inclusion criteria . The costs of SSI vary according to surgical procedures , country , publication year , study design and accounting method . Only two studies estimated the additional cost of SSI after discharge . All 15 studies included healthcare costs and none measured patient/family re sources . In 10 studies , the costs were calculated based on accounting . Three studies used estimated costs from the ratio of costs to charges and two studies used charge data in place of cost data . It will become increasingly important for future studies to perform multi-centre prospect i ve surveys , establish a st and ard method for cost accounting , include the cost of healthcare services following hospitalization and consider the morbidity cost to patients themselves from a societal perspective OBJECTIVE The purpose of this study was to compare the efficacy of chlorhexidine and povidone iodine for cleansing the operative field for vaginal surgery . STUDY DESIGN This was a r and omized controlled trial that compared 10 % povidone iodine and 4 % chlorhexidine gluconate as surgical scrubs . Our primary end point was the proportion of contaminated specimens ( defined as total bacterial colony counts of > /=5000 colony-forming units ) per group found throughout the surgical procedures . All patients received st and ard infection prophylaxis that included preoperative intravenous antibiotics . Immediately before antibiotic administration and baseline aerobic and anaerobic cultures of the vaginal flora were obtained , which were followed by cultures at 30 minutes after the surgical scrub and hourly thereafter throughout each patient 's surgery . RESULTS A total of 50 patients were enrolled between October 2002 and September 2003 . There were no differences between the povidone iodine ( n = 27 ) and chlorhexidine ( n = 23 ) groups with respect to age , race , exogenous hormone use , body mass index , gravity , parity , preoperative mean colony counts , or operative time . Among the first set of intraoperative specimens ( which were obtained 30 minutes after the surgical scrub ) , 63 % of the cultures ( 17/27 ) from the povidone iodine group and 22 % of the cultures ( 5/23 ) from the chlorhexidine group were classified as contaminated ( P = .003 ; relative risk , 6.12 ; 95 % CI , 1.7 , 21.6 ) . Subsequent cultures failed to demonstrate significant differences . CONCLUSION Chlorhexidine gluconate was more effective than povidone iodine in decreasing the bacterial colony counts that were found in the operative field for vaginal hysterectomy BACKGROUND Previous studies have demonstrated higher infection rates following orthopaedic procedures on the foot and ankle as compared with procedures involving other areas of the body . Previous studies also have documented the difficulty of eliminating bacteria from the forefoot prior to surgery . The purpose of the present study was to evaluate the efficacy of three different surgical skin-preparation solutions in eliminating potential bacterial pathogens from the foot . METHODS A prospect i ve study was undertaken to evaluate 125 consecutive patients undergoing surgery of the foot and ankle . Each lower extremity was prepared with one of three r and omly selected solutions : DuraPrep ( 0.7 % iodine and 74 % isopropyl alcohol ) , Techni-Care ( 3.0 % chloroxylenol ) , or ChloraPrep ( 2 % chlorhexidine gluconate and 70 % isopropyl alcohol ) . After preparation , quantitative culture specimens were obtained from three locations : the hallux nailfold ( the hallux site ) , the web spaces between the second and third and between the fourth and fifth digits ( the toe site ) , and the anterior part of the tibia ( the control site ) . RESULTS In the Techni-Care group , bacteria grew on culture of specimens obtained from 95 % of the hallux sites , 98 % of the toe sites , and 35 % of the control sites . In the DuraPrep group , bacteria grew on culture of specimens obtained from 65 % of the hallux sites , 45 % of the toe sites , and 23 % of the control sites . In the ChloraPrep group , bacteria grew on culture of specimens from 30 % of the hallux sites , 23 % of the toe sites , and 10 % of the control sites . ChloraPrep was the most effective agent for eliminating bacteria from the halluces and the toes ( p < 0.0001 ) . CONCLUSIONS The use of effective preoperative preparation solution is an important step in limiting surgical wound contamination and preventing infection , particularly in foot and ankle surgery . Of the three solutions tested in the present study , the combination of chlorhexidine and alcohol ( ChloraPrep ) was most effective for eliminating bacteria from the forefoot prior to surgery BACKGROUND Currently , there are various antiseptics used for cleaning the skin before surgery , but there is no st and ard procedure in practice . Chlorhexidine and povidone-iodine are the most preferred compounds among antiseptics . Both are proved to be safe and effective for skin disinfection . In this study , our aim was to investigate the combined effects of chlorhexidine and povidone-iodine on the skin 's flora before neurosurgical intervention , consecutively . METHODS R and omly , 50 cranial and 50 spine neurosurgery cases were assigned to the study . The first culture was obtained after hair removal and before cleaning the skin with any antiseptic . The second culture was obtained after the skin had been cleaned with chlorhexidine for 3 minutes . Then , the skin was cleaned twice with povidone-iodine for 30 seconds , and the third and fourth cultures were taken from the skin incision area . Bacteria were identified by means of st and ard laboratory identification methods . Positive culture results were compared statistically among order of cultures obtained . RESULTS In the
Output:
| Chlorhexidine should be used preferentially for preoperative antisepsis in clean-contaminated surgery |
MS213723 | ***TASK*** the task is to summarize an input biomedical literature in six sentences
***INPUT*** the input is a biomedical literature
***OUTPUT*** the output is the summary of an input biomedical literature in six sentences
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Input: CONTEXT Cognitive decline , mood , behavioral and sleep disturbances , and limitations of activities of daily living commonly burden elderly patients with dementia and their caregivers . Circadian rhythm disturbances have been associated with these symptoms . OBJECTIVE To determine whether the progression of cognitive and noncognitive symptoms may be ameliorated by individual or combined long-term application of the 2 major synchronizers of the circadian timing system : bright light and melatonin . DESIGN , SETTING , AND PARTICIPANTS A long-term , double-blind , placebo-controlled , 2 x 2 factorial r and omized trial performed from 1999 to 2004 with 189 residents of 12 group care facilities in the Netherl and s ; mean ( SD ) age , 85.8 ( 5.5 ) years ; 90 % were female and 87 % had dementia . INTERVENTIONS R and om assignment by facility to long-term daily treatment with whole-day bright ( + /- 1000 lux ) or dim ( + /- 300 lux ) light and by participant to evening melatonin ( 2.5 mg ) or placebo for a mean ( SD ) of 15 ( 12 ) months ( maximum period of 3.5 years ) . MAIN OUTCOME MEASURES St and ardized scales for cognitive and noncognitive symptoms , limitations of activities of daily living , and adverse effects assessed every 6 months . RESULTS Light attenuated cognitive deterioration by a mean of 0.9 points ( 95 % confidence interval [ CI ] , 0.04 - 1.71 ) on the Mini-Mental State Examination or a relative 5 % . Light also ameliorated depressive symptoms by 1.5 points ( 95 % CI , 0.24 - 2.70 ) on the Cornell Scale for Depression in Dementia or a relative 19 % , and attenuated the increase in functional limitations over time by 1.8 points per year ( 95 % CI , 0.61 - 2.92 ) on the nurse-informant activities of daily living scale or a relative 53 % difference . Melatonin shortened sleep onset latency by 8.2 minutes ( 95 % CI , 1.08 - 15.38 ) or 19 % and increased sleep duration by 27 minutes ( 95 % CI , 9 - 46 ) or 6 % . However , melatonin adversely affected scores on the Philadelphia Geriatric Centre Affect Rating Scale , both for positive affect ( -0.5 points ; 95 % CI , -0.10 to -1.00 ) and negative affect ( 0.8 points ; 95 % CI , 0.20 - 1.44 ) . Melatonin also increased withdrawn behavior by 1.02 points ( 95 % CI , 0.18 - 1.86 ) on the Multi Observational Scale for Elderly Subjects scale , although this effect was not seen if given in combination with light . Combined treatment also attenuated aggressive behavior by 3.9 points ( 95 % CI , 0.88 - 6.92 ) on the Cohen-Mansfield Agitation Index or 9 % , increased sleep efficiency by 3.5 % ( 95 % CI , 0.8%-6.1 % ) , and improved nocturnal restlessness by 1.00 minute per hour each year ( 95 % CI , 0.26 - 1.78 ) or 9 % ( treatment x time effect ) . CONCLUSIONS Light has a modest benefit in improving some cognitive and noncognitive symptoms of dementia . To counteract the adverse effect of melatonin on mood , it is recommended only in combination with light . TRIAL REGISTRATION controlled-trials.com/is rct n Identifier : IS RCT N93133646 The effects of immediate-release melatonin on circadian rest-activity profiles , cognition , and mood were investigated in ten elderly individuals with self-reported sleep-wake disturbances . Melatonin ( 6 mg ) , administered 2 hr before habitual bedtime , enhanced the rest-activity rhythm and improved sleep quality as observed in a reduction in sleep onset latency and in the number of transitions from sleep to wakefulness . However , total sleep time was not significantly increased nor was wake within sleep significantly reduced . The ability to remember previously learned items improved along with a significant reduction in depressed moods . No side effects or contraindications were reported by any of our participants during the 10 day trials . These data suggest that melatonin can safely improve some aspects of sleep , memory , and mood in the elderly in short-term use Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more We used in vitro neurogenesis-based human neural stem cell ( hNSCs ) assays and rodent in vivo behavioral assays to identify potential novel antidepressants . A combination of buspirone and melatonin displayed antidepressant activity in these assays whereas neither buspirone nor melatonin alone showed any antidepressant-like profile . After evaluating numerous combination ratios , we determined that low dose buspirone 15 mg combined with melatonin-SR 3 mg yielded optimal antidepressant efficacy in our pre- clinical platform . The low dose of buspirone suggested that antidepressant efficacy might be achieved with only minimal adverse event liability . Based on these data , we conducted an exploratory 6-week , multi-center , double-blind , r and omized , placebo- and comparator-controlled study of the combination of buspirone and melatonin in subjects with acute Major Depressive Disorder ( MDD ) . The combination treatment revealed a significant antidepressant response in subjects with MDD on several measures ( Clinical Global Impression of Severity and Improvement , Inventory of Depressive Symptomatology ) compared to either placebo or buspirone 15 mg monotherapy . These preliminary findings have clinical implication s and suggest that a platform of pre- clinical neurogenesis matched with confirmatory behavioral assays may be useful as a drug discovery strategy Patients with winter depression ( seasonal affective disorder ( SAD ) ) commonly complain of sleepiness . Sleepiness can be objective ly measured by spectral analysis of the waking electroencephalogram ( EEG ) in the 1–10 Hz b and . The waking EEG was measured every 3 h in 16 female SAD patients and 13 age-matched control women throughout a total sleep deprivation of 30 h. Melatonin ( or placebo ) under double-blind conditions was administered subsequently ( 0.5 mg at 1700 h for 6 days ) , appropriately timed to phase advance circadian rhythms , followed by re assessment in the laboratory for 12 h. The increase in EEG power density in a narrow theta b and ( 5–5.99 Hz , derivation Fz – Cz ) during the 30 h protocol was significantly attenuated in patients compared with controls ( difference between linear trends p=0.037 ) . Sleepiness ( p=0.092 ) and energy ( p=0.045 ) self-ratings followed a similar pattern . Six patients improved after sleep deprivation ( ⩾50 % reduction on SIGH-SAD22 score ) . EEG power density dynamics was correlated with clinical response to sleep deprivation : the steeper the build-up ( as in controls ) , the better the improvement ( p<0.05 ) . There was no differential effect of melatonin or placebo on any measure ; both treatments stabilized the improvement . Overall , patients with winter depression manifest similar wake EEG characteristics as long sleepers or late chronotype with respect to an insufficient build-up of homeostatic sleep pressure . Sleep deprivation was an effective antidepressant treatment for some patients , but evening melatonin was not more efficacious than placebo in sustaining this antidepressant effect Background In many mammals , the duration of the nocturnal melatonin elevation regulates seasonal changes in reproductive hormones such as luteinizing hormone ( LH ) . Melatonin 's effects on human reproductive endocrinology are uncertain . It is thought that the same hypothalamic pulse generator may both trigger the pulsatile release of GnRH and LH and also cause hot flashes . Thus , if melatonin suppressed this pulse generator in postmenopausal women , it might moderate hot flashes . This clinical trial tested the hypothesis that melatonin could suppress LH and relieve hot flashes . Methods Twenty postmenopausal women troubled by hot flashes underwent one week of baseline observation followed by 4 weeks of a r and omized controlled trial of melatonin or matched placebo . The three r and omized treatments were melatonin 0.5 mg 2.5–3 hours before bedtime , melatonin 0.5 mg upon morning awakening , or placebo capsules . Twelve of the women were admitted to the GCRC at baseline and at the end of r and omized treatment for 24-hour sampling of blood for LH . Morning urine sample s were collected twice weekly to measure LH excretion . Subjective responses measured throughout baseline and treatment included sleep and hot flash logs , the CESD and QIDS depression self-ratings , and the SAFTEE physical symptom inventory . Results Urinary LH tended to increase from baseline to the end of treatment . Contrasts among the 3 r and omized groups were statistically marginal , but there was relative suppression combining the groups given melatonin as contrasted to the placebo group ( p < 0.01 one-tailed , Mann-Whitney U = 14 . ) Similar but not significant results were seen in blood LH . There were no significant contrasts among groups in hot flashes , sleep , depression , or side-effect measures and no significant adverse effects of any sort . Conclusion The data are consistent with the hypothesis that melatonin suppresses LH in postmenopausal women . An effect related to the duration of nocturnal melatonin elevation is suggested . Effects of melatonin on reproductive endocrinology should be studied further in younger women and in men . Larger studies of melatonin effects on postmenopausal symptoms would be worthwhile Five patients with winter depression received low doses of melatonin in the afternoon , and five patients received placebo capsules . Melatonin treatment significantly decreased depression ratings compared to placebo . If these findings are replicated in a larger sample with documentation of expected phase shifts , the phase shift hypothesis will be substantially supported Objectives : We sought to report the efficacy of oral melatonin as treatment for chronic tinnitus and to determine whether particular subsets of tinnitus patients have greater benefit from melatonin therapy than others . Methods : This was a prospect i ve , r and omized , double-blind , crossover clinical trial in an ambulatory tertiary referral otology and neurotology practice . Adults with chronic tinnitus were r and omized to 3 mg melatonin or placebo nightly for 30 days followed by a 1-month washout period . Each group then crossed into the opposite treatment arm for 30 days . The tests audiometric tinnitus matching ( TM ) , Tinnitus Severity Index ( TSI ) , Self Rated Tinnitus ( SRT ) , Pittsburgh Sleep Quality Index ( PSQI ) , and Beck Depression Inventory ( BDI ) were administered at the outset and every 30 days thereafter to assess the effects of each intervention . Results : A total of 61 subjects completed the study . A significantly greater decrease in TM and SRT scores ( p < 0.05 ) from baseline was observed after treatment with melatonin relative to the effect observed with placebo . Male gender , bilateral tinnitus , noise exposure , no prior tinnitus treatment , absence of depression and /or anxiety at baseline , and greater pretreatment TSI scores were associated with a positive response to melatonin . Absence of depression and /or anxiety at baseline , greater pretreatment TSI scores , and greater pretreatment SRT scores were found to be positively associated with greater likelihood of improvement in both tinnitus and sleep with use of melatonin ( p < 0.05 ) . Conclusions : Melatonin is associated with a statistically significant decrease in tinnitus intensity and improved sleep quality in patients with chronic tinnitus . Melatonin is most effective in men , those without a history of depression , those who have not undergone prior tinnitus treatments , those with more severe and bilateral tinnitus , and those with a history of noise exposure BACKGROUND Low nighttime levels of melatonin have been demonstrated in patients with insomnia , and melatonin has been shown to have hypnotic properties in some groups of such subjects . Low melatonin levels have also been observed in patients with schizophrenia ; however , there is little literature on the efficacy of exogenous melatonin in treating insomnia associated with schizophrenia . METHOD Stable DSM-IV schizophrenic out patients ( N = 40 ) with initial insomnia of at least 2 weeks ' duration were r and omly assigned to augment their current medications with either flexibly dosed melatonin ( 3 - 12 mg/night ; N = 20 ) or placebo ( N = 20 ) . By use of a question naire , double-blind assessment s of aspects of sleep functioning were obtained daily across the next 15 days . The study was conducted between March and December 2002 . RESULTS The modal stable dose of melatonin was 3 mg . Relative to placebo , melatonin significantly improved the quality and depth of nighttime sleep , reduced the number of nighttime awakenings , and increased the duration of sleep without producing a morning hangover ( p < .05 ) . Subjectively , melatonin also significantly reduced sleep-onset latency , heightened freshness on awakening , improved mood ,
Output:
| The two meta-analyses did not show any significant effect of melatonin .
Although some studies were positive , there was no clear evidence of a therapeutic- or prophylactic effect of melatonin against depression or depressive symptoms |
MS213724 | ***TASK*** the task is to summarize an input biomedical literature in six sentences
***INPUT*** the input is a biomedical literature
***OUTPUT*** the output is the summary of an input biomedical literature in six sentences
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Input: Memory performance by four age groups ( 30 - 45 years , 46 - 60 years , 61 - 75 years , and 76 - 90 years ) was compared on a multi-trial verbal recall task with 20-minute and 1-day delay free recall and recognition trials . The rate of acquisition across 5 learning trials was similar for all ages except the youngest group whose performance was constrained by a ceiling effect . The level of acquisition achieved was less in the two oldest groups . Words gained across trials and words lost across trials made similar contributions to the shape of the learning curve for the acquisition trials . Subjective organization decreased with age , but remained strongly related to the number of words recalled during acquisition for all age groups . The two oldest age groups demonstrated significant declines in words recalled on the 20-minute and 1-day delay trials . A subset of the oldest group demonstrated more rapid forgetting at the 1-day delay when participants from all age conditions were matched on acquisition . Thus , many aspects of free recall were impaired with age , and variance measurement of recall showed greater inter-individual differences with increasing age . This increase in individual differences could reflect a single form of age-related memory impairment , or it could indicate that memory impairment in the elderly is due to multiple processes . The importance of testing across the life span and using tests that examine a variety of memory components and processes for establishing norms and clarifying age-related deficits are discussed This study describes the neural circuitry underlying temporally separated components of working memory ( WM ) performance-stimulus encoding , maintenance of information during a delay , and the response to a probe . While other studies have applied event-related fMRI to separate epochs of WM tasks , this study differs in that it employs a methodology that does not make any a priori assumptions about the shape of the hemodynamic response ( HDR ) . This is important because no one model of the HDR is valid across the range of activated brain regions and stimulus types . Systematic modeling inaccuracies may lead to the misattribution of activity to adjacent events . Twelve healthy subjects performed a numerical version of the Sternberg Item Recognition Paradigm adapted for rapid presentation event-related fMRI . This paradigm emphasized maintenance rather than manipulative WM processes and used a subcapacity WM load . WM trials with different delay lengths were compared to fixation . The HDR of the entire WM trial for each trial type was estimated using a finite impulse response ( FIR ) . Regional activity associated with the Encode , Delay , and Probe epochs was identified using contrasts that were based on the FIR estimates and by examining the HDRs . Each epoch was associated with a distinct but overlapping pattern of regional activity . Activation of the dorsolateral prefrontal cortex , thalamus , and basal ganglia was exclusively associated with the probe . This suggests that frontostriatal neural circuitry participates in selecting an appropriate response based on the contents of WM Estrogen Therapy ( ET ) may protect against age-related cognitive decline and neuropsychiatric disorders ( e.g. Alzheimer 's disease ) . The biological basis for this putative neuroprotective effect is not fully understood , but may include modulation of cholinergic systems . Cholinergic dysfunction has been implicated in age-related memory impairment and Alzheimer 's disease . However , to date no one has investigated the effect of long-term ET on brain cholinergic muscarinic receptor aging , and related this to cognitive function . We used Single Photon Emission Tomography ( SPET ) and (R , R)[(123)I]-I-QNB , a novel lig and with high affinity for m(1)/m(4 ) muscarinic receptors , to examine the effect of long-term ET and age on brain m(1)/m(4 ) receptors in healthy females . We included 10 younger premenopausal subjects and 22 postmenopausal women ; 11 long-term ET users ( all treated following surgical menopause ) and 11 ET never-users ( surgical menopause , n=2 ) . Also , verbal memory and executive function was assessed in all postmenopausal subjects . Compared to young women , postmenopausal women ( ET users and never-users combined ) had significantly lower muscarinic receptor density in all brain regions examined . ET users also had higher muscarinic receptor density than ET never-users in all the brain regions , and this reached statistical significance in left striatum and hippocampus , lateral frontal cortex and thalamus . Moreover , in ET users , (R , R)[(123)I]-I-QNB binding in left hippocampus and temporal cortex was significantly positively correlated with plasma estradiol levels . We also found evidence for improved executive function in ET users as compared to ET never-users . However , there was no significant relationship between receptor binding and cognitive function within any of the groups . In healthy postmenopausal women use of long-term ET is associated with reduced age-related differences in muscarinic receptor binding , and this may be related to serum estradiol levels Estradiol has been shown to interact with the cholinergic system to affect cognition in postmenopausal women . This study further investigated the interaction of estradiol and cholinergic system functioning on verbal memory and attention in two groups of healthy younger ( ages 50 - 62 ) and older ( ages 70 - 81 ) postmenopausal women . Twenty-two postmenopausal women were r and omly and blindly placed on 1 mg of 17-beta estradiol orally for 1 month then 2 mg for 2 months or matching placebo pills after which they participated in three anticholinergic challenge sessions when verbal memory and attention were assessed . Subjects were administered either the antimuscarinic drug scopolamine ( SCOP ) , the antinicotinic drug mecamylamine ( MECA ) , or placebo . After the first challenge phase , they were crossed over to the other hormone treatment for another 3 months and repeated the challenges . Results showed that estradiol pretreatment significantly attenuated the anticholinergic drug-induced impairments on a test of episodic memory ( the Buschke Selective Reminding Task ) for the younger group only , while estradiol treatment impaired performance of the older group . The results suggest that younger subjects may experience more cholinergic benefit from estradiol treatment than older subjects , supporting the concept of a critical period for postmenopausal estrogen use CONTEXT Postmenopausal women have a greater risk than men of developing Alzheimer disease , but studies of the effects of estrogen therapy on Alzheimer disease have been inconsistent . On July 8 , 2002 , the study drugs , estrogen plus progestin , in the Women 's Health Initiative ( WHI ) trial were discontinued because of certain increased health risks in women receiving combined hormone therapy . OBJECTIVE To evaluate the effect of estrogen plus progestin on the incidence of dementia and mild cognitive impairment compared with placebo . DESIGN , SETTING , AND PARTICIPANTS The Women 's Health Initiative Memory Study ( WHIMS ) , a r and omized , double-blind , placebo-controlled clinical trial , began enrolling participants from the Women 's Health Initiative ( WHI ) estrogen plus progestin trial in May 1996 . Of the 4894 eligible participants of the WHI study , 4532 ( 92.6 % ) postmenopausal women free of probable dementia , aged 65 years or older , and recruited from 39 of 40 WHI clinical centers were enrolled in the WHIMS . INTERVENTION Participants received either 1 daily tablet of 0.625 mg of conjugated equine estrogen plus 2.5 mg of medroxyprogesterone acetate ( n = 2229 ) , or a matching placebo ( n = 2303 ) . MAIN OUTCOME MEASURES Incidence of probable dementia ( primary outcome ) and mild cognitive impairment ( secondary outcome ) were identified through a structured clinical assessment . RESULTS The mean ( SD ) time between the date of r and omization into WHI and the last Modified Mini-Mental State Examination ( 3MSE ) for all WHIMS participants was 4.05 ( 1.19 ) years . Overall , 61 women were diagnosed with probable dementia , 40 ( 66 % ) in the estrogen plus progestin group compared with 21 ( 34 % ) in the placebo group . The hazard ratio ( HR ) for probable dementia was 2.05 ( 95 % confidence interval [ CI ] , 1.21 - 3.48 ; 45 vs 22 per 10 000 person-years ; P = .01 ) . This increased risk would result in an additional 23 cases of dementia per 10 000 women per year . Alzheimer disease was the most common classification of dementia in both study groups . Treatment effects on mild cognitive impairment did not differ between groups ( HR , 1.07 ; 95 % CI , 0.74 - 1.55 ; 63 vs 59 cases per 10 000 person-years ; P = .72 ) . CONCLUSIONS Estrogen plus progestin therapy increased the risk for probable dementia in postmenopausal women aged 65 years or older . In addition , estrogen plus progestin therapy did not prevent mild cognitive impairment in these women . These findings , coupled with previously reported WHI data , support the conclusion that the risks of estrogen plus progestin outweigh the benefits UNLABELLED The aim of the double-blind , placebo-controlled study was to investigate the effects of a continuous combined estrogen-progestogen treatment ( Climodien , Lafamme ) as compared with estrogen alone on vigilance in insomniac postmenopausal syndrome patients , objectified by EEG mapping . METHODS In a 3-arm , 2-month parallel group design phase , patients received a combination of estradiol valerate 2 mg and the novel progestogen dienogest 3 mg ( Climodien 2/3 ) or estradiol valerate 2 mg alone or placebo . In a subsequent open-label phase , all patients received estradiol valerate 2 mg+dienogest 2 mg ( Climodien 2/2 ) . EEG mapping was carried out before and after the 2-month double-blind phase as well as after the 2-month open-label treatment . RESULTS As compared with placebo , Climodien 2/3 induced a marked and highly significant increase in absolute power in all frequency b and s , specifically in alpha-2 activity . Moreover , a significant increase in relative alpha-2 power , a decrease in relative delta and beta power as well as an acceleration of the dominant frequency and of the delta and alpha centroids suggested a marked improvement in vigilance . In contrast , under estradiol valerate 2 mg alone , only a slight augmentation of alpha and attenuation of relative delta and beta power occurred , suggesting only a slight vigilance improvement as compared with placebo . Thus , dienogest 2 mg increased the estrogen effect , which was also confirmed by a statistical evaluation of the differences between Climodien 2/3 and estradiol valerate alone ( augmentation of alpha-2 , attenuation of relative beta , acceleration of the dominant frequency ) . Moreover , Climodien 2/2 also markedly increased alpha-2 power , decreased relative beta-2 power and accelerated the alpha centroid . Finally , comparing Climodien 2/3 with Climodien 2/2 , there was even a dose-efficacy relation . CONCLUSIONS Estradiol valerate 2 mg improves vigilance slightly , thereby confirming previous findings . The additional administration of dienogest does not minimize the effect of estrogen , but on the contrary increases it , which makes the combination superior to both placebo and estradiol valerate alone . Vigilance improvement may be of great therapeutic benefit to menopausal syndrome patients at a time when increased adaptability is needed to adjust to increasing sexual , marital , occupational and social difficulties known to occur specifically in this period of life Recent research in rodents suggests that extended and chronic hormone therapy can exacerbate memory impairments and irreversibly damage cells . However , aerobic fitness regimens have been shown to spare brain tissue and cognitive function . In addition , interactions between estrogen treatment and exercise have been reported in rodents . However , whether aerobic fitness and hormone treatments show interactive effects on human brain tissue and cognition has yet to be determined . Here we report two unique and important results : ( a ) HRT treatment up to 10 years in duration spares gray matter in prefrontal cortex and is associated with better performance on measures of executive function , whereas HRT treatment beyond 10 years in duration increases the degree of prefrontal deterioration and amplifies the decline on measures of executive functioning ( b ) higher fitness levels augment the effects of shorter duration s of hormone treatment and ameliorate the declines associated with prolonged hormone treatment In the last ten years , numerous mechanisms by which sex steroids modify cortical function have been described . For example , estrogen replacement improves verbal memory in women , and animal studies have shown effects of estrogen on hippocampal synaptogenesis and function . Little is known about sex steroid effects on other aspects of memory , such as frontal lobe-mediated working memory . We examined the relationships between working memory and sex steroid concentrations and whether sex steroid supplementation would modify age-related loss of working memory in older men and women . Before hormone supplementation , working memory , tested with the Subject Ordered Pointing Test ( SOP ) , was worse in older subjects than younger subjects , and there was no evidence of gender differences at either age . Testosterone supplementation improved working memory in older men , but a similar enhancement of working memory was not found in older women supplemented with estrogen . In men , testosterone and estrogen effects were reciprocalwith better working memory related to a higher testosterone to estrogen ratio .
Output:
| RESULTS There is some evidence for a beneficial effect of estrogen alone on verbal memory in younger naturally post-menopausal women and more consistent evidence from small-n studies of surgically post-menopausal women .
There is stronger evidence of a detrimental effect of conjugated equine estrogen plus medroxyprogesterone acetate on verbal memory in younger and older post-menopausal women .
Observational studies and pharmacological models of menopause provide initial evidence of improvements in executive function with hormone therapy .
Future studies should include measures of executive function and should address pressing clinical questions ; including what formulation of combination hormone therapy is cognitively neutral/beneficial , yet effective in treating hot flashes in the early post-menopause |
MS213725 | ***TASK*** the task is to summarize an input biomedical literature in six sentences
***INPUT*** the input is a biomedical literature
***OUTPUT*** the output is the summary of an input biomedical literature in six sentences
***DOCUMENTATION***
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Input: Objective : The underlying changes in biological processes that are associated with reported changes in mental and physical health in response to meditation have not been systematic ally explored . We performed a r and omized , controlled study on the effects on brain and immune function of a well‐known and widely used 8‐week clinical training program in mindfulness meditation applied in a work environment with healthy employees . Methods : We measured brain electrical activity before and immediately after , and then 4 months after an 8‐week training program in mindfulness meditation . Twenty‐five subjects were tested in the meditation group . A wait‐list control group ( N = 16 ) was tested at the same points in time as the meditators . At the end of the 8‐week period , subjects in both groups were vaccinated with influenza vaccine . Results : We report for the first time significant increases in left‐sided anterior activation , a pattern previously associated with positive affect , in the meditators compared with the nonmeditators . We also found significant increases in antibody titers to influenza vaccine among subjects in the meditation compared with those in the wait‐list control group . Finally , the magnitude of increase in left‐sided activation predicted the magnitude of antibody titer rise to the vaccine . Conclusions : These findings demonstrate that a short program in mindfulness meditation produces demonstrable effects on brain and immune function . These findings suggest that meditation may change brain and immune function in positive ways and underscore the need for additional research Background — Although numerous studies have reported that cardiac rehabilitation ( CR ) is associated with reduced mortality after myocardial infa rct ion , less is known about its association with mortality after percutaneous coronary intervention . Methods and Results — We performed a retrospective analysis of data from a prospect ively collected registry of 2395 consecutive patients who underwent percutaneous coronary intervention in Olmsted County , Minnesota , from 1994 to 2008 . The association of CR with all-cause mortality , cardiac mortality , myocardial infa rct ion , or revascularization was assessed with 3 statistical techniques : propensity score – matched analysis ( n=1438 ) , propensity score stratification ( n=2351 ) , and regression adjustment with propensity score in a 3-month l and mark analysis ( n=2009 ) . During a median follow-up of 6.3 years , 503 deaths ( 199 cardiac ) , 394 myocardial infa rct ions , and 755 revascularization procedures occurred in the study subjects . Participation in CR , noted in 40 % ( 964 of 2395 ) of the cohort , was associated with a significant decrease in all-cause mortality by all 3 statistical techniques ( hazard ratio , 0.53 to 0.55 ; P<0.001 ) . A trend toward decreased cardiac mortality was also observed in CR participants ; however , no effect was observed for subsequent myocardial infa rct ion or revascularization . The association between CR participation and reduced mortality rates was similar for men and women , for older and younger patients , and for patients undergoing elective or nonelective percutaneous coronary intervention . Conclusions — We found that CR participation after percutaneous coronary intervention was associated with a significant reduction in mortality rates . These findings add support to published clinical practice guidelines , performance measures , and insurance coverage policies that recommend CR for patients after percutaneous coronary intervention CONTEXT Observational studies have shown that psychosocial factors are associated with increased risk for cardiovascular morbidity and mortality , but the effects of behavioral interventions on psychosocial and medical end points remain uncertain . OBJECTIVE To determine the effect of 2 behavioral programs , aerobic exercise training and stress management training , with routine medical care on psychosocial functioning and markers of cardiovascular risk . DESIGN , SETTING , AND PATIENTS R and omized controlled trial of 134 patients ( 92 male and 42 female ; aged 40 - 84 years ) with stable ischemic heart disease ( IHD ) and exercise-induced myocardial ischemia . Conducted from January 1999 to February 2003 . INTERVENTIONS Routine medical care ( usual care ) ; usual care plus supervised aerobic exercise training for 35 minutes 3 times per week for 16 weeks ; usual care plus weekly 1.5-hour stress management training for 16 weeks . MAIN OUTCOME MEASURES Self-reported measures of general distress ( General Health Question naire [ GHQ ] ) and depression ( Beck Depression Inventory [ BDI ] ) ; left ventricular ejection fraction ( LVEF ) and wall motion abnormalities ( WMA ) ; flow-mediated dilation ; and cardiac autonomic control ( heart rate variability during deep breathing and baroreflex sensitivity ) . RESULTS Patients in the exercise and stress management groups had lower mean ( SE ) BDI scores ( exercise : 8.2 [ 0.6 ] ; stress management : 8.2 [ 0.6 ] ) vs usual care ( 10.1 [ 0.6 ] ; P = .02 ) ; reduced distress by GHQ scores ( exercise : 56.3 [ 0.9 ] ; stress management : 56.8 [ 0.9 ] ) vs usual care ( 53.6 [ 0.9 ] ; P = .02 ) ; and smaller reductions in LVEF during mental stress testing ( exercise : -0.54 % [ 0.44 % ] ; stress management : -0.34 % [ 0.45 % ] ) vs usual care ( -1.69 % [ 0.46 % ] ; P = .03 ) . Exercise and stress management were associated with lower mean ( SE ) WMA rating scores ( exercise : 0.20 [ 0.07 ] ; stress management : 0.10 [ 0.07 ] ) in a subset of patients with significant stress-induced WMA at baseline vs usual care ( 0.36 [ 0.07 ] ; P = .02 ) . Patients in the exercise and stress management groups had greater mean ( SE ) improvements in flow-mediated dilation ( exercise : mean [ SD ] , 5.6 % [ 0.45 % ] ; stress management : 5.2 % [ 0.47 % ] ) vs usual care patients ( 4.1 % [ 0.48 % ] ; P = .03 ) . In a subgroup , those receiving stress management showed improved mean ( SE ) baroreflex sensitivity ( 8.2 [ 0.8 ] ms/mm Hg ) vs usual care ( 5.1 [ 0.9 ] ms/mm Hg ; P = .02 ) and significant increases in heart rate variability ( 193.7 [ 19.6 ] ms ) vs usual care ( 132.1 [ 21.5 ] ms ; P = .04 ) . CONCLUSION For patients with stable IHD , exercise and stress management training reduced emotional distress and improved markers of cardiovascular risk more than usual medical care alone PURPOSE Patients with various medical conditions benefit from eliciting the relaxation response ( RR ) , using a variety of techniques , but few studies have focused on chronic heart failure ( CHF ) . We evaluated the efficacy of an RR intervention program on the quality of life ( QOL ) and exercise capacity of CHF patients by conducting a single-blind , 3-arm , r and omized , controlled trial . METHODS Between April 2000 and June 2002 , we enrolled 95 patients with moderate severity CHF from the Veterans Affairs Boston Healthcare System . Patients in the study intervention group attended a weekly RR group for 15 weeks and were requested to practice the techniques at home twice a day . A 15-week cardiac education ( EDU ) program was used as an alternative intervention , and usual care ( UC ) was the control group . The QOL question naires and a bicycle test were administered at baseline and after intervention or 15 to 19 weeks . RESULTS Eighty-three ( 87 % ) of the 95 enrolled patients completed both baseline and post-intervention QOL measures ( 31 RR , 24 EDU , and 28 UC ) . No dropout bias was observed . The RR group had significantly better QOL change scores in peace-spiritual scales than did the UC group ( P = .02 ) , adjusting for baseline scores , time between assessment s , age , education , diet , and medication , whereas no significant difference was observed between the EDU and UC groups . A similar trend was observed in emotional QOL ( RR and UC group comparison , P = .07 ) . No statistically significant intervention effect on physical QOL or exercise capacity was observed . CONCLUSIONS A short RR intervention can improve some aspects of QOL in CHF patients OBJECTIVES This study sought to estimate the extent to which behavioral and pathophysiological risk factors account for the association between psychological distress and incident cardiovascular events . BACKGROUND The intermediate processes through which psychological distress increases the risk of cardiovascular disease ( CVD ) are incompletely understood . An underst and ing of these processes is important for treating psychological distress in an attempt to reduce CVD risk . METHODS In a prospect i ve study of 6,576 healthy men and women ( ages 50.9 + /- 13.1 years ) , we measured psychological distress ( using the 12-item version of the General Health Question naire > or=4 ) and behavioral ( smoking , alcohol , physical activity ) and pathophysiological ( C-reactive protein , fibrinogen , total and high-density lipoprotein cholesterol , obesity , hypertension ) risk factors at baseline . The main outcome was CVD events ( hospitalization for nonfatal myocardial infa rct ion , coronary artery bypass , angioplasty , stroke , heart failure , and CVD-related mortality ) . RESULTS Cigarette smoking , physical activity , alcohol intake , C-reactive protein , and hypertension were independently associated with psychological distress . There were 223 incident CVD events ( 63 fatal ) over an average follow-up of 7.2 years . The risk of CVD increased in relation to presence of psychological distress in age- and sex-adjusted models ( hazard ratio : 1.54 , 95 % confidence interval : 1.09 to 2.18 , p = 0.013 ) . In models that were adjusted for potential mediators , behavioral factors explained the largest proportion of variance ( approximately 65 % ) , whereas pathophysiological factors accounted for a modest amount ( C-reactive protein approximately 5.5 % , hypertension , approximately 13 % ) . CONCLUSIONS The association between psychological distress and CVD risk is largely explained by behavioral processes . Therefore , treatment of psychological distress that aims to reduce CVD risk should primarily focus on health behavior change BACKGROUND Previous studies demonstrated the effects of progressive muscle relaxation training ( PMRT ) on improvements in the health outcomes of cardiac patients . This study examined the effects of PMRT on the psychologic status and symptoms of older Chinese patients with heart failure . METHODS In a longitudinal , r and omized , and controlled study , 59 patients were allocated to receive a PMRT program and 62 were provided with the attention placebo . The PMRT program included two PMRT sessions , one revision workshop , twice-daily PMRT home practice s , and a biweekly telephone follow-up call . The attention placebo included a regular telephone call at a schedule similar to that made by the interventionist of the PMRT program with the intervention group . Main outcome measures , including psychologic distress , dyspnea , and fatigue , were taken at baseline , the 8th week , and the 14th week . RESULTS A medium effect on psychologic distress in favor of the PMRT program was detected . Patients practicing PMRT however only demonstrated a nonsignificant trend of greater improvement in symptom status . CONCLUSION Progressive muscle relaxation training seems to be useful as an adjunctive nonpharmacologic treatment modality in the management of heart failure Background Mental stress has been linked to increased morbidity and mortality in coronary artery disease and to atherosclerosis progression . Experimental studies have suggested that damage to the endothelium may be an important mechanism . Methods and Results Endothelial function was studied in 10 healthy men ( aged 50.4±9.6 years ) and in 8 non – insulin-dependent diabetic men ( aged 52.0±7.2 years ) . Brachial artery flow-mediated dilation ( FMD , endothelium dependent ) and response to 50 & mgr;g of sublingual glyceryl trinitrate ( GTN , endothelium independent ) were measured noninvasively by use of high-resolution ultrasound before and after ( 30 , 90 , and 240 minutes ) a st and ardized mental stress test . The same protocol without mental stress was repeated on a separate occasion in the healthy men . In healthy subjects , FMD ( 5.0±2.1 % ) was significantly ( P < 0.01 ) reduced at 30 and 90 minutes after mental stress ( 2.8±2.3 % and 2.3±2.4 % , respectively ) and returned toward normal after 4 hours ( 4.1±2.0 % ) . Mental stress had no effect on the response to GTN . In the repeated studies without mental stress , FMD did not change . The diabetic subjects had lower FMD than did the control subjects ( 3.0±1.5 % versus 5.0±2.1 % , respectively;P = 0.02 ) but showed no changes in FMD ( 2.7±1.1 % after 30 minutes , 2.8±1.9 % after 90 minutes , and 3.1±2.3 % after 240 minutes ) or GTN responses after mental stress . Conclusions These findings suggest that brief episodes of mental stress , similar to those encountered in everyday life , may cause transient ( up to 4 hours ) endothelial dysfunction in healthy young individuals . This might represent a mechanistic link between mental stress and atherogenesis Background —Blacks have disproportionately high rates of
Output:
| Conclusions Mind – body practice s have encouraging results for patients with cardiac disease . |
MS213726 | ***TASK*** the task is to summarize an input biomedical literature in six sentences
***INPUT*** the input is a biomedical literature
***OUTPUT*** the output is the summary of an input biomedical literature in six sentences
***DOCUMENTATION***
***EXAMPLES***
Input: Although reports of decreased plasma taurine in trauma , sepsis and critical illness are available , very little is known about the relationships among changes in plasma taurine , other amino acid levels and metabolic variables . We analyzed a large series of plasma amino acid profiles obtained in trauma patients with sepsis who were undergoing total parenteral nutrition . The correlations between plasma taurine , other amino acid levels , parenteral substrate doses and metabolic and cardiorespiratory variables were assessed by regression analysis . Post-traumatic hypotaurinemia was followed by partial recovery toward less abnormal values when sepsis developed . Levels of taurine were directly and significantly related to levels of glutamate , aspartate , beta-alanine and phosphoethanolamine ( and unrelated to other amino acids ) . Levels of these amino acids increased simultaneously with increasing doses of leucine , isoleucine and valine in total parenteral nutrition . Decreasing taurine was associated with increasing lactate , arteriovenous O(2 ) concentration difference and respiratory index , and with decreasing cholesterol and cardiac index . These results characterize the relationships between plasma taurine and other amino acid levels in sepsis , provide evidence of amino acid interactions that may support taurine availability and show more severe decreases in plasma taurine with the worsening of metabolic and cardiorespiratory patterns Objective : l-arginine supplementation in sepsis is controversial . Septic shock has been alternatively viewed as an l-arginine-deficient state or as a syndrome caused by excess nitric oxide , an end-product of l-arginine metabolism . Design : R and omized , placebo-controlled , and double-blinded ( investigators , veterinarians , and pharmacists ) . Setting : Laboratory . Subjects : Purpose -bred , 1- to 2-yr-old , 10- to 12-kg beagles . Interventions : The effects of parenteral l-arginine alone or in combination with N-acetylcysteine were compared with vehicle alone in a well-characterized canine model of Escherichia coli peritonitis . Two doses were studied that delivered approximately 1.5-fold ( 10 mg·kg−1·hr−1 ) and 15-fold ( 100 mg·kg−1·hr−1 ) the l-arginine dose typically administered with st and ard total parenteral nutrition . Animals in the low- and high-dose l-arginine arms were further r and omized to receive vehicle alone or N-acetylcysteine ( 20 mg·kg−1·hr−1 ) as an antioxidant to prevent peroxynitrite formation . Measurements and Main Results : The main measurements were hemodynamics , plasma arginine and ornithine , serum nitrate/nitrite , laboratory studies for organ injury , and survival . Both doses of l-arginine similarly increased mortality ( p = .02 ) , and worsened shock ( p = .001 for reduced mean arterial pressure ) . These effects were associated with significant increases in plasma arginine ( p = .0013 ) and ornithine ( p = .0021 ) . In addition , serum nitrate/nitrite ( p = .02 ) , liver enzymes ( p = .08 ) , and blood urea nitrogen/creatinine ratios ( p = .001 ) rose , whereas arterial pH ( p = .001 ) and bicarbonate levels ( p = .001 ) fell . N-acetylcysteine did not significantly decrease any of the harmful effects of l-arginine . Thus , parenteral l-arginine monotherapy was markedly harmful in animals with septic shock . Conclusions : These findings suggest that supplemental parenteral l-arginine , at doses above st and ard dietary practice s , should be avoided in critically ill patients with septic shock Asymmetric dimethylarginine ( ADMA ) is an endogenous inhibitor of endothelial nitric oxide ( NO ) synthase . Its concentration is elevated in patients with end-stage renal disease ( ESRD ) , in part because it is excreted via the kidneys . In this study , the plasma concentrations of ADMA , symmetric dimethylarginine , and L-arginine were determined in relation to plasma nitrate levels ( as an index of NO formation ) for a group of 80 patients with ESRD . The effects of two treatment methods , i.e. , hemodialysis ( HD ) and peritoneal dialysis ( PD ) , and the role of the presence of atherosclerotic disease were evaluated . Forty-three patients receiving HD and 37 patients receiving PD were compared with healthy control subjects . Plasma L-arginine and dimethylarginine levels were determined by HPLC , using precolumn derivatization with o-phthaldialdehyde . Plasma nitrate levels were determined by gas chromatography-mass spectrometry . Predialysis ADMA concentrations in HD-treated patients were approximately sixfold higher than those in the control group ( 6.0+/-0.5 versus 1.0+/-0.1 micromol/L ; P < 0.05 ) . Plasma nitrate concentrations were significantly lower in HD-treated patients , which suggests that ADMA may inhibit NO synthase . In contrast , plasma ADMA levels and nitrate concentrations in PD-treated patients were similar to those in control subjects . Plasma L-arginine concentrations were not significantly decreased in patients with ESRD . ADMA concentrations were significantly decreased 5 h after HD , compared with baseline values . ADMA levels were significantly higher in HD-treated patients with manifest atherosclerotic disease than in HD-treated patients without atherosclerotic disease ( 7.31+/-0.70 versus 3.95+/-0.52 micromol/L ; P < 0.05 ) . This study confirms that ADMA is accumulated in ESRD . PD-treated patients exhibit significantly lower ADMA levels than do HD-treated patients . Accumulation of ADMA may be a risk factor for the development of endothelial dysfunction and cardiovascular disease in patients with ESRD Objective To investigate the role of nitric oxide in the regulation of vascular tone in patients with the sepsis syndrome . Design Prospect i ve , intervention study . Setting Tertiary care hospital . Patients Fifteen patients admitted to our medical intensive care unit with the diagnosis of sepsis syndrome by defined criteria . Interventions Eight patients received Nω-nitro-L-arginine was followed by hypertension ( mean blood pressure increased from 89 ± 8 to a maximum of 140 ± 12 mm Hg ) accompanied by a decrease in cardiac index ( from 3.51 ± 0.39 to a minimum of 2.65 ± 0.21 L/min/m2 ) and an increase in right atrial and pulmonary artery occlusion pressure . Systemic vascular resistance index increased from 1871.1 ± 302.3 to 3825.6 ± 244.4 dyne·sec/cm5·m2 , and pulmonary vascular resistance increased from 533.2 ± 125.8 to 816.0 ± 117.3 dyne·sec/cm5·m2 . These changes induced by Nω-nitro-L-arginine were reversed by the administration of L-arginine . The administration of L-arginine to another group of patients caused transient hypotension ( from 103 ± 6 to 81 ± 10 mm Hg ) and an increase in cardic index ( from 3.57 ± 0.15 to 4.74 ± 0.54 L/min/m2 ) . Both systemic and pulmonary vascular resistance indices decreased ( from 1987.6 ± 163.9 to 1251.4 ± 231.5 dyne·sec/cm5·m2 , and from 486.1 ± 65.2 to 380.5 ± 70.3 dyne·sec/cm5·m2 ) . Parallel to the increase in oxygen transport due to the increase in cardiac output , oxygen consumption index increased significantly 1 min after L-arginine ( from 127.0 ± 19.0 to 182.5 ± 37.3 mL/min/m2 ) . All mentioned changes were statistically significant ( p<.05 ) . Conclusions A continuous basal release of nitric oxide plays a role in the regulation of systemic and pulmonary vascular tone in patients with sepsis syndrome . L-arginine has systemic and pulmonary vasodilatory actions . ( Crit Care Med 1993 ; 21:1287–1295 Vascular risk factors increase the risk of developing Alzheimer 's disease . Increased concentrations of circulating homocysteine are associated with an increased risk of both vascular disease and Alzheimer 's disease . Asymmetric dimethylarginine ( ADMA ) is an endogenous inhibitor of nitric oxide synthase . There is an increase in the concentration of ADMA in the circulation in vascular disease . We measured the concentrations of homocysteine , ADMA and nitric oxide ( as nitrate and nitrite ) in the plasma of 25 patients with Alzheimer 's disease and 25 control subjects . There was a highly significant increase in the plasma concentration of homocysteine ( P<0.001 ) and ADMA ( P<0.0001 ) and a highly significant decrease in the plasma concentration of nitric oxide ( P<0.0001 ) among the Alzheimer 's patients . In the combined patient and control groups a highly significant positive correlation was found between the plasma concentrations of homocysteine and ADMA ( r=0.782 , P<0.0001 ) . In addition , significant negative correlations were detected between the plasma concentration of nitric oxide and the plasma concentration of homocysteine ( r=-0.592 , P<0.0001 ) and ADMA ( r=-0.789 , P<0.0001 ) . These significant correlations were found to persist , even when they were restricted to the Alzheimer 's patients . The inhibition of endothelial nitric oxide synthesis by ADMA impairs cerebral blood flow , which may contribute to the development of Alzheimer 's disease . Endothelial dysfunction is also associated with atherosclerosis and stroke , which are important risk factors for Alzheimer 's disease . Inflammation plays an important role in Alzheimer 's disease and the inhibition of endothelial nitric oxide by ADMA may increase the concentration of inflammatory mediators in the brain . The inhibition of neuronal nitric oxide synthesis by ADMA may cause cognitive dysfunction in Alzheimer 's disease Sepsis has been associated with specific plasma amino acid patterns . Sixty-five patients were prospect ively investigated as to whether these patterns are indeed sepsis specific , or specific for metabolic stress without concomitant sepsis , or associated with the presence of organ failure . Virtually all aminoacid levels were decreased by 10–30 % ( p < 0.05 ) , whereas cystine and phenyl-alanine were significantly elevated . These changes were more pronounced in severe sepsis . Organ failure was not associated with significantly altered amino acid profiles . No differences were found between sepsis and stress without signs of sepsis . In addition , imminent death was not associated with aberrant amino acid profiles . We conclude that sepsis and metabolic stress are associated with changes in plasma amino acid profiles , but that such changes are aspeciflc and therefore poor indicators of disease severity Acute inflammation impairs vascular function . Based on the association between endothelial dysfunction and plasma concentrations of L-arginine and the endogenous nitric oxide synthase inhibitor ADMA ( asymmetrical dimethylarginine ) , we hypothesized that the ratio between L-arginine and ADMA could be affected by experimental inflammation . Plasma concentrations of L-arginine , ADMA and SDMA ( symmetrical dimethylarginine ) were studied at baseline and 3.5 h after intravenous administration of Escherichia coli endotoxin [ LPS ( lipopolysaccharide ) , 20 units/kg of body mass ; n = 8 ] or placebo ( n = 9 ) in healthy males . L-Arginine and dimethylarginines were quantified after solid-phase extraction by reversed-phase HPLC . Body temperature , heart rate and leucocyte count increased after LPS administration ( P < 0.01 for all ) . LPS administration decreased plasma concentrations of L-arginine from 66 micromol/l [ 95 % CI ( confidence interval ) : 56 , 88 ] at baseline to 48 micromol/l ( CI : 40 , 60 ) after 3.5 h ( P < 0.02 ) , but did not affect ADMA and SDMA concentrations . Consequently , the L-arginine/ADMA ratio declined significantly from a median of 159 ( CI : 137 , 193 ) to 135 ( CI : 103 , 146 ) ; a decrease of 25 ( CI : -68 , -13 ; P < 0.02 ) . L-Arginine , ADMA , SDMA and the L-arginine/ADMA ratio remained constant over time in controls . Acute inflammation reduces the L-arginine/ADMA ratio which could contribute to impaired vascular function Objective To determine the effect of trauma on arginase , an arginine-metabolizing enzyme , in cells of the immune system in humans . Summary Background Data Arginase , classically considered an enzyme exclusive to the liver , is now known to exist in cells of the immune system . Arginase expression is induced in these cells by cytokines interleukin ( IL ) 4 , IL-10 , and transforming growth factor
Output:
| Plasma concentrations of plasma L-arginine are substantially decreased in patients with sepsis in the absence of trauma or surgery . |
MS213727 | ***TASK*** the task is to summarize an input biomedical literature in six sentences
***INPUT*** the input is a biomedical literature
***OUTPUT*** the output is the summary of an input biomedical literature in six sentences
***DOCUMENTATION***
***EXAMPLES***
Input: OBJECTIVES This was a r and omized controlled pilot trial to evaluate the effectiveness of cupping therapy for neck pain in video display terminal ( VDT ) workers . METHODS Forty VDT workers with moderate to severe neck pain were recruited from May , 2011 to February , 2012 . Participants were r and omly allocated into one of the two interventions : 6 sessions of wet and dry cupping or heating pad application . The participants were offered an exercise program to perform during the participation period . A 0 to 100 numeric rating scale ( NRS ) for neck pain , measure yourself medical outcome profile 2 score ( MYMOP2 score ) , cervical spine range of motion ( C-spine ROM ) , neck disability index ( NDI ) , the EuroQol health index ( EQ-5D ) , short form stress response inventory ( SRI-SF ) and fatigue severity scale ( FSS ) were assessed at several points during a 7-week period . RESULTS Compared with a heating pad , cupping was more effective in improving pain ( adjusted NRS difference : -1.29 [ 95 % CI -1.61 , -0.97 ] at 3 weeks ( p=0.025 ) and -1.16 [ -1.48 , -0.84 ] at 7 weeks ( p=0.005 ) ) , neck function ( adjusted NDI difference : -0.79 [ -1.11 , -0.47 ] at 3 ( p=0.0039 ) and 7 weeks ( p<0.0001 ) ) and discomfort ( adjusted MYMOP2 difference score : -0.72 [ -1.04 to -0.40 ] at 3 weeks and -0.92 [ -1.24 , -0.60 ] at 7 weeks ) . Significant improvement in EQ-5D was observed at 7 weeks ( 1.0 [ 0.88 , 1.0 ] with cupping and 0.91 [ 0.86 , 0.91 ] with heating pad treatment , p=0.0054 ) . Four participants reported mild adverse events of cupping . CONCLUSION Two weeks of cupping therapy and an exercise program may be effective in reducing pain and improving neck function in VDT workers Introduction . Cupping has been used since antiquity in the treatment of pain conditions . In this pilot study , we investigated the effect of traditional cupping therapy on chronic nonspecific neck pain ( CNP ) and mechanical sensory thresholds . Methods . Fifty CNP patients were r and omly assigned to treatment ( TG , n = 25 ) or waiting list control group ( WL , n = 25 ) . TG received a single cupping treatment . Pain at rest ( PR ) , pain related to movement ( PM ) , quality of life ( SF-36 ) , Neck Disability Index ( NDI ) , mechanical detection ( MDT ) , vibration detection ( MDT ) , and pressure pain thresholds ( PPT ) were measured before and three days after a single cupping treatment . Patients also kept a pain and medication diary ( PaDi , MeDi ) during the study . Results . Baseline characteristics were similar in the two groups . After cupping TG reported significantly less pain ( PR : −17.9 mm VAS , 95%CI −29.2 to −6.6 ; PM : −19.7 , 95%CI −32.2 to −7.2 ; PaDi : −1.5 points on NRS , 95%CI −2.5 to −0.4 ; all P < 0.05 ) and higher quality of life than WL ( SF-36 , Physical Functioning : 7.5 , 95%CI 1.4 to 13.5 ; Bodily Pain : 14.9 , 95%CI 4.4 to 25.4 ; Physical Component Score : 5.0 , 95%CI 1.4 to 8.5 ; all P < 0.05 ) . No significant effect was found for NDI , MDT , or VDT , but TG showed significantly higher PPT at pain- areas than WL ( in lg(kPa ) ; pain-maximum : 0.088 , 95%CI 0.029 to 0.148 , pain-adjacent : 0.118 , 95%CI 0.038 to 0.199 ; both P < 0.01 ) . Conclusion . A single application of traditional cupping might be an effective treatment for improving pain , quality of life , and hyperalgesia in CNP Background : Chronic neck pain is a major public health burden with only limited evidence for the effectiveness of complementary therapies . This study aim ed to test the efficacy of cupping massage in patients with neck pain . Patients and Methods : Patients with chronic non-specific neck pain were r and omly assigned to cupping massage or a wait list control . The intervention group received 5 cupping massages on a twice-weekly basis while the control patients continued their usual treatments . The primary outcome measure was neck pain intensity ( 0 - 100 mm visual analogue scale ( VAS ) ) after 3 weeks . Secondary outcomes included pain on movement , functional disability , health-related quality of life , mechanical detection and pain thresholds and adverse events . Results : 50 patients ( 52.6 ± 10.3 years , 92 % female ) were r and omised to either cupping massage or a wait list ( N = 25 each ) . Patients in the cupping group reported significantly less neck pain post intervention ( difference per protocol -14.3 mm , 95 % confidence interval ( CI ) -27.7 to -1.0 , p = 0.037 ; difference intention-to-treat -10.8 mm , 95 % CI -21.5 to -0.1 , p = 0.047 ) . Significant group differences in favour of the intervention were further found for pain on movement ( p = 0.019 ) and functional disability ( p < 0.001 ) , the quality -of-life subscales pain ( p = 0.002 ) and mental health ( p = 0.003 ) and the mental component summary ( p = 0.036 ) . Changes were also found for pressure pain sensitivity at the site of maximal pain ( p = 0.022 ) . Five adverse events were reported . Conclusions : Cupping massage appears to be effective in reducing pain and increasing function and quality of life in patients with chronic non-specific neck pain . More rigorous studies are needed to confirm and extend these results Chronic neck pain is a major public health problem with very few evidence -based complementary treatment options . This study aim ed to test the efficacy of 12 weeks of a partner-delivered home-based cupping massage , compared to the same period of progressive muscle relaxation in patients with chronic non-specific neck pain . Patients were r and omly assigned to self-directed cupping massage or progressive muscle relaxation . They were trained and asked to undertake the assigned treatment twice weekly for 12 weeks . Primary outcome measure was the current neck pain intensity ( 0–100 mm visual analog scale ; VAS ) after 12 weeks . Secondary outcome measures included pain on motion , affective pain perception , functional disability , psychological distress , wellbeing , health-related quality of life , pressure pain thresholds and adverse events . Sixty one patients ( 54.1±12.7 years ; 73.8%female ) were r and omized to cupping massage ( n = 30 ) or progressive muscle relaxation ( n = 31 ) . After treatment , both groups showed significantly less pain compared to baseline however without significant group differences . Significant effects in favor of cupping massage were only found for wellbeing and pressure pain thresholds . In conclusion , cupping massage is no more effective than progressive muscle relaxation in reducing chronic non-specific neck pain . Both therapies can be easily used at home and can reduce pain to a minimal clinical ly relevant extent . Cupping massage may however be better than PMR in improving well-being and decreasing pressure pain sensitivity but more studies with larger sample s and longer follow-up periods are needed to confirm these results . Trial Registration Clinical Trials.gov OBJECTIVES To determine the efficacy of wet-cupping for treating persistent nonspecific low back pain . BACKGROUND Wet-cupping therapy is one of the oldest known medical techniques . It is still used in several contemporary societies . Very minimal empirical study has been conducted on its efficacy . DESIGN R and omized controlled trial with two parallel groups . Patients in the experimental group were offered the option of referral to the wet-cupping service ; all accepted that option . The control group received usual care . SETTING Medical clinic in Kermanshah , Iran . PARTICIPANTS In total , 98 patients aged 17 - 68 years with nonspecific low back pain ; 48 were r and omly assigned to experimental group and 50 to the control group . INTERVENTION Patients in the experimental group were prescribed a series of three staged wet-cupping treatments , placed at 3 days intervals ( i.e. , 0 , 3 , and 6 days ) . Patients in the control group received usual care from their general practitioner . MAIN OUTCOME MEASURES Three outcomes assessed at baseline and again 3 months following intervention : the McGill Present Pain Index , Oswestry Pain Disability Index , and the Medication Quantification Scale . RESULTS Wet-cupping care was associated with clinical ly significant improvement at 3-month follow-up . The experimental group who received wet-cupping care had significantly lower levels of pain intensity ( [ 95 % confidence interval ( CI ) 1.72 - 2.60 ] mean difference=2.17 , p<0.01 ) , pain-related disability ( 95 % CI=11.18 - 18.82 , means difference=14.99 , p<0.01 ) , and medication use ( 95 % CI=3.60 - 9.50 , mean difference=6.55 , p<0.01 ) than the control group . The differences in all three measures were maintained after controlling for age , gender , and duration of lower back pain in regression models ( p<0.01 ) . CONCLUSIONS Traditional wet-cupping care delivered in a primary care setting was safe and acceptable to patients with nonspecific low back pain . Wet-cupping care was significantly more effective in reducing bodily pain than usual care at 3-month follow-up Background In this preliminary trial we investigated the effects of dry cupping , an ancient method for treating pain syndromes , on patients with chronic non-specific neck pain . Sensory mechanical thresholds and the participants ' self-reported outcome measures of pain and quality of life were evaluated . Methods Fifty patients ( 50.5 ± 11.9 years ) were r and omised to a treatment group ( TG ) or a waiting-list control group ( WL ) . Patients in the TG received a series of 5 cupping treatments over a period of 2 weeks ; the control group did not . Self-reported outcome measures before and after the cupping series included the following : Pain at rest ( PR ) and maximal pain related to movement ( PM ) on a 100-mm visual analogue scale ( VAS ) , pain diary ( PD ) data on a 0 - 10 numeric rating scale ( NRS ) , Neck Disability Index ( NDI ) , and health-related quality of life ( SF-36 ) . In addition , the mechanical-detection thresholds ( MDT ) , vibration-detection thresholds ( VDT ) , and pressure-pain thresholds ( PPT ) were determined at pain-related and control areas . Results Patients of the TG had significantly less pain after cupping therapy than patients of the WL group ( PR : Δ-22.5 mm , p = 0.00002 ; PM : Δ-17.8 mm , p = 0.01 ) . Pain diaries ( PD ) revealed that neck pain decreased gradually in the TG patients and that pain reported by the two groups differed significantly after the fifth cupping session ( Δ-1.1 , p = 0.001 ) . There were also significant differences in the SF-36 subscales for bodily pain ( Δ13.8 , p = 0.006 ) and vitality ( Δ10.2 , p = 0.006 ) . Group differences in PPT were significant at pain-related and control areas ( all p < 0.05 ) , but were not significant for MDT or VDT . Conclusions A series of five dry cupping treatments appeared to be effective in relieving chronic non-specific neck pain . Not only subjective measures improved , but also mechanical pain sensitivity differed significantly between the two groups , suggesting that cupping has an influence on functional pain processing . Trial registration The trial was registered at clinical trials.gov ( NCT01289964 ) The research aim ed to investigate the effectiveness of cupping therapy ( CT ) in changes on skin surface temperature ( SST ) for relieving chronic neck and shoulder pain ( NSP ) among community residents . A single-blind experimental design constituted of sixty subjects with self-perceived NSP . The subjects were r and omly allocated to two groups . The cupping group received CT at SI 15 , GB 21 , and LI 15 acupuncture points , and the control group received no intervention . Pain was assessed using the SST , visual analog scale ( VAS ) , and blood pressure ( BP ) . The main results were SST of GB 21 acupuncture point raised from 30.6 ° C to 32.7 ° C and from 30.7 ° C to 30.6 ° C in the control group . Neck pain intensity ( NPI ) severity scores were reduced from 9.7 to 3.6 in the cupping group and from 9.7 to 9.5 in the control group . The SST and NPI differences between the groups were statistically significant ( P < 0.001 ) . One treatment of CT is shown to increase SST . In conjunction with the physiological effect the subjective experience of NSP is reduced in intensity . Further studies are required to improve the underst and ing and potential long-term effects of CT Background : Pneumatic pulsation therapy may combine the effects of
Output:
| Cupping was found to reduce neck pain in patients compared with no intervention or active control groups , or as an add-on treatment . |
MS213728 | ***TASK*** the task is to summarize an input biomedical literature in six sentences
***INPUT*** the input is a biomedical literature
***OUTPUT*** the output is the summary of an input biomedical literature in six sentences
***DOCUMENTATION***
***EXAMPLES***
Input: STUDY OBJECTIVE To compare operative outcomes and postoperative pain of laparoscopic hysterectomy ( LH ) versus minilaparoscopic hysterectomy ( MLH ) . DESIGN R and omized controlled trial ( Canadian Task Force Classification I ) . SETTING Tertiary care center . PATIENTS Seventy-six women scheduled to undergo a hysterectomy for a supposed benign gynecologic condition . INTERVENTIONS Participants were r and omly assigned to LH ( n = 38 ) or MLH ( n = 38 ) . MLH was performed with use of 3-mm ports . Both patients and assessors of the postoperative outcomes were blinded to the size of port used , and patients ' wounds were concealed by st and ard-size nontransparent dressings . MEASUREMENTS Primary outcome was postoperative pain ( both rest and incident on coughing and abdominal pain , as well as shoulder pain ) by use of a 100-mm visual analogue scale . MAIN RESULTS The two groups were similar in terms of operative outcomes . No intraoperative conversion from MLH to both LH and open surgery occurred . No significant difference in pain scores at 1 , 3 , 8 , and 24 hours after surgery between groups was found . Rescue analgesic requirement was similar in the MLH and LH groups ( 21.1 % vs 13.2 % , p = .54 ) . CONCLUSIONS Ports can safely be reduced in size without a negative impact on the surgeon 's ability to perform LH . MLH appears to have no advantage over LH in terms of postoperative pain Objective The aim of this study was to investigate the optimum dosage of dexmedetomidine for prevention of postanesthetic shivering . Methods One-hundred thirty two ASA physical status I-II patients scheduled for elective laparoscopic total hysterectomy were enrolled in this r and omised , placebo-controlled study . Patients were r and omly allocated to receive dexmedetomidine in four groups : group S ( 0.9 % normal saline ) , group D0.5 ( dexmedetomidine 0.5 µg/kg ) , group D0.75 ( dexmedetomidine 0.75 µg/kg ) , group D1.0 ( dexmedetomidine 1.0 µg/kg ) . Time to extubation and tympanic temperature during and after operation were measured . Shivering was grade d ( 0 - 3 scale ) upon patients arrival to the PACU and every ten minutes thereafter up to forty minutes . Sedation and first rescue analgesic time at the PACU were evaluated . Results The incidence of shivering was significantly lower in group D0.75 and D1.0 than in group S ( P < 0.05 ) . There were significantly fewer patients with a shivering score of 2 or 3 in groups D0.75 and D1.0 than in group S ( P < 0.05 , P < 0.001 ) . Extubation time was shorter in group S than in groups D0.75 and D1.0 ( P < 0.05 ) . Tympanic temperature at 40 minutes postoperatively in the recovery room was higher in group S than in the other dexmedetomidine groups ( P < 0.05 ) Fewer patients required rescue analgesia in groups D0.75 and D1.0 than in group S ( P < 0.001 ) , and the time to rescue analgesia was longer in group D1.0 than in group S ( P < 0.001 ) . Modified Observer 's Assessment of Alertness/Sedation ( MOAA/S ) at arrival in the PACU was lower in all dexmedetomidine groups than in group S ( P < 0.05 ) . Conclusions Our results suggest that dexmedetomidine 0.75 or 1.0 µg/kg provides effective prophylaxis against postoperative shivering as well as an analgesic effect . Though potential for intraoperative requirement for atropine , sedation in the immediate recovery period and delayed extubation time with dexmedetomidine was noted , there were no major clinical impacts on the overall recovery from anesthesia BACKGROUND : In this r and omized , controlled , observer-blinded study , we evaluated analgesia provided by transversus abdominis plane ( TAP ) block after elective total laparoscopic hysterectomy in terms of reduced postoperative morphine consumption as the primary end point . METHODS : Fifty-two patients were r and omly divided into 2 groups : patients in group T ( TAP , n = 26 ) received an ultrasound-guided bilateral TAP block with 40 mL of 0.375 % levobupivacaine and morphine patient-controlled analgesia , whereas patients in group C ( control , n = 26 ) received morphine patient-controlled analgesia . Secondary outcomes included pain measurements ( Numeric Rating Scale from 0 to 10 ) during the first 24 hours postoperatively , times to postanesthesia care unit discharge , times to surgical ward discharge , incidence of postoperative nausea and vomiting , functional capacity measurements in terms of 2-minute walking test , and first oral solid intake . RESULTS : Demographic and anthropometric variables were similar in the 2 groups . The total dose of morphine consumed by patients during postanesthesia care unit stay was 6 ( 0–8 ) mg in group T vs 8 ( 5.5–8.5 ) mg in group C ( P = 0.154 ) . Postoperative morphine consumption during the first 24 hours was 10.55 ± 10.24 mg in group C vs 10.73 ± 13.45 mg in group T ( P = 0.950 ) . The 95 % confidence interval of the difference between means of 24-hour morphine consumption was −7.45 to + 7.09 . The 2 groups were comparable . There were no significant differences in secondary outcome variables between groups . CONCLUSIONS : TAP block did not reduce morphine consumption during the first postoperative 24 hours after elective total laparoscopic hysterectomy STUDY OBJECTIVE To compare the use of low pneumoperitoneum pressure ( LPP ; 8 mm Hg ) vs st and ard pneumoperitoneum pressure ( SPP ; 12 mm Hg ) during mini-laparoscopic hysterectomy ( MLH ) . DESIGN R and omized controlled trial ( Canadian Task Force classification I ) . SETTING Tertiary care center . PATIENTS Forty-two consecutive women scheduled to undergo MLH to treat benign uterine disease . INTERVENTIONS Women were r and omly selected to undergo MLH using LPP ( n = 20 ) or SPP ( n = 22 ) . MLH was performed via 3-mm ancillary ports . MEASUREMENTS AND MAIN RESULTS The primary outcome was to evaluate changes in abdominal and shoulder-tip pain via a 100-mm visual analog scale at 1 , 3 , and 24 hours postoperatively . All procedures were completed via mini-laparoscopy without the need to increase intra-abdominal pressure or convert to conventional laparoscopy or open surgery . Intraoperatively , 1 episode of severe bradycardia occurred in the LPP group , whereas no intraoperative complications were recorded in the SPP group ( p = .47 ) . No postoperative complications were recorded ( p > .99 ) . Abdominal pain was similar between groups at each time point . Incidence and intensity of shoulder-tip pain at 1 and 3 hours postoperatively was lower in the LPP group than in the SPP group ( p < .05 ) , whereas no between-group differences were observed at 24 hours ( p > .05 ) . Rescue analgesic requirement did not differ statistically between the LPP and SPP groups ( 20 % vs 41 % , respectively ; p = .19 ; odds ratio , 2.7 ; 95 % confidence interval , 0.69 - 11.08 ) . CONCLUSION In experienced h and s , use of LPP is safe and feasible . During performance of MLH , compared with SPP , LPP is a simple method that offers advantages of less shoulder-tip pain OBJECTIVE The objective of the study was to determine whether transversus abdominis plane ( TAP ) block reduces postoperative pain when compared with trocar site infiltration of bupivacaine in gynecological laparoscopy . STUDY DESIGN This was a prospect i ve , r and omized , double-blinded clinical trial using patients as their own controls . Women undergoing gynecologic laparoscopy using a 4-port symmetrical technique were r and omly assigned to right- or left-sided TAP block using 30 mL of 0.25 % bupivacaine with epinephrine . Two cohorts of patients were studied . Cohort 1 consisted of anesthesiologist-administered ultrasound-guided TAP block . Cohort 2 consisted of surgeon-administered laparoscopic-guided TAP block . In both cohorts , contralateral port sites were infiltrated with an equal amount of bupivacaine in divided doses . All patients received intraoperative acetaminophen and ketorolac . Postoperative abdominal pain was assessed at 1 , 2 , 4 , 6 , 8 , 12 , 18 , 24 , and 48 hours on the block and contralateral sides , before and after palpation , using the 10 point visual analog scale . A 2 point difference in the reported pain scores was considered clinical ly meaningful . RESULTS Eighty-eight patients were eligible for statistical analysis : 45 and 43 patients in cohorts 1 and 2 , respectively . In both cohorts , most patients reported equal pain on the block side and local side . In cohort 1 , there was a statistically significant difference in mean reported pain scores at 2 hours and across time favoring the ultrasound-guided block ; however , this did not reach clinical significance . There was no statistically significant difference found at all other time points or when pain scores were objective ly assessed after palpation of the incisions . When comparing laparoscopic-guided block with local infiltration , there was no statistically significant difference in reported mean pain scores at all time points or after palpation . CONCLUSION As part of this multimodal analgesic regimen , neither block method provided a significant clinical benefit compared with trocar site bupivacaine infiltration BACKGROUND : Apart from being antiemetic , glucocorticoids have an analgesic property . The optimal dose of dexamethasone in the management of pain after surgery has not been established . In this placebo-controlled , dose-finding study , we evaluated the analgesic effect of three doses of dexamethasone after laparoscopic hysterectomy . METHODS : We r and omized 129 women scheduled for laparoscopic hysterectomy to receive placebo , dexamethasone 5 mg ( D5 ) , 10 mg ( D10 ) , or 15 mg ( D15 ) IV before the induction of anesthesia . The patients were anesthetized with propofol and remifentanil in a st and ardized manner . Until the first postoperative morning , postoperative pain was managed with IV oxycodone using patient-controlled analgesia . The visual analog scale scores for pain and side effects , and the amounts of the analgesics were recorded for 3 days after surgery . RESULTS : The total dose of oxycodone ( 0–24 h after surgery ) was smaller in the D15 ( 0.34 mg/kg [ 0.11–0.87 ] ) group than in the placebo group ( 0.55 mg/kg [ 0.19–1.13 ] ) ( P = 0.003 ) . The doses of oxycodone during Hours 0–2 after surgery were smaller in the D10 ( 0.17 mg/kg [ 0.03–0.36 ] ) and D15 ( 0.17 mg/kg [ 0.03–0.35 ] ) groups than in the placebo ( 0.26 mg/kg [ 0.10–0.48 ] ) ( P = 0.001 , D10 versus placebo ; P < 0.001 , D15 versus placebo ) group . During Hours 2–24 after surgery , however , the doses of oxycodone were equal in the placebo , D5 , D10 , and D15 groups ( 0.31 mg/kg [ 0.03–0.78 ] , 0.22 mg/kg [ 0.03–0.92 ] , 0.24 mg/kg [ 0.05–0.87 ] , and 0.20 mg/kg [ 0–0.65 ] , respectively ) . The visual analog scale scores for pain at rest , in motion , or at cough did not differ in the study groups . The incidence of dizziness was lower in the D15 group than in the placebo group ( P = 0.001 ) , the D5 group ( P = 0.006 ) , and the D10 group ( P = 0.030 ) during the first 24 h after surgery . During the later course of recovery , the incidence of dizziness did not differ among the four study groups . CONCLUSIONS : IV dexamethasone 15 mg before induction of anesthesia decreases the oxycodone consumption during the first 24 h after laparoscopic hysterectomy . During first 2 h after surgery , dexamethasone 10 mg reduces the oxycodone consumption as effectively as the 15 mg dose PURPOSE The purpose of this study was to compare the effects of ondansetron combined
Output:
| Limited evidence hindered recommendations on alpha-2-agonists .
Inconsistent evidence was found in the studies investigating pregabalin and transversus abdominis plane block , and no evidence was found for intraperitoneal local anesthetics , port site infiltration , or single-port laparoscopy .
Measures to lower peritoneal insufflation pressure or humidify or heat insufflated gas seem to reduce the incidence of shoulder pain , but not abdominal pain . |
MS213729 | ***TASK*** the task is to summarize an input biomedical literature in six sentences
***INPUT*** the input is a biomedical literature
***OUTPUT*** the output is the summary of an input biomedical literature in six sentences
***DOCUMENTATION***
***EXAMPLES***
Input: OBJECTIVE For long-term treatment effects , patients with subacute back pain need to adhere to treatment recommendations beyond the prescribed exercise treatment . Adherence rates are as low as 30 % , so we developed a cognitive-behavioural training programme to enhance patients ' self-efficacy , maximise severity perceptions and reduce barrier perceptions . METHOD A 2 x 4 ( group x time ) repeated measurement design was applied . Forty-seven patients with non-specific , subacute back pain were r and omly assigned to a training group ( exercise treatment plus cognitive-behavioural training programme ) or a control group ( exercise treatment only ) . RESULTS Repeated measures ANOVA revealed significant main and interaction effects ; the training group reported enhanced self-efficacy and severity perceptions , reduced barrier perceptions , and self-reported that they exercised more often than the control group over time . However , no group differences regarding pain intensity emerged . CONCLUSION Our findings demonstrate that a short and inexpensive cognitive-behavioural training programme is an effective tool to enable back pain patients to follow treatment recommendations on a regular basis . PRACTICE IMPLICATION S The short and simple intervention can easily be conducted by personnel , other than psychologists , i.e. , physiotherapists Study Design . A r and omized controlled design superimposed on treatment as usual was used to compare the effects of a cognitive-behavior intervention aim ed at preventing chronicity with two different forms of information . Objective . To develop a coping-oriented preventive intervention applicable in primary care , and to compare its impact with educational information . Summary of Background Data . Preventing long-term disability result ing from spinal pain has proved difficult . The information provided by health care professions and early interventions aim ed at preventing long-term disability may be important , but little scientific evidence exists concerning their use . Methods . A protocol for a six-session cognitive-behavior group intervention was developed on the basis of earlier research . The main focus was to prevent long-term disability by changing patients ’ behaviors and beliefs so they can cope better with their problems . Comparison groups received either a pamphlet shown earlier to have an effect , or a more extensive information package consisting of six installments . All the groups continued to receive treatment as usual in primary care . There were 243 patients with acute or subacute spinal pain who perceived that they were at risk for developing a chronic problem . These patients were r and omized to the cognitive-behavioral intervention or one of the two information groups . Because the aim was to prevent long-term disability , the key outcome variables at the 1-year follow-up assessment were sick absenteeism and health care use . Other variables were pain , function , fear-avoidance beliefs , and cognitions . Results . The comparison groups reported benefits . However , the risk for a long-term sick absence developing was lowered ninefold for the cognitive-behavior intervention group as compared with the risk for the information groups ( relative risk , 9.3 ) . Participants in the cognitive-behavior group also reported a significant decrease in perceived risk . In addition , the cognitive-behavior group demonstrated a significant decrease in physician and physical therapy use as compared with two groups receiving information , in which such use increased . All three groups tended to improve on the variables of pain , fear-avoidance , and cognitions . Conclusions . This study demonstrates that a cognitive-behavior group intervention can lower the risk of a long-term disability developing . These findings underscore the significance of early interventions that specifically aim to prevent chronic problems . This approach might be applied to primary care setting Background To describe the design of a population based r and omized controlled trial ( RCT ) , including a cost-effectiveness analysis , comparing participative ergonomics interventions between 2–8 weeks of sick leave and Grade d Activity after 8 weeks of sick leave with usual care , in occupational back pain management . Methods Design : An RCT and cost-effectiveness evaluation in employees sick-listed for a period of 2 to 6 weeks due to low back pain . Interventions used are 1 . Communication between general practitioner and occupational physician plus Participative Ergonomics protocol performed by an ergonomist . 2 . Grade d Activity based on cognitive behavioural principles by a physiotherapist . 3 . Usual care , provided by an occupational physician according to the Dutch guidelines for the occupational health management of workers with low back pain . The primary outcome measure is return to work . Secondary outcome measures are pain intensity , functional status and general improvement . Intermediate variables are kinesiophobia and pain coping . The cost-effectiveness analysis includes the direct and indirect costs due to low back pain . The outcome measures are assessed before r and omization ( after 2–6 weeks on sick leave ) and 12 weeks , 26 weeks and 52 weeks after first day of sick leave . Discussion The combination of these interventions has been subject of earlier research in Canada . The results of the current RCT will : 1 . crossvali date the Canadian findings in an different sociocultural environment ; 2 . add to the cost-effectiveness on treatment options for workers in the sub acute phase of low back pain . Results might lead to alterations of existing (inter)national guidelines Abstract Objective : To evaluate effectiveness of an exercise programme in a community setting for patients with low back pain to encourage a return to normal activities . Design : R and omised controlled trial of progressive exercise programme compared with usual primary care management . Patients ' preferences for type of management were elicited independently of r and omisation . Participants : 187 patients aged 18 - 60 years with mechanical low back pain of 4 weeks to 6 months ' duration . Interventions : Exercise classes led by a physiotherapist that included strengthening exercises for all main muscle groups , stretching exercises , relaxation session , and brief education on back care . A cognitive-behavioural approach was used . Main outcome measures : Assessment s of debilitating effects of back pain before and after intervention and at 6 months and 1 year later . Measures included Rol and disability question naire , Aberdeen back pain scale , pain diaries , and use of healthcare services . Results : At 6 weeks after r and omisation , the intervention group improved marginally more than the control group on the disability question naire and reported less distressing pain . At 6 months and 1 year , the intervention group showed significantly greater improvement in the disability question naire score ( mean difference in changes 1.35 , 95 % confidence interval 0.13 to 2.57 ) . At 1 year , the intervention group also showed significantly greater improvement in the Aberdeen back pain scale ( 4.44 , 1.01 to 7.87 ) and reported only 378 days off work compared with 607 in the control group . The intervention group used fewer healthcare re sources . Outcome was not influenced by patients ' preferences . Conclusions : The exercise class was more clinical ly effective than traditional general practitioner management , regardless of patient preference , and was cost effective . Key messages Patients with back pain need to return to normal activities as soon as possible but are often afraid that movement or activity may be harmful An exercise programme led by a physiotherapist in the community and based on cognitive-behavioural principles helped patients to cope better with their pain and function better even one year later Patients ' preferences for type of management did not affect outcome Patients in the intervention group tended to use fewer healthcare re sources and took fewer days off work This type of exercise programme should be more widely Study Design . R and omized controlled trial . Objectives . To investigate the effectiveness and costs of a mini-intervention , provided in addition to the usual care , and the incremental effect of a work site visit for patients with subacute disabling low back pain . Summary of Background Data . There is lack of data on cost-effectiveness of brief interventions for patients with prolonged low back pain . Methods . A total of 164 patients with subacute low back pain were r and omized to a mini-intervention group ( A ) , a work site visit group ( B ) , or a usual care group ( C ) . Groups A ( n = 56 ) and B ( n = 51 ) underwent one assessment by a physician plus a physiotherapist . Group B received a work site visit in addition . Group C served as controls ( n = 57 ) and was treated in municipal primary health care . All patients received a leaflet on back pain . Pain , disability , specific and generic health-related quality of life , satisfaction with care , days on sick leave , and use and costs of health care consumption were measured at 3- , 6- , and 12-month follow-ups . Results . During follow-up , fewer subjects had daily pain in Groups A and B than in Group C ( Group A vs. Group C , P = 0.002 ; Group B vs. Group C , P = 0.030 ) . In Group A , pain was less bothersome ( Group A vs. Group C , P = 0.032 ) and interfered less with daily life ( Group A vs. Group C , P = 0.040 ) than among controls . Average days on sick leave were 19 in Group A , 28 in Group B , and 41 in Group C ( Group A vs. Group C , P = 0.019 ) . Treatment satisfaction was better in the intervention groups than among the controls , and costs were lowest in the mini-intervention group . Conclusions . Mini-intervention reduced daily back pain symptoms and sickness absence , improved adaptation to pain and patient satisfaction among patients with subacute low back pain , without increasing health care costs . A work site visit did not increase effectiveness Stopping r and omized trials early because of an apparent benefit is a growing phenomenon . A recent systematic review found that the number of r and omized trials stopped early for benefit has more than doubled since 1990 ( 1 ) . To protect and promote the interests of trial participants , investigators may feel ethically obligated to stop a trial early because of the unexpected harm or apparent benefit of a study treatment . If a study treatment 's benefit far outweighs its adverse effects , is it not unethical to continue enrolling patients in a trial in which , as is typically the case , patients have a 50 % chance of receiving a placebo or an inferior treatment ? In this article , we argue that stopping a r and omized trial early for apparent benefit is often unethical and can be justified only under restricted circumstances . If the scientific community were to accept our arguments , then the approach that investigators , institutional review boards , and data monitoring committees take to the practice of stopping trials early for apparent benefit would substantially change . Ethical Considerations Emanuel and colleagues ( 2 ) describe a framework of 7 requirements for determining whether clinical research is ethical . We use this framework to identify and assess the ethical issues raised by stopping trials early because of apparent benefit ( Table ) . Table . Ethical Violations Result ing from Stopping a Trial Early for Apparent Benefit Scientific Validity The purpose of a trial of alternative interventions is to generate an estimate of treatment effect that closely approximates the true effect and is not misleading . This requires application of scientific procedures that yield valid and reliable data and thus minimize both systematic and r and om error . A systematic review of r and omized trials stopped early for apparent benefit ( 1 ) found that many of the trials yielded implausibly large treatment effects ; the median relative risk was 0.53 . Apparent large treatment effects occurred much more frequently when trials accrued only a small number of events . The odds of a treatment effect larger than the overall median relative risk of 0.53 was 28 times greater ( 95 % CI , 11 to 73 ) among trials in which fewer than the median of 66 events accrued than among trials in which more events accrued . These results , which are consistent with predictions from statistical theory ( 3 ) , suggest that stopping trials early for apparent benefit will systematic ally overestimate treatment effects . The scientific validity of trials that are stopped early is further compromised when trials yield inconclusive data about outcomes that did not influence trial truncation but are nonetheless important to patients , such as disease-free survival , symptom control , quality of life , and adverse effects of treatment . For example , a trial of vitamin E supplementation in premature newborns that was stopped early because of an apparent reduction in intracranial hemorrhage ( 4 ) failed to detect the increase in sepsis associated with vitamin E supplementation that subsequent trials identified ( 5 ) . Social or Scientific Value and Favorable RiskBenefit Ratio It is underst and able that investigators focus their ethical obligations on research participants . Such focus , however , risks neglecting obligations to society . The tendency of truncated trials to overestimate the effect of a treatment on the end point that result ed in trial truncation and to yield insufficient data about other important outcomes endangers the wider community to whom the results will be applied ( 6 ) . On review ing the results of a truncated trial , astute clinicians might appropriately conclude that the benefits of the intervention remain uncertain . However , less skeptical clinicians might assume that the results are true and inappropriately expose patients to the intervention and its unknown harms . Consider the results of a trial in which the investigators continued to enroll patients even though prespecified criteria for early stopping were met . Two interim analyses of a r and omized trial of 5 versus 4 courses of chemotherapy in patients with acute myeloid leukemia ( 7 ) found apparent large benefits to the 5-course regimen ( relative odds reduction of 53 % [ CI , 23 % to 71 % ; P= 0.003 ] in the first analysis and 45 % [ CI , 20 % to 62 % ; P= 0.0002 ] in the second analysis ) . Finding these results too good to be true , the data monitoring committee recommended continuing the trial , which ultimately showed a trend in favor of the 4-course regimen . Had the investigators terminated the trial in accordance with their stopping rule , subsequent patients with leukemia may have experienced the toxicity of an additional course of chemotherapy without benefit . Harm result ing from the misleading findings of truncated trials can be compounded if the findings influence the recommendations of clinical practice guideline panels . Investigators conducting a trial that involved patients undergoing vascular surgery ( 8) stopped the trial early when 2 of 53 patients r and omly assigned to receive the -blocker bisoprolol and 18 of 59 control patients had major cardiovascular events ( relative risk reduction , 90 % [ CI , 59 % to 98 % ] ) . These results contributed to recommendations by the American Heart
Output:
| On average , people with subacute LBP who receive MBR will do better than if they receive usual care , but it is not clear whether they do better than people who receive some other type of treatment . |
MS213730 | ***TASK*** the task is to summarize an input biomedical literature in six sentences
***INPUT*** the input is a biomedical literature
***OUTPUT*** the output is the summary of an input biomedical literature in six sentences
***DOCUMENTATION***
***EXAMPLES***
Input: BACKGROUND The role of rituximab in combination with different CHOP ( cyclophosphamide , doxorubicin , vincristine , and prednisone)-like chemotherapy regimens in young patients with good-prognosis diffuse large-B-cell lymphoma remains to be defined . We aim ed to compare CHOP-like chemotherapy and rituximab with CHOP-like chemotherapy alone in these patients . METHODS 824 patients who were from 18 countries ; aged 18 - 60 years ; and who had no risk factors or one risk factor according to age-adjusted International Prognostic Index ( IPI ) , stage II-IV disease , or stage I disease with bulk were enrolled . These patients were r and omly assigned to six cycles of CHOP-like chemotherapy and rituximab ( n=413 ) or to six cycles of CHOP-like chemotherapy alone ( n=411 ) . Bulky and extranodal sites received additional radiotherapy . The primary endpoint was event-free survival ; secondary endpoints were response , progression under therapy , progression-free survival , overall survival , and frequency of toxic effects . Analyses were done by intention to treat and per protocol . This trial is registered at http://www . clinical trials.gov , NCT 00064116 . FINDINGS After a median follow-up of 34 months ( range 0.03 - 61 ) , patients assigned chemotherapy and rituximab had increased 3-year event-free survival compared with those assigned chemotherapy alone ( 79 % [ 95 % CI 75 - 83 ] vs 59 % [ 54 - 64 ] ; difference between groups 20 % [ 13 - 27 ] , log-rank p<0.0001 ) , and had increased 3-year overall survival ( 93 % [ 90 - 95 ] vs 84 % [ 80 - 88 ] ; difference between groups 9 % [ 3 - 13 ] , log-rank p=0.0001 ) . Event-free survival was affected by treatment group , presence of bulky disease , and age-adjusted IPI : after chemotherapy and rituximab , a favourable subgroup ( ie , IPI=0 , no bulk ) could be defined from a less-favourable subgroup ( ie , IPI=1 or bulk , or both ) . Groups did not differ in the frequency of adverse events . INTERPRETATION Rituximab added to six cycles of CHOP is an effective treatment for young patients with good-prognosis diffuse large-B-cell lymphoma . The definition of two prognostic subgroups allows for a more refined therapeutic approach for these patients PURPOSE To compare low-dose ( 30 Gy ) radiotherapy ( RT ) with observation ( OBS ) in limited-stage aggressive lymphoma patients achieving complete remission ( CR ) after chemotherapy , and to measure conversion from partial response ( PR ) to CR with high-dose ( 40 Gy ) RT . PATIENTS AND METHODS From 1984 to 1992 , stage I ( with risk factors ) and II adults with diffuse aggressive lymphoma in CR after eight cycles of cyclophosphamide , doxorubicin , vincristine , and prednisone ( CHOP ) were r and omly assigned to 30 Gy involved-field RT or OBS . PR patients received 40 Gy RT . RESULTS Among 172 CR patients , the 6-year disease-free survival ( DFS ) was 73 % for low-dose RT versus 56 % for OBS ( two-sided P = .05 ) . Failure-free survival ( two-sided P = .06 ) , and time to progression ( two-sided P = .06 ) also favored RT . Intent-to-treat analyses yielded similar results . No survival differences were observed . Three RT versus 15 OBS patients relapsed in initial disease sites . At 6 years , failure-free survival was 63 % in PR patients ; conversion to CR did not significantly influence clinical outcome . CONCLUSION For patients in CR after CHOP , low-dose RT prolonged DFS and provided local control , but no survival benefit was observed . The majority of PR patients were event-free at 6 years despite residual radiographic abnormalities . Future efforts should be directed toward improved imaging and more effective systemic therapies PURPOSE Chemoradiotherapy has been considered st and ard treatment for patients with limited-stage aggressive lymphoma on the basis of trials conducted before the introduction of the International Prognostic Index . To evaluate this approach in elderly patients with low-risk localized lymphoma , we conducted a trial comparing chemoradiotherapy with chemotherapy alone . PATIENTS AND METHODS Previously untreated patients older than 60 years with localized stage I or II histologically aggressive lymphoma and no adverse prognostic factors of the International Prognostic Index were r and omly assigned to receive either four cycles of cyclophosphamide , doxorubicin , vincristine , and prednisone ( CHOP ) plus involved-field radiotherapy ( 299 patients ) or chemotherapy alone with four cycles of CHOP ( 277 patients ) . RESULTS With a median follow-up time of 7 years , event-free and overall survival did not differ between the two treatment groups ( P = .6 and P = .5 , respectively ) . The 5-year estimates of event-free survival were 61 % for patients receiving chemotherapy alone and 64 % for patients receiving CHOP plus radiotherapy ; the 5-year estimates of overall survival were 72 % and 68 % , respectively . In a multivariate analysis , overall survival was affected by stage II disease ( P < .001 ) and male sex ( P = .03 ) . CONCLUSION In this large prospect i ve study , CHOP plus radiotherapy did not provide any advantage over CHOP alone for the treatment of low-risk localized aggressive lymphoma in elderly patients BACKGROUND The MInT study was the first to show improved 3-year outcomes with the addition of rituximab to a CHOP ( cyclophosphamide , doxorubicin , vincristine , and prednisone)-like regimen in young patients with good-prognosis diffuse large-B-cell lymphoma . Extended follow-up was needed to establish long-term effects . METHODS In the r and omised open-label MInT study , patients from 18 countries ( aged 18 - 60 years with none or one risk factor according to the age-adjusted International Prognostic Index [ IPI ] , stage II-IV disease or stage I disease with bulk ) were r and omly assigned to receive six cycles of a CHOP-like chemotherapy with or without rituximab . Bulky and extranodal sites received additional radiotherapy . R and omisation was done central ly with a computer-based tool and was stratified by centre , bulky disease , age-adjusted IPI , and chemotherapy regimen by use of a modified minimisation algorithm that incorporated a stochastic component . Patients and investigators were not masked to treatment allocation . The primary endpoint was event-free survival . Analyses were by intention to treat . This observational study is a follow-up of the MInT trial , which was stopped in 2003 , and is registered at Clinical Trials.gov , number NCT00400907 . FINDINGS The intention-to-treat population included 410 patients assigned to chemotherapy alone and 413 assigned to chemotherapy plus rituximab . After a median follow-up of 72 months ( range 0·03 - 119 ) , 6-year event-free survival was 55·8 % ( 95 % CI 50·4 - 60·9 ; 166 events ) for patients assigned to chemotherapy alone and 74·3 % ( 69·3 - 78·6 ; 98 events ) for those assigned to chemotherapy plus rituximab ( difference between groups 18·5 % , 11·5 - 25·4 , log-rank p<0·0001 ) . Multivariable analyses showed that event-free survival was affected by treatment group , presence of bulky disease , and age-adjusted IPI and that overall survival was affected by treatment group and presence of bulky disease only . After chemotherapy and rituximab , a favourable subgroup ( IPI=0 , no bulk ) could be defined from a less favourable subgroup ( IPI=1 or bulk , or both ; event-free survival 84·3 % [ 95 % CI 74·2 - 90·7 ] vs 71·0 % [ 65·1 - 76·1 ] , log-rank p=0·005 ) . 18 ( 4·4 % , 95 % CI 2·6 - 6·9 ) second malignancies occurred in the chemotherapy-alone group and 16 ( 3·9 % , 2·2 - 6·2 ) in the chemotherapy and rituximab group ( Fisher 's exact p=0·730 ) . INTERPRETATION Rituximab added to six cycles of CHOP-like chemotherapy improved long-term outcomes for young patients with good-prognosis diffuse large-B-cell lymphoma . The definition of two prognostic subgroups allows a more refined therapeutic approach to these patients than does assessment by IPI alone . FUNDING Hoffmann-La Roche PURPOSE To evaluate the effect of rituximab in limited-stage diffuse large B-cell lymphoma ( DLBCL ) , we conducted a multicenter phase II trial combining rituximab with three cycles of CHOP ( cyclophosphamide , doxorubicin , vincristine , and prednisone ; R-CHOP ) followed by involved-field radiation therapy ( IFRT ) . PATIENTS AND METHODS Southwest Oncology Group ( SWOG ) study S0014 enrolled patients with newly diagnosed , aggressive , CD20-expressing non-Hodgkin 's lymphoma ( NHL ) . Patients had limited-stage disease and at least one adverse risk factor as defined by the stage-modified International Prognostic Index ( nonbulky stage II disease , age > 60 years , WHO performance status of 2 , or elevated serum lactate dehydrogenase ) . Four doses of rituximab were infused on days -7 , 1 , 22 , and 43 , and CHOP was administered on days 3 , 24 , and 45 , followed 3 weeks later by 40 to 46 Gy of IFRT . RESULTS Sixty patients with aggressive NHL were eligible . With the median follow-up of 5.3 years , treatment result ed in a progression-free survival ( PFS ) of 93 % at 2 years and 88 % at 4 years . Overall survival ( OS ) was 95 % at 2 years and 92 % at 4 years . These results were compared with those from a historic group of patients treated without rituximab on S8736 , demonstrating PFS of 78 % and OS of 88 % at 4 years . CONCLUSION In limited-stage DLBCL , the addition of rituximab to three cycles of CHOP plus IFRT met prespecified study criteria of efficacy , with 2-year PFS of at least 84 % , meriting further investigation . There is a pattern of continuing relapse with modest survival gains . We hypothesize that such a pattern may be the result of biologic differences between limited- and advanced-stage lymphoma PURPOSE To analyze the long-term outcome of patients included in the Lymphome Non Hodgkinien study 98 - 5 ( LNH98 - 5 ) comparing cyclophosphamide , doxorubicin , vincristine , and prednisone ( CHOP ) to rituximab plus CHOP ( R-CHOP ) in elderly patients with diffuse large B-cell lymphoma . PATIENTS AND METHODS LNH98 - 5 was a r and omized study that included 399 previously untreated patients , age 60 to 80 years , with diffuse large B-cell lymphoma . Patients received eight cycles of classical CHOP ( cyclophosphamide 750 mg/m(2 ) , doxorubicin 50 mg/m(2 ) , vincristine 1.4 mg/m(2 ) , and prednisone 40 mg/m(2 ) for 5 days ) every 3 weeks . In R-CHOP , rituximab 375 mg/m(2 ) was administered the same day as CHOP . Survivals were analyzed using the intent-to-treat principle . RESULTS Median follow-up is 5 years at present . Event-free survival , progression-free survival , disease-free survival , and overall survival remain statistically significant in favor of the combination of R-CHOP ( P = .00002 , P < .00001 , P < .00031 , and P < .0073 , respectively , in the log-rank test ) . Patients with low-risk or high-risk lymphoma according to the age-adjusted International Prognostic Index have longer survivals if treated with the combination . No long-term toxicity appeared to be associated with the R-CHOP combination . CONCLUSION Using the combination of R-CHOP leads to significant improvement of the outcome of elderly patients with diffuse large B-cell lymphoma , with significant survival benefit maintained during a 5-year follow-up . This combination should become the st and ard for treating these patients PURPOSE To evaluate the usefulness of adjuvant radiotherapy to sites of previous bulky disease in patients with advanced diffuse large cell lymphoma ( DLCL ) who were in complete remission after chemotherapy . METHODS AND MATERIAL Two-hundred and eighteen patients were initially treated with combined chemotherapy
Output:
| Conclusion : Consolidation RT could significantly improve outcomes of DLBCL patients who achieved a CR to RCHOP . |
MS213731 | ***TASK*** the task is to summarize an input biomedical literature in six sentences
***INPUT*** the input is a biomedical literature
***OUTPUT*** the output is the summary of an input biomedical literature in six sentences
***DOCUMENTATION***
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Input: Prognosis studies are investigations of future events or the evaluation of associations between risk factors and health outcomes in population s of patients ( 1 ) . The results of such studies improve our underst and ing of the clinical course of a disease and assist clinicians in making informed decisions about how best to manage patients . Prognostic research also informs the design of intervention studies by helping define subgroups of patients who may benefit from a new treatment and by providing necessary information about the natural history of a disorder ( 2 ) . There has recently been a rapid increase in the use of systematic review methods to synthesize the evidence on research questions related to prognosis . It is essential that investigators conducting systematic review s thoroughly appraise the method ologic quality of included studies to be confident that a study 's design , conduct , analysis , and interpretation have adequately reduced the opportunity for bias ( 3 , 4 ) . Caution is warranted , however , because inclusion of method ologically weak studies can threaten the internal validity of a systematic review ( 4 ) . This follows abundant empirical evidence that inadequate attention to biases can cause invalid results and inferences ( 5 - 9 ) . However , there is limited consensus on how to appraise the quality of prognosis studies ( 1 ) . A useful framework to assess bias in such studies follows the basic principles of epidemiologic research ( 10 , 11 ) . We focus on 6 areas of potential bias : study participation , study attrition , prognostic factor measurement , confounding measurement and account , outcome measurement , and analysis . The main objectives of our review of review s are to describe methods used to assess the quality of prognosis studies and to describe how well current practice s assess potential biases . Our secondary objective is to develop recommendations to guide future quality appraisal , both within single studies of prognostic factors and within systematic review s of the evidence . We hope this work facilitates future discussion and research on biases in prognosis studies and systematic review s. Methods Literature Search and Study Selection We identified systematic review s of prognosis studies by search ing MEDLINE ( 1966 to October 2005 ) using the search strategy recommended by McKibbon and colleagues ( 12 ) . This strategy combines broad search terms for systematic review s ( systematic review .mp ; meta- analysis .mp ) and a sensitive search strategy for prognosis studies ( cohort , incidence , mortality , follow-up studies , prognos * , predict * , or course ) . We also search ed the reference lists of included review s and method ologic papers to identify other relevant publications . We restricted our search to English- language publications . One review er conducted the search and selected the studies . Systematic review s , defined as review s of published studies with a comprehensive search and systematic selection , were included if they assessed the method ologic quality of the included studies by using 1 or more explicit criteria . We excluded studies if they were meta-analyses of independent patient data only , if their primary goal was to investigate the effectiveness of an intervention or specific diagnostic or screening tests , or if they included studies that were not done on humans . Data Extraction and Synthesis Individual items included in the quality assessment of the systematic review s were recorded as they were reported in the publication ( that is , the information that would be available to readers and future review ers ) . We review ed journal Web sites and contacted the authors of the systematic review s for additional information when authors made such an offer in their original papers . When review s assessed different study design s by using different sets of quality items , we extracted only those items used to assess cohort studies . We constructed a comprehensive list of distinct items that the review s used to assess the quality of their included studies . The full text of each review was screened . All items used by the review authors to assess the quality of studies were extracted into a computerized spreadsheet by 1 review er . Two experienced review ers , a clinical epidemiologist and an epidemiologist , independently synthesized the quality items extracted from the prognosis review s to determine how well the systematic review s assessed potential biases . We did this in 3 steps : 1 ) identified distinct concepts or domains addressed by the quality items ; 2 ) grouped each extracted quality item into the appropriate domain or domains ; and 3 ) identified the domains necessary to assess potential biases in prognosis studies . We then used this information to assess how well the review s ' quality assessment included items from the domains necessary to assess potential biases . After completing each of the first 3 steps , the review ers met to attempt to reach a consensus . The consensus process involved each review er presenting his or her observations and results , followed by discussion and debate . A third review er was available in cases of persistent disagreement or uncertainty . In the first step , all domains addressed by the quality items were identified . The first review er iteratively and progressively defined the domains as items were extracted from the included review s. The second review er defined domains from a r and om list of all extracted quality items . Limited guidance was provided to the review ers so that their assessment s and definitions of domains would be independent . The review ers agreed on a final set of domains that adequately and completely defined all of the extracted items . In the second step , review ers independently grouped each extracted item into the appropriate domains . Review ers considered each extracted item by asking , What is each particular quality item addressing ? or What are the review 's authors getting at with the particular quality assessment item ? . Items were grouped into the domain or domains that best represented the concepts being addressed . For example , the extracted items at least 80 % of the group originally identified was located for follow-up and follow-up was sufficiently complete or does n't jeopardize validity were each independently classified by both review ers as assessing the domain completeness of follow-up adequate , whereas the extracted item quantification and description of all subjects lost to follow-up was classified as assessing the domain completeness of follow-up described . In the third step , we identified the domains necessary to assess potential biases . Each review er considered the ability of the identified domains to adequately address , at least in part , 1 of the following 6 potential biases : 1 ) study participation , 2 ) study attrition , 3 ) prognostic factor measurement , 4 ) confounding measurement and account , 5 ) outcome measurement , and 6 ) analysis . Domains were considered to adequately address part of the framework if information garnered from that domain would inform the assessment of potential bias . For example , both review ers judged that the identified domain study population represents source population or population of interest assessed potential bias in a prognosis study , whereas the domain research question definition did not , although the latter is an important consideration in assessing the inclusion of studies in a systematic review . Finally , on the basis of our previous ratings , we looked at whether each review included items from the domains necessary to assess the 6 potential biases . We calculated the frequency of systematic review s by assessing each potential bias and the number of review s that adequately assessed bias overall . From this systematic synthesis , we developed recommendations for improving quality appraisal in future systematic review s of prognosis studies . We used Microsoft Access and Excel 2002 ( Microsoft Corp. , Redmond , Washington ) for data management and SAS for Windows , version 9.1 ( SAS Institute , Inc. , Cary , North Carolina ) for descriptive statistics . Role of the Funding Sources The funding sources , the Canadian Institutes of Health Research , the Canadian Chiropractic Research Foundation , the Ontario Chiropractic Association , and the Ontario Ministry of Health and Long Term Care , did not have a role in the collection , analysis , or interpretation of the data or in the decision to su bmi t the manuscript for publication . Results We identified 1384 potentially relevant articles . Figure 1 shows a flow chart of studies that were included and excluded . Figure 2 shows the number of review s identified by year of publication . We excluded 131 systematic review s of prognosis studies that did not seem to include any quality assessment of the included studies ; this represented 44 % of prognosis review s. We included 163 review s of prognosis studies in our analysis ( 13 - 175 ) . The most common topics were cancer ( 15 % ) , musculoskeletal disorders and rheumatology ( 13 % ) , cardiovascular ( 10 % ) , neurology ( 10 % ) , and obstetrics ( 10 % ) . Other review s included a wide range of health and health care topics . Sixty-three percent of the review s investigated the association between a specific prognostic factor and a particular outcome ; the remainder investigated multiple prognostic factors or models . The number of primary studies included in each systematic review ranged from 3 to 167 ( median , 18 [ interquartile range , 12 to 31 ] ) . A complete description of the included review s is available from the authors on request . Figure 1 . Flow diagram of inclusion and exclusion criteria of systematic review s. Figure 2 . Number of systematic review s of prognosis studies identified over time . Quality Items One hundred fifty-three review s provided adequate detail to allow extraction of quality items . Eight hundred eighty-two distinct quality items were extracted from the review s. Most review s developed their own set of quality items , with only a few applying criteria from previous review s. Most quality items Studies on humans show that depressive disorder is associated with an increased risk of developing cognitive dysfunction , and animal studies suggest that antidepressants may have neuroprotective abilities . On the basis of these observations , it was hypothesized that treatment with antidepressants may decrease the risk of developing dementia in patients with depression . We investigated whether continued treatment with antidepressants is associated with a decreased rate of dementia in a population of patients discharged from psychiatric healthcare service with a diagnosis of depression . We used register data on all prescribed antidepressants in all patients discharged from psychiatric healthcare service with a diagnosis of depression and with subsequent diagnoses of dementia in Denmark from 1995 to 2005 . A total of 37 658 patients with a diagnosis of depression at their first psychiatric contact and who were exposed to antidepressants after discharge were included in the study . A total of 2007 patients ( 5.3 % ) were subsequently diagnosed with dementia of any kind . The rate of dementia decreased during periods of two or more prescriptions of older antidepressants compared with the period of only one prescription of older antidepressants [ relative risk (RR)=0.83 ( 95 % confidence interval (CI)=0.70–0.98 ) ] . This finding was replicated with Alzheimer ’s disease as the outcome [ RR=0.66 ( 95 % CI=0.47–0.94 ) ] but not with dementia of other kinds as the outcome [ RR=0.88 ( 95 % CI=0.73–1.06 ) ] . In contrast , during periods of continued use of selective serotonin reuptake inhibitors or newer nonselective serotonin reuptake inhibitors , the rate of dementia was not decreased , regardless of the subtype of dementia . It was concluded that continued long-term treatment with older antidepressants is associated with a reduced rate of dementia in patients treated in psychiatric healthcare setting s , whereas continued treatment with other kinds of antidepressants is not . Method ological reasons for these findings can not be excluded because of the nonr and omized nature of data CONTEXT Adjunctive restorative therapies administered during the first few months after stroke , the period with the greatest degree of spontaneous recovery , reduce the number of stroke patients with significant disability . OBJECTIVE To examine the effect of escitalopram on cognitive outcome . We hypothesized that patients who received escitalopram would show improved performance in neuropsychological tests assessing memory and executive functions than patients who received placebo or underwent Problem Solving Therapy . DESIGN R and omized trial . SETTING Stroke center . PARTICIPANTS One hundred twenty-nine patients were treated within 3 months following stroke . The 12-month trial included 3 arms : a double-blind placebo-controlled comparison of escitalopram ( n = 43 ) with placebo ( n = 45 ) , and a nonblinded arm of Problem Solving Therapy ( n = 41 ) . OUTCOME MEASURES Change in scores from baseline to the end of treatment for the Repeatable Battery for the Assessment of Neuropsychological Status ( RBANS ) and Trail-Making , Controlled Oral Word Association , Wechsler Adult Intelligence Scale-III Similarities , and Stroop tests . RESULTS We found a difference among the 3 treatment groups in change in RBANS total score ( P < .01 ) and RBANS delayed memory score ( P < .01 ) . After adjusting for possible confounders , there was a significant effect of escitalopram treatment on the change in RBANS total score ( P < .01 , adjusted mean change in score : escitalopram group , 10.0 ; nonescitalopram group , 3.1 ) and the change in RBANS delayed memory score ( P < .01 , adjusted mean change in score : escitalopram group , 11.3 ; nonescitalopram group , 2.5 ) . We did not observe treatment effects in other neuropsychological measures . CONCLUSIONS When compared with patients who received placebo or underwent Problem Solving Therapy , stroke patients who received escitalopram showed improvement in global cognitive functioning , specifically in verbal and visual memory functions . This beneficial effect of escitalopram was independent of its effect on depression . The utility of antidepressants in the process of poststroke recovery should be further investigated . Trial Registration clinical trials.gov Identifier : NCT00071643 A prospect i ve analysis of risk factors for Alzheimer 's disease was a major objective of the Canadian Study of Health and Aging , a nationwide , population -based study . Of 6,434 eligible subjects aged 65 years or older in 1991 , 4,615 were alive in 1996 and participated in the follow-up study . All participants were cognitively normal in 1991 when they completed a risk factor question naire . Their cognitive status was reassessed 5 years later by using a similar two-phase procedure , including a screening interview , followed by a clinical examination when indicated . The analysis included 194 Alzheimer 's disease cases and 3,894 cognitively normal controls . Increasing age , fewer years of education , and the apolipoprotein E epsilon4 allele were significantly associated with increased risk of Alzheimer 's disease . Use of nonsteroidal anti-inflammatory drugs , wine consumption , coffee consumption ,
Output:
| Age was identified as a likely modifier of the association between antidepressant use and some form of cognitive impairment or AD/dementia .
Antidepressant drug usage is associated with AD/dementia and this is particularly evident if usage begins before age 65 .
This association may arise due to confounding by depression or depression severity .
However , biological mechanisms potentially linking antidepressant exposure to dementia have been described , so an etiological effect of antidepressants is possible . |
MS213732 | ***TASK*** the task is to summarize an input biomedical literature in six sentences
***INPUT*** the input is a biomedical literature
***OUTPUT*** the output is the summary of an input biomedical literature in six sentences
***DOCUMENTATION***
***EXAMPLES***
Input: Purpose Staff behaviours to optimise patient safety may be influenced by burnout , depression and strength of the safety culture . We evaluated whether burnout , symptoms of depression and safety culture affected the frequency of medical errors and adverse events ( selected using Delphi techniques ) in ICUs . Methods Prospect i ve , observational , multicentre ( 31 ICUs ) study from August 2009 to December 2011 . Results Burnout , depression symptoms and safety culture were evaluated using the Maslach Burnout Inventory ( MBI ) , CES-Depression scale and Safety Attitudes Question naire , respectively . Of 1,988 staff members , 1,534 ( 77.2 % ) participated . Frequencies of medical errors and adverse events were 804.5/1,000 and 167.4/1,000 patient-days , respectively . Burnout prevalence was 3 or 40 % depending on the definition ( severe emotional exhaustion , depersonalisation and low personal accomplishment ; or MBI score greater than −9 ) . Depression symptoms were identified in 62/330 ( 18.8 % ) physicians and 188/1,204 ( 15.6 % ) nurses/nursing assistants . Median safety culture score was 60.7/100 [ 56.8–64.7 ] in physicians and 57.5/100 [ 52.4–61.9 ] in nurses/nursing assistants . Depression symptoms were an independent risk factor for medical errors . Burnout was not associated with medical errors . The safety culture score had a limited influence on medical errors . Other independent risk factors for medical errors or adverse events were related to ICU organisation ( 40 % of ICU staff off work on the previous day ) , staff ( specific safety training ) and patients ( workload ) . One-on-one training of junior physicians during duties and existence of a hospital risk-management unit were associated with lower risks . Conclusions The frequency of selected medical errors in ICUs was high and was increased when staff members had symptoms of depression The presence of hope has been found to influence an individual 's ability to cope with stressful situations . The objective of this study is to evaluate the relationship between medical errors , hope and burnout among practicing physicians using vali date d metrics . Prospect i ve cohort study was conducted among hospital based physicians practicing in Japan ( N = 836 ) . Measures included the vali date d Burnout Scale , self- assessment of medical errors and Herth Hope Index ( HHI ) . The main outcome measure was the frequency of self-perceived medical errors , and Poisson regression analysis was used to evaluate the association between hope and medical error . A total of 361 errors were reported in 836 physician-years . We observed a significant association between hope and self-report of medical errors . Compared with the lowest tertile category of HHI , incidence rate ratios ( IRRs ) of self-perceived medical errors of physicians in the highest category were 0.44 ( 95%CI , 0.34 to 0.58 ) and 0.54 ( 95%CI , 0.42 to 0.70 ) respectively , for the 2nd and 3rd tertile . In stratified analysis by hope score , among physicians with a low hope score , those who experienced higher burnout reported higher incidence of errors ; physicians with high hope scores did not report high incidences of errors , even if they experienced high burnout . Self-perceived medical errors showed a strong association with physicians ' hope , and hope modified the association between physicians ' burnout and self-perceived medical errors AIMS We examined the impact of workplace relationships ( perceived organizational support , supervisor-nurse relationships and teamwork ) on the engagement , well-being , organizational commitment and turnover intentions of nurses working in Australian and USA hospitals . BACKGROUND In a global context of nurse shortages , knowledge about factors impacting nurse retention is urgently sought . We postulated , using the Social Exchange Theory , that nurses ' turnover intentions would be affected by several factors and especially their relationships at work . DESIGN Based on the literature review , data were collected via a self-report survey to test the hypotheses . METHODS A self-report survey was used to gather data in 2010 - 2012 from 510 r and omly chosen nurses from Australian hospitals and 718 nurses from US hospitals . A multi-group structural equation modelling analysis identified significant paths and compared the impact between countries . RESULTS The findings indicate that this model was more effective in predicting the correlations between variables for nurses in Australia compared with the USA . Most paths predicted were confirmed for Australia , except for the impact of teamwork on organizational commitment and turnover , plus the impact of engagement on turnover . In contrast , none of the paths related to supervisor-subordinate relationships was significant for the USA ; neither were the paths from teamwork to organizational commitment or turnover . CONCLUSION Our findings suggest that well-being is a predictor of turnover intentions , meaning that healthcare managers need to consider nurses ' well-being in everyday decision-making , especially in the cost-cutting paradigm that pervades healthcare provision in nearly every country . This is important because nurses are in short supply and this situation will continue to worsen , because many countries have an ageing population RATIONALE The stressful work environment of ICUs can lead to burnout . Burnout can impact on the welfare and performance of caregivers , and may lead them to resign their job . The shortage of ICU caregivers is becoming a real threat for health care leaders . OBJECTIVES To investigate the factors associated with burnout on a national level in order to determine potential important factors . METHODS Prospect i ve , multicenter , observational survey of all caregivers from 74 of the 92 Swiss ICUs , measuring the prevalence of burnout among the caregivers and the pre-specified center- , patient- and caregiver-related factors influencing its prevalence . MEASUREMENTS AND MAIN RESULTS Out of the 4322 question naires distributed from March 2006 to April 2007 , 3052 ( 71 % ) were returned , with a response rate of 72 % by center , 69 % from nurse-assistants , 73 % from nurses and 69 % from physicians . A high proportion of female nurses among the team was associated with a decreased individual risk of high burnout ( OR 0.98 , 95 % CI:0.97 - 0.99 for every % ) . The caregiver-related factors associated with a high risk of burnout were being a nurse-assistant , being a male , having no children and being under 40 years old . CONCLUSIONS The findings of this study seem to open a new frontier concerning burnout in ICUs , highlighting the importance of team composition . Our results should be confirmed in a prospect i ve multicenter , multinational study . Whether our results can be exported to other medical setting s where team-working is pivotal remains to be investigated CONTEXT Medical errors are associated with feelings of distress in physicians , but little is known about the magnitude and direction of these associations . OBJECTIVE To assess the frequency of self-perceived medical errors among resident physicians and to determine the association of self-perceived medical errors with resident quality of life , burnout , depression , and empathy using vali date d metrics . DESIGN , SETTING , AND PARTICIPANTS Prospect i ve longitudinal cohort study of categorical and preliminary internal medicine residents at Mayo Clinic Rochester . Data were provided by 184 ( 84 % ) of 219 eligible residents . Participants began training in the 2003 - 2004 , 2004 - 2005 , and 2005 - 2006 academic years and completed surveys quarterly through May 2006 . Surveys included self- assessment of medical errors and linear analog scale assessment of quality of life every 3 months , and the Maslach Burnout Inventory ( depersonalization , emotional exhaustion , and personal accomplishment ) , Interpersonal Reactivity Index , and a vali date d depression screening tool every 6 months . MAIN OUTCOME MEASURES Frequency of self-perceived medical errors was recorded . Associations of an error with quality of life , burnout , empathy , and symptoms of depression were determined using generalized estimating equations for repeated measures . RESULTS Thirty-four percent of participants reported making at least 1 major medical error during the study period . Making a medical error in the previous 3 months was reported by a mean of 14.7 % of participants at each quarter . Self-perceived medical errors were associated with a subsequent decrease in quality of life ( P = .02 ) and worsened measures in all domains of burnout ( P = .002 for each ) . Self-perceived errors were associated with an odds ratio of screening positive for depression at the subsequent time point of 3.29 ( 95 % confidence interval , 1.90 - 5.64 ) . In addition , increased burnout in all domains and reduced empathy were associated with increased odds of self-perceived error in the following 3 months ( P=.001 , P<.001 , and P=.02 for depersonalization , emotional exhaustion , and lower personal accomplishment , respectively ; P=.02 and P=.01 for emotive and cognitive empathy , respectively ) . CONCLUSIONS Self-perceived medical errors are common among internal medicine residents and are associated with substantial subsequent personal distress . Personal distress and decreased empathy are also associated with increased odds of future self-perceived errors , suggesting that perceived errors and distress may be related in a reciprocal cycle PURPOSE To investigate if differences in antecedents of severe and nonsevere medication errors exist . DESIGN A longitudinal study of 6 months of data from 279 nursing units in 146 r and omly selected hospitals in the United States ( US ) . METHODS Antecedents of severe and nonsevere medication errors included work environment factors ( work dynamics and RN hours ) , team factors ( communication with physicians and nurses ' expertise ) , person factors ( nurses ' education and experience ) , patient factors ( age , health status , and previous hospitalization ) , and medication-related support services . Generalized estimating equations with a negative binomial distribution were used with nursing units as the unit of analysis . FINDINGS None of the antecedents allowed predicting both types of medication errors . Nurses ' expertise had a negative and medication-related support services had a positive association with nonsevere medication errors . Nurses ' educational level had a significant nonlinear relationship with severe medication errors only : As the percentage of unit BSN-prepared nurses increased , severe medication errors decreased until the percentage of BSN-prepared nurses reached 54 % . In contrast , RN experience had a statistically significant relationship with nonsevere medication errors only and nursing units with more experienced nurses reported more nonsevere medication errors . CONCLUSIONS Severe and nonsevere medication errors might have different antecedents . CLINICAL RELEVANCE Error prevention and management strategies should be targeted to specific types of medication errors for best results AIM Whether mental stress negatively impacts team performance during cardio-pulmonary resuscitation ( CPR ) remains controversial ; this may partly be explained by differences in stress measures used in previous studies . Our aim was to compare self-reported , biochemical and physiological stress measures in regard to CPR performance . METHODS This prospect i ve , observational study was conducted at the simulator center of the University Hospital Basel , Switzerl and . Self-reported ( feeling stressed and overwhelmed [ stress/overload ] ) , biochemical ( plasma cortisol ) and physiological ( heart rate , heart rate variability ) stress measures were assessed in 28 residents ( teams of 2 ) before , during and after resuscitation . Team performance was defined as time to start CPR and h and s-on time during the first 180 s. RESULTS At baseline , significant negative correlations of heart rate variability with stress/overload and heart rate , as well as positive correlations of heart rate and cortisol were found . During resuscitation , self-reported , biochemical and physiological stress measures did not correlate significantly . There was no association of baseline stress measures with performance . During CPR , stress/overload was significantly associated with time to start CPR ( regression coefficient 12.01 ( 95 % CI 0.65 , 23.36 ) , p=0.04 ) , while heart rate was negatively associated with time to start CPR ( regression coefficient -0.78 ( 95 % CI -1.44 , -0.11 ) , p=0.027 ) and positively with h and s-on time ( regression coefficient 2.22 ( 95 % CI 0.53 , 3.92 ) , p=0.015 ) . CONCLUSIONS Self-reported stress ( stress/overload ) was the only predictor for low CPR performance . Biochemical measures showed no association , and physiological measures ( heart rate ) showed an inverse association , which may be due to physical activity , limiting its value as a mental stress marker in this acute setting The influence of teammates ' shared mental models on team processes and performance was tested using 56 undergraduate dyads who " flew " a series of missions on a personal-computer-based flight-combat simulation . The authors both conceptually and empirically distinguished between teammates ' task- and team-based mental models and indexed their convergence or " sharedness " using individually completed paired-comparisons matrices analyzed using a network-based algorithm . The results illustrated that both shared-team- and task-based mental models related positively to subsequent team process and performance . Furthermore , team processes fully mediated the relationship between mental model convergence and team effectiveness . Results are discussed in terms of the role of shared cognitions in team effectiveness and the applicability of different interventions design ed to achieve such convergence Patient care in hospital setting s requires coordinated team performance . Studies in other industries show that successful teams adapt their coordination processes to the situational task requirements . This prospect i ve field study aim ed to test a new observation system and investigate patterns of adaptive coordination within operating room teams . A trained observer recorded coordination activities during
Output:
| We found support for the existence of independent associations between teamwork , clinician occupational well-being and patient safety . |
MS213733 | ***TASK*** the task is to summarize an input biomedical literature in six sentences
***INPUT*** the input is a biomedical literature
***OUTPUT*** the output is the summary of an input biomedical literature in six sentences
***DOCUMENTATION***
***EXAMPLES***
Input: BACKGROUND Supplemental oxygen in patients with chronic obstructive pulmonary disease ( COPD ) and exercise hypoxaemia improves exercise capacity and dyspnoea . However , the benefit of oxygen during pulmonary rehabilitation in these patients is still unknown . METHODS Twenty five patients with stable COPD ( mean ( SD ) forced expiratory volume in one second ( FEV1 ) 0.76 ( 0.29 ) l and 30.0 (9.89)% predicted , arterial oxygen tension ( Pao 2 ) 8.46 ( 1.22 ) kPa , arterial carbon dioxide tension ( Paco 2 ) 6.32 ( 1.01 ) kPa ) and significant arterial desaturation on exercise ( 82.0 (10.4)% ) were entered onto a pulmonary rehabilitation programme . Patients were r and omised to train whilst breathing oxygen ( OT ) ( n = 13 ) or air ( AT ) ( n = 12 ) , both at 4 l/min . Assessment s included exercise tolerance and associated dyspnoea using the shuttle walk test ( SWT ) and Borg dyspnoea score , health status , mood state , and performance during daily activities . RESULTS The OT group showed a significant reduction in dyspnoea after rehabilitation compared with the AT group ( Borg mean difference –1.46 ( 95 % CI –2.72 to –0.19 ) ) but there were no differences in other outcome measures : SWT difference –23.6 m ( 95 % CI –70.7 to 23.5 ) , Chronic Respiratory Disease Question naire 3.67 ( 95 % CI –7.70 to 15.1 ) , Hospital Anxiety and Depression Scale 1.73 ( 95 % CI –2.32 to 5.78 ) , and London Chest Activity of Daily Living Scale –2.18 ( 95 % CI –7.15 to 2.79 ) . At baseline oxygen significantly improved SWT ( mean difference 27.3 m ( 95 % CI 14.7 to 39.8 ) and dyspnoea ( –0.68 ( 95 % CI –1.05 to –0.31 ) ) compared with placebo air . CONCLUSIONS This study suggests that supplemental oxygen during training does little to enhance exercise tolerance although there is a small benefit in terms of dyspnoea . Patients with severe disabling dyspnoea may find symptomatic relief with supplemental oxygen Supplemental oxygen improves exercise tolerance of normoxemic and hypoxemic chronic obstructive pulmonary disease ( COPD ) patients . We determined whether nonhypoxemic COPD patients undergoing exercise training while breathing supplemental oxygen achieve higher intensity and therefore improve exercise capacity more than patients breathing air . A double-blinded trial was performed involving 29 nonhypoxemic patients ( 67 years , exercise SaO2 > 88 % ) with COPD ( FEV1 = 36 % predicted ) . All exercised on cycle ergometers for 45 minutes , 3 times per week for 7 weeks at high-intensity targets . During exercise , they received oxygen ( 3 L/minute ) ( n = 14 ) or compressed air ( 3 L/minute ) ( n = 15 ) . Both groups had a higher exercise tolerance after training and when breathing oxygen . However , the oxygen-trained group increased the training work rate more rapidly than the air-trained group . The mean + /- SD work rate during the last week was 62 + /- 19 W ( oxygen-trained group ) and 52 + /- 22 W ( air-trained group ) ( p < 0.01 ) . After training , endurance in constant work rate tests increased more in the oxygen-trained group ( 14.5 minutes ) than in the air-trained group ( 10.5 minutes ) ( p < 0.05 ) . At isotime , the breathing rate decreased four breaths per minute in the oxygen-trained group and one breath per minute in the air-trained group ( p = 0.001 ) . We conclude that supplemental oxygen provided during high-intensity training yields higher training intensity and evidence of gains in exercise tolerance in laboratory testing PURPOSE To quantify the effects of acute oxygen supplementation on lower limb blood flow ( QLEG ) , O2 delivery ( QO2LEG ) , and O2 uptake ( VO2LEG ) during exercise and to determine whether the metabolic capacity of the lower limb is exhausted at peak exercise during room air breathing in patients with COPD . METHODS Oxygen ( FIO2 = 0.75 ) and air were r and omly administered to 14 patients with COPD ( FEV1 : 35 + /- 2 % pred , mean + /- SEM ) during two symptom-limited incremental cycle exercise tests . Before exercise , a cannula was installed in a radial artery and a thermodilution catheter inserted in the right femoral vein . At each exercise step , five-breath averages of respiratory rate , tidal volume , and ventilation ( VE ) , dyspnea and leg fatigue scores , arterial and venous blood gases , and QLEG were obtained . From these measurements , VO2LEG was calculated . RESULTS Peak exercise capacity increased from 46 + /- 3 W in room air to 59 + /- 5 W when supplemental oxygen was used ( P < 0.001 ) . QLEG , QO2LEG , and VO2LEG were greater at peak exercise with O2 than with air ( P < 0.05 ) . During submaximal exercise , dyspnea score and VE were significantly reduced with O2 ( P < 0.05 ) , whereas QLEG , VO2LEG , and leg fatigue were similar under both experimental conditions . The improvement in peak exercise work rate correlated with the increase in peak QO2LEG ( r = 0.66 , P < 0.01 ) , peak VO2LEG ( r = 0.53 , P < 0.05 ) , and reduction in dyspnea at iso-exercise intensity ( r = 0.56 , P < 0.05 ) . CONCLUSION The improvement in peak exercise capacity with oxygen supplementation could be explained by the reduction in dyspnea at submaximal exercise and the increases in QO2LEG and VO2LEG , which enabled the exercising muscles to perform more external work . These data indicate that the metabolic capacity of the lower limb muscles was not exhausted at peak exercise during room air breathing in these patients with COPD BACKGROUND Oxygen conserving devices may lead to substantial increases in the duration of oxygen provided . A study was undertaken to compare the performance of a pulsed dose oxygen delivery ( PDOD ) system with continuous flow oxygen or air during a maximal walking test . METHODS Fourteen patients with chronic obstructive pulmonary disease ( COPD ) and arterial oxygen desaturation on exercise ( mean ( SD ) forced expiratory volume in one second ( FEV1 ) 0.83 ( 0.28 ) l , arterial oxygen pressure ( Pao 2 ) 8.38 ( 1.24 ) kPa , arterial carbon dioxide pressure ( Paco 2 ) 5.95 ( 0.86 ) kPa ) were r and omised to perform a walking test using air administered via a cylinder or continuous flow oxygen at 2 l/min or by a PDOD system . RESULTS There was no significant difference in the mean arterial oxygen saturation ( Sao 2 ) using the PDOD system or with continuous flow oxygen ( p = 0.33 ) . Patients showed greatest desaturation whilst walking with the air cylinder ( Sao 2 79.2 (8.59)% ) which was significantly different from the desaturation with both continuous flow oxygen ( 87.6 (5.85)% , p = 0.001 ) and PDOD ( 85.6 (7.36)% , p = 0.004 ) . There was no significant difference between the distance walked using oxygen delivered at 2 l/min by continuous flow or via the PDOD ( p = 0.72 ; CI 0.34 to 1.08 ) . The mean ( SD ) distance walked on continuous flow oxygen ( 203.6 ( 106.1 ) m ) and PDOD ( 207.9 ( 109.8 ) m ) was significantly greater than the distance walked with the air cylinder ( 188.6 ( 110.02 ) m ) ; ( 1.12 fold increase in distance , CI 1.01 to 1.23 , p = 0.02 , and 1.14 fold increase in distance , CI 1.01 to 1.28 , p = 0.03 , respectively ) . CONCLUSIONS These findings suggest that the pulsed dose oxygen conserving device was as effective as continuous flow oxygen in maintaining arterial oxygen saturation and that the use of this device was associated with similar improvements in exercise tolerance to patients taking continuous flow oxygen therapy A r and omized , controlled , single-blind study was performed on 20 patients with chronic obstructive pulmonary disease and exercise-induced hypoxaemia . Ten patients each were r and omly assigned to one of two groups , one training with air and the other training with oxygen . There were no significant differences between the groups regarding values measured prior to the study . The patients trained 3 times per week for 30 minutes each time for a duration of 8 weeks . The training consisted of interval walking on a treadmill ( intensity set according to Borg ratings ) with either air or oxygen administered through a nasal cannula at a rate of 5 l/min . Training significantly improved the 6-minute walking distance by 20 % and 14 % in the air and oxygen group , respectively , when the patients were tested on air . In the same test the air group significantly decreased Borg ratings for perceived exertion . Borg ratings for dyspnoea and perceived exertion significantly decreased in the oxygen group when they were tested on oxygen . It was concluded that oxygen supplementation did not further improve the training effect , compared with training with air , in patients with chronic obstructive pulmonary disease and exercise-induced hypoxaemia Supplemental oxygen has acute beneficial effects on exercise performance in patients with chronic obstructive pulmonary disease ( COPD ) . The purpose of this study was to investigate whether oxygen-supplemented training enhances the effects of training while breathing room air in patients with severe COPD . A r and omized controlled trial was performed in 24 patients with severe COPD who developed hypoxaemia during incremental cycle exercise ( arterial oxygen saturation ( Sa , O2 ) < 90 % at peak exercise ) . All patients participated in an in-patient pulmonary rehabilitation programme of 10 weeks duration . They were assigned either to general exercise training while breathing room air ( GET/RA group : forced expiratory volume in one second ( FEV1 ) 38 % of predicted ; arterial oxygen tension ( Pa , O2 ) 10.5 kPa at rest ; Pa , O2 7.3 kPa at peak exercise ) , or to GET while breathing supplemental oxygen ( GET/O2 group : FEV1 29 % pred ; Pa , O2 10.2 kPa at rest ; Pa , O2 7.2 kPa at peak exercise ) . Sa , O2 was not allowed to fall below 90 % during the training . The effects on exercise performance while breathing air and oxygen , and on quality of life were compared . Maximum workload ( Wmax ) significantly increased in the GET/RA group ( mean ( SD ) 17 ( 15 ) W , p<0.01 ) , but not in the GET/O2 group ( 7 ( 25 ) W ) . Six minute walking distance ( 6MWD ) , stair-climbing , weight-lifting exercise ( all while breathing room air ) and quality of life significantly increased in both groups . Acute administration of oxygen improved exercise performance before and after training . Training significantly increased Wmax , peak carbon dioxide production ( V'CO2 ) and 6MWD while breathing oxygen in both groups . Differences between groups were not significant . Pulmonary rehabilitation improved exercise performance and quality of life in both groups . Supplementation of oxygen during the training did not add to the effects of training on room air In 159 chronic obstructive pulmonary disease ( COPD ) patients ( 139 males , mean age 62 + /- 8 yrs , arterial oxygen tension ( PaO2 ) 7.2 + /- 0.9 kPa ) , on long-term oxygen therapy ( LTOT ) , we evaluated the effects of portable oxygen therapy both on the daily duration of oxygen therapy and on daily activities . They were given two types of LTOT at r and om : group A ( n = 75 ) , oxygen concentrators only ( OC ) ; group B ( n = 84 ) , either small oxygen cylinders plus OC ( B1 = 51 ) or liquid oxygen ( B2 = 33 ) . The patients were followed-up for one year by means of : a ) medical examination every three months ; b ) monthly home interviews concerning the daily duration of oxygen therapy , the utilization of the devices and the daily activities of the patients ; c ) a measurement of the daily oxygen usage . The results show that : 1 ) there are no significant clinical and functional differences between groups A and B at the onset of and throughout the study ; 2 ) in group B the daily use of oxygen therapy is significantly longer than in group A ( 17 + /- 3.5 h.day-1 vs 14 + /- 3 h.day-1 , p less than 0.01 ) without any difference between groups B1 and B2 ; 3 ) outdoor walking activities are different between groups A and B , at least in those patients using oxygen more than 18 h.day-1 . Only 60 % of patients in group B ( 55 % of B1 ; 67
Output:
| Oxygen improved breathlessness , SaO2/PaO2 and VE at isotime with endurance exercise testing .
Oxygen improved SaO2/PaO2 and reduced VE at Isotime .
This review provides some evidence from small , single assessment studies that ambulatory oxygen improves exercise performance in people with moderate to severe COPD . |
MS213734 | ***TASK*** the task is to summarize an input biomedical literature in six sentences
***INPUT*** the input is a biomedical literature
***OUTPUT*** the output is the summary of an input biomedical literature in six sentences
***DOCUMENTATION***
***EXAMPLES***
Input: Background : The objective is to study the effect of after-birth oral colonization by a probiotic Escherichia coli strain in infants of allergic mothers to reduce occurrence of allergy later in life . Methods : In a controlled clinical trial , 158 infants were r and omly divided into groups of ( i ) 56 colonized infants of allergic mothers , ( ii ) 57 control infants of allergic mothers , and ( iii ) 45 control infants of healthy mothers . Incidence rates of bacterial pathogens in stool and levels of anti-E. coli immunoglobulins and some cytokines in serum were determined , and secretory IgA was monitored in stool filtrates and maternal milk . Clinical check-ups of infants aged 4 days , 3 and 6 months , 2 , 3 and 5 years were carried out and clinical symptoms of allergy were monitored . One milliliter of the probiotic E. coli strain was administered to infants of allergic mothers at first within 48 h after birth and subsequently 3 times a week over a period of 4 weeks . Control infants of allergic and healthy mothers were monitored in these intervals as well . Results : Presence of the E. coli strain was monitored in stool sample s throughout the study . At the conclusion of the study , allergy symptoms were found in 14 infants of control allergic mothers , 7 infants of healthy mothers , and in 2 colonized infants of allergic mothers . Colonization affected levels of several cytokines and specific anti-E. coli antibodies . Conclusions : After birth , targeted colonization of the intestine by a probiotic E. coli strain can be an effective means of allergy prevention in infants of allergic mothers Background The ' hygiene hypothesis ' suggests that early exposure to microbes can be protective against atopic disease . The intestinal microbial flora could operate as an important postnatal regulator of the Th1/Th2 balance . The aim of the study was to investigate the association between early intestinal colonisation and the development of asthma in the first 3 years of life . Methods In a prospect i ve birth cohort , 117 children were classified according to the Asthma Predictive Index . A positive index included wheezing during the first three years of life combined with eczema in the child in the first years of life or with a parental history of asthma . A faecal sample was taken at the age of 3 weeks and cultured on selective media . Results Asthma Predictive Index was positive in 26/117 ( 22 % ) of the children . The prevalence of colonisation with Bacteroides fragilis was higher at 3 weeks in index+ compared to index- children ( 64 % vs. 34 % p < 0,05 ) . Bacteroides fragilis and Total Anaerobes counts at 3 weeks were significantly higher in children with a positive index as compared with those without . After adjusting for confounders a positive association was found between Bacteroides fragilis colonisation and Asthma Predictive Index ( odds ratio : 4,4 ; confidence interval : 1,7 – 11,8 ) . Conclusion Bacteroides fragilis colonisation at age 3 weeks is an early indicator of possible asthma later in life . This study could provide the means for more accurate targeting of treatment and prevention and thus more effective and better controlled modulation of the microbial milieu BACKGROUND It is debated whether a low total diversity of the gut microbiota in early childhood is more important than an altered prevalence of particular bacterial species for the increasing incidence of allergic disease . The advent of powerful , cultivation-free molecular methods makes it possible to characterize the total microbiome down to the genus level in large cohorts . OBJECTIVE We sought to assess microbial diversity and characterize the dominant bacteria in stool during the first year of life in relation to atopic eczema development . METHODS Microbial diversity and composition were analyzed with barcoded 16S rDNA 454-pyrosequencing in stool sample s at 1 week , 1 month , and 12 months of age in 20 infants with IgE-associated eczema and 20 infants without any allergic manifestation until 2 years of age ( Clinical Trials.gov ID NCT01285830 ) . RESULTS Infants with IgE-associated eczema had a lower diversity of the total microbiota at 1 month ( P = .004 ) and a lower diversity of the bacterial phylum Bacteroidetes and the genus Bacteroides at 1 month ( P = .02 and P = .01 ) and the phylum Proteobacteria at 12 months of age ( P = .02 ) . The microbiota was less uniform at 1 month than at 12 months of age , with a high interindividual variability . At 12 months , when the microbiota had stabilized , Proteobacteria , comprising gram-negative organisms , were more abundant in infants without allergic manifestation ( Empirical Analysis of Digital Gene Expression in R [ edgeR ] test : P = .008 , q = 0.02 ) . CONCLUSION Low intestinal microbial diversity during the first month of life was associated with subsequent atopic eczema Background A modest number of prospect i ve studies of the composition of the intestinal microbiota and eczema in early life have yielded conflicting results . Objective To examine the relationship between the bacterial diversity of the gut and the development of eczema in early life by methods other than stool culture . Methods Fecal sample s were collected from 21 infants at 1 and 4 months of life . Nine infants were diagnosed with eczema by the age of 6 months ( cases ) and 12 infants were not ( controls ) . After conducting denaturating gradient gel electrophoresis ( DGGE ) of stool sample s , we compared the microbial diversity of cases and controls using the number of electrophoretic b and s and the Shannon index of diversity ( H ' ) as indicators . Results Control subjects had significantly greater fecal microbial diversity than children with eczema at ages 1 ( mean H ' for controls = 0.75 vs. 0.53 for cases , P = 0.01 ) and 4 months ( mean H ' for controls = 0.92 vs. 0.59 for cases , P = 0.02 ) . The increase in diversity from 1 to 4 months of age was significant in controls ( P = 0.04 ) but not in children who developed eczema by 6 months of age ( P = 0.32 ) . Conclusion Our findings suggest that reduced microbial diversity is associated with the development of eczema in early life BACKGROUND Alterations in intestinal microflora have been linked to the development of allergic disease . Recent studies suggest that healthy infant immune development may depend on the establishment of a diverse gut microbiota rather than the presence or absence of specific microbial strains . OBJECTIVES We investigated the relationship between diversity of gut microbiota in the early postnatal period and subsequent development of eczema and atopy in the first year of life . METHODS Fecal sample s were collected 1 wk after birth from 98 infants at high risk of allergic disease , who were followed prospect ively to age 12 months . Fecal microbial diversity was assessed by terminal restriction fragment length polymorphism ( T-RFLP ) using restriction enzymes Sau96I and AluI , with a greater number of peaks representing greater diversity of bacterial communities . RESULTS Microbial diversity at day 7 was significantly lower in infants with eczema at age 12 months as compared to infants without eczema ( AluI mean number of peaks 13.1 vs. 15.5 , p = 0.003 , 95 % CI for difference in means -3.9 , -0.8 ; Sau96I 14.7 vs. 17.2 , p = 0.03 , 95 % CI -4.9 , -0.3 ) . No differences were observed for atopic compared to non-atopic infants , or infants with two allergic parents compared to those with one or no allergic parent . CONCLUSIONS A more diverse intestinal microbiota in the first week of life is associated with a reduced risk of subsequent eczema in infants at increased risk of allergic disease . Interventions that enhance microbial diversity in early life may provide an effective means for the prevention of eczema in high-risk infants Background Deviations in composition and diversity of intestinal microbiota in infancy have been associated with both the development and recurrence of atopic eczema . Thus , we decided to use a deep and global microarray-based method to characterize the diversity and temporal changes of the intestinal microbiota in infancy and to define specific bacterial signatures associated with eczema . Faecal microbiota at 6 and 18 months of age were analysed from 34 infants ( 15 with eczema and 19 healthy controls ) selected from a prospect i ve follow-up study based on the availability of faecal sample s. The infants were originally r and omized to receive either Lactobacillus rhamnosus GG or placebo . Results Children with eczema harboured a more diverse total microbiota than control subjects as assessed by the Simpson ’s reciprocal diversity index of the microarray profiles . Composition of the microbiota did not differ between study groups at age of 6 months , but was significantly different at age of 18 months as assessed by MCPP ( p=0.01 ) . At this age healthy children harboured 3 -fold greater amount of members of the Bacteroidetes ( p=0.01 ) . Microbiota of children suffering from eczema had increased abundance of the Clostridium clusters IV and XIVa , which are typically abundant in adults . Probiotic Lactobacillus rhamnosus GG supplementation in early infancy was observed to have minor long-term effects on the microbiota composition . Conclusion A diverse and adult-type microbiota in early childhood is associated with eczema and it may contribute to the perpetuation of eczema BACKGROUND Changes in the human microbiome have been suggested as a risk factor for a number of lifestyle-related disorders , such as atopic diseases , possibly through a modifying influence on immune maturation in infancy . OBJECTIVES We aim ed to explore the association between neonatal fecal flora and the development of atopic disorders until age 6 years , hypothesizing that the diversity of the intestinal microbiota influences disease development . METHODS We studied the intestinal microbiota in infants in the Copenhagen Prospect i ve Study on Asthma in Childhood , a clinical study of a birth cohort of 411 high-risk children followed for 6 years by clinical assessment s at 6-month intervals , as well as at acute symptom exacerbations . Bacterial flora was analyzed at 1 and 12 months of age by using molecular techniques based on 16S rRNA PCR combined with denaturing gradient gel electrophoresis , as well as conventional culturing . The main outcome measures were the development of allergic sensitization ( skin test and specific serum IgE ) , allergic rhinitis , peripheral blood eosinophil counts , asthma , and atopic dermatitis during the first 6 years of life . RESULTS We found that bacterial diversity in the early intestinal flora 1 and 12 months after birth was inversely associated with the risk of allergic sensitization ( serum specific IgE P = .003 ; skin prick test P = .017 ) , peripheral blood eosinophils ( P = .034 ) , and allergic rhinitis ( P = .007 ) . There was no association with the development of asthma or atopic dermatitis . CONCLUSIONS Reduced bacterial diversity of the infant 's intestinal flora was associated with increased risk of allergic sensitization , allergic rhinitis , and peripheral blood eosinophilia , but not asthma or atopic dermatitis , in the first 6 years of life . These results support the general hypothesis that an imbalance in the intestinal microbiome is influencing the development of lifestyle-related disorders , such as allergic disease Background The extended ' hygiene hypothesis ' suggests that the initial composition of the infant gut microbiota is a key determinant in the development of atopic disease . Several studies have demonstrated that the microbiota of allergic and non-allergic infants are different even before the development of symptoms , with a critical time window during the first 6 months of life . The aim of the study was to investigate the association between early intestinal colonisation and the development of asthma in the first 3 years of life using DGGE ( denaturing gradient gel electrophoresis ) . Methods In a prospect i ve birth cohort , 110 children were classified according to the API ( Asthma Predictive Index ) . A positive index included wheezing during the first three years of life combined with eczema in the child in the first years of life or with a parental history of asthma . A fecal sample was taken at the age of 3 weeks and analysed with DGGE using universal and genus specific primers . Results The Asthma Predictive Index was positive in 24/110 ( 22 % ) of the children . Using universal V3 primers a b and corresponding to a Clostridum coccoides XIVa species was significantly associated with a positive API . A Bacteroides fragilis subgroup b and was also significantly associated with a positive API . A final DGGE model , including both b and s , allowed correct classification of 73 % ( 80/110 ) of the cases . Conclusion Fecal colonisation at age 3 weeks with either a Bacteroides fragilis subgroup or a Clostridium coccoides subcluster XIVa species is an early indicator of possible asthma later in life . These findings need to be confirmed in a new longitudinal follow-up study BACKGROUND The intestinal
Output:
| In the microbiota of allergic children whose intestinal microbiota was assessed at the onset of allergic symptoms , there was a higher count of Bacteroides ; a lower count of Akkermansia muciniphila , Faecalibacterium prausnitzii , and Clostridium ; a higher prevalence of B. adolescentis ; a lower prevalence of B. catenulatum and Staphylococcus aureus ; and a lower bacterial diversity |
MS213735 | ***TASK*** the task is to summarize an input biomedical literature in six sentences
***INPUT*** the input is a biomedical literature
***OUTPUT*** the output is the summary of an input biomedical literature in six sentences
***DOCUMENTATION***
***EXAMPLES***
Input: BACKGROUND Although much research has focused on identifying factors that influence breastfeeding initiation and duration , many high-risk factors are nonmodifiable demographic variables . Predisposing factors for low breastfeeding duration rates that are amenable to supportive interventions should be identified . The purpose of this study was to assess the effect of maternal confidence ( breastfeeding self-efficacy ) on breastfeeding duration . METHOD A prospect i ve survey was conducted with 300 women in the last trimester of pregnancy recruited from the antenatal clinic of a large metropolitan hospital in Brisbane , Australia . Telephone interviews were conducted at 1 week and 4 months postpartum to assess infant feeding methods and breastfeeding confidence using the Breastfeeding Self-Efficacy Scale . RESULTS Although 92 percent of participants initiated breastfeeding , by 4 months postpartum almost 40 percent discontinued and only 28.6 percent were breastfeeding exclusively ; the most common reason for discontinuation was insufficient milk supply . Antenatal and 1-week Breastfeeding Self-Efficacy Scale scores were significantly related to breastfeeding outcomes at 1 week and 4 months . Mothers with high breastfeeding self-efficacy were significantly more likely to be breastfeeding , and doing so exclusively , at 1 week and 4 months postpartum than mothers with low breastfeeding self-efficacy . CONCLUSIONS Maternal breastfeeding self-efficacy is a significant predictor of breastfeeding duration and level . Integrating self-efficacy enhancing strategies may improve the quality of healthcare that healthcare professionals deliver and may increase a new mother 's confidence in her ability to breastfeed , and to persevere if she does encounter difficulties Background & Methods To examine the relationship between breastfeeding and maternally-rated infant temperament at age 3 months , 316 infants in the prospect i ve Cambridge Baby Growth Study , UK had infant temperament assessed at age 3 months by mothers using the Revised Infant Behavior Question naire , which produces scores for three main dimensions of temperament derived from 14 subscales . Infant temperament scores were related to mode of infant milk feeding at age 3 months ( breast only ; formula milk only ; or mixed ) with adjustment for infant 's age at assessment and an index of deprivation . Results Infant temperament dimension scores differed across the three infant feeding groups , but appeared to be comparable between exclusive breast-fed and mixed-fed infants . Compared to formula milk-fed infants , exclusive breast-fed and mixed-fed infants were rated as having lower impulsivity and positive responses to stimulation ( adjusted mean [ 95 % CI ] “ Surgency/Extraversion ” in formula-fed vs. mixed-fed vs. breast-fed groups : 4.3 [ 4.2–4.5 ] vs. 4.0 [ 3.8–4.1 ] vs. 4.0 [ 3.9–4.1 ] ; p-heterogeneity = 0.0006 ) , lower ability to regulate their own emotions ( “ Orienting/Regulation ” : 5.1 [ 5.0–5.2 ] , vs. 4.9 [ 4.8–5.1 ] vs. 4.9 [ 4.8–5.0 ] ; p = 0.01 ) , and higher emotional instability ( “ Negative affectivity ” : 2.8 [ 2.6–2.9 ] vs. 3.0 [ 2.8–3.1 ] vs. 3.0 [ 2.9–3.1 ] ; p = 0.03 ) . Conclusions Breast and mixed-fed infants were rated by their mothers as having more challenging temperaments in all three dimensions ; particular subscales included greater distress , less smiling , laughing , and vocalisation , and lower soothability . Increased awareness of the behavioural dynamics of breastfeeding , a better expectation of normal infant temperament and support to cope with difficult infant temperament could potentially help to promote successful breastfeeding OBJECTIVE : Postpartum anxiety screening does not typically occur , despite changes in life roles and responsibility after childbirth . We sought to determine the prevalence of postpartum anxiety during the maternity hospitalization and its associations with maternal and child outcomes . We further aim ed to compare correlates of anxiety with correlates of depression . METHODS : For a r and omized controlled trial of mothers with “ well ” newborns ≥34 weeks ’ gestation comparing 2 post – hospital discharge care models , mothers completed baseline in-person interviews during the postpartum stay and telephone surveys at 2 weeks , 2 months , and 6 months to assess health care use , breastfeeding duration , anxiety , and depression . All participants intended to breastfeed . State anxiety scores ≥40 on the State Trait Anxiety Inventory ( STAI ) and depression scores ≥12 on the Edinburgh Postnatal Depression Survey ( EPDS ) were considered positive . RESULTS : A total of 192 ( 17 % ) of 1123 participating mothers had a positive baseline STAI ; 62 ( 6 % ) had a positive EPDS . Primiparity was associated with a positive STAI ( 20 % vs 15 % , P = .02 ) , but not a positive EPDS ( 4 % vs 7 % , P = .05 ) . Positive STAI scores were associated with cesarean delivery ( 22 % vs 15 % , P = .001 ) , reduced duration of breastfeeding ( P = .003 ) , and increased maternal , but not infant total unplanned health care utilization within 2 weeks of delivery ( P = .001 ) . Positive STAI scores occurred more frequently than positive EPDS scores at each assessment through 6 months postpartum . CONCLUSIONS : Postpartum state anxiety is a common , acute phenomenon during the maternity hospitalization that is associated with increased maternal health care utilization after discharge and reduced breastfeeding duration . State anxiety screening during the postpartum stay could improve these outcomes Several pilot studies have provided evidence that mindfulness-based intervention is beneficial during pregnancy , yet its effects in mothers during the early parenting period are unknown . The purpose of the present pilot study was to examine the effectiveness of a mindfulness-based intervention in breast-feeding mothers . We developed and tested an 8-week mindfulness-based intervention aim ed at improving maternal self-efficacy , mindfulness , self-compassion , satisfaction with life , and subjective happiness , and at reducing psychological distress . A r and omized controlled , between-groups design was used with treatment and control groups ( n = 26 ) and pretest and posttest measures . ANCOVA results indicated that , compared to the control group , mothers in the treatment group scored significantly higher on maternal self-efficacy , some dimensions of mindfulness ( observing , acting with awareness , non-judging , and non-reactivity ) , and self-compassion ( self-kindness , mindfulness , over- identification , and total self-compassion ) . In addition , mothers who received the treatment exhibited significantly less anxiety , stress , and psychological distress . The results supported previous research findings about the benefits of mindfulness-based intervention in women from the perinatal and postpartum periods through the early parenting period . Additional research is needed to vali date our findings in non-breast-feeding mothers and to examine the intervention ’s indirect benefits in terms of family relationships and child development Background Despite high levels of breastfeeding initiation in Australia , only 47 percent of women are breastfeeding ( exclusively or partially ) six months later , with marked differences between social groups . It is important to identify women who are at increased risk of early cessation of breastfeeding . Methods Data from the three arms of a r and omised controlled trial were pooled and analysed as a cohort using logistic regression to identify which factors predicted women continuing to feed any breast milk at six months postpartum . The original trial included 981 primiparous women attending a public , tertiary , women 's hospital in Melbourne , Australia in 1999–2001 . The trial evaluated the effect of two mid-pregnancy educational interventions on breastfeeding initiation and duration . In the 889 women with six month outcomes available , neither intervention increased breastfeeding initiation nor duration compared to st and ard care . Independent variables were included in the predictive model based on the literature and discussion with peers and were each tested individually against the dependent variable ( any breastfeeding at six months ) . Results Thirty-three independent variables of interest were identified , of which 25 qualified for inclusion in the preliminary regression model ; 764 observations had complete data available . Factors remaining in the final model that were positively associated with breastfeeding any breast milk at six months were : a very strong desire to breastfeed ; having been breastfed oneself as a baby ; being born in an Asian country ; and older maternal age . There was an increasing association with increasing age . Factors negatively associated with feeding any breast milk at six months were : a woman having no intention to breastfeed six months or more ; smoking 20 or more cigarettes per day pre-pregnancy ; not attending childbirth education ; maternal obesity ; having self-reported depression in the six months after birth ; and the baby receiving infant formula while in hospital . Conclusion In addition to the factors commonly reported as being associated with breastfeeding in previous work , this study found a negative association between breastfeeding outcomes and giving babies infant formula in hospital , a high maternal body mass index , and self-reported maternal depression or anxiety in the six months after the baby was born . Interventions that seek to increase breastfeeding should consider focusing on women who wish to breastfeed but are at high risk of early discontinuation Background Very low birthweight infants are at risk for deficits in cognitive and language development , as well as attention and behaviour problems . Maternal sensitive behaviour ( i.e. awareness of infant cues and appropriate responsiveness to those cues ) in interaction with her very low birthweight infant is associated with better outcomes in these domains ; however , maternal anxiety interferes with the mother 's ability to interact sensitively with her very low birthweight infant . There is a need for brief , cost-effective and timely interventions that address both maternal psychological distress and interactive behaviour . The Cues and Care trial is a r and omized controlled trial of an intervention design ed to reduce maternal anxiety and promote sensitive interaction in mothers of very low birthweight infants . Methods and design Mothers of singleton infants born at weights below 1500 g are recruited in the neonatal intensive care units of 2 tertiary care hospitals , and are r and omly assigned to the experimental ( Cues ) intervention or to an attention control ( Care ) condition . The Cues intervention teaches mothers to attend to their own physiological , cognitive , and emotional cues that signal anxiety and worry , and to use cognitive-behavioural strategies to reduce distress . Mothers are also taught to underst and infant cues and to respond sensitively to those cues . Mothers in the Care group receive general information about infant care . Both groups have 6 contacts with a trained intervener ; 5 of the 6 sessions take place during the infant 's hospitalization , and the sixth contact occurs after discharge , in the participant mother 's home . The primary outcome is maternal symptoms of anxiety , assessed via self-report question naire immediately post-intervention . Secondary outcomes include maternal sensitive behaviour , maternal symptoms of posttraumatic stress , and infant development at 6 months corrected age . Discussion The Cues and Care trial will provide important information on the efficacy of a brief , skills-based intervention to reduce anxiety and increase sensitivity in mothers of very low birthweight infants . A brief intervention of this nature may be more readily implemented as part of st and ard neonatal intensive care than broad-based , multi-component interventions . By intervening early , we aim to optimize developmental outcomes in these high risk infants . Trial Registration Current Controlled Trials IS RCT N00918472The Cues and Care Trial : A r and omized controlled trial of an intervention to reduce maternal anxiety and improve developmental outcomes in very low birthweight AIM Depressive and anxiety symptoms are common in new mothers . The aim of this study is to explore the link between postpartum psychological adjustment and feeding preferences of the mothers . METHODS Sixty mothers and newborns were enrolled in this prospect i ve , longitudinal study . Maternal depressive symptoms were screened by the Edinburgh Postpartum Depression Scale ( EPDS ) , and maternal anxiety level was assessed by the State-Trait Anxiety Inventory at 1 month postpartum . The Multidimensional Scale of Perceived Social Support was used for the assessment of maternal social support . The Adult Attachment Scale was used to determine the attachment style of the mother . Infants were examined and evaluated at 1 and 4 months of life . RESULTS All mothers started breastfeeding their infants postpartum ; 91 % and 68.1 % continued exclusive breastfeeding at 1 and 4 months , respectively . The first-month median EPDS score of mothers who breastfeed at the fourth month was statistically significantly lower than those who were not breastfeeding ( 6 and 12 , respectively ) ( P = 0001 ) . The first-month median EPDS score of mothers with secure attachment was lower than the median score of mothers with insecure attachment ( 5 and 9 , respectively ) ( P < 0001 ) . Exclusive breastfeeding rate was not statistically different among mothers with secure and insecure attachment styles . The median state and trait anxiety scores and social support scores of mothers were not different between groups according to breastfeeding status . CONCLUSIONS This study has shown an association between higher EPDS scores and breastfeeding cessation by 4 months after delivery BACKGROUND Maternal eating disorders ( ED ) have been shown to increase the risk of feeding difficulties in the offspring . Very few studies , however , have investigated whether the effect of a maternal ED on childhood feeding is a direct effect or whether it can be ascribed to other child or maternal factors . We aim ed to determine the role of maternal anxiety and depression in mediating the risk for feeding difficulties in infants of women with ED . METHODS A prospect i ve study comparing women with lifetime ED ( 441 ) and without any lifetime psych
Output:
| Results indicated that women with symptoms of PPA are less likely to breastfeed exclusively and more likely to terminate breastfeeding earlier .
Some evidence also suggests that those experiencing PPA are less likely to initiate breastfeeding and more likely to supplement with formula in the hospital .
In those who do breastfeed , PPA reduces self-efficacy , increases breastfeeding difficulties , and may negatively affect breastfeeding behaviors and breast milk composition .
However , in combination with a review linking depression with similar negative infant-feeding sequelae , the findings provide evidence for the effect of negative postpartum mood on breastfeeding . |
MS213736 | ***TASK*** the task is to summarize an input biomedical literature in six sentences
***INPUT*** the input is a biomedical literature
***OUTPUT*** the output is the summary of an input biomedical literature in six sentences
***DOCUMENTATION***
***EXAMPLES***
Input: [11C]Pittsburgh compound B ( [11C]PIB ) and [18F]‐2‐fluoro‐2‐deoxy‐D‐glucose ( [18F]FDG ) PET measure fibrillar amyloid‐β load and glucose metabolism , respectively . We evaluated the impact of these tracers on the diagnostic process in a memory clinic population BACKGROUND Subjects with a mild cognitive impairment ( MCI ) have a memory impairment beyond that expected for age and education yet are not demented . These subjects are becoming the focus of many prediction studies and early intervention trials . OBJECTIVE To characterize clinical ly subjects with MCI cross-sectionally and longitudinally . DESIGN A prospect i ve , longitudinal inception cohort . SETTING General community clinic . PARTICIPANTS A sample of 76 consecutively evaluated subjects with MCI were compared with 234 healthy control subjects and 106 patients with mild Alzheimer disease ( AD ) , all from a community setting as part of the Mayo Clinic Alzheimer 's Disease Center/Alzheimer 's Disease Patient Registry , Rochester , Minn. MAIN OUTCOME MEASURES The 3 groups of individuals were compared on demographic factors and measures of cognitive function including the Mini-Mental State Examination , Wechsler Adult Intelligence Scale-Revised , Wechsler Memory Scale-Revised , Dementia Rating Scale , Free and Cued Selective Reminding Test , and Auditory Verbal Learning Test . Clinical classifications of dementia and AD were determined according to the Diagnostic and Statistical Manual of Mental Disorders , Revised Third Edition and the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer 's Disease and Related Disorders Association criteria , respectively . RESULTS The primary distinction between control subjects and subjects with MCI was in the area of memory , while other cognitive functions were comparable . However , when the subjects with MCI were compared with the patients with very mild AD , memory performance was similar , but patients with AD were more impaired in other cognitive domains as well . Longitudinal performance demonstrated that the subjects with MCI declined at a rate greater than that of the controls but less rapidly than the patients with mild AD . CONCLUSIONS Patients who meet the criteria for MCI can be differentiated from healthy control subjects and those with very mild AD . They appear to constitute a clinical entity that can be characterized for treatment interventions Purpose [11C]PIB and [18F]FDDNP are PET tracers for in vivo detection of the neuropathology underlying Alzheimer ’s disease ( AD ) . [18F]FDG is a glucose analogue and its uptake reflects metabolic activity . The purpose of this study was to examine longitudinal changes in these tracers in patients with AD or mild cognitive impairment ( MCI ) and in healthy controls . Methods Longitudinal , paired , dynamic [11C]PIB and [18F]FDDNP ( 90 min each ) and static [18F]FDG ( 15 min ) PET scans were obtained in 11 controls , 12 MCI patients and 8 AD patients . The mean interval between baseline and follow-up was 2.5 years ( range 2.0–4.0 years ) . Parametric [11C]PIB and [18F]FDDNP images of binding potential ( BPND ) and [18F]FDG st and ardized uptake value ratio ( SUVr ) images were generated . Results A significant increase in global cortical [11C]PIB BPND was found in MCI patients , but no changes were observed in AD patients or controls . Subsequent regional analysis revealed that this increase in [11C]PIB BPND in MCI patients was most prominent in the lateral temporal lobe ( p < 0.05 ) . For [18F]FDDNP , no changes in global BPND were found . [18F]FDG uptake was reduced at follow-up in the AD group only , especially in frontal , parietal and lateral temporal lobes ( all p < 0.01 ) . Changes in global [11C]PIB binding ( ρ = −0.42 , p < 0.05 ) and posterior cingulate [18F]FDG uptake ( ρ = 0.54 , p < 0.01 ) were correlated with changes in Mini-Mental-State Examination score over time across groups , whilst changes in [18F]FDDNP binding ( ρ = −0.18 , p = 0.35 ) were not . Conclusion [11C]PIB and [18F]FDG track molecular changes in different stages of AD . We found increased amyloid load in MCI patients and progressive metabolic impairment in AD patients . [18F]FDDNP seems to be less useful for examining disease progression Objective : To investigate the 10-year risk of dementia in subjects with mild cognitive impairment ( MCI ) ages 40 to 85 years . Methods : We selected subjects from a memory clinic if they met one of the following definitions of MCI : cognitive complaints ( n = 181 ) , aging-associated cognitive decline ( AACD ) ( n = 163 ) , mild functional impairment ( n = 86 ) , or amnestic MCI ( n = 64 ) . Subjects were reassessed after 2 , 5 , and 10 years . The risk of dementia was calculated with Kaplan-Meier statistics . Analyses were conducted in the entire sample and in subgroups of subjects aged 40 to 54 years , 55 to 69 years , and 70 to 85 years . Results : The 10-year risk of dementia was 0.27 ( 95 % CI 0.20 to 0.34 ) in subjects with cognitive complaints , 0.28 ( 95 % CI 0.21 to 0.35 ) in subjects with AACD , 0.44 ( 95 % CI 0.32 to 0.56 ) in subjects with mild functional impairment , and 0.48 ( 95 % CI 0.35 to 0.61 ) in subjects with amnestic MCI . Ninety-one percent of the demented subjects had probable AD . The risk of dementia increased with increasing age for all MCI definitions ( p < 0.001 ) . Depending on the MCI definition used , the risk for dementia ranged from 0 to 0.06 in subjects aged 40 to 54 years , from 0.37 to 0.52 in subjects aged 55 to 69 years , and from 0.77 to 1.0 in subjects aged 70 to 85 years . Conclusions : The majority of subjects with MCI do not progress to dementia at the long term . Age strongly influences the dementia risk . MCI often represents the predementia stage of a neurodegenerative disorder in elderly subjects but rarely in younger subjects CONTEXT Small single-center studies have shown that cerebrospinal fluid ( CSF ) biomarkers may be useful to identify incipient Alzheimer disease ( AD ) in patients with mild cognitive impairment ( MCI ) , but large-scale multicenter studies have not been conducted . OBJECTIVE To determine the diagnostic accuracy of CSF beta-amyloid(1 - 42 ) ( Abeta42 ) , total tau protein ( T-tau ) , and tau phosphorylated at position threonine 181 ( P-tau ) for predicting incipient AD in patients with MCI . DESIGN , SETTING , AND PARTICIPANTS The study had 2 parts : a cross-sectional study involving patients with AD and controls to identify cut points , followed by a prospect i ve cohort study involving patients with MCI , conducted 1990 - 2007 . A total of 750 individuals with MCI , 529 with AD , and 304 controls were recruited by 12 centers in Europe and the United States . Individuals with MCI were followed up for at least 2 years or until symptoms had progressed to clinical dementia . MAIN OUTCOME MEASURES Sensitivity , specificity , positive and negative likelihood ratios ( LRs ) of CSF Abeta42 , T-tau , and P-tau for identifying incipient AD . RESULTS During follow-up , 271 participants with MCI were diagnosed with AD and 59 with other dementias . The Abeta42 assay in particular had considerable intersite variability . Patients who developed AD had lower median Abeta42 ( 356 ; range , 96 - 1075 ng/L ) and higher P-tau ( 81 ; range , 15 - 183 ng/L ) and T-tau ( 582 ; range , 83 - 2174 ng/L ) levels than MCI patients who did not develop AD during follow-up ( 579 ; range , 121 - 1420 ng/L for Abeta42 ; 53 ; range , 15 - 163 ng/L for P-tau ; and 294 ; range , 31 - 2483 ng/L for T-tau , P < .001 ) . The area under the receiver operating characteristic curve was 0.78 ( 95 % confidence interval [ CI ] , 0.75 - 0.82 ) for Abeta42 , 0.76 ( 95 % CI , 0.72 - 0.80 ) for P-tau , and 0.79 ( 95 % CI , 0.76 - 0.83 ) for T-tau . Cut-offs with sensitivity set to 85 % were defined in the AD and control groups and tested in the MCI group , where the combination of Abeta42/P-tau ratio and T-tau identified incipient AD with a sensitivity of 83 % ( 95 % CI , 78%-88 % ) , specificity 72 % ( 95 % CI , 68%-76 % ) , positive LR , 3.0 ( 95 % CI , 2.5 - 3.4 ) , and negative LR , 0.24 ( 95 % CI , 0.21 - 0.28 ) . The positive predictive value was 62 % and the negative predictive value was 88 % . CONCLUSIONS This multicenter study found that CSF Abeta42 , T-tau , and P-tau identify incipient AD with good accuracy , but less accurately than reported from single-center studies . Intersite assay variability highlights a need for st and ardization of analytical techniques and clinical procedures Abstract OBJECTIVES To determine the 2-year outcome from 16 different current classifications of mild cognitive impairment ( MCI ) in a population -based sample . DESIGN Prospect i ve cohort study : baseline and 2-year follow-up phases . SETTING Large-scale multicenter study , United Kingdom . PARTICIPANTS : Thirteen thous and four individuals aged 65 and older from the Medical Research Council Cognitive Function and Ageing Study . From this , a sub sample of 2,640 individuals was selected and completed a more-detailed cognitive assessment . Individuals who underwent further assessment were asked to complete annual or 2-year follow-ups . MEASUREMENTS Information on sociodemographic status , general health , cognitive impairment and functional ability were collected using a structured interview . Individuals were classified according to 16 different definitions of MCI . These were applied retrospectively . RESULTS The dominant outcome across definitions was an impairment that was not classifiable or reversion to normality . Progression to dementia was variable and generally poor . Overall progression was highest in classifications in which impairment extended to memory and nonmemory domains . Predictability was age dependent in some but not all classifications . CONCLUSION Current classifications of MCI have variable outcomes in population -based sample s. Progression to dementia is relatively rare and is dependent on age and definition . Selection criteria developed for the clinic are based on a " high risk " approach that leads to exclusion of a large percentage of the impaired population who are neither normal nor demented and for whom no intervention options are currently available . A refined definition of this construct is urgently needed if MCI is to be used to predict dementia in population -based studies UNLABELLED Patients with mild cognitive impairment ( MCI ) represent a risk population for progressing to dementia of the Alzheimer type ( DAT ) . However , clinical criteria do not ensure reliable individual prognosis in these patients . The objective of this longitudinal , prospect i ve study was to examine the value of (18)F-FDG PET of cerebral glucose metabolism and of genetic susceptibility , as defined by an APOEepsilon4-positive genotype , with regard to the early diagnosis of DAT in patients with MCI . METHODS In 30 patients with the diagnosis of MCI ( 16 female , 14 male ; age , 70 + /- 8 y ) , baseline and follow-up examinations ( mean observation period , 16 mo ) were performed . In all patients , the APOE genotype was assessed and cerebral glucose metabolism was evaluated at baseline using cranial (18)F-FDG PET . Individual PET data were screened for findings suggestive of Alzheimer 's disease ( AD ) , with the help of an automated computer program . After stereotactical normalization of the PET images , this program performs an observer-independent statistical comparison with an age-matched reference data base ( n = 22 ) . RESULTS In 43 % of all MCI subjects , a PET scan suggestive of AD pathology according to our predefined criteria was observed at baseline ( PET+ ) ; 57 % of all MCI patients were carriers of the APOE epsilon4 allele ( e4 + ) . In 40 % of all patients , progression of symptoms within the observation period justified the clinical diagnosis of probable DAT at the time of follow-up reevaluation . Statistical evaluation revealed the best results for
Output:
| Conclusion : Systematic and comprehensive assessment of studies of 18FDG-PET for prediction of conversion from MCI to AD dementia reveals many studies have method ological limitations according to Cochrane diagnostic test accuracy gold st and ards , and shows accuracy remains highly variable , including in the most recent studies . |
MS213737 | ***TASK*** the task is to summarize an input biomedical literature in six sentences
***INPUT*** the input is a biomedical literature
***OUTPUT*** the output is the summary of an input biomedical literature in six sentences
***DOCUMENTATION***
***EXAMPLES***
Input: OBJECTIVE Because universal psychoeducational eating disorder prevention programs have had little success , we developed and evaluated two interventions for high-risk population s : a healthy weight control intervention and a dissonance-based intervention . METHOD Adolescent girls ( N = 148 ) with body image concerns were r and omized to one of these interventions or to a waitlist control group . Participants completed baseline , termination , and 1 , 3 , and 6-month follow-up surveys . RESULTS Participants in both interventions reported decreased thin-ideal internalization , negative affect , and bulimic symptoms at termination and follow-up relative to controls . However , no effects were observed for body dissatisfaction or dieting and effects diminished over time . DISCUSSION Results provide evidence that both interventions effectively reduce bulimic pathology and risk factors for eating disturbances This study evaluated a targeted intervention design ed to alleviate body image and eating problems in adolescent girls that was delivered over the internet so as to increase access to the program . The program consisted of six , 90-minute weekly small group , synchronous on-line sessions and was facilitated by a therapist and manual . Participants were 73 girls ( mean age=14.4 years , SD=1.48 ) who self-identified as having body image or eating problems and were r and omly assigned to an intervention group ( n=36 ) ( assessed at baseline , post-intervention and at 2- and 6-months follow-up ) or a delayed treatment control group ( n=37 ) ( assessed at baseline and 6–7 weeks later ) . Clinical ly significant improvements in body dissatisfaction , disordered eating , and depression were observed at post-intervention and maintained at follow-up . Internet delivery was enthusiastically endorsed . The program offers a promising approach to improve body image and eating problems that also addresses geographic access problems Although it is widely accepted that dieting increases the risk for bulimic pathology , this hypothesis has not been tested in a r and omized experiment . Accordingly , the authors conducted an experimental test of the dietary restraint model by r and omly assigning nonobese women ( N = 82 ) to either a 6-week , low-calorie diet or a waitlist control condition . The diet intervention result ed in significant weight loss , confirming that dieting was successfully manipulated . Contrary to the restraint model , dieting result ed in significant decreases in bulimic symptoms relative to the control condition . Results converge with past findings from r and omized obesity prevention and treatment trials and provide evidence that dieting does not promote bulimic pathology ; rather , effective decreases in caloric intake appear to reduce bulimic symptoms Project GRAD ( Graduate Ready for Activity Daily ) was a r and omized controlled study to teach university seniors behavioral skills necessary for increasing and /or maintaining physical activity habits in preparation for the transition to working adult roles after graduation . This study examines the secondary effects of this intervention on body image concerns among college-aged men and women . Three hundred thirty-eight undergraduates ( 54 % female , M age = 24 years , SD = 1.95 ; M Body Mass Index = 24.26 , SD = 4.0 ) were studied . The sample was 61 % Anglo , 16 % Latino , 16 % Asian/Pacific Isl and er , 4 % African American , and 3 % Native American/Other . Body image concerns were assessed at pre- and posttreatment using 2 subscales of the Eating Disorder Inventory : Drive for Thinness and Body Dissatisfaction . Because the latter concentrates on body parts typically associated with female concerns ( e.g. , thighs , hips , buttocks ) , a parallel scale was developed to target body parts that may be of more concern to men ( e.g. , legs , shoulders , arms , stomach ) . Results indicated that compared to the control group , women in the intervention showed a significant increase in drive for thinness without any changes in body dissatisfaction . For men , there were no significant changes in drive for thinness or body dissatisfaction . These results suggest that physical activity interventions may have some negative consequences of increasing concerns about thinness in women . This negative effect occurred despite intervention content design ed to prevent concern over eating , dieting , and the importance of weight . Health promotion studies should include assessment s of potential negative side effects BACKGROUND Body image dissatisfaction during adolescence is common but not benign . School-based interventions have the potential for wide reach , but scalability of previous programmes is limited by a reliance on external facilitators . AIMS To assess the acceptability , feasibility and efficacy of a teacher-delivered body image intervention . METHOD A pilot clustered r and omised controlled trial in which 16 classes of adolescent girls were allocated to a 6-session body image programme ( n = 261 ) , or usual curriculum control ( n = 187 ) ( registration : IS RCT N42594993 ) . RESULTS Students in the intervention group had significantly improved body esteem and self-esteem and reduced thin-ideal internalisation . Effects for body esteem and thin-ideal internalisation were maintained for 3 months . There were no group differences for eating pathology , peer factors or depression . Acceptability , feasibility and efficacy varied between schools . CONCLUSIONS Teacher-delivered body image lessons have promise but further work is needed to increase efficacy and make interventions suitable across a range of schools This study assessed the impact of a school-based program aim ed at preventing disordered eating . The program was based on the media-literacy approach and has interactive format . The program was assessed under strong method ological conditions . Seven schools with 263 Spanish adolescent girls in the area of Barcelona , were r and omly assigned to either the complete prevention program condition , the partial program condition or the non-treatment control condition , and assessed at pre , post and 6-month follow-up . The program was effective in generating positive changes at follow-up . The effects sizes ( ES(d ) = 0.29 to ES(d ) = 0.38 ) were greater , on average , than that obtained up to now in selective-universal programs , and similar or greater than that achieved by targeted prevention programs . The results indicate a greater and relevant effect size of the intervention in those participants who completed the inter-session interactive activities ( ES(d ) = 0.29 to ES(d ) = 0.45 ) although the differences were not significant . These results suggest the importance of monitoring adherence to the activities in all programs defined as " interactive " . The implication s and limitations of this study are discussed OBJECTIVE Although several prospect i ve studies have identified factors that increase risk for eating disorders , little is known about when these risk factors emerge and escalate , or when they begin to predict future eating disorder onset . The objective of this report was to address these key research gaps . METHOD Data were examined from a prospect i ve study of 496 community female adolescents ( M = 13.5 , SD = 0.7 at baseline ) who completed eight annual assessment s of potential risk factors and eating disorders from preadolescence to young adulthood . RESULTS Three variables exhibited positive linear increases : Perceived pressure to be thin , thin-ideal internalization , and body dissatisfaction ; three were best characterized as quadratic effects : dieting ( essentially little change ) ; negative affectivity ( overall decrease ) , and BMI ( overall increase ) . Elevated body dissatisfaction at ages 13 , 14 , 15 , and 16 predicted DSM-5 eating disorders onset in the 4-year period after each assessment , but the predictive effects of other risk factors were largely confined to age 14 ; BMI did not predict eating disorders at any age . DISCUSSION The results imply that these risk factors are present by early adolescence , although eating disorders tend to emerge in late adolescence and early adulthood . These findings emphasize the need for efficacious eating disorder prevention programs for early adolescent girls , perhaps targeting 14-year olds , when risk factors seem to be most predictive . In early adolescence , it might be fruitful to target girls with body dissatisfaction , as this was the most consistent predictor of early eating disorder onset in this study OBJECTIVE To assess the impact of an obesity prevention intervention on use of self-induced vomiting/laxatives ( purging ) and diet pills to control weight in girls in early adolescence . DESIGN We matched and r and omly assigned 10 middle schools to an intervention or a control condition in a r and omized controlled trial . Longitudinal multivariable analyses using generalized estimating equations were conducted with data from 480 girls to examine the effects of the intervention on the risk of reporting a new case of purging or diet pill use to control weight at follow-up 21 months later , while controlling for ethnicity and school matched pairs . Girls who reported purging or using diet pills at baseline were excluded from analyses . SETTING Middle schools . PARTICIPANTS Four hundred eighty girls in early adolescence aged 10 to 14 years ( mean age , 11.5 years ) . INTERVENTION The Planet Health obesity prevention program was implemented during 2 school years and was design ed to promote healthful nutrition and physical activity and to reduce television viewing . OUTCOME Reduced risk of using self-induced vomiting/laxatives or diet pills to control weight in the past 30 days . RESULTS After the intervention , we found 14 ( 6.2 % ) of 226 girls in control schools and 7 ( 2.8 % ) of 254 girls in intervention schools reported purging or using diet pills to control their weight ( P = .003 ) . In a multivariable generalized estimating equation model , girls in intervention schools were less than half as likely to report purging or using diet pills at follow-up compared with girls in control schools ( odds ratio , 0.41 ; 95 % confidence interval , 0.22 - 0.75 ) . CONCLUSION These findings provide promising evidence that school-based interventions may effectively integrate prevention of both obesity and disordered weight-control behaviors This two-group experimental study evaluated the effectiveness of a cognitive-behavioral body image intervention , adapted from an effective clinical intervention , with normal college females . Participants included non clinical , freshman college women who were assigned r and omly to either the experimental intervention or the control group ( brief educational session ) . Participants were assessed prior to the intervention and again 1 month later on dieting behavior , body image , fear of fat , and anxiety concerning physical appearance . Although it was hypothesized that each of these variables would be lower in the experimental group , none of these results , except for a trend for decreased dieting , were found . Overall these results of slightly reduced dieting behavior are consistent with other research targeting primary and secondary prevention . This intervention 's failure to impact body image and eating behaviors of college students illustrates the continuing challenge of eating disorders prevention CONTEXT Eating disorders , an important health problem among college-age women , may be preventable , given that modifiable risk factors for eating disorders have been identified and interventions have been evaluated to reduce these risk factors . OBJECTIVE To determine if an Internet-based psychosocial intervention can prevent the onset of eating disorders ( EDs ) in young women at risk for developing EDs . SETTING San Diego and the San Francisco Bay Area in California . PARTICIPANTS College-age women with high weight and shape concerns were recruited via campus e-mails , posters , and mass media . Six hundred thirty-seven eligible participants were identified , of whom 157 were excluded , for a total sample of 480 . Recruitment occurred between November 13 , 2000 , and October 10 , 2003 . Intervention A r and omized controlled trial of an 8-week , Internet-based cognitive-behavioral intervention ( Student Bodies ) that included a moderated online discussion group . Participants were studied for up to 3 years . MAIN OUTCOME MEASURES The main outcome measure was time to onset of a sub clinical or clinical ED . Secondary measures included change in scores on the Weight Concerns Scale , Global Eating Disorder Examination Question naire , and Eating Disorder Inventory drive for thinness and bulimia subscales and depressed mood . Moderators of outcome were examined . RESULTS There was a significant reduction in Weight Concerns Scale scores in the Student Bodies intervention group compared with the control group at postintervention ( P < .001 ) , 1 year ( P < .001 ) , and 2 years ( P < .001 ) . The slope for reducing Weight Concerns Scale score was significantly greater in the treatment compared with the control group ( P = .02 ) . Over the course of follow-up , 43 participants developed sub clinical or clinical EDs . While there was no overall significant difference in onset of EDs between the intervention and control groups , the intervention significantly reduced the onset of EDs in 2 subgroups identified through moderator analyses : ( 1 ) participants with an elevated body mass index ( BMI ) ( > or = 25 , calculated as weight in kilograms divided by height in meters squared ) at baseline and ( 2 ) at 1 site , participants with baseline compensatory behaviors ( eg , self-induced vomiting , laxative use , diuretic use , diet pill use , driven exercise ) . No intervention participant with an elevated baseline BMI developed an ED , while the rates of onset of ED in the comparable BMI control group ( based on survival analysis ) were 4.7 % at 1 year and 11.9 % at 2 years . In the subgroup with a BMI of 25 or higher , the cumulative survival incidence was significantly lower at 2 years for the intervention compared with the control group ( 95 % confidence interval , 0 % for intervention group ; 2.7 % to 21.1 % for control group ) . For the San Francisco Bay Area site sample with baseline compensatory behaviors , 4 % of participants in the intervention group developed EDs at 1 year and 14.4 % , by 2 years . Rates for the comparable control group were 16 % and 3
Output:
| Findings indicated small to moderate effect sizes on reduction of ED risk factors or symptoms which occurred up to three-year post-intervention .
Cognitive behavioural therapy ( CBT ) interventions had the largest effect size ( -0.40 , 95 % CI -0.55 to -0.26 ) on dieting outcome at 9-month follow-up while the healthy weight intervention reduced ED risk factors and body mass index .
No indicated prevention interventions were found to be effective in reducing ED risk factors .
CONCLUSIONS There are a number of promising preventive interventions for ED risk factors including CD , CBT and ML .
Whether these actually lower ED incidence is , however , uncertain . |
MS213738 | ***TASK*** the task is to summarize an input biomedical literature in six sentences
***INPUT*** the input is a biomedical literature
***OUTPUT*** the output is the summary of an input biomedical literature in six sentences
***DOCUMENTATION***
***EXAMPLES***
Input: The introduction , more than half a century ago , of properly r and omised trials in which the treatment allocation was rigorously concealed was a watershed in the evaluation of treatment effects.1 But this major advance did not come out of the blue : as was highlighted at a recent conference in Oxford ( Beating biases in therapeutic research : historical perspectives , www.wuhmo.ox.ac.uk/docs/BeatingBiases.html ) , attempts to combat bias in therapeutic evaluation had in fact been made during the preceding few centuries.2–4 In the 18th century , the traditional practice of cl aim ing therapeutic achievement on the basis of pathophysiological theories and anecdotal “ successes ” started to be challenged by medical non-conformists who wrote careful , prospect i ve , analytical accounts of medical treatments , some of which included comparison with a control group.4 These “ arithmetic observationists and experimentalists”4 recognised the need In a prospect i ve study of stress fractures the hypothesis that a shock-absorbing orthotic device worn within military boots could lessen the incidence of stress fractures was tested . The incidence of metatarsal , tibial , and femoral stress fractures was lower in the orthotic group , but only the latter difference was statistically significant . The time of onset and the location of stress fractures between orthotic and nonorthotic users did not differ . These findings suggest that the incidence of femoral stress fractures , which are the most dangerous type of stress fracture because of their high risk of developing into displaced fractures , can be reduced by an orthotic device Sedentary individuals , particularly new military recruits , who start a physical training program have a substantial risk of developing an overuse injury of the lower limb . In this study we investigated the effect of neoprene insoles on the incidence of overuse injuries during 9 weeks of basic military training . The experimental group consisted of 237 r and omly selected new recruits , while 1151 recruits were the control group . Insoles were given to the experimental group and compliance was monitored . A panel of doctors documented and classi fied all injuries occurring during the 9 week period . A total of 54 ( 22.8 % ) and 237 ( 31.9 % ) injuries were reported in the experimental and control groups , re spectively . In both groups , the majority of injuries were overuse ( experimental group , 90.7 % ; control group , 86.4 % ) . The mean weekly incidence of total overuse injuries and tibial stress syndrome was significantly lower ( P < 0.05 ) in the experimental group . The mean incidence of stress fractures was lower in the experimental group but not significantly so ( 0.05 < P < 0.1 ) . This study shows that the incidence of total overuse injuries and tibial stress syndrome during 9 weeks of basic military training can be reduced by wearing insoles In a prospect i ve study of stress fractures the hypothesis that training with custom made biomechanical shoe orthoses could lessen the incidence of stress fractures in infantry recruits was tested . Recruits were assigned r and omly to groups and given soft biomechanical orthoses or semirigid biomechanical orthoses and compared with a control group that did not train in biomechanical orthoses . All recruits wore infantry boots with soles design ed like those of basketball shoes . Recruits were examined biweekly during 14 weeks of basic training . The incidence of stress fractures was 15.7 % for the recruits with the semirigid biomechanical orthoses , 10.7 % for the recruits with the soft biomechanical orthoses , and 27 % for the control group . The soft biomechanical orthoses were tolerated better by the recruits than were the semirigid devices . Among trainees at high risk for stress fractures , prophylactic use of custom made biomechanical orthoses may be warranted BACKGROUND Only about a third of people with asthma attend an annual review . Clinicians need to identify cost-effective ways to improve access and ensure regular review . AIM To compare the cost-effectiveness of nurse-led telephone with face-to-face asthma review s. DESIGN OF STUDY Cost-effectiveness analysis based on a 3-month r and omised controlled trial . SETTING Four general practice s in Engl and . METHOD Adults due an asthma review were r and omised to telephone or face-to-face consultations . Trial nurses recorded proportion review ed , duration of consultation , and abortive calls/missed appointments . Data on use of healthcare re sources were extracted from GP records . Cost-effectiveness was assessed from the health service perspective ; sensitivity analyses were based on proportion review ed and duration of consultation . RESULTS A total of 278 people with asthma were r and omised to surgery ( n = 141 ) or telephone ( n = 137 ) review . Onehundred- and -one ( 74 % ) of those with asthma in the telephone group were review ed versus 68 ( 48 % ) in the surgery group ( P < 0.001 ) . Telephone consultations were significantly shorter ( mean duration telephone = 11.19 minutes [ st and ard deviation { SD } = 4.79 ] versus surgery = 21.87 minutes [ SD = 6.85 ] , P < 0.001 ) . Total respiratory healthcare costs per patient over 3 months were similar ( telephone = pounds sterling 64.49 [ SD = 73.33 ] versus surgery = pounds sterling 59.48 [ SD = 66.02 ] , P = 0.55 ) . Total costs of providing 101 telephone versus 68 face-to-face asthma review s were also similar ( telephone = pounds sterling 725.84 versus surgery = pounds sterling 755.70 ) , but mean cost per consultation achieved was lower in the telephone arm ( telephone = pounds sterling 7.19 [ SD = 2.49 ] versus surgery = pounds sterling 11.11 [ SD = 3.50 ] ; mean difference = - pounds sterling 3.92 [ 95 % confidence interval = - pounds sterling 4.84 to pounds sterling 3.01 ] , P < 0.001 ) . CONCLUSIONS Telephone consultations enable a greater proportion of asthma patients to be review ed at no additional cost to the health service . This mode of delivering care improves access and reduces cost per consultation achieved The utility of shock-absorbing boot and sneaker inserts for reducing the occurrence of lower limb pain among male US Army basic trainees was evaluated . Every other training unit was given inserts . The inserts were issued prior to the start of training when combat boots and sneakers were fitted . According to post-training question naires and the participants ' medical records , the inserts did not have any preventive effect on occurrence of lower limb problems during training . Five hundred seventeen trainees were issued inserts , 397 were followed but not issued inserts , and 218 were not issued but purchased them on their own . Thirty-eight percent of those issued inserts had lower limb pain problems compared with 29 % of those not issued inserts and 38 % of those who bought their own . There was no statistical difference between these rates of occurrence . Prior to training , there were minor differences between the groups ' scores on physical fitness test scores and run times . These differences disappeared during training so that there were no differences among the groups on either training or clinical variables during or after basic training As part of a larger study of the effect of foot shape on functioning , 47 Royal Australian Air Force recruits with flexible flat feet who were embarking on a 10-week basic training course took part in a r and omized controlled trial of orthotic therapy . In particular , recruits were assigned at r and om to an untreated group or a group that received Australian Orthotics Laboratory , three-quarter-length , flexible , shoe inserts . The groups were assessed at baseline and week 8 . Outcome measures included pain , injury , foot health , and quality of life . The untreated group ( n = 22 ) had a greater proportion of heavier recruits than did the treated group ( n = 25 ) . There were no significant differences in outcome measures at baseline . Only one-half of the group assigned to orthotic therapy wore the orthotics most or all of the time . At the end of the trial , although the results were not statistically significant , those who were provided with orthotics and wore them had the least lower limb pain and the best general foot health and quality of life . Notably , none of the recruits who wore their orthotics most or all of the time sustained a training injury A prospect i ve controlled trial was carried out to determine the usefulness of a viscoelastic polymer insole in prevention of stress fractures and stress reactions of the lower extremities . The subjects were 3,025 US Marine recruits who were followed for 12 weeks of training at Parris Isl and , South Carolina . Polymer and st and ard mesh insoles were systematic ally distributed in boots that were issued to members of odd and even numbered platoons . The most important finding was that an elastic polymer insole with good shock absorbency properties did not prevent stress reactions of bone during a 12-week period of vigorous physical training . To control for the confounding effects of running in running shoes , which occurred for about one and one-half hours per week for the first five weeks , we also examined the association of age of shoes and cost of shoes with injury incidence . A slight trend of increasing stress injuries by increasing age of shoes was observed . However , this trend did not account for the similarity of rates in the two insole groups . In addition , we observed a strong trend of decreasing stress injury rate by history of increasing physical activity , as well as a higher stress injury rate in White compared to Black recruits . The results of the trial were not altered after controlling for these factors . This prospect i ve study confirms previous clinical reports of the association of stress fractures with physical activity history . The clinical application of a shock absorbing insole as a preventive for lower extremity stress reactions is not supported in these uniformly trained recruits . The findings are relevant to civilian population Background : Foot orthoses are widely prescribed both to treat existing pathological conditions and to prevent overuse injuries , but little is known about the effect of their material composition and fabrication technique on patient comfort and the incidence of overuse injuries . Material s and Methods : The acceptance rates and comfort scores of soft custom , soft prefabricated , semirigid biomechanical , and semirigid prefabricated orthoses and their effect on the incidence of stress fractures , ankle sprains , and foot problems were studied in a prospect i ve , r and omized , single-blinded clinical trial among 874 infantry recruits during basic training . Results : A statistically significantly lower number of recruits given soft prefabricated orthoses ( 53 % ) finished basic training in their assigned devices than in the soft custom group ( 72 % ) , in the semirigid biomechanical group ( 75 % ) , and in the semirigid prefabricated group ( 82 % ) ( p = .003 ) . For recruits who finished training in their assigned orthoses , the soft custom ( 3.54 ) and soft prefabricated ( 3.43 ) orthoses had significantly higher comfort scores than the semirigid biomechanical ( 3.23 ) and prefabricated ( 3.17 ) orthoses , ( p = .0001 ) . There was no statistically significant difference in the incidence of stress fractures , ankle sprains , or foot problems between recruits using the different types of orthoses . Conclusions : These findings suggest that if a foot orthosis is being dispensed as prophylaxis for overuse injuries in an active , healthy population , there is little justification for prescribing semirigid biomechanical orthoses . Their cost is high compared to other types of orthoses , without an advantage in comfort or a reduction in stress fractures , ankle sprains , and foot problems
Output:
| It is not clear why telephone consultations are briefer , i.e. if it is due to loss of physical examination time , discussion of fewer problems , less health promotion , less social speech or if it is achieved at the expense of patient-centredness or holistic care .
In a recent pilot study of out-of-hours telephone consultations ( Heaney D , personal communication 2005 ) clinical quality , while difficult to measure reliably , appeared worryingly poor .
While most patients have access to telephones , the most disadvantaged may only have access to expensive mobile devices .
In addition , some minority groups such as those who are hard of hearing ( 43 % of those over 70 years11 ) and those who do not use English as a first language may be disadvantaged by systems that insist on the telephone being the first point of contact .
Currently , telephone consulting appears to be rather indiscriminately used for many very different problems , presentations and patient groups despite scant information on quality of care , patient acceptability and impact on workload .
Particularly as this form of consultation appears to be increasingly used and in new ways it is important to establish for which types of consultation and problems and for which patients it is most appropriate . |
MS213739 | ***TASK*** the task is to summarize an input biomedical literature in six sentences
***INPUT*** the input is a biomedical literature
***OUTPUT*** the output is the summary of an input biomedical literature in six sentences
***DOCUMENTATION***
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Input: OBJECTIVE To monitor clinical , microbiological and host-derived alterations occurring around teeth and titanium implants during the development of experimental gingivitis/mucositis and their respective healing sequence in humans . MATERIAL AND METHODS Fifteen subjects with healthy or treated periodontal conditions and restored with dental implants underwent an experimental 3-week period of undisturbed plaque accumulation in the m and ible . Subsequently , a 3-week period with optimal plaque control was instituted . At Days 0 , 7 , 14 , 21 , 28 , 35 and 42 , the presence/absence of plaque deposits around teeth and implants was assessed , ( plaque index [ PlI ] ) and the gingival/mucosal conditions were evaluated ( gingival index[GI ] ) . Subgingival/submucosal plaque sample s and gingival/mucosal crevicular fluid ( CF ) sample s were collected from two pre-determined sites around each experimental unit . CF sample s were analyzed for matrix-metalloproteinase-8 ( MMP-8 ) and interleukin-1beta ( IL-1β ) . Microbial sample s were analyzed using DNA-DNA hybridization for 40 species . RESULTS During 3 weeks of plaque accumulation , the median PlI and GI increased significantly at implants and teeth . Implant sites yielded a greater increase in the median GI compared with tooth sites . Over the 6-week experimental period , the CF levels of MMP-8 were statistically significantly higher at implants compared with teeth ( P<0.05 ) . The CF IL-1β levels did not differ statistically significantly between teeth and implants ( P>0.05 ) . No differences in the total DNA counts between implant and tooth sites were found at any time points . No differences in the detection frequency were found for putative periodontal pathogens between implant and tooth sites . CONCLUSION Peri-implant soft tissues developed a stronger inflammatory response to experimental plaque accumulation when compared with that of their gingival counterparts . Experimental gingivitis and peri-implant mucositis were reversible at the biomarker level . Clinical ly , however , 3 weeks of resumed plaque control did not yield pre-experimental levels of gingival and peri-implant mucosal health indicating that longer healing periods are needed AIM To determine the incidence of peri-implantitis in individuals with mucositis in a 5-year follow-up study . MATERIAL AND METHODS A sample of 212 partially edentulous individuals , rehabilitated with dental implants , underwent periodontal and peri-implant clinical examinations in 2005 ( baseline ) . Five years later , 80 individuals who had been diagnosed with mucositis in the baseline examination were re-examined . These individuals were divided into two groups : one group with preventive maintenance during the study period ( GTP ; n = 39 ) , and another group without preventive maintenance ( GNTP ; n = 41 ) . The following parameters were clinical ly evaluated : plaque index , bleeding on periodontal and peri-implant probing , periodontal and peri-implant probing depth , suppuration and peri-implant bone loss . The influence of biological and behavioural risk variables associated with the occurrence of peri-implantitis was analysed using univariate and multivariate logistic regression analyses . RESULTS The incidence of peri-implantitis in the global sample was 31.2 % ( GNTP = 43.9 % and GTP = 18.0 % ) . CONCLUSION The absence of preventive maintenance in individuals with pre-existing peri-implant mucositis was associated with a high incidence of peri-implantitis . Clinical parameters , such as bleeding on peri-implant probing , periodontal probing depth and the presence of periodontitis were associated with a higher risk of developing peri-implantitis PURPOSE To evaluate the effect of irrigation with 0.06 % chlorhexidine ( PerioGard ) ( CHX ) using a powered oral irrigator ( Water Pik ) with a special subgingival irrigating tip ( Pik Pocket Subgingival Tip ) compared to rinsing with 0.12 % chlorhexidine gluconate once daily . MATERIAL S AND METHODS Following a prophylaxis , patients were r and omly assigned to an irrigation or a rinse group . The following clinical parameters were measured at baseline and at the 3-month end of the study : Modified Gingival Index ( MGI ) , Plaque Index ( PI ) , Bleeding Index ( BI ) , and Calculus Index ( CI ) . Also , a Stain Index ( SI ) was measured at 3 months . RESULTS Patients irrigating with diluted CHX showed a statistically significant reduction ( P < 0.05 ) from their baseline in the MGI , PI , BI , and CI scores at 3 months . In the rinse group both MGI and BI showed statistically significant reduction from their baseline ( P < 0.05 ) at 3 months . The rinse group showed a nonsignificant ( P > 0.05 ) increase from baseline in CI and a nonsignificant decrease in PI . Intergroup comparisons showed that CHX irrigation produced statistically significantly greater reductions than CHX rinsing in the PI , MGI , and SI . The irrigation group also showed a greater reduction in BI and CI than the rinsing group but these differences were not statistically significant ( P = 0.12 ) . The results of this study suggest that use of diluted 0.06 % CHX when used in a powered irrigator may be a valuable adjunct to oral health in patients with implants OBJECTIVES To evaluate clinical ly and radiographically immediate implants 5 years after insertion and to compare them with delayed-placed implants in the same subjects . MATERIAL AND METHODS Twenty-two consecutive patients that needed at least two implants for replacing hopeless teeth , one immediately upon extraction and the other in a delayed fashion ( at least 4 months post- extraction ) were selected in this prospect i ve cohort study . Post- extraction immediate implants ( II ) and delayed implants ( DI ) groups were defined . One and 5 years after implant loading , clinical and radiographical outcome variables were recorded and analysed both at site and at implant level . Intra-group and inter-group comparisons were performed . RESULTS The intergroup comparison did not show significant differences for plaque index , bleeding on probing and suppuration . These parameters worsen in both groups along the study . This trend was stronger for the plaque index in the group II , which increased from 15.6 % at 1 year to 25.9 % at 5 years ( P < 0.04 ) . One year after loading , the sites with probing depth ≥5 mm were higher for the group II compared to DI ( 2.5 % vs. 0 % ; P = 0.049 ) . At the end of the study , no significant statistical differences were found . Radiographically , bone crestal changes did not yield significant differences . During the follow-up period , 25 % of the implants ( 26.4 % in group II and 23.5 % in DI ) showed biological complications : mucositis ( 20 % ) and /or periimplantitis ( 5.8 % ) . No differences between groups were found . CONCLUSIONS Within the same patients , the implants placed with the immediate protocol demonstrated a higher tendency to crestal bone loss and to peri-implantitis , although these differences were not statistically significant AIM Supportive therapy to maintain dental implants is increasingly important . This study examined the effect of a 0.3 % triclosan/2 % copolymer dentifrice on oral biofilms and gingival inflammation ( GI ) on dental implants and peri-implant tissues . MATERIAL S AND METHODS One hundred and twenty adults with a dental implant and contra-lateral tooth were enrolled in this 6 month , double-blind , two-treatment , parallel group study . Sixty subjects were r and omly assigned to a triclosan/copolymer dentifrice test group and 60 subjects to a fluoride dentifrice control group and instructed to brush twice daily for 6 months . At baseline , 3 , and 6 months , a calibrated dentist assessed dental plaque , GI and collected supragingival dental plaque for microbiological analysis . RESULTS Subjects in the triclosan/copolymer group demonstrated significantly lower levels of dental plaque , gingivitis , and bleeding on probing at 3 and 6 months at both the implant and contra-lateral tooth compared with the fluoride group ( p<0.05 ) . There were significantly fewer Gram-negative anaerobes in the triclosan/copolymer group ( p<0.05 ) including > 90 % reductions in Aggregatibacter actinomycetemcomitans , Campylobacter rectus , Eubacterium saburreum , Fusobacterium nucleatum , Porphyromonas gingivalis , Prevotella melaninogenica , Solobacterium moorei , and Tannerella forsythia . CONCLUSIONS Twice daily use of a triclosan/copolymer dentifrice may enhance dental implant maintenance by reducing dental plaque and GI PURPOSE The aim of the present study was to investigate plaque levels following sonic-powered and manual toothbrushing in subjects with dental implants . MATERIAL S AND METHODS This study included 36 male and 47 female partially edentulous patients ( age range 45 - 78 years , mean age 59.8 years ) that were r and omly assigned to one of two treatment groups : the sonic toothbrush group ( n = 42 ; Philips Sonicare FlexCare ® toothbrush ) or the manual toothbrush group ( n = 41 ; Oral-B P40 ® ) . Clinical , microbiological and immunological examinations were performed blinded at baseline and after 3 , 6 , 9 and 12 months . Microbiological analyses were performed by real-time polymerase chain reaction . Immunological analyses ( prostagl and in E2 ) were performed by chromatography-electrospray spectrometry . RESULTS The plaque index difference between baseline and 12 months at implants showed no significant difference between sonic or manual toothbrushing in a two-sided Mann-Whitney test ( W = 773.5 , P = 0.426 , 95 % CI -0.64 to 0.20 ) . At the end of the study , there were no significant changes in plaque index , bleeding on probing , gingival index , pocket probing depth , gingival recession , clinical attachment level or the microbiological and immunological outcomes at implants or teeth in either group . CONCLUSIONS This study uncovered no significant difference between sonic and manual toothbrushing for plaque reduction at implants and teeth . Both toothbrushes maintain healthy peri-implant soft tissue PURPOSE This double-blind r and omized controlled trial assessed the effect of subgingival ozone ( O3 , gaseous ozone , HealOzone MK II , KaVo ) and /or hydrogen peroxide ( H2O2 ) on the development of peri-implant mucositis . MATERIAL S AND METHODS Twenty subjects ( mean age , 60 ± 7.7 years ) with 80 implants ( 4 implants each ) were recruited . First , a 2-week pretrial phase took place to achieve healthy gingiva . Subsequently , partial gum shields were constructed for the experimental area ( around the 4 implants ) ; subjects were asked to refrain from brushing in that area by wearing the gum shield . The following treatments were r and omly applied ( for 60 seconds ) to implant sites on days 0 , 7 , and 14 : ( 1 ) air ( O2 ) and saline ( 0.9 % NaCl ) ( control group ) , ( 2 ) O2 and H2O2 ( 3 % ) , ( 3 ) O3 and saline , and ( 4 ) O3 and H2O2 . Plaque , gingival , and bleeding indices were recorded on days 0 , 7 , 14 , and 21 . RESULTS Significant differences were seen among the treatments ( P < .01 ) in plaque ( F = 16.68 ) , modified gingival ( F = 7.86 ) , and bleeding ( F = 18.42 ) indices . O3 + saline and O3 + H2O2 produced optimum gingival health scores and were equally effective and the most effective in controlling bleeding ( mean score = 0.05 ) , while O2 + saline was the least effective ( mean score = 0.56 ) . CONCLUSION Ozone showed great potential for management of peri-implant mucositis OBJECTIVE The aim of this prospect i ve study was to assess the outcomes of an implant maintenance protocol for implants supporting a full-arch rehabilitation . MATERIAL S AND METHODS Sixty-one patients ( 28 women and 33 men ) treated with immediately loaded full-arch rehabilitation , both m and ibular and maxillary , supported by a combination of two tilted and two axial implants , were included in the study . Patients were scheduled for follow-up visits every 6 months for + 2 years , then yearly up to 4 years . Each patient received professional oral hygiene treatment and detailed oral hygiene instructions . During each visit , modified plaque index , bleeding index and probing depth were assessed . The presence of peri-implant tissue inflammation was also evaluated . RESULTS Mean observation time , considering both m and ible and maxilla , was 18.3 months ranging from 6 months to 5 years . Both plaque and bleeding indexes frequency decreased over time . Probing depth was stable ( 2.46 ± 0.5 mm at 4 years ) . Only three implants were lost due to peri-implantitis ( 1.4 % at 12 months ) , whereas the incidence of peri-implant
Output:
| The choice of control interventions showed great variability .
Therapy of PM is a prerequisite for the prevention of peri-implantitis |
MS213740 | ***TASK*** the task is to summarize an input biomedical literature in six sentences
***INPUT*** the input is a biomedical literature
***OUTPUT*** the output is the summary of an input biomedical literature in six sentences
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Input: BACKGROUND Treatment with cetuximab , a monoclonal antibody directed against the epidermal growth factor receptor , improves overall and progression-free survival and preserves the quality of life in patients with colorectal cancer that has not responded to chemotherapy . The mutation status of the K-ras gene in the tumor may affect the response to cetuximab and have treatment-independent prognostic value . METHODS We analyzed tumor sample s , obtained from 394 of 572 patients ( 68.9 % ) with colorectal cancer who were r and omly assigned to receive cetuximab plus best supportive care or best supportive care alone , to look for activating mutations in exon 2 of the K-ras gene . We assessed whether the mutation status of the K-ras gene was associated with survival in the cetuximab and supportive-care groups . RESULTS Of the tumors evaluated for K-ras mutations , 42.3 % had at least one mutation in exon 2 of the gene . The effectiveness of cetuximab was significantly associated with K-ras mutation status ( P=0.01 and P<0.001 for the interaction of K-ras mutation status with overall survival and progression-free survival , respectively ) . In patients with wild-type K-ras tumors , treatment with cetuximab as compared with supportive care alone significantly improved overall survival ( median , 9.5 vs. 4.8 months ; hazard ratio for death , 0.55 ; 95 % confidence interval [ CI ] , 0.41 to 0.74 ; P<0.001 ) and progression-free survival ( median , 3.7 months vs. 1.9 months ; hazard ratio for progression or death , 0.40 ; 95 % CI , 0.30 to 0.54 ; P<0.001 ) . Among patients with mutated K-ras tumors , there was no significant difference between those who were treated with cetuximab and those who received supportive care alone with respect to overall survival ( hazard ratio , 0.98 ; P=0.89 ) or progression-free survival ( hazard ratio , 0.99 ; P=0.96 ) . In the group of patients receiving best supportive care alone , the mutation status of the K-ras gene was not significantly associated with overall survival ( hazard ratio for death , 1.01 ; P=0.97 ) . CONCLUSIONS Patients with a colorectal tumor bearing mutated K-ras did not benefit from cetuximab , whereas patients with a tumor bearing wild-type K-ras did benefit from cetuximab . The mutation status of the K-ras gene had no influence on survival among patients treated with best supportive care alone . ( Clinical Trials.gov number , NCT00079066 . Support for prospect i ve registration of protocol s for systematic review s has been gathering momentum . The PRISMA statement , a guideline for reporting systematic review s and meta-analyses of studies that evaluate health-care interventions , advocates registration . Well-conducted systematic review s are accepted as the best- quality evidence to inform policy and practice , and the dramatic upward trend in the number of systematic review s published annually ( fi gure ) is set to continue . However , there is currently no single facility for identifying this type of research in advance of the appearance of the results of the review . There is concern about and evidence of publication and selective outcome -reporting biases associated with systematic review s. An open registry of review s captured at the protocol stage would facilitate good practice in systematic review s by providing transparency of the review process and outcomes . Discrepancies between the methods of the published review and those planned in the registered protocol could be more readily identifi ed . Registration might also encourage full publication of the review ’s fi ndings and transparency in changes to methods that could bias fi ndings . In both the prevention and revelation of potential bias , registration should improve quality and increase confi dence that policy or practice informed by the fi ndings of systematic review s are indeed drawing on best- quality evidence . A registry of protocol s of systematic review s could assist those planning new review s and updating existing ones . Easy access to information about ongoing review s should help to optimise the use of fi nite re sources by enabling funding and commissioning agencies to avoid unnecessary duplication and encourage collaboration . A comprehensive registry could also create opportunities for method ological and other research , both within and across disciplines . Existing access to systematic - review protocol s is limited to the outputs of individual organisations , such as the Cochrane and Campbell Collaborations and the Joanna Briggs Institute . The National Public Health Service for Wales is piloting an All Wales Systematic Review s Register , but , up to now , there has been no central ised comprehensive registry of systematic - review protocol s. We are developing an international facility to register the details of ongoing systematic review s in health and social care . Our registry is being established with the existing platform and infrastructure that supports the Data base of Abstract s of Review s of Eff ects ( DARE ) , the NHS Economic Evaluations Data base ( NHS EED ) and the Health Technology Assessment ( HTA ) data base produced by the Centre for Review s and Dissemination . The initial scope of the registry will be limited to systematic review s of the eff ectiveness of health interventions . However , the longterm aim is for the registry to include details of all ongoing systematic review s with a health-related outcome in the broadest sense . Ultimately , inclusion will encompass systematic review s of health-care interventions , and review s of the social determinants of health , of service delivery , and of risk factors and genetic associations . Our web-based registry will off er free public access , be electronically search able , and open to all prospect i ve registrants . Registration will require the provision of a minimum data set , the completeness of which will be checked automatically before registration . After acceptance , the registry ’s entry and protocol for the review , if available , will be loaded on the data base as a permanent entry and a unique identifi cation number issued . An audit trail for any amendments to the information will be available within the record . Links to result ing publications will be added . These provisions ensure that the registry will match the relevant criteria required of clinical trials registries
Output:
| We did not observe any significant association between overall or progression-free survival , neither when considering all colorectal cancer patients nor for subgroup analyses ( metastatic , anti-EGFR [ epidermal growth factor receptor ] treatment , or KRAS wild type ) .
We have found no clear evidence to support an association between the KRAS-LCS6 genotype and overall or progression-free survival among colorectal cancer patients , even after conducting subgroup analyses by stage and anti-EGFR treatment status . |
MS213741 | ***TASK*** the task is to summarize an input biomedical literature in six sentences
***INPUT*** the input is a biomedical literature
***OUTPUT*** the output is the summary of an input biomedical literature in six sentences
***DOCUMENTATION***
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Input: OBJECTIVE To assess the process variables involved in a weight loss program for African-American adolescent girls . Several process variables have been identified as affecting success in in vivo weight loss programs for adults and children , including program adherence , self-efficacy , and social support . The current study sought to broaden the underst and ing of these process variables as they pertain to an intervention program that is presented using the Internet . It was hypothesized that variables such as program adherence , dietary self-efficacy , psychological factors , and family environment factors would mediate the effect of the experimental condition on weight loss . RESEARCH METHODS AND PROCEDURES Participants were 57 adolescent African-American girls who joined the program with one obese parent ; family pairs were r and omized to either a behavioral or control condition in an Internet-based weight loss program . Outcome data ( weight loss ) are reported for the first 6 months of the intervention . RESULTS Results partially supported the hypotheses . For weight loss among adolescents , parent variables pertaining to life and family satisfaction were the strongest mediating variables . For parental weight loss , changes in dietary practice s over the course of 6 months were the strongest mediators . DISCUSSION The identification of factors that enhance or impede weight loss for adolescents is an important step in improving weight loss programs for this group . The current findings suggest that family/parental variables exert a strong influence on weight loss efforts for adolescents and should be considered in developing future programs OBJECTIVES Motivating adolescents to adopt proper nutrition and physical activity behaviors is important in this nation 's fight to prevent obesity and chronic diseases . This study was conducted to determine which health education delivery method would elicit a greater behavior change . METHOD The intervention was conducted in three schools ( control , computer-based , and traditional education ) . RESULTS Students who received the computer-based intervention showed increased knowledge ( p<0.001 ) , physical activity ( p=0.001 ) , self-efficacy ( p<0.001 ) , and social support ( p<0.001 ) , and decreased meals skipped ( p<0.001 ) . CONCLUSION The computer-based group showed more positive behavior changes . However , future programs may be enhanced by including group discussion and individual feedback Background Childhood obesity has reached epidemic proportions in developed countries . Sedentary screen-based activities such as video gaming are thought to displace active behaviors and are independently associated with obesity . Active video games , where players physically interact with images onscreen , may have utility as a novel intervention to increase physical activity and improve body composition in children . The aim of the Electronic Games to Aid Motivation to Exercise ( eGAME ) study is to determine the effects of an active video game intervention over 6 months on : body mass index ( BMI ) , percent body fat , waist circumference , cardio-respiratory fitness , and physical activity levels in overweight children . Methods / Design Three hundred and thirty participants aged 10–14 years will be r and omized to receive either an active video game up grade package or to a control group ( no intervention ) . Discussion An overview of the eGAME study is presented , providing an example of a large , pragmatic r and omized controlled trial in a community setting . Reflection is offered on key issues encountered during the course of the study . In particular , investigation into the feasibility of the proposed intervention , as well as robust testing of proposed study procedures is a critical step prior to implementation of a large-scale trial . Trial registration Australian New Zeal and Clinical Trials Registry PURPOSE To examine the feasibility and efficacy of a theory-driven and family-based program delivered online to promote healthy lifestyles and weights in Chinese American adolescents . METHODS A r and omized controlled study of a web-based intervention was developed and conducted in 54 Chinese American adolescents ( ages , 12 - 15 years ) and their families . Data on anthropometry , blood pressure , dietary intake , physical activity , and knowledge and self-efficacy regarding physical activity and nutrition were collected at baseline and 2 , 6 , and 8 months after the baseline assessment . Data were analyzed using linear mixed modeling . RESULTS The intervention result ed in significant decreases in waist-to-hip ratio and diastolic blood pressure and increases in vegetable and fruit intake , level of physical activity , and knowledge about physical activity and nutrition . CONCLUSION This web-based behavior program for Chinese American adolescents and their families seems feasible and effective in the short-term . Long-term effects remain to be determined . This type of program can be adapted for other minority ethnic groups who are at high-risk for overweight and obesity and have limited access to programs that promote healthy lifestyles PURPOSE To compare the effectiveness of two school-based internet obesity prevention programs for diverse adolescents on body mass index ( BMI ) , health behaviors , and self-efficacy , and to explore moderators of program efficacy . It was hypothesized that the addition of coping skills training to a health education and behavioral support program would further enhance health outcomes . METHODS A r and omized clinical trial with cluster r and omization by class and repeated measures with follow-up at 3 and 6 months was conducted ( n = 384 ) . BMI was assessed by use of st and ard procedures . Sedentary behavior , physical activity , nutrition behavior , self-efficacy , and satisfaction were assessed with self-report measures . Data analysis consisted of mixed model analyses with autoregressive covariance structure for repeated data by use of intent-to-treat procedures . RESULTS The mean age of students was 15.31 years ( ±0.69 ) , with a mean BMI of 24.69 ( ±5.58 ) . The majority were girls ( 62 % ) and of diverse race/ethnicity ( 65 % non-white ) . There were no significant differences between groups on any outcomes and no change in BMI over time . There were significant improvements in health behaviors ( sedentary behavior , moderate and vigorous physical activity , healthy eating , fruit and vegetable intake , sugar beverages , and junk food intake ) and self-efficacy . Gender and lesson completion moderated select health outcomes . There was excellent participation and high satisfaction with the programs . CONCLUSIONS School-based internet obesity prevention programs are appealing to adolescents and improve health behaviors . The differential effect of coping skills training may require longer follow-up OBJECTIVE To evaluate the impact of a school-based health behavior intervention known as Planet Health on obesity among boys and girls in grade s 6 to 8 . DESIGN R and omized , controlled field trial with 5 intervention and 5 control schools . Outcomes were assessed using preintervention ( fall 1995 ) and follow-up measures ( spring 1997 ) , including prevalence , incidence , and remission of obesity . PARTICIPANTS A group of 1295 ethnically diverse grade 6 and 7 students from public schools in 4 Massachusetts communities . INTERVENTION Students participated in a school-based interdisciplinary intervention over 2 school years . Planet Health sessions were included within existing curricula using classroom teachers in 4 major subjects and physical education . Sessions focused on decreasing television viewing , decreasing consumption of high-fat foods , increasing fruit and vegetable intake , and increasing moderate and vigorous physical activity . MAIN OUTCOME MEASURES Obesity was defined as a composite indicator based on both a body mass index and a triceps skinfold value greater than or equal to age- and sex-specific 85th percentiles . Because schools were r and omized , rather than students , the generalized estimating equation method was used to adjust for individual-level covariates under cluster r and omization . RESULTS The prevalence of obesity among girls in intervention schools was reduced compared with controls , controlling for baseline obesity ( odds ratio , 0.47 ; 95 % confidence interval , 0.24 - 0.93 ; P = .03 ) , with no differences found among boys . There was greater remission of obesity among intervention girls vs. control girls ( odds ratio , 2.16 ; 95 % confidence interval , 1.07 - 4.35 ; P = .04 ) . The intervention reduced television hours among both girls and boys , and increased fruit and vegetable consumption and result ed in a smaller increment in total energy intake among girls . Reductions in television viewing predicted obesity change and mediated the intervention effect . Among girls , each hour of reduction in television viewing predicted reduced obesity prevalence ( odds ratio , 0.85 ; 95 % confidence interval , 0.75 - 0.97 ; P = .02 ) . CONCLUSION Planet Health decreased obesity among female students , indicating a promising school-based approach to reducing obesity among youth OBJECTIVE A r and omized controlled trial tested the efficacy of an internet-based lifestyle behavior modification program for African-American girls over a 2-year period of intervention . RESEARCH METHODS AND PROCEDURES Fifty-seven overweight ( mean BMI percentile , 98.3 ) African-American girls ( mean age , 13.2 years ) were r and omly assigned to an interactive behavioral internet program or an internet health education program , the control condition . Overweight parents were also participants in the study . Forty adolescent-parent dyads ( 70 % ) completed the 2-year trial . Outcome data including BMI , body weight , body composition , and weight loss behaviors were collected at baseline and at 6-month intervals . A computer server tracked use of the web sites . RESULTS An intention-to-treat statistical approach was used , with the last observation carried forward . In comparison with the control condition , adolescents in the behavioral program lost more mean body fat ( BF ) ( -1.12 + /- 0.47 % vs. 0.43 + /- 0.47 % BF , p < 0.05 ) , and parents in the behavioral program lost significantly more mean body weight ( -2.43 + /- 0.66 vs. -0.35 + /- 0.64 kg , p < 0.05 ) during the first 6 months . This weight loss was regained over the next 18 months . After 2 years , differences in fat for adolescents ( -0.08 + /- 0.71 % vs. 0.84 + /- 0.72 % BF ) and weight for parents ( -1.1 + /- 0.91 vs. -0.60 + /- 0.89 kg ) did not differ between the behavioral and control programs . DISCUSSION An internet-based weight management program for African-American adolescent girls and their parents result ed in weight loss during the first 6 months but did not yield long-term loss due to reduced use of the web site over time OBJECTIVE . This study examined the efficacy of an Internet-facilitated intervention for weight maintenance and binge eating in adolescents . METHODS . A total of 105 adolescent male and female high school students at risk for overweight ( mean age : 15.1 ± 1.0 years ) were r and omly assigned to a 16-week online intervention , StudentBodies2-BED ( n = 52 ) , or the wait-list control group ( n = 53 ) . RESULTS . Participants in the StudentBodies2-BED group had significantly lower BMI z scores and BMI from baseline assessment to follow-up assessment , compared with the wait-list control group . In addition , significant reductions in objective binge episodes and subjective binge episodes from baseline assessment to posttreatment assessment and from baseline assessment to follow-up assessment were observed among StudentBodies2-BED participants . The StudentBodies2-BED group also reported significantly reduced weight and shape concerns from posttreatment assessment to follow-up assessment and from baseline assessment to follow-up assessment . Participants in the StudentBodies2-BED group who engaged in objective overeating or binge eating episodes at baseline assessment experienced a significantly greater reduction in BMI at follow-up assessment , compared with the wait-list control group . CONCLUSIONS . Results suggest that an Internet-facilitated intervention is moderately effective in short-term weight loss and weight maintenance and yields a large reduction in binge eating . This study also demonstrates that weight management and reduction of eating disorder psychopathological features can be achieved simultaneously by using an easily disseminated , Internet-facilitated program Background : Because physical inactivity poses serious health risks , interventions are urgently needed to reverse the increasingly sedentary lifestyles of adolescent girls . Objective : The aim of this study was to determine the feasibility of " Girls on the Move , " an individually tailored computerized physical activity ( PA ) program plus nurse counseling intervention , in increasing PA . Methods : A pretest-posttest control group design was used with 77 racially diverse sedentary girls in Grade s 6 , 7 , and 8 from two middle schools . Each of the instructional grade s was r and omly assigned to either an intervention or control condition . After completing computerized question naires , each girl in the control group received a h and out listing the PA recommendations . To encourage PA , each girl in the intervention group received computerized , individually tailored feedback messages based on her responses to the question naires , individual counseling from the school 's pediatric nurse practitioner ( PNP ) , and telephone calls and mailings from a trained research assistant . At 12 weeks , girls in both groups responded to the question naires . Results : No differences in self-reported PA emerged between the intervention and control groups at Weeks 1 ( baseline ) and 12 ( postintervention ) . Repeated measures ANOVA showed a significant interaction between group and time for social support for PA , F(1 , 69 ) = 5.73 , p = .019 , indicating that the intervention group had significantly greater social support across time than did the control group . From baseline to postintervention , social support increased for the intervention group but decreased for the control group . Discussion : Reasons for the lack of significant differences between the groups on the PA measures were cited . Important information that could inform subsequent studies that test interventions to increase youth PA was acquired from conducting
Output:
| BMI provides the most useful population -level measure of overweight and obesity as it is the same for both sexes and for all ages worldwide .
Measures of central obesity such as the waist : hip ratio and waist circumference can provide more robust indices of overall obesity-related health risk than BMI alone .
Overweight and obese children are likely to stay obese into adulthood and are more likely to develop non-communicable diseases like diabetes and cardiovascular diseases at a younger age .
In addition to a higher risk of obesity and non-communicable diseases later in life , affected children experience adverse outcomes such as breathing difficulties , increased risk of fractures , hypertension , and early markers of cardiovascular disease , different forms of cancers , insulin resistance , and psychological effects .
Childhood obesity is associated with a higher chance of obesity , premature death , and disability in adulthood .
If a child is overweight before eight years of age , obesity in adulthood is likely to be more severe .
Child and adolescent obesity is also associated with increased risk of emotional problems .
Teens with weight problems tend to have much lower self-esteem and are less popular with their peers .
Depression , anxiety , and obsessive compulsive disorder can also occur as a result of childhood obesity .
Reducing the incidence of obesity in childhood can help children grow into adults with normal body weights and the tools necessary to sustain a health weight .
Haerens , et al. explains the importance of school-based programs in dealing with the serious problem of childhood obesity and overweight .
The school setting is known as having a powerful influence on student 's eating and physical activities .
Programs that may have a more positive impact are those that help increase physical activity and promote healthy foods in youth .
Previous studies looking at the implementation of diet and exercise programs in schools were effective in changing food habits and increasing physical activity ; however , few of these studies showed a reduction in body weight .
The Planet Health study , conducted over a period of two years , focused on healthy life style and showed a reduction in obesity in girls but not in boys .
The program was found to be a potential low cost method to positively impact public health and health behaviours . |
MS213742 | ***TASK*** the task is to summarize an input biomedical literature in six sentences
***INPUT*** the input is a biomedical literature
***OUTPUT*** the output is the summary of an input biomedical literature in six sentences
***DOCUMENTATION***
***EXAMPLES***
Input: Background — Frailty is an emerging concept in medicine yet to be explored as a risk factor in cardiac surgery . Where elderly patients are increasingly referred for cardiac surgery , the prevalence of a frail group among these is also on the rise . We assessed frailty as a risk factor for adverse outcomes after cardiac surgery . Methods and Results — Functional measures of frailty and clinical data were collected prospect ively for all cardiac surgery patients at a single center . Frailty was defined as any impairment in activities of daily living ( Katz index ) , ambulation , or a documented history of dementia . Of 3826 patients , 157 ( 4.1 % ) were frail . Frail patients were older , were more likely to be female , and had risk factors for adverse surgical outcomes . By logistic regression , frailty was an independent predictor of in-hospital mortality ( odds ratio 1.8 , 95 % CI 1.1 to 3.0 ) , as well as institutional discharge ( odds ratio 6.3 , 95 % CI 4.2 to 9.4 ) . Frailty was an independent predictor of reduced midterm survival ( hazard ratio 1.5 , 95 % CI 1.1 to 2.2 ) . Conclusions — Frailty is a risk for postoperative complications and an independent predictor of in-hospital mortality , institutional discharge , and reduced midterm survival . Frailty screening improves risk assessment in cardiac surgery patients and may identify a subgroup of patients who may benefit from innovative processes of care OBJECTIVES The purpose of this study was to test the value of gait speed , a clinical marker for frailty , to improve the prediction of mortality and major morbidity in elderly patients undergoing cardiac surgery . BACKGROUND It is increasingly difficult to predict the elderly patient 's risk posed by cardiac surgery because existing risk assessment tools are incomplete . METHODS A multicenter prospect i ve cohort of elderly patients undergoing cardiac surgery was assembled at 4 tertiary care hospitals between 2008 and 2009 . Patients were eligible if they were 70 years of age or older and were scheduled for coronary artery bypass and /or valve replacement or repair . The primary predictor was slow gait speed , defined as a time taken to walk 5 m of ≥ 6 s. The primary end point was a composite of in-hospital post-operative mortality or major morbidity . RESULTS The cohort consisted of 131 patients with a mean age of 75.8 ± 4.4 years ; 34 % were female patients . Sixty patients ( 46 % ) were classified as slow walkers before cardiac surgery . Slow walkers were more likely to be female ( 43 % vs. 25 % , p = 0.03 ) and diabetic ( 50 % vs. 28 % , p = 0.01 ) . Thirty patients ( 23 % ) experienced the primary composite end point of mortality or major morbidity after cardiac surgery . Slow gait speed was an independent predictor of the composite end point after adjusting for the Society of Thoracic Surgeons risk score ( odds ratio : 3.05 ; 95 % confidence interval : 1.23 to 7.54 ) . CONCLUSIONS Gait speed is a simple and effective test that may identify a subset of vulnerable elderly patients at incrementally higher risk of mortality and major morbidity after cardiac surgery BACKGROUND AND PURPOSE The interpretation of patient scores on clinical tests of physical mobility is limited by a lack of data describing the range of performance among people without disabilities . The purpose of this study was to provide data for 4 common clinical tests in a sample of community-dwelling older adults . SUBJECTS Ninety-six community-dwelling elderly people ( 61 - 89 years of age ) with independent functioning performed 4 clinical tests . METHODS Data were collected on the Six-Minute Walk Test ( 6MW ) , Berg Balance Scale ( BBS ) , and Timed Up & Go Test ( TUG ) and during comfortable- and fast-speed walking ( CGS and FGS ) . Intraclass correlation coefficients ( ICCs ) were used to determine the test-retest reliability for the 6MW , TUG , CGS , and FGS measurements . Data were analyzed by gender and age ( 60 - 69 , 70 - 79 , and 80 - 89 years ) cohorts , similar to previous studies . Means , st and ard deviations , and 95 % confidence intervals for each measurement were calculated for each cohort . RESULTS The 6MW , TUG , CGS , and FGS measurements showed high test-retest reliability ( ICC [2,1]=.95-.97 ) . Mean test scores showed a trend of age-related declines for the 6MW , BBS , TUG , CGS , and FGS for both male and female subjects . DISCUSSION AND CONCLUSION Preliminary descriptive data suggest that physical therapists should use age-related data when interpreting patient data obtained for the 6MW , BBS , TUG , CGS and FGS . Further data on these clinical tests with larger sample sizes are needed to serve as a reference for patient comparisons Gremeaux V , Deley G , Duclay J , Antoine D , Hannequin A , Casillas JM : The 200-m fast-walk test compared with the 6-min walk test and the maximal cardiopulmonary test : A pilot study . Objective : The 200-m fast-walk test has been proposed as a high- intensity performance test in healthy , elderly subjects . Adaptation of low-risk coronary artery disease patients during this test were compared with those in a 6-min walk test and a maximal cardiopulmonary exercise test . Design : Thirty patients with stable coronary artery disease ( 51.9 ± 8.7 yrs ) , referred to the cardiac rehabilitation department , performed a cardiopulmonary exercise test , then a 200-m fast-walk test and a 6-min walk test in a r and om order , before and after the training period ( 6 wks , 3 days per week ) . Heart rate was monitored during each test . Peak workload of cardiopulmonary exercise test , distance walked on the 6-min walk test , and time to perform the 200-m fast-walk test were measured . A sub sample of ten patients performed the exercise test with gas exchange measurements , with ventilatory threshold determination . Results : All subjects completed walk tests without complaint or incidents . Compared with the cardiopulmonary exercise test , the cardiac relative intensity was higher during the 200-m fast-walk test than during the 6-min walk test , both before ( 89.6 % vs. 78.1 % of cardiopulmonary exercise test maximal heart rate ; P < 0.05 ) and after ( 83.8 % vs. 74.3 % ; P < 0.05 ) training . Among the sub sample of ten patients , the 200-m fast-walk test heart rate was significantly higher than the ventilatory threshold heart rate , which did not differ from the 6-min walk test heart rate . The 200-m fast-walk test time significantly decreased after training ( −9.1 % , P < 0.01 ) . Conclusion : In patients with coronary artery disease at low risk , the 200-m fast-walk test explores higher levels of cardiorespiratory capacity than the 6-min walk test . Thus , this could be a useful field test in complement to the cardiopulmonary exercise test to assess functional capacity improvement and up date training targets regularly during the course of high-intensity rehabilitation programs in this population OBJECTIVE To estimate the minimal clinical ly important difference ( MCID ) for the 6-minute walk test ( 6MWT ) and the 200-m fast-walk test ( FWT ) in patients with coronary artery disease ( CAD ) during a cardiac rehabilitation program . DESIGN Prospect i ve study using distribution- and anchor-based methods . SETTING Out patients from a cardiac rehabilitation unit . PARTICIPANTS Stable patients with CAD ( N=81 ; 77 men ; mean±SD age , 58.1±8.7y ) enrolled 31±12.1 days after an acute coronary syndrome ( ACS ) . INTERVENTIONS Not applicable . MAIN OUTCOME MEASURES 6MWT and 200-m FWT results before and after an 8-week cardiac rehabilitation program and at the 6th and 12th sessions . Patients and physiotherapists who supervised the training were asked to provide a global rating of perceived change in walking ability while blinded to changes in walk test performances . RESULTS Mean change in 6MWT distance ( 6MWD ) in patients who reported no change was -6.5 m versus 23.3 m in those who believed their performance had improved ( P<.001 ) . This result was consistent with the MCID determined by using the distribution method ( 23 m ) . Considering a 25-m cutoff , positive and negative predictive values were 0.9 and .63 , respectively . Conversely , there was no difference in 200-m FWT performance between these 2 groups ( 0.1 vs -1.4s , respectively ) . There was poor agreement with the physiotherapist 's perceived change . CONCLUSIONS The MCID for 6MWD in patients with CAD after ACS was 25 m . This result will help physicians interpret 6MWD change and help research ers estimate sample sizes in further studies using 6MWD as an endpoint BACKGROUND Our purpose was to evaluate the reliability , validity , and responsiveness of the 6-minute walk test ( 6MWT ) in patients with heart failure ( HF ) enrolled in the R and omized Evaluation of Strategies for Left Ventricular Dysfunction ( RESOLVD ) pilot study . METHODS A total of 768 patients was enrolled in a multicenter r and omized clinical trial evaluating the effect of c and esartan , enalapril , and metoprolol on left ventricular ejection fraction ( LVEF ) , 6MWT distance , neurohormones , and quality of life . The 6MWT was performed once at screening and twice at baseline , 18 weeks , and 43 weeks by a st and ardized method . RESULTS Test-retest reliability at baseline ( intraclass correlation coefficient [ ICC ] = 0.90 ) , 18 weeks ( ICC = 0.88 ) , and 43 weeks ( ICC = 0.91 ) was very good . Baseline 6MWT distance was weakly inversely correlated to the quality -of-life cumulative score ( r = -0.26 , P = .0001 ) and moderately inversely correlated to the New York Heart Association functional classification ( NYHA-FC ) ( r = -0.43 , P = .001 ) . In the RESOLVD study , the 6MWT was not responsive to change when effect sizes and st and ardized response means were used . Disease-specific quality of life was responsive to change in patients treated with c and esartan and enalapril and NYHA-FC was responsive to change in the c and esartan and enalapril combination and for enalapril alone with small effect sizes . The 6MWT , NYHA-FC , and quality of life were not responsive to change during the metoprolol or placebo phase . CONCLUSIONS The 6MWT is highly reproducible in patients with symptoms of HF . It is somewhat correlated to NYHA-FC and quality of life . Overall , quality of life was most responsive to change , whereas 6MWT and NYHA-FC were comparable but less responsive to change in the RESOLVD study BACKGROUND We investigated the effects of c and esartan ( an angiotensin II antagonist ) alone , enalapril alone , and their combination on exercise tolerance , ventricular function , quality of life ( QOL ) , neurohormone levels , and tolerability in congestive heart failure ( CHF ) . METHODS AND RESULTS Seven hundred sixty-eight patients in New York Heart Association functional class ( NYHA-FC ) II to IV with ejection fraction ( EF ) < 0.40 and a 6-minute walk distance ( 6MWD ) < 500 m received either c and esartan ( 4 , 8 , or 16 mg ) , c and esartan ( 4 or 8 mg ) plus 20 mg of enalapril , or 20 mg of enalapril for 43 weeks . There were no differences among groups with regard to 6MWD , NYHA-FC , or QOL . EF increased ( P = NS ) more with c and esartan-plus-enalapril therapy ( 0.025+/-0.004 ) than with c and esartan alone ( 0.015+/-0.004 ) or enalapril alone(0.015+/-0.005 ) . End-diastolic ( EDV ) and end-systolic ( ESV ) volumes increased less with combination therapy ( EDV 8+/-4 mL ; ESV 1+/-4 mL ; P<0.01 ) than with c and esartan alone ( EDV 27+/-4 mL ; ESV 18+/-3 mL ) or enalapril alone ( EDV 23+/-7 mL ; ESV 14+/-6 mL ) . Blood pressure decreased with combination therapy ( 6+/-1/4+/-1 mm Hg ) compared with c and esartan or enalapril alone ( P<0.05 ) . Aldosterone decreased ( P<0.05 ) with combination therapy ( 23.2+/-5.3 pg/mL ) at 17 but not 43 weeks compared with c and esartan ( 0.7+/-7.8 pg/mL ) or enalapril ( -0.8+/-11 . 3 pg/mL ) . Brain natriuretic peptide decreased with combination therapy ( 5.8+/-2.7 pmol/L ; P<0.01 ) compared with c
Output:
| The results did not show the relation between the six-minute walk distance and adverse events after CABG .
The predictive power of the distance walked for death in HF patients undergoing cardiac surgery was not found .
It is not yet proved if the change in the six-minute walk distance is associated with prognosis . |
MS213743 | ***TASK*** the task is to summarize an input biomedical literature in six sentences
***INPUT*** the input is a biomedical literature
***OUTPUT*** the output is the summary of an input biomedical literature in six sentences
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Input: The majority of patients with systemic sclerosis ( SSc ) have gastrointestinal ( GI ) tract involvement , but therapies using prokinetic agents are usually unsatisfactory . Ghrelin stimulates gastric motility in healthy human volunteers . In this study , we investigated whether ghrelin could improve gastric emptying in patients with gastrointestinal symptoms due to SSc . The study was performed in a r and omized , double-blind , placebo-controlled crossover fashion on two occasions . Ten SSc patients with GI tract involvement received an infusion of either ghrelin ( 5.0 μg/kg ) or saline , and gastric emptying rate was evaluated by ¹³C-acetic acid breath test . Gastric emptying was significantly accelerated by ghrelin infusion in patients with SSc ( ghrelin vs. saline : 43.3 ± 11.4 min vs. 53.4 ± 5.4 min , P=0.03 ) . No serious adverse effects were observed . Our results suggest that ghrelin might represent a new therapeutic approach for GI tract involvement in patients with SSc OBJECTIVES This paper aims to investigate the efficacy of intravenous immunoglobulin ( IVIG ) for skin sclerosis in diffuse cutaneous systemic sclerosis ( dcSSc ) by a r and omised , double-blind , placebo-controlled , multicentre trial ( DBT ) with subsequent long-term observational and readministration studies . METHODS In DBT , IVIG ( 400mg/kg/day for 5 consecutive days : a single course ) or placebo ( P ) was intravenously administered to 63 dcSSc patients of 17 medical institutions in Japan , and changes in the modified Rodnan skin thickness score ( MRSS ) 12 weeks after administration or at discontinuation were compared as a primary endpoint . Patients with a 5-point or more improvement in the MRSS were continuously observed ( long-term observational study ) , whereas IVIG was administered to those with less than a 5-point improvement ( readministration study ) . RESULTS In DBT , changes in the MRSS ( mean±SD ) were -3.3±4.2 and -4.2±4.6 in IVIG and P groups , respectively , and were not significantly different . Non-responder patients were subsequently subjected to the readministration study , and the change in the MRSS ( LS-mean±SEM ) at 60 weeks after the first administration was -8.3±1.0 in the IVIG → IVIG ( GG ) group treated with two courses of IVIG administration and -4.1±1.1 in the P → IVIG ( PG ) group treated with a single course of IVIG administration . The GG group represented a significant improvement in the MRSS against the PG group ( p=0.0040 ) . CONCLUSIONS Although the primary endpoint was not achieved in DBT , repeated administration of IVIG for two courses may be effective for skin sclerosis in dcSSc . Further investigation by the administration of plural courses will be necessary Objective To assess the safety and effectiveness of imatinib mesylate in the treatment of diffuse cutaneous systemic sclerosis ( dcSSc ) . Methods In this phase IIa , open-label , single-arm clinical trial , 30 patients with dcSSc were treated with imatinib 400 mg daily . Patients were monitored monthly for safety assessment s. Modified Rodnan skin scores ( MRSS ) were assessed every 3 months . Pulmonary function testing , chest radiography , echocardiography and skin biopsies were performed at baseline and after 12 months of treatment . Results Twenty-four patients completed 12 months of therapy . 171 adverse events ( AE ) with possible relation to imatinib were identified ; 97.6 % were grade 1 or 2 . Twenty-four serious AE were identified , two of which were attributed to study medication . MRSS decreased by 6.6 points or 22.4 % at 12 months ( p=0.001 ) . This change was evident starting at the 6-month time point ( Δ=−4.5 ; p<0.001 ) and was seen in patients with both early and late-stage disease . Forced vital capacity ( FVC ) improved by 6.4 % predicted ( p=0.008 ) , and the diffusion capacity remained stable . The improvement in FVC was significantly greater in patients without interstitial lung disease . Health-related quality of life measures improved or remained stable . Blinded dermatopathological analysis confirmed a significant decrease in skin thickness and improvement in skin morphology . Conclusions Treatment with imatinib was tolerated by most patients in this cohort . Although AE were common , most were mild to moderate . In this open-label experience , improvements in skin thickening and FVC were observed . Further investigation of tyrosine kinase inhibition for dcSSc in a double-blind r and omised placebo controlled trial is warranted . Clinical Trials.gov , Objective . A prospect i ve observational study of mycophenolate mofetil ( MMF ) treatment in patients with diffuse progressive cutaneous systemic sclerosis ( SSc ) of recent onset . Methods . Twenty-five previously untreated consecutive patients with recent-onset ( < 24 mo ) diffuse progressive cutaneous SSc received MMF as the only disease-modifying therapy . Modified Rodnan skin score ( mRSS ) and affected body surface area ( BSA ) were compared from initiation of MMF to study end . Pulmonary function tests performed at the same institution before therapy and at study end were available in 15 patients . Histopathology and real-time PCR assessment of fibrosis-related gene expression were performed before and after treatment in skin biopsies from 3 patients . Results . At 18.2 ± 8.73 months of MMF therapy ( median 2000 mg/day ) the mRSS decreased from 24.56 ± 8.62 to 14.52 ± 10.9 ( p = 0.0004 ) and the affected BSA from 36 % ± 16 % to 14 % ± 13.3 % ( p = 0.00001 ) . Pulmonary function tests remained stable from initiation of MMF to the end of the study . Skin histopathology showed a remarkable reduction in accumulation of fibrotic tissue . Real-time PCR of skin biopsies demonstrated a marked decrease in expression of fibrosis-related genes . Conclusion . Patients with diffuse progressive cutaneous SSc of recent onset treated with MMF experienced marked improvement in skin involvement and stabilization of pulmonary function . Skin biopsies from 3 patients demonstrated histopathological improvement and decreased expression of fibrosis-related genes The association of cyclophosphamide ( CYC ) and prednisone ( PRED ) for the treatment of lung fibrosis in systemic sclerosis ( SSc ) was only evaluated in uncontrolled studies , although in idiopathic interstitial lung disease ( ILD ) this association seems to be beneficial in patients with non-specific interstitial pneumonia ( NSIP ) . Objectives : To treat SSc-ILD in a prospect i ve open-label controlled study based on lung pattern during 12 months of treatment . Methods : A 3-year analysis was also performed . Twenty-four consecutive patients with SSc and ILD were su bmi tted to an open lung biopsy . Eighteen patients ( NSIP ) were r and omized in two groups : CYC versus CYC + PRED during 12 months . Lung function tests ( diffusion lung capacity of monoxide carbone corrected for hemoglobin concentration ( DLCO-Hb ) , forced vital capacity ( FVC ) , total lung capacity ) and Modified Rodnan Skin Score ( MRSS ) were performed before , after one of treatment and after 3 years from the end of the treatment . Results : Pulmonary function tests were similar in both groups on baseline . After 1 year of treatment , FVC% was comparable between CYC groups ( p = 0.72 ) and in CYC + PRED ( p = 0.40 ) . Three years after the end of treatment , FVC% values ( p = 0.39 in group CYC and p = 0.61 in CYC + PRED and p = 0.22 in CYC + PRED ) and DLCO-Hb ( p = 0.54 in CYC and p = 0.28 in CYC + PRED ) were similar compared to 1 year of treatment . We observed a reduction of the MRSS in the CYC + PRED group after 1 year of treatment ( p = 0.02 ) ; although after 3 years , MRSS values remained stable in both groups . Conclusions : CYC was effective to stabilize lung function parameters in NSIP lung pattern of SSc disease for 3 years after the end of a 1-year therapy Objective The primary objective of the study was to explore safety and tolerability of hyperimmune caprine serum ( AIMS PRO ) in established diffuse cutaneous systemic sclerosis ( SSc ) . Secondary objectives included assessment of potential efficacy and biological activity and exploration of c and i date biomarkers . Methods This was a double-blind parallel group r and omised placebo-controlled clinical trial . After informed consent 20 patients with established diffuse cutaneous SSc of greater than 3 years duration not receiving immunosuppressive therapy were r and omised to receive either active ( n=10 ) or placebo formulation ( n=10 ) by subcutaneous twice weekly injection over 26 weeks . Clinical assessment s were evaluated over 26 weeks . Results There were no safety concerns during this study . Frequency of adverse events was not different between active and placebo groups . Mean modified Rodnan Skin Score ( mRSS ) fell by 1.4±4.7 units with active treatment but increased by 2.1±6.4 units on placebo when baseline values were compared with 26 weeks and responder analysis showed clinical ly meaningful improvement in mRSS at 26 weeks in 5 ( 50 % ) of actively treated patients compared with 1 ( 10 % ) in the control group ( p=0.062 ) . PIIINP ( µg/L ) showed a comparatively larger increase in the treatment group compared with the placebo group , ( p=0.0118 ) . Conclusions These results confirm tolerability and safety of this novel biological agent in established diffuse SSc . The value of a placebo treated control group in small clinical trials evaluating skin disease in SSc is confirmed . Potential improvement in mRSS and changes in PIIINP in cases receiving active therapy suggest that this intervention may be of clinical benefit and warrants further evaluation OBJECTIVES To evaluate the effect of adaptive oral hygiene devices and orofacial exercise to improve gingival health among adults with systemic sclerosis ( SSc ) . METHODS Forty-eight patients with SSc were assigned r and omly to the multifaceted oral health intervention or usual dental care control group . Participants in the intervention group received a rechargeable , powered Oral-B ® oscillating-rotating-pulsating toothbrush and a Reach ® Access ™ Flosser that has a toothbrush-like h and le . For those with an oral aperture of less than 40 mm , orofacial exercises were taught . Participants in the control group were each given a manual toothbrush and dental floss . Participants in both groups received instructions and demonstration on the use of the devices , and were requested to perform the respective intervention twice a day for 6 months . Evaluations were at baseline , 3- , and 6-months . The main outcome was gingival index ( GI ) , an indicator of gingival inflammation . RESULTS Both groups showed significant reduction in GI scores at 6 months ( ps<0.005 ) . Reduction in GI scores of the intervention group at 6 months was 20.8 % which is considered to be clinical ly significant . Compared to the control group , the intervention group showed a significant and larger reduction in GI score by 8 % at 6 months ( p=0.0007 ) . CONCLUSIONS Results support the use of adaptive devices and orofacial exercise to improve gingival health in adults with SSc when compared to use of manual toothbrushing and finger-held flossing . Recommending and educating patients with SSc to use adaptive devices to clean the tooth surfaces looks promising for long-term oral health improvement Drug development for SSc has been hindered by the relative paucity of vali date d outcome measures and biomarkers for use in clinical trials . The Scleroderma Clinical Trials Consortium ( SCTC ) conducted an interactive session at the Scleroderma International Workshop in Cambridge , UK in July 2011 to discuss clinical trial design in SSc . The following issues were discussed : 1 ) primary outcome for trials of SSc - skin vs. lung vs. composite ; 2 ) ischaemic digital ulcers in SSc - healing vs. repair vs. composite ; 3 ) pulmonary arterial hypertension in SSc ; and 4 ) neglected aspects of SSc - opportunities for study or of lower priority and feasibility . R and omised controlled trials with collection of biospecimens are necessary to assess efficacy of therapeutic agents , vali date novel outcome measures , and discover and vali date potential biomarkers for each of these areas . Although SSc is a rare , heterogeneous disease , collaborative efforts led by the SCTC and other international networks will ultimately improve the design of clinical trials of promising therapies for SSc Introduction Pulmonary involvement represents a major cause of death of systemic sclerosis ( SSc ) patients . Recent data suggest that tyrosine kinase inhibitors , such as imatinib , may be a therapeutic option for SSc patients . However , preliminary published clinical trials were inconclusive about imatinib efficacy and showed side effects . The purpose of this study was to verify efficacy and tolerability of low-dose imatinib on interstitial lung disease in a cohort of SSc patients unresponsive to cyclophosphamide therapy . Methods Thirty consecutive SSc patients with active pulmonary involvement , unresponsive
Output:
| Our systematic review of the last 4 years of treatment emphasizes known treatment strategies already in practice , but also identifies new therapeutic approaches with additional biologic agents and hematopoietic stem cell transplantation |
MS213744 | ***TASK*** the task is to summarize an input biomedical literature in six sentences
***INPUT*** the input is a biomedical literature
***OUTPUT*** the output is the summary of an input biomedical literature in six sentences
***DOCUMENTATION***
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Input: AIMS To evaluate the diagnostic and therapeutic procedures which were followed in a European Organization for Research and Treatment of Cancer ( EORTC ) r and omized clinical trial investigating the role of radiotherapy in breast-conserving treatment ( BCT ) for ductal carcinoma in situ ( DCIS ) of the breast . METHODS The medical files of 824 of the 1010 r and omized patients ( 82 % ) were review ed during site visits to 30 participating institutes . RESULTS Large variations occurred , particularly in the surgical procedures and histopathological work-up which were performed . Important risk factors like tumour size and margin status were poorly quantified in the medical files . CONCLUSIONS These findings emphasize the need for establishing uniform guidelines for diagnostic and therapeutic procedures for DCIS , and for clearly defined risk factors for recurrence after BCT for DCIS . Because of its r and omized nature , the main question of the trial , i.e. the effect of radiotherapy on the risk of local recurrence , will not be influenced by variation . The risk of local recurrence in itself , and hence the success of BCT for DCIS , may however be influenced by the quality of the initial procedures that were conducted AIM The primary aims were to study risk factors for an ipsilateral breast event ( IBE ) after sector resection for ductal carcinoma in situ of the breast ( DCIS ) in a trial comparing adjuvant radiotherapy to no therapy and to assess predictive factors for response to radiotherapy . Secondary aims were to analyse reproducibility of the histopathological evaluation and to estimate correctness of diagnosis in the trial . SETTING A r and omised trial in Sweden ( the SweDCIS trial ) , including 1046 women with a median of 5.2 years of follow-up in a population , offered routine mammographic screening . METHODS A case-cohort design with a total of 161 cases of IBE ( 42 of those being members of the subcohort ) and 284 sample d for the sub-cohort . Ninety five percent of the participants ' slides could be retrieved and were re-evaluated by three experienced pathologists . RESULTS Low nuclear grade ( NG 1 - 2 ) and absence of necrosis halves the risk of IBE in both irradiated and non-irradiated patients . Lesion size , margins of excision and age at diagnosis did not modify these associations . The presence of necrosis modified the effect of radiotherapy : relative risk was 0.40 with necrosis present and 0.07 with necrosis absent ( p-value for interaction 0.068 ) . In all subsets of prognostic factors , radiotherapy conferred a substantial benefit . The risk factors for in situ and invasive IBE were similar . The agreement between pathologists was moderate ( kappa=0.486 ) . Correctness of diagnosis in the subcohort of SweDCIS was 84.8 % . CONCLUSION Although nuclear grade and necrosis carry prognostic information , we could not define a group with very low risk after sector resection alone . Radiotherapy has a protective effect in all substrata of risk factors studied . The interaction between the presence of necrosis and radiotherapy is a clinical ly and biologically relevant research area PURPOSE Evaluate the effects of radiotherapy after sector resection for ductal carcinoma in situ of the breast ( DCIS ) in patient groups as defined by age , size of the lesion , focality , completeness of excision and mode of detection . PATIENTS AND METHODS A total of 1,067 women in Sweden were r and omly assigned to either postoperative radiotherapy ( RT ) or control from 1987 to 1999 , and 1,046 were followed for a mean of 8 years . The main outcome was new ipsilateral breast cancer events and distant metastasis-free survival analyzed according to intention to treat . RESULTS There were 64 ipsilateral events in the RT arm and 141 in the control group corresponding to a risk reduction of 16.0 percentage points at 10 years ( 95 % CI , 10.3 % to 21.6 % ) and a relative risk of 0.40 ( 95 % CI , 0.30 to 0.54 ) . There was no statistically significant difference in distant metastasis-free survival . There was an effect modification by age , yielding a low effect of RT in women younger than 50 , but substantial protection in women older than 60 years . The age effect was not confounded by focality , lesion size , completeness of excision , or detection mode . There was no group as defined by our stratification variables that had a low risk without radiotherapy . CONCLUSION Our results indicate that younger women have a low protective effect of conventional RT after sector resection . Older women benefit substantially . We caution that the age effect was seen in a subgroup analysis . Further search with conventional clinical variables for a low risk group that does not need RT does not seem fruitful BACKGROUND Inadequate surgical excision with residual involvement of resection margins by tumour after breast conservation results in increased local recurrence rates . To reduce this risk positive margins are , therefore , usually excised . Systemic treatment with tamoxifen or chemotherapy reduces local recurrence , along with radiotherapy . However , no studies to date have examined the correlation between chemoendocrine treatment , together with radiotherapy , and local relapse in patients with unexcised involved resection margins , having had breast conservation treatment . PATIENTS AND METHODS The histopathology reports were review ed of 184 patients who were treated from June 1991 to August 1995 within our r and omised study of neoadjuvant versus adjuvant chemoendocrine therapy with mitozantrone and methotrexate ( 2 M ) + /- mitomycin-C ( 3 M ) and tamoxifen , used concurrently with radiation following conservation surgical treatment . Histological resection margin was considered positive if ductal carcinoma in situ ( DCIS ) or invasive carcinoma was present microscopically less than 1 mm from the excision margin . RESULTS Although 38 % of patients had unexcised microscopically involved margins , local relapse rate as first site of relapse was only 1.9 % after a median follow up of 57 months . There was no difference in distant relapse ( P = 0.2 ) and survival ( P = 0.5 ) between the positive and negative margins groups . CONCLUSIONS The presence of positive unexcised margins does not have a significant effect on outcome in patients who are treated with chemoendocrine therapy together with radiotherapy . Further clinical trials are required PURPOSE The European Organisation for Research and Treatment of Cancer conducted a r and omized trial investigating the role of radiotherapy ( RT ) after local excision ( LE ) of ductal carcinoma-in-situ ( DCIS ) of the breast . We analyzed the efficacy of RT with 10 years follow-up on both the overall risk of local recurrence ( LR ) and related to clinical , histologic , and treatment factors . PATIENTS AND METHODS After complete LE , women with DCIS were r and omly assigned to no further treatment or RT ( 50 Gy ) . One thous and ten women with mostly ( 71 % ) mammographically detected DCIS were included . The median follow-up was 10.5 years . RESULTS The 10-year LR-free rate was 74 % in the group treated with LE alone compared with 85 % in the women treated by LE plus RT ( log-rank P < .0001 ; hazard ratio [ HR ] = 0.53 ) . The risk of DCIS and invasive LR was reduced by 48 % ( P = .0011 ) and 42 % ( P = .0065 ) respectively . Both groups had similar low risks of metastases and death . At multivariate analysis , factors significantly associated with an increased LR risk were young age ( < or = 40 years ; HR = 1.89 ) , symptomatic detection ( HR = 1.55 ) , intermediately or poorly differentiated DCIS ( as opposed to well-differentiated DCIS ; HR = 1.85 and HR = 1.61 respectively ) , cribriform or solid growth pattern ( as opposed to clinging/micropapillary subtypes ; HR = 2.39 and HR = 2.25 respectively ) , doubtful margins ( HR = 1.84 ) , and treatment by LE alone ( HR = 1.82 ) . The effect of RT was homogeneous across all assessed risk factors . CONCLUSION With long-term follow-up , RT after LE for DCIS continued to reduce the risk of LR , with a 47 % reduction at 10 years . All patient subgroups benefited from RT Selection of patients for r and omised clinical trials may have a large impact on the applicability of the study results to the general population presenting the same disorder . However , clinical characteristics and outcome data on non-entered patients are usually not available . The effects of patient selection for the EORTC 10853 trial investigating the role of radiotherapy in breast conserving therapy for ductal carcinoma in situ have been studied , in an analysis of all patients treated for ductal carcinoma in situ in five participating institutes . The reasons for not entering patients were evaluated and treatment results of the r and omised patients were compared to those not entered . A total of 910 patients were treated for ductal carcinoma in situ . Of these , 477 ( 52 % ) were ineligible , with the size of the lesion being the main reason for in eligibility ( 30 % of all ductal carcinoma in situ ) . Of the 433 eligible patients , 278 ( 64 % ) were r and omised into the trial . The main reasons for non-entry of eligible patients were either physicians ' preference for one of the treatment arms ( 26 % ) or patients ' refusal ( 9 % ) . These percentages showed significant variation among the institutes . At 4 years follow-up , those patients not entered in the trial and treated with local excision and radiotherapy , had higher local recurrence rates than the patients r and omised in the trial and treated with the same approach , ( 17 vs 2 % , P=0.03 ) . The patients treated with local excision alone had equal local recurrence rates ( 11 % in both groups ) . Selection of patients may explain the differences in outcome of the r and omised patients , and those not-entered . Thus , the results of this trial may not be applicable to all patients with ductal carcinoma in situ In EORTC trial 10853 , patients with histologically confirmed surgical clearance of ductal carcinoma in situ ( DCIS ) are being r and omised to observation alone or to receive external radiation to the breast ( 50 Gy ) . So far , 190 patients have been entered from 27 centres . An analysis has been conducted of patients with DCIS presenting to 6 of the participating hospitals . Within these centres there was a total of 216 patients with biopsy confirmed DCIS , without invasion , between 1985 and 1989 . However only 77 ( 36 % ) were entered into the trial . The major reason for non-entry was that DCIS was too extensive ( 76/139 , 55 % ) , so that in situ disease extended to the margins of excision . Other reasons for exclusion included prior breast cancer ( 18 % ) , delay in histological diagnosis ( 6 % ) and a lump measuring more than 3 cm in diameter ( 4 % ) . Only 6 patients ( 4 % ) refused to take part in the trial . Thus the eventual results of the trial may be applicable only to a minority of patients with DCIS The aim of this work is to report the preliminary results of the Hungarian multicentric r and omised DCIS study . Between 2000 and 2007 , 278 patients with ductal carcinoma in situ ( DCIS ) treated by breast-conserving surgery were r and omised according to predetermined risk groups . Low/intermediate-risk patients ( n=29 ) were r and omised to 50 Gy whole-breast irradiation ( WBI ) or observation . High-risk cases ( n=235 ) were allocated to receive 50 Gy WBI vs. 50 Gy WBI plus 16 Gy tumour bed boost . Very high-risk patients ( patients with involved surgical margins ; n=14 ) were r and omised to 50 Gy WBI plus 16 Gy tumour bed boost or reoperation ( reexcision plus radiotherapy or mastectomy alone ) . Immunohistochemistry ( IHC ) was performed to detect the expression of potential molecular prognostic markers ( ER , PR , Her2 , p53 , Bcl-2 and Ki-67 ) . At a median follow-up of 36 months no recurrence was observed in the low/intermediate- and very high-risk patient groups . In the high-risk group , 4 ( 1.7 % ) local recurrences and 1 ( 0.4 % ) distant metastasis occurred . No patient died of breast cancer . In the high-risk group of patients , the 3- and 5-year probability of local recurrence was 1.1 % and 3.1 % , respectively . The positive immunostaining for Her2 ( 38 % ) , p53 ( 37 % ) and Ki-67 ( 44 % ) correlated with a high nuclear grade . Significant inverse correlation was found between the expression of ER ( 77 % ) , PR ( 67 % ) , Bcl-2 ( 64 % ) and grade . Preliminary results suggest that breast-conserving surgery followed by radiotherapy yields an annual local recurrence rate of less than 1 % in patients with DCIS . IHC of molecular prognostic markers can assist to gain insight into the biologic heterogeneity of DCIS BACKGROUND As a consequence of mammographic breast screening programmes , ductal carcinoma in situ is diagnosed with increasing frequency . Mastectomy for localised ductal carcinoma in situ is
Output:
| All the subgroups analysed benefited from addition of radiotherapy .
This review confirms the benefit of adding radiotherapy to breast conserving surgery for the treatment of all women diagnosed with DCIS .
No long-term toxicity from use of radiotherapy was identified |
MS213745 | ***TASK*** the task is to summarize an input biomedical literature in six sentences
***INPUT*** the input is a biomedical literature
***OUTPUT*** the output is the summary of an input biomedical literature in six sentences
***DOCUMENTATION***
***EXAMPLES***
Input: As genetic tests for common gene variants and multifactorial , lifestyle‐related conditions become available , it will be increasingly important to determine the psychological and behavioral impact of this emerging class of genetic tests . Our aim was to examine the potential impact of genetic testing for heart disease susceptibility on psychological predictors of smoking cessation . Two hundred and sixty‐one smokers were asked to imagine that they had undergone a test for heart disease risk . They were r and omly assigned to a genetic test scenario ( low‐ or high‐risk result ) or an oxidative test scenario ( high‐risk result ) . Smokers in the genetic test‐high risk group reported greater intention to quit smoking than smokers in the oxidative test‐high risk group ( p = 0.009 ) ; 30 % of this was mediated by their holding stronger beliefs that quitting would reduce their heart disease risk ( outcome expectations ) ( p = 0.011 ) . The effect of genetic test‐high risk feedback on outcome expectations was greatest amongst smokers with no heart disease family history ( p = 0.038 ) . The results suggest that genetic testing for heart disease risk may enhance interventions design ed to improve health via increasing smoking cessation rates . Whether the findings hold true in studies that use real rather than hypothetical genetic tests remains to be seen Background : As genetic testing for health risk becomes increasingly available , it becomes important to study the prospect i ve impact of testing on modifiable health behavior . Purpose : This study examines the impact of genetic testing for alpha-1 antitrypsin ( AAT ) deficiency , a condition that usually results in emphysema in individuals exposed to cigarette smoke . We evaluated whether AAT testing , performed in the home and with minimal contact ( reading material s including advice on cessation ) , results in quit attempts and abstinence . Methods : Identified smokers ( N=199 ) from a larger study of genetic testing were surveyed 3 months following receipt of their AAT genotype . The primary endpoint was the incidence of quit attempts . Results : Smokers who tested severely AAT deficient were significantly more likely to report a 24-hr quit attempt ( 59 % ) than were those who tested normal ( 26 % ) . Carriers had a 34 % quit attempt rate . Severely AAT deficient smokers were more likely than both carriers and normals to seek information on treatment , use pharmacotherapy for smoking cessation , and report greater reductions in their smoking . There were no group differences in 3-month abstinence rates . Conclusions : Knowledge of severe AAT deficiency , but not carrier status , may motivate smokers toward cessation . The AAT testing experience may have consequences for outcomes of other genetic conditions with modifiable health behaviors PURPOSE Markers of genetic susceptibility to tobacco-related cancers could personalize harms of smoking and motivate cessation . Our objective was to assess whether a multicomponent intervention that included feedback about genetic susceptibility to lung cancer increased risk perceptions and rates of smoking cessation compared with a st and ard cessation intervention . EXPERIMENTAL DESIGN Our design was a two-arm trial with eligible smokers r and omized in a 1:2 ratio to Enhanced Usual Care or Biomarker Feedback ( BF ) . Surveys were conducted at baseline , 6 , and 12 months later . The setting was an inner city community health clinic . African-American patients who were current smokers ( n = 557 ) were identified by chart abstract ion and provider referral . All smokers received a self-help manual and , if appropriate , nicotine patches . Smokers in the BF arm also were offered a blood test for genotyping the GST(3 ) gene ( GSTM1 ) , sent a test result booklet , and called up to four times by a health educator . Prevalent abstinence was assessed by self-report of having smoked no cigarettes in the prior 7 days at the 6- and 12-month follow-ups and sustained abstinence , i.e. , not smoking at either follow-up or in-between . RESULTS Smoking cessation was greater for the BF arm than the Enhanced Usual Care arm ( 19 % versus 10 % , respectively ; P < 0.006 ) at 6 months but not at 12 months . CONCLUSIONS Smokers agreed to genetic feedback as part of a multicomponent cessation program . Although the program increased short-term cessation rates compared with st and ard intervention , genetic feedback of susceptibility may not benefit smokers with high baseline risk perceptions Twin studies document substantial heritability for successful abstinence from smoking . A genome-wide association study has identified markers whose allele frequencies differ with nominal P<0.005 in nicotine-dependent clinical trial participants who were successful vs unsuccessful in abstaining from smoking ; many of these results are also supported by data from two additional sample s. More study is required to precisely determine the variance in quitting success that can be accounted for by the single-nucleotide polymorphisms that are currently identified and to precisely classify individuals who may display varying degrees of genetic vs environmental effects into quitters or nonquitters . However , the data at h and do allow us to model the effects of genotypic stratification in smoking cessation trials . We identify relationships between the costs of identifying and genotyping prospect i ve trial participants vs the costs of performing the clinical trials . We quantitate the increasing savings that result from genetically stratified design s as recruiting/genotyping costs go down and trial costs increase . This model helps to define the circumstances in which genetically stratified design s may enhance power and reduce costs for smoking cessation clinical trials This trial tests the hypothesis that confirming a clinical diagnosis of familial hypercholesterolemia ( FH ) by finding a genetic mutation reduces patients ' perceptions of control over the disease and adherence to risk‐reducing behaviors . Three hundred forty‐one families , comprising 341 hypercholesterolemia prob and s and 128 adult relatives , were r and omized to one of two groups : ( a ) routine clinical diagnosis ; ( b ) routine clinical diagnosis plus genetic testing ( mutation search ing in prob and s and direct gene testing in relatives ) . The main outcome measures were perceptions of control over hypercholesterolemia , adherence to cholesterol‐lowering medication , diet , physical activity , and smoking . There was no support for the main hypothesis : finding a mutation had no impact on perceived control or adherence to risk‐reducing behavior ( all P‐values > 0.10 ) . While all groups believed that lowering cholesterol was an effective way of reducing the risk of a heart attack , participants in whom a mutation was found believed less strongly in the efficacy of diet in reducing their cholesterol level ( P = 0.02 at 6 months ) and showed a trend in believing more strongly in the efficacy of cholesterol‐lowering medication ( P = 0.06 at 6 months ) . In conclusion , finding a mutation to confirm a clinical diagnosis of FH in a previously aware population does not reduce perceptions of control or adherence to risk‐reducing behaviors . The pattern of findings leads to the new hypothesis that genetic testing does not affect the extent to which people feel they have control over a condition , but does affect their perceptions of how control is most effectively achieved . Further work is needed to determine whether similar results will be obtained in population s with little previous awareness of their risks . © 2004 Wiley‐Liss , OBJECTIVES It is well-known that smoking causes many diseases including cancers . Informing smokers of their genotypes associated with the vulnerability to the harms of smoking may be effective measures for smoking cessation . The present study examined the effects of genotype notification of an oncogene ( L-myc ) genotype to smokers on their behavior to quit smoking . METHODS Subjects were 562 employees of a bank who answered to be a smoker for a question naire used at annual health checkup at workplace from July to December 2002 . Those enrolled on August , October , and December were allocated into the genotype notification group ( intervention group ) , and the rest into the controls . Among 286 smokers allocated into the intervention group , 257 participants ( 89.9 % ) agreed to genotype testing . One year after the enrollment , a follow-up question naire survey was conducted for all smokers including controls . RESULTS Those who stated to have quitted smoking were 22 ( 8.0 % ) among the 276 controls and 15 ( 5.8 % ) among the 257 genotype notified participants , providing that the odds ratio ( OR ) of cessation for the intervention was 0.64 ( 95 % confidence interval , 0.32 - 1.28 ) . No psychological problems associated with genotype notification were observed . CONCLUSION The present study did not show positive effects of genotype notification on smoking cessation rate . To elevate the cessation rate , methods to explain and notify genotypes should be improved This study examined the role of dopaminergic genes in prospect i ve smoking cessation and response to bupropion treatment in a placebo-controlled clinical trial . Smokers of European ancestry ( N=418 ) provided blood sample s for genetic analysis and received either bupropion or placebo ( 10 weeks ) plus counseling . Assessment s included the dopamine D2 receptor ( DRD2 ) genotype , dopamine transporter ( SLC6A3 ) genotype , demographic factors , and nicotine dependence . Smoking status was verified at the end of treatment ( EOT ) and at 6-month follow-up . The results provided evidence for a significant DRD2 * SLC6A3 interaction effect on prolonged smoking abstinence and time to relapse at EOT , independent of treatment condition . Such effects were no longer significant at 6-month follow-up , however . These results provide the first evidence from a prospect i ve clinical trial that genes that alter dopamine function may influence smoking cessation and relapse during the treatment phase OBJECTIVE To determine the relationship between joint variation in 2 dopaminergic genes and the likelihood of nonsmoking following treatment with bupropion sustained release ( SR ) . DESIGN Three hundred twenty-three participants in a bupropion SR smoking cessation effectiveness trial with 12-month follow-up were genotyped for variants of dopamine receptor gene DRD2 and dopamine transporter SLC6A3 . MAIN OUTCOME MEASURES Self-reported 7-day point prevalence of nonsmoking . RESULTS Neither genotype alone was associated with 7-day point-prevalent nonsmoking at the 12-month follow-up . However , in the presence of the DRD2 A1 allele , SLC6A3 status was significantly associated with the likelihood of nonsmoking at the 12-month follow-up ( individuals with DRD2 A1 + and SLC6A3 9- were more likely to be smoking ) . In the absence of the DRD2 A1 allele , the association between SLC6A3 status and nonsmoking was nonsignificant . CONCLUSION Although these results are suggestive , a more compelling test is needed of the hypothesis that dopaminergic gene interaction underlies , in part , the likelihood of smoking following treatment with bupropion SR . Most likely this will come from larger studies involving prospect i ve r and omization to treatment based on genotype Risk information for Alzheimer disease ( AD ) may be communicated through susceptibility gene disclosure , even though this is not currently in clinical use . The REVEAL Study is the first r and omized clinical trial of risk assessment for AD with apolipoprotein E ( APOE ) genotype and numerical risk estimate disclosure . We examined whether APOE genotype and numerical risk disclosure to asymptomatic individuals at high risk for AD alters health behaviors . One hundred sixty-two participants were r and omized to either intervention ( APOE disclosure ) or control ( no genotype disclosure ) groups . Subjects in both groups received numerical lifetime risk estimates of future AD development based on sex and family history of AD . The intervention group received their APOE genotype . Subjects were informed that no proven preventive measures for AD existed and given an information sheet on preventative therapies under investigation . Participants who learned they were ϵ4 positive were significantly more likely than ϵ4 negative participants to report AD-specific health behavior change 1 year after disclosure ( adjusted odds ratio : 2.73 ; 95 % confidence interval : 1.14 , 6.54 ; P=0.02 ) . Post hoc analyses revealed similar significant associations between numerical lifetime risk estimates and self-report of AD-specific health behavior change . Despite lack of preventive measures for AD , knowledge of APOE genotype , numerical lifetime risk , or both , influences health behavior BACKGROUND To evaluate whether feedback of genetic information regarding an L-myc polymorphism , identified as impacting on tobacco-related cancer risk , has an influence on smoking cessation , an intervention study was conducted . METHODS We recruited smokers from first-visit out patients at Aichi Cancer Center Hospital . Six hundred and seventeen participated and were allocated into two groups : the biomarker feedback group ( BF ) and the follow-up smoking status group ( FS ) . The subjects were asked for their smoking status at enrolment and at 3- and 9-month follow-ups . BF subjects were notified about their L-myc genotype . RESULTS The smoking cessation rate at 9-month follow-up was essentially the same for both BF and FS cases , at 18.8 % and 17.0 % , respectively ( P = 0.798 ) . However , a difference in the rate was evident with non-cancer subjects ( 12.7 % and 8.4 % , respectively , P = 0.237 ) , especially in females ( 15.0 % and 4.2 % , respectively , P = 0.024 ) . The non-cancer subjects informed of their genotype were more likely to quit smoking than the FS patients ; particularly in those having a risky genotype
Output:
| The authors observed positive short-term effects on risk perception , motivation to quit smoking and smoking cessation , but these effects fade at longer follow-ups .
Importantly , the authors did not find any evidence of adverse effect of testing negative on the risk-predisposing gene .
This systematic review does not provide solid evidence for the proposed beneficial effects of genetic testing for smoking-related diseases on smoking cessation , but does suggest the presence of an immediate motivational effect , such that genetic testing result ed in higher risk perception and more motivation to quit smoking |
MS213746 | ***TASK*** the task is to summarize an input biomedical literature in six sentences
***INPUT*** the input is a biomedical literature
***OUTPUT*** the output is the summary of an input biomedical literature in six sentences
***DOCUMENTATION***
***EXAMPLES***
Input: Cancer diagnosis affects the psychological well-being of both patients and their partners , and effective coping has been suggested to be a conjoint process of mutual support . Ninety-four married women with early stage cancer and their partners were r and omly assigned to couples-based coping training ( CanCOPE ) , individual coping training for the woman , or a medical education control . Couples ' observed support communication and self-reported psychological distress , coping effort , and sexual adjustment were assessed at diagnosis , after cancer surgery , and at 6- and 12-month follow-ups . CanCOPE produced significant improvements in couples ' supportive communication , reduced psychological distress and coping effort , and improved sexual adjustment . Training in couples rather than individual coping was more effective in facilitating adaptation to cancer PURPOSE The analysis of complications in a prospect i ve r and omized trial comparing two preoperative brachytherapy low-dose rates in early stage cervical cancer is presented . METHODS AND MATERIAL S Between 1985 and 1988 , 204 patients with Stage I and limited Stage II cervical cancer were r and omized to receive one of two preoperative brachytherapy low-dose rates ( 0.4 and 0.8 Gy/hr ) . The objective of this trial was to determine the benefits , if any , of the higher-dose rate within the therapeutic arsenal for this patient population , in terms of survival , local control , and complications . The type and severity of all complications were evaluated according to a common glossary and a strict follow-up schedule was established given that the treatment of cervical cancer is multidisciplinary , involving gynecologists , surgeons , and radiotherapists . RESULTS Overall survival : 85 % at 2 years and local control : 93 % at 2 years , were similarly distributed between the two groups . Regardless of their nature and severity , 139 and 175 complications were observed among 63 % and 75 % of patients , in the 0.4 and 0.8 Gy/h dose rate groups respectively . Gynecologic and urinary complications were the most frequent ( 38 % and 28 % of all complications ) , followed by vascular ( 15 % ) , digestive ( 10 % ) , nervous ( 5 % ) and cutaneous ( 5 % ) . A total of 14 and 17 severe complications ( Grade 3 ) were observed in 7 % and 13 % of patients , respectively in the 0.4 and 0.8 Gy/h dose rate groups ( p = 0.12 ) . Nonparametric survival methods used to compare the time to the first complication did not show a significant difference between the two groups : 62 % and 72 % at 2 years ( p = 0.27 ) . When the first complication and its evolution were considered ( early complications ) , the prevalence of complications was not significantly different between the two groups : 28 % vs. 34 % at 2 years ( p = 0.31 ) . In this prospect i ve trial , patients were regularly followed-up and complications of varying nature and severity were observed in succession during follow-up . When successive complications and their evolution were taken into account , the prevalence of complications was significantly greater in the higher-dose rate group : 30 % vs. 45 % at 2 years ( p = 0.03 ) . CONCLUSION The results of this trial showed that long-term effects of treatment , when represented by prevalence of complications over time , were more frequent in the higher dose rate group . This underlines the importance of the regular follow-up of patients and of coding , not only the occurrence of all complications , but also their evolution over time PURPOSE The purpose of this pilot study was to evaluate the efficacy of the clitoral therapy device ( Eros Therapy ) in alleviating sexual dysfunction in irradiated cervical cancer patients . METHODS AND MATERIAL S Eligible patients had a history of cervical cancer treated with radiotherapy and self-reported sexual dysfunction of sexual arousal and /or orgasmic disorders . Patients used the noninvasive , nonpharmacologic clitoral therapy device using a h and -held , battery-powered vacuum to cause clitoral engorgement four times weekly for 3 months during foreplay and self-stimulation . Study instruments included the Female Sexual Function Index , Derogatis Interview for Sexual Functioning , and Dyadic Adjustment Scale . The outcome evaluation was performed at 3 months . RESULTS Between 2001 and 2002 , 15 women were enrolled and 13 completed the study . The median patient age and radiotherapy-enrollment interval was 43.5 years and 2 years , respectively . At baseline , all patients reported symptoms of sexual arousal and /or orgasmic disorders , and some also had sexual desire and pain disorders . At 3 months , statistically significant improvements were seen in all domains tested , including sexual desire , arousal , lubrication , orgasm , sexual satisfaction , and reduced pain . The median Female Sexual Function Index total score increased from 17 to 29.4 ( maximal score , 36 ; p < 0.001 ) . The median Derogatis Interview for Sexual Functioning total raw score increased from 46 to 95 ( maximal score , 118 ; p < 0.001 ) . At baseline , the Derogatis Interview for Sexual Functioning total T-score corresponded to the bottom 10th percentile of normal sexual functioning . At 3 months , the total T-score placed the patients at the normalcy cutoff . Gynecologic examinations revealed improved mucosal color and moisture and vaginal elasticity and decreased bleeding and ulceration . CONCLUSION Our results from this pilot study suggest that the clitoral therapy device may alleviate sexual dysfunction in irradiated cervical cancer patients . A r and omized , controlled trial is warranted to assess the full benefits of this approach Gynaecological malignancy has an immense impact on the well-being of women . For many women , however , treatment such as surgery is curative and healthcare intervention focuses on the physiological status of the women . The psychological , social and sexual consequences of the malignancy and its treatment have received little attention in research or in practice . The present study used a mixed quantitative and qualitative design to analyse a specialist nurse intervention ( including psychosexual intervention ) , and to explain the impact of the illness on women 's lives . The qualitative arm of the study collected interview data from 20 women and six partners . The r and omized controlled trial sample consisted of 36 women , with data collected using a quality of life measure ( the EORTC QLQ-C30 ) and the Lasry Sexual Functioning scale . This paper focuses on the r and omized controlled trial data , which identified that sexual functioning and quality of life were improved in the active group who received specialist psychosexual counselling . However , the validity of the sexual functioning scale is challenged by the qualitative results of the study , which emphasize the social meaning of sexuality PURPOSE The association between radiotherapy for gynecological carcinoma and sexual dysfunction is well established . Regular vaginal dilation is widely recommended to these women as a way for them to maintain vaginal health and good sexual functioning . However , the compliance rate with this recommendation is low . The purpose of this study was to test the effectiveness of a group psychoeducational program based on the " information-motivation-behavioral skills " model of behavior change in increasing the rate of compliance . METHODS AND MATERIAL S Thirty-two women with Stage I or II cervical or endometrial carcinoma who were being treated with radiotherapy were r and omized and received either the experimental group program or the control intervention that consisted of written information and brief counseling . Outcome measures included global sexual health , knowledge about sexuality and cancer , fears about sexuality after cancer , and vaginal dilation compliance . RESULTS Younger women attending the experimental program ( 44.4 % ) were significantly more likely to follow recommendations for vaginal dilation than those who received the control intervention ( 5.6 % ) . Women , regardless of age , who received the experimental intervention reported less fear about sex after cancer treatment . The older women who received the experimental intervention gained more sexual knowledge . There was no evidence that the experimental intervention improved global sexual health . CONCLUSIONS This is the first controlled study to provide evidence of an intervention 's effectiveness 1 . in increasing women 's vaginal dilation following radiotherapy for gynecological carcinoma and 2 . in reducing their fears about sex after cancer . Most women , particularly younger women , are unlikely to follow the recommendation to dilate unless they are given assistance in overcoming their fears and taught behavioral skills BACKGROUND AND PURPOSE Radiation-induced tissue fibrosis is a common adverse effect of curative treatment for pelvic cancer . Pilot studies testing alpha-tocopherol and pentoxifylline provide evidence of clinical regression of superficial radiation fibrosis after radiotherapy . PATIENTS AND METHODS Twenty-seven eligible research volunteers with a minimum of one grade 3 or 4 disability ( LENT SOMA ) due to previous radiotherapy were entered into the study . Volunteers were given dl-alpha tocopheryl acetate 500 mg twice a day orally plus pentoxifylline 400 mg twice a day orally over a period of 6 months . Clinical assessment of late side effects recorded using LENT SOMA scales was selected as the primary endpoint , taken at baseline and at 6 and 12 months post- registration . Patient self- assessment of function and quality of life was assessed as a secondary endpoint using the EORTC QLQ-C30 core question naire and the EORTC QLQ-CR38 pelvic module . Magnetic resonance imaging was undertaken in 13/23 evaluable volunteers before and after 6 months of therapy . RESULTS At 12 months post- registration there were 4 out of 23 responders . At 6 months post- registration there was a statistically significant improvement ( i.e. reduction ) in the median of the LENT SOMA summed scores in all areas assessed apart from ' male sexual dysfunction ' , ' vulva ' and ' vagina ' which were unchanged at 6 months . The median total LENT SOMA score at baseline and 6 months was 49 and 34 , respectively , with a median change in total LENT SOMA score between baseline and 6 months of 9 ( IQR 7 - 18 ) ( P<0.001 ) . The maximum LENT SOMA scores improved over the study period , with a total number of 82 maximum grade 3 or 4 normal tissue scores at baseline ( median of four complications per person ) reduced to a total number of 67 maximum grade 3 or 4 scores at 6 months post- registration ( median of 3 complications per person ) , i.e. a median reduction in severe complications of one per person . LENT SOMA scores at 12 months were similar to those observed at 6 month suggesting no further improvement nor deterioration in late side effects . These findings were , however , not reflected in the patient self- assessment of function and quality of life , raising question about the possibility of observer bias in recording LENT SOMA scores . No significant changes were reported on magnetic resonance images at 6 months from baseline . CONCLUSIONS Despite only seeing four a priori defined responders in this pilot study testing dl-alpha tocopheryl acetate plus pentoxifylline in patients suffering complications of pelvic radiotherapy , changes in LENT SOMA scores suggest beneficial effects . However , we are not convinced that these effects are real , since no significant changes in symptoms and functional status were recorded by detailed prospect i ve patient self- assessment Abstract Conization is known to be an adequate treatment for cervical dysplasia and CIS . However , there are practically no papers on the long-term morbidity after conization . A prospect i ve interview survey of sexual function was done with 64 patients with conizations , the follow-up period being 1 year . There was found to be a significant decrease in the number of patients with dysmenorrhea and dyspareunia and there was no change in libido , experience of orgasm , coital frequency , or in overall satisfaction of sex life . Thus , in these respects , conization is a suitable conservative method when treating dysplasia and CIS
Output:
| Studies of a Clinical Nurse Specialist intervention , Psychoeducational Group Therapy and a Couple-Coping intervention , did not show any significant benefit .
There is no convincing evidence to support the use of any interventions for psychosexual dysfunction in women treated for gynaecological cancer . |
MS213747 | ***TASK*** the task is to summarize an input biomedical literature in six sentences
***INPUT*** the input is a biomedical literature
***OUTPUT*** the output is the summary of an input biomedical literature in six sentences
***DOCUMENTATION***
***EXAMPLES***
Input: BACKGROUND In the non-curative setting , the sequence in which anticancer agents are used , singly or in combination , may be important if patients are to receive the maximum period of disease control with the minimum of adverse effects . We compared sequential and combination chemotherapy strategies in patients with unpretreated advanced or metastatic colorectal cancer , who were regarded as not potentially curable irrespective of response . METHODS We studied patients with advanced colorectal cancer , starting treatment with non-curative intent . 2135 unpretreated patients were r and omly assigned to three treatment strategies in the ratio 1:1:1 . Strategy A ( control group ) was single-agent fluorouracil ( given with levofolinate over 48 h every 2 weeks ) until failure , then single-agent irinotecan . Strategy B was fluorouracil until failure , then combination chemotherapy . Strategy C was combination chemotherapy from the outset . Within strategies B and C , patients were r and omly assigned to receive , as the combination regimen , fluorouracil plus irinotecan ( groups B-ir and C-ir ) or fluorouracil plus oxaliplatin ( groups B-ox and C-ox ) . The primary endpoint was overall survival , analysed by intention to treat . This study is registered as an International St and ard R and omised Controlled Trial , number IS RCT N 79877428 . RESULTS Median survival of patients allocated to control strategy A was 13.9 months . Median survival of each of the other groups was longer ( B-ir 15.0 , B-ox 15.2 , C-ir 16.7 , and C-ox 15.4 months ) . However , log-rank comparison of each group against control showed that only C-ir -- the first-line combination strategy including irinotecan -- satisfied the statistical test for superiority ( p=0.01 ) . Overall comparison of strategy B with strategy C was within the predetermined non-inferiority boundary of HR=1.18 or less ( HR=1.06 , 90 % CI 0.97 - 1.17 ) . INTERPRETATION Our data challenge the assumption that , in this non-curative setting , maximum tolerable treatment must necessarily be used first-line . The staged approach of initial single-agent treatment up grade d to combination when required is not worse than first-line combination , and is an alternative option for discussion with patients Summary Background When cure is impossible , cancer treatment should focus on both length and quality of life . Maximisation of time without toxic effects could be one effective strategy to achieve both of these goals . The COIN trial assessed preplanned treatment holidays in advanced colorectal cancer to achieve this aim . Methods COIN was a r and omised controlled trial in patients with previously untreated advanced colorectal cancer . Patients received either continuous oxaliplatin and fluoropyrimidine combination ( arm A ) , continuous chemotherapy plus cetuximab ( arm B ) , or intermittent ( arm C ) chemotherapy . In arms A and B , treatment continued until development of progressive disease , cumulative toxic effects , or the patient chose to stop . In arm C , patients who had not progressed at their 12-week scan started a chemotherapy-free interval until evidence of disease progression , when the same treatment was restarted . R and omisation was done central ly ( via telephone ) by the MRC Clinical Trials Unit using minimisation . Treatment allocation was not masked . The comparison of arms A and B is described in a companion paper . Here , we compare arms A and C , with the primary objective of establishing whether overall survival on intermittent therapy was non-inferior to that on continuous therapy , with a predefined non-inferiority boundary of 1·162 . Intention-to-treat ( ITT ) and per- protocol analyses were done . This trial is registered , IS RCT N27286448 . Findings 1630 patients were r and omly assigned to treatment groups ( 815 to continuous and 815 to intermittent therapy ) . Median survival in the ITT population ( n=815 in both groups ) was 15·8 months ( IQR 9·4–26·1 ) in arm A and 14·4 months ( 8·0–24·7 ) in arm C ( hazard ratio [ HR ] 1·084 , 80 % CI 1·008–1·165 ) . In the per- protocol population ( arm A , n=467 ; arm C , n=511 ) , median survival was 19·6 months ( 13·0–28·1 ) in arm A and 18·0 months ( 12·1–29·3 ) in arm C ( HR 1·087 , 0·986–1·198 ) . The upper limits of CIs for HRs in both analyses were greater than the predefined non-inferiority boundary . Preplanned subgroup analyses in the per- protocol population showed that a raised baseline platelet count , defined as 400 000 per μL or higher ( 271 [ 28 % ] of 978 patients ) , was associated with poor survival with intermittent chemotherapy : the HR for comparison of arm C and arm A in patients with a normal platelet count was 0·96 ( 95 % CI 0·80–1·15 , p=0·66 ) , versus 1·54 ( 1·17–2·03 , p=0·0018 ) in patients with a raised platelet count ( p=0·0027 for interaction ) . In the per- protocol population , more patients on continuous than on intermittent treatment had grade 3 or worse haematological toxic effects ( 72 [ 15 % ] vs 60 [ 12 % ] ) , whereas nausea and vomiting were more common on intermittent treatment ( 11 [ 2 % ] vs 43 [ 8 % ] ) . Grade 3 or worse peripheral neuropathy ( 126 [ 27 % ] vs 25 [ 5 % ] ) and h and –foot syndrome ( 21 [ 4 % ] vs 15 [ 3 % ] ) were more frequent on continuous than on intermittent treatment . Interpretation Although this trial did not show non-inferiority of intermittent compared with continuous chemotherapy for advanced colorectal cancer in terms of overall survival , chemotherapy-free intervals remain a treatment option for some patients with advanced colorectal cancer , offering reduced time on chemotherapy , reduced cumulative toxic effects , and improved quality of life . Subgroup analyses suggest that patients with normal baseline platelet counts could gain the benefits of intermittent chemotherapy without detriment in survival , whereas those with raised baseline platelet counts have impaired survival and quality of life with intermittent chemotherapy and should not receive a treatment break . Funding Cancer Research UK PURPOSE To compare the efficacy of cediranib ( a vascular endothelial growth factor receptor tyrosine kinase inhibitor [ VEGFR TKI ] ) with that of bevacizumab ( anti-VEGF-A monoclonal antibody ) in combination with chemotherapy as first-line treatment for advanced metastatic colorectal cancer ( mCRC ) . PATIENTS AND METHODS HORIZON III [ Cediranib Plus FOLFOX6 Versus Bevacizumab Plus FOLFOX6 in Patients With Untreated Metastatic Colorectal Cancer ] had an adaptive phase II/III design . Patients r and omly assigned 1:1:1 received mFOLFOX6 [ oxaliplatin 85 mg/m(2 ) and leucovorin 400 mg/m(2 ) intravenously followed by fluorouracil 400 mg/m(2 ) intravenously on day 1 and then continuous infusion of 2,400 mg/m(2 ) over the next 46 hours every 2 weeks ] with cediranib ( 20 or 30 mg per day ) or bevacizumab ( 5 mg/kg every 14 days ) . An independent end-of-phase II analysis concluded that mFOLFOX6/cediranib 20 mg met predefined criteria for continuation ; subsequent patients received mFOLFOX6/cediranib 20 mg or mFOLFOX6/bevacizumab ( r and omly assigned 1:1 ) . The primary objective was to compare progression-free survival ( PFS ) . RESULTS In all , 1,422 patients received mFOLFOX6/cediranib 20 mg ( n = 709 ) or mFOLFOX6/bevacizumab ( n = 713 ) . Primary analysis revealed no significant difference between arms for PFS ( hazard ratio [ HR ] , 1.10 ; 95 % CI , 0.97 to 1.25 ; P = .119 ) , overall survival ( OS ; HR , 0.95 ; 95 % CI , 0.82 to 1.10 ; P = .541 ) , or overall response rate ( 46.3 % v 47.3 % ) . Median PFS and OS were 9.9 and 22.8 months for mFOLFOX6/cediranib and 10.3 and 21.3 months for mFOLFOX6/bevacizumab . The PFS upper 95 % CI was outside the predefined noninferiority limit ( HR < 1.2 ) . Common adverse events with more than 5 % incidence in the cediranib arm included diarrhea , neutropenia , and hypertension . Cediranib-treated patients completed fewer chemotherapy cycles than bevacizumab-treated patients ( median 10 v 12 cycles ) . Patient-reported outcomes ( PROs ) were significantly less favorable in cediranib-treated versus bevacizumab-treated patients ( P < .001 ) . CONCLUSION Cediranib activity , in terms of PFS and OS , was comparable to that of bevacizumab when added to mFOLFOX6 ; however , the predefined boundary for PFS noninferiority was not met . The cediranib safety profile was consistent with previous studies but led to less favorable PROs compared with bevacizumab . Investigation of oral TKIs in CRC continues This study investigated the antitumour and chemosensitizing effects of celecoxib in the treatment of advanced colorectal cancer . A total of 90 patients were r and omly divided into two groups : group CF was treated with a combination of celecoxib and the folinic acid-fluorouracil-oxaliplatin ( FOLFOX4 ) regimen ; and group F was treated with the FOLFOX4 regimen alone . Immunohistochemical analysis of tumour tissues for cyclooxygenase-2 ( COX-2 ) protein was performed . With regard to short-term efficacy , the response and disease control rates were significantly greater in group CF than group F. A log-rank test showed that the 3-year survival rate was significantly greater in group CF than group F. It was concluded that the addition of celecoxib to the FOLFOX4 regimen increased the short-term efficacy and the 3-year survival rate , and improved the quality of life of patients with advanced colorectal cancer . The antitumour and chemosensitizing effects of celecoxib appeared to be independent of COX-2
Output:
| In recent years , the proportion of patients with synchronous compared with metachronous mCRC enrolled in first-line systemic therapy RCTs increased .
Uniform definitions and consistent reporting of the proportion of synchronous versus metachronous metastases could improve cross- study comparisons and interpretation of reported data in all mCRC studies |
MS213748 | ***TASK*** the task is to summarize an input biomedical literature in six sentences
***INPUT*** the input is a biomedical literature
***OUTPUT*** the output is the summary of an input biomedical literature in six sentences
***DOCUMENTATION***
***EXAMPLES***
Input: Objective : To retrospectively investigate the outcome and toxicity of concurrent chemo-radiotherapy in the treatment of locally advanced vulvar cancer ( LAVC ) . Patients and Methods : Between 1996 and 2007 , 28 consecutive patients with LAVC were treated with chemoradiation ( 20 primary tumors and 8 loco-regional recurrences ) . Treatment consists of 2 separate courses of external-beam radiotherapy ( 40 Gy-2 weeks split-20 Gy ) . During each course of radiotherapy , 5-fluorouracil ( 1000 mg/m2/d ) , was given as a continuous intravenous infusion over the first 4 days , and mitomycin-C ( 10 mg/m2 on day 1 ) , as a bolus intravenous injection . Outcome measures were rates of complete and partial response , loco-regional control , progression-free survival , overall survival , and toxicity . Results : The median follow-up was 42 months and the median age of patients was 68 years . Twenty patients ( 72 % ) achieved complete remission , 4 patients ( 14 % ) partial remission , for an overall response rate of 86 % . Four patients ( 14 % ) had progressive disease directly after chemo-radiotherapy . The actuarial rates of loco-regional control , progression-free survival and overall survival at 4 years were 75 % , 71 % , and 65 % , respectively . There was no treatment break for acute toxicity . Vulvar desquamation was the main acute treatment-related side effect ( 93 % ) . Three patients developed transient grade 2 neutropenia or thrombocytopenia . Mild skin fibrosis and atrophy ( n = 6 , 21 % ) , radiation ulcer ( n = 4 , 14 % , in one patient treatment was needed ) , telangectasia ( n = 3 , 11 % ) , and lymphoedema ( n = 2 , 7 % ) were the most common late toxicity of chemoradiation . Conclusion : These data support the use of concurrent chemoradiotherapy as an effective alternative to primary ultra-radical surgery to treat LAVC with an acceptable toxicity profile Objective Vulvectomy for vulvar malignancy can affect sexual functioning based on anatomic , physiologic , psychologic , and relational mechanisms . The aims of this study were to prospect ively investigate sexual adjustment of women with vulvar malignancy during a follow-up period of 1 year after vulvectomy and to compare the results with healthy control women . Methods In this prospect i ve controlled study , participants completed the Beck Depression Inventory scale , World Health Organization-5 Well-being scale , Dyadic Adjustment Scale , Short Sexual Functioning Scale , and Specific Sexual Problems Question naire to assess various aspects of psychosocial and sexual functioning just before surgery , 6 months , and 1 year after treatment . Results Twenty-nine women with vulvar malignancy and 29 healthy controls completed the survey . Compared with the presurgery status , no significant differences were found in psychologic , relational , and sexual functioning in women after surgery for vulvar malignancy . Compared with healthy control women , women with vulvar malignancy reported significantly lower psychologic well-being and quality of partner relationship , both before and after treatment . Moreover , significantly more patients with vulvar malignancy reported preoperative and postoperatively sexual dysfunctions than healthy controls , including entry and deep dyspareunia , abdominal pain during intercourse , reduced ability to achieve orgasm , and reduced intensity of orgasm . Conclusions This prospect i ve study yielded no differences in psychosocial and sexual functioning for women with vulvar malignancy before and after vulvectomy . However , when compared with healthy controls , patients with vulvar malignancy are at high risk for sexual dysfunctions , both before and after surgical treatment PURPOSE To investigate the safety and clinical utility of the sentinel node procedure in early-stage vulvar cancer patients . PATIENTS AND METHODS A multicenter observational study on sentinel node detection using radioactive tracer and blue dye was performed in patients with T1/2 ( < 4 cm ) squamous cell cancer of the vulva . When the sentinel node was found to be negative at pathologic ultrastaging , inguinofemoral lymphadenectomy was omitted , and the patient was observed with follow-up for 2 years at intervals of every 2 months . Stopping rules were defined for the occurrence of groin recurrences . RESULTS From March 2000 until June 2006 , a sentinel node procedure was performed in 623 groins of 403 assessable patients . In 259 patients with unifocal vulvar disease and a negative sentinel node ( median follow-up time , 35 months ) , six groin recurrences were diagnosed ( 2.3 % ; 95 % CI , 0.6 % to 5 % ) , and 3-year survival rate was 97 % ( 95 % CI , 91 % to 99 % ) . Short-term morbidity was decreased in patients after sentinel node dissection only when compared with patients with a positive sentinel node who underwent inguinofemoral lymphadenectomy ( wound breakdown in groin : 11.7 % v 34.0 % , respectively ; P < .0001 ; and cellulitis : 4.5 % v 21.3 % , respectively ; P < .0001 ) . Long-term morbidity also was less frequently observed after removal of only the sentinel node compared with sentinel node removal and inguinofemoral lymphadenectomy ( recurrent erysipelas : 0.4 % v 16.2 % , respectively ; P < .0001 ; and lymphedema of the legs : 1.9 % v 25.2 % , respectively ; P < .0001 ) . CONCLUSION In early-stage vulvar cancer patients with a negative sentinel node , the groin recurrence rate is low , survival is excellent , and treatment-related morbidity is minimal . We suggest that sentinel node dissection , performed by a quality -controlled multidisciplinary team , should be part of the st and ard treatment in selected patients with early-stage vulvar cancer Abstract Objective To measure the long‐term impact of surgical treatment for vulval cancer upon health‐related quality of life and pelvic floor outcomes during the first year of therapy . Methods Prospect i ve , longitudinal , mixed‐ methods study . Twenty‐three women aged > 18 years with a new diagnosis of vulval cancer were recruited . The EORTC QLQ C30 , SF‐36 and an electronic pelvic floor assessment question naire ( ePAQ‐PF ) were administered at baseline ( pre‐treatment ) and 3 , 6 , 9 and 12 months post‐treatment . Mixed effects repeated measures models ( all adjusted for age and BMI ) were used to investigate changes over time and differences between cancer stage . Qualitative interviews were carried out with 11 of the women and analysed using a thematic approach . Results Mean age was 59.9 years ( SD = 15.3 ; range = 23.8–86.6 yrs ) . Mean BMI was 30.0 ( SD = 4.5 ; range = 24.4–38.2 ) . Sixteen women had early ( Stage 1 to 2B ) , and seven women had advanced stage disease ( Stage 3 to 4B ) . Question naire scores revealed that physical and social functioning , fatigue , pain and general sex life were significantly worse at 12 months than pre‐treatment ( p = < 0.05 ) . Qualitative analysis revealed multiple treatment side effects which were perceived as severe and enduring . Women with advanced vulval cancer had significantly worse SF‐36 mental health scores at 12 months compared to women with early stage disease ( p = 0.037 ) . Conclusions Surgery for vulval cancer has long‐term implication s which can be persistent 12 months post‐treatment . High rates of morbidity relating to lymphoedema and sexual function re‐enforce the need for specialist clinics to support women who suffer these complications . © 2015 The Authors . Psycho‐Oncology published by John Wiley & Sons OBJECTIVES To determine the efficacy and toxicity of radiation therapy and concurrent weekly cisplatin chemotherapy in achieving a complete clinical and pathologic response when used for the primary treatment of locally-advanced vulvar carcinoma . METHODS Patients with locally-advanced ( T3 or T4 tumors not amenable to surgical resection via radical vulvectomy ) , previously untreated squamous cell carcinoma of the vulva were treated with radiation ( 1.8 Gy daily × 32 fractions=57.6 Gy ) plus weekly cisplatin ( 40 mg/m(2 ) ) followed by surgical resection of residual tumor ( or biopsy to confirm complete clinical response ) . Management of the groin lymph nodes was st and ardized and was not a statistical endpoint . Primary endpoints were complete clinical and pathologic response rates of the primary vulvar tumor . RESULTS A planned interim analysis indicated sufficient activity to reopen the study to a second stage of accrual . Among 58 evaluable patients , there were 40 ( 69 % ) who completed study treatment . Reasons for prematurely discontinuing treatment included : patient refusal ( N=4 ) , toxicity ( N=9 ) , death ( N=2 ) , other ( N=3 ) . There were 37 patients with a complete clinical response ( 37/58 ; 64 % ) . Among these women there were 34 who underwent surgical biopsy and 29 ( 78 % ) who also had a complete pathological response . Common adverse effects included leukopenia , pain , radiation dermatitis , pain , or metabolic changes . CONCLUSIONS This combination of radiation therapy plus weekly cisplatin successfully yielded high complete clinical and pathologic response rates with acceptable toxicity Objective The aim of this study was to prospect ively monitor the patients ’ quality of life ( QoL ) after vulvar cancer surgery . Design The design was prospect i ve clinical study . Setting The study was set in the Department of Obstetrics and Gynecology , 2nd Medical Faculty of the Charles University and University Hospital Motol , Prague , Czech Republic . Methods A group of 36 patients underwent vulvar cancer surgery : 24 patients were subject to inguinofemoral lymphadenectomy ( RAD ) and 12 to sentinel lymph node biopsy . To evaluate QoL , the European Organisation for Research and Treatment of Cancer , QoL question naires ( QLQ-C30 and QLQ-CX24 ) were administered to patients before and 6 and 12 months after surgery . Results In patients with vulvar cancer after inguinofemoral lymphadenectomy , increased fatigue and impaired lymphedema were observed . In the group of patients after sentinel lymph node biopsy , none of the QoL variables worsened postoperatively . Comparing both groups 12 months after surgery , the RAD group had significantly worse outcomes in body image and cognitive functioning than the sentinel lymph node biopsy group . Patients in the RAD group , who received adjuvant radiotherapy ( n = 13 ) , had worse QoL in symptom experience ( P < 0.05 ) at 6 and 12 months after the surgery than patients without radiotherapy ( n = 11 ) . Conclusions Less radical surgery showed objective ly better QoL results PURPOSE To determine the safety of sentinel lymph node biopsy as a replacement for inguinal femoral lymphadenectomy in selected women with vulvar cancer . PATIENTS AND METHODS Eligible women had squamous cell carcinoma , at least 1-mm invasion , and tumor size ≥ 2 cm and ≤ 6 cm . The primary tumor was limited to the vulva , and there were no groin lymph nodes that were clinical ly suggestive of cancer . All women underwent intraoperative lymphatic mapping , sentinel lymph node biopsy , and inguinal femoral lymphadenectomy . Histologic ultra staging of the sentinel lymph node was prescribed . RESULTS In all , 452 women underwent the planned procedures , and 418 had at least one sentinel lymph node identified . There were 132 node-positive women , including 11 ( 8.3 % ) with false-negative nodes . Twenty-three percent of the true-positive patients were detected by immunohistochemical analysis of the sentinel lymph node . The sensitivity was 91.7 % ( 90 % lower confidence bound , 86.7 % ) and the false-negative predictive value ( 1-negative predictive value ) was 3.7 % ( 90 % upper confidence bound , 6.1 % ) . In women with tumor less than 4 cm , the false-negative predictive value was 2.0 % ( 90 % upper confidence bound , 4.5 % ) . CONCLUSION Sentinel lymph node biopsy is a reasonable alternative to inguinal femoral lymphadenectomy in selected women with squamous cell carcinoma of the vulva BACKGROUND AND PURPOSE As late radiotherapy toxicity impacts negatively on the quality -of-life of cancer survivors and is often under reported , a study was set up to prospect ively collect patient-reported data in an unselected series of patients with gynaecological malignancy . Aim 1 - To provide 3 year results for the longitudinal study . Aim 2 - To improve the question naire used to collect data by identifying redundant items and modifying for use to collect Common Terminology Criteria for Adverse Events ( CTCAE ) data . MATERIAL AND METHODS Aim 1 - Patient reported outcome data were collected prospect ively by 226 patients before and up to 3 years following radiotherapy for gynaecological cancer using a question naire developed to collect
Output:
| Conclusions Vulva cancer treatment is associated with considerable morbidity deteriorating QoL. To date , there is no vali date d PROM available that provides adequate coverage of VC-related issues . |
MS213749 | ***TASK*** the task is to summarize an input biomedical literature in six sentences
***INPUT*** the input is a biomedical literature
***OUTPUT*** the output is the summary of an input biomedical literature in six sentences
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Input: We studied premature atherosclerosis with carotid Doppler ultrasonography in active acromegaly before and after treatment . Patients ( n = 27 ) with active acromegaly and 12 age- , gender- , and body mass index-matched healthy individuals were included in the study . Carotid intima – media thickness was decreased significantly in the inactive group after treatment ( median : 0.6 mm , interquartile range [ IQR ] : 0.55 - 0.80 ] ) when compared with the active group ( median : 0.9 mm [ IQR : 0.75 - 1.15 ] , P < .0001 ) , but there was no significant difference between the inactive and control groups . There was a correlation between homeostasis model of assessment –insulin resistance ( P = .01 , r = .41 ) and growth hormone ( GH ; P < .0001 , r = .46 ) . In conclusion , premature atherosclerosis was demonstrated in active acromegaly patients probably as a consequence of insulin resistance and direct vascular effects of GH and /or insulin-like growth factor 1 BACKGROUND Acromegaly is known to be associated to vascular damage characterized by an increase of vascular wall thickness and an impairment of vascular function . AIM The aim of this study was to evaluate the effect of medical treatment with the GH receptor antagonist pegvisomant on vascular structure and function in acromegalic patients resistant to somatostatin analogues . PATIENTS Ten patients ( 4 males and 6 females , 28 - 58 yr ) and 20 sex- , age- , and body mass index-matched healthy controls entered the study . All patients were treated for 18 months with pegvisomant at doses ranging from 10 to 40 mg/day . OUTCOME MEASURES Primary outcome measures were measurement of carotid arteries intima-media thickness ( IMT ) , and brachial arteries flow mediated dilation ( FMD ) ; secondary outcome measures were blood pressure , blood glucose and lipids levels . RESULTS Carotid arteries maximal IMT was significantly higher in patients than in controls at baseline ( 1.18±0.59 vs 0.69±0.13 , p=0.001 ) and slightly , but not significantly , decreased after treatment ( 0.97±0.17 ) . Brachial arteries FMD was significantly lower in patients than controls at baseline ( 7.5±2.5 vs 13.1±1.4 , p<0.001 ) and significantly increased after treatment ( 8.8±3.7 , p=0.016 ) . Systolic ( SBP ) and diastolic ( DBP ) blood pressure values , serum glucose and insulin levels and homeostasis model assessment ( HOMA ) index were higher , whereas HDL-cholesterol levels were lower in patients than controls at baseline . After treatment , SBP and DBP , as well as serum glucose and insulin levels and HOMA index significantly decreased whereas no significant change was found in serum lipid profile . CONCLUSIONS The results of the current study suggested that long-term treatment with pegvisomant induced a slight reduction of carotid arteries wall thickness and a significant improvement of brachial arteries vascular function in patients with acromegaly resistant to somatostatin analogues UNLABELLED Vascular changes are common in acromegaly ( ACM ) . Current therapies can normalise the levels of both growth hormone ( GH ) and insulin-like growth factor ( IGF1 ) . OBJECTIVE To establish whether the ACM vascular changes in patients with effectively managed disease are different from those in patients with an active condition . METHODS 64 ACM patients were tested for serum GH ( r and om and during an oral glucose tolerance test ) and IGF1 . Ultrasonography of the right common carotid ( RCC ) explored structural ( the carotid diameter and intima-media thickness index ( IMT ) ) and functional ( the augmentation index ( AIx ) , elastic modulus ( Ep ) , and local pulse wave velocity ( PWV ) ) arterial parameters in the ACM patients ( groups A and B ) and an age- and sex-matched control group of 21 patients without acromegaly ( group C ) . RESULTS The ACM patients were divided into 2 subgroups that had similar cardiovascular risk factor profiles : A ( n=10 , with controlled ACM ) , and B ( n=54 , with active ACM ) . The AIx was higher in groups A ( 27.7 % [ 2.2 - 54.3 ] ) and B ( 20.0 % [ - 38.2 - 97.1 ] ) than in group C ( 3.5 % [ - 11.3 - 31.1 ] ) , p=0.01 and 0.002 , respectively . The group B patients presented with poorer functional carotid wall parameters than the control subjects : Ep-95.5 [ 33 - 280 ] KPa vs. 77.5 [ 39 - 146 ] KPa , p=0.01 ; and PWV-6 [ 3.6 - 10.4 ] m/s vs. 5.4 [ 3.9 - 7.2 ] m/s , p=0.03.The ACM patients had greater RCC diameters ( 6.4 ± 0.6 mm vs. 5.7 ± 0.6 mm , p<0.001 ) and IMT values ( 0.72 ± 0.13 mm vs. 0.58 ± 0.08 mm , p<0.001 ) than the subjects in group C. CONCLUSIONS Both the controlled and active ACM patients showed structural arterial changes . After 1 year of disease control , the patients with controlled ACM showed improvements in the functional , but not the structural , arterial parameters compared with the patients with an active condition OBJECTIVE Transsphenoidal surgery results in biochemical remission of acromegaly in 45–80 % of patients ; however , few studies have addressed the impact of transsphenoidal surgery on cardiovascular function in acromegalic patients . The aim of this prospect i ve study was to investigate the effects of postoperative GH/IGF‐I normalization on echocardiographic parameters and blood pressure ( BP ) in a series of patients with active acromegaly Objective : The aim of this study was to assess flow-mediated dilatation ( FMD ) of the brachial artery in patients with acromegaly . Subjects and Methods : We prospect ively evaluated 25 patients with acromegaly ( 14 females , 11 males ; aged 42 ± 12 years ; growth hormone ( GH ) levels 34 ± 14 ng/ml ) and 27 control subjects ( 15 females , 12 males ; aged 45 ± 8 years ; GH levels 3 ± 1.5 ng/ml ) . The patients and controls were matched for age , gender , body mass index , cigarette smoking , blood pressure , lipid levels , diabetes mellitus , hypertension , and its duration . Endothelial function , measured as FMD of the brachial artery using ultrasound , was calculated in the 2 groups . The endothelial function was evaluated by assessing 1-min postischemic FMD of the brachial artery . Results : The FMD was lower in patients with acromegaly ( 9.97 ± 3.5 % ) than in controls ( 16.1 ± 3.4 % ) , and the difference was statistically significant ( p = 0.0001 ) . Conclusion : Endothelial dysfunction may develop in the pre clinical phase of atherosclerosis in patients with acromegaly . Endothelium-dependent FMD may be impaired in acromegalic patients , and measurement of endothelial function may identify high-risk individuals earlier OBJECTIVE To evaluate the effect of a 6-month treatment with slow-release lanreotide ( LAN ) on cardiovascular risk and atherosclerosis in 24 normotensive patients with active acromegaly ( GH=67.4 + /- 12.6 mU/l , IGF -- I=866.0 + /- 55.8 microg/l ) and 24 healthy subjects sex- , age- and body mass index-matched with the patients ( as controls ) . DESIGN Open , prospect i ve , multicenter . METHODS The following were measured before and after 6 months of LAN treatment ( dose 60 - 90 mg/month ) : fasting GH , IGF-I , LDL , HDL and total cholesterol , triglyceride , glucose , glycosylated hemoglobin , insulin and fibrinogen levels , intima-media thickness ( IMT ) and blood systolic and diastolic peak velocity ( SPV and DPV respectively ) in both common carotids . RESULTS At study entry , insulin , total and LDL cholesterol , triglyceride and fibrinogen levels were higher while HDL cholesterol levels were lower in patients than in controls . At the right ( 0.88 + /- 0.04 vs 0.77 + /- 0.03 mm , P=0.05 ) and left ( 0.93 + /- 0.03 vs 0.78 + /- 0.02 mm , P=0.01 ) common carotid IMT was significantly higher in patients than in controls ; 12 patients and two controls showed an IMT of > or = 1 mm ( chi(2)=8.2 , P=0.004 ) . After 6 months of LAN treatment , disease control was achieved in 15 patients ( 62.5 % ) . Insulin , triglyceride and fibrinogen levels were significantly decreased , and a trend toward a decrease of IMT in the right ( from 0.90 + /- 0.05 to 0.78 + /- 0.04 mm , P=0.06 ) and left ( from 0.95 + /- 0.04 to 0.84 + /- 0.04 mm , P=0.06 ) common carotid arteries was observed only in patients with disease control , while SPV and DPV did not change . CONCLUSIONS LAN treatment for 6 months significantly lowered GH , IGF-I , insulin and fibrinogen levels and reduced IMT of both common carotid arteries in normotensive patients with acromegaly It is well established , that the increased mortality in patients with acromegaly is due to cardiac diseases . Cardiomyopathy is the predominant cardiac alteration in patients with acromegaly . There are less data about coronary heart disease or coronary calcifications . Electron beam computed tomography ( EBCT ) is the st and ard imaging modality for identification of coronary artery calcifications ( CAC ) and can determine the extent and severity of coronary atherosclerosis . Coronary risk was evaluated by the Framingham risk score ( FRS ) . The prospect i ve study included 30 patients with acromegaly ( mean age 53+/-14 year ; 16 females , 14 males ; BMI 28.1+/-3.6 kg/m ( 2 ) ; mean+/-SD ) , 12 patients had active disease ( IGF-1 751+/-338 microg/L ; GH 25.6+/-36.4 microg/L ) , 9 were well-controlled ( IGF-1 157+/-58 microg/L ; GH 1.8+/-1.1 microg/L ) under somatostatin analogue octreotide ( n=5 ) , dopamine agonists ( n=2 ) , and the GH receptor antagonist pegvisomant ( n=2 ; GH levels were not determined in this subgroup ) and 9 were cured IGF-1 ( 148+/-57 microg/L ; GH 0.5+/-0.2 microg/L ) . Increased left ventricular muscle mass index ( LVMI > 132 g/m ( 2 ) ) was focused in 53 % , hypercholesterinemia in 63 % , hypertension in 43 % , diabetes mellitus/impaired glucose tolerance in 27 % , and smokers in 53 % ( pack per year 9+/-15 yr ) . For quantification of CAC the EBCT was used and the Agatston calcium score was determined . Results were composed to established age and sex adjusted percentile distribution of CAC . CAC was present in 53 % , high CAC score ( 75 ( th ) percentile ) in 37 % and were categorized as cardiovascular high risk patients . FRS was related to the CAC score ( p=0.008 , r (2)=0.22 ) and the disease duration ( p=0.002 , r (2)=0.29 ) . The CAC score correlated with LVMI ( p=0.02 , r (2)=0.17 ) , the disease duration of acromegaly ( p=0.004 , r (2)=0.36 ) , and the FRS ( p=0.008 , r (2)=0.22 ) . Patients with a high CAC score had a longer disease duration of 9.6+/-4.7 versus 5.4+/-2.8 years with CAC<75 ( th ) percentile ( p=0.02 ) . In summary , the disease duration and consequently the accompanying metabolic disorders appear to influence the degree of CAC in patients with acromegaly . The observations underline the importance of early and sufficient treatment of acromegaly in high risk patients BACKGROUND Data on coronary heart disease ( CHD ) are scanty and matter of argument in acromegalic patients . OBJECTIVE
Output:
| Conclusions IMT , FMD and arterial stiffness are impaired in acromegaly showing that these patients may be at increased risk of atherosclerosis .
In patients with active disease these pre clinical markers of atherosclerosis are worse compared to patients with inactive disease but the role of diabetes and hypertension is prevailing on growth hormone excess |
MS213750 | ***TASK*** the task is to summarize an input biomedical literature in six sentences
***INPUT*** the input is a biomedical literature
***OUTPUT*** the output is the summary of an input biomedical literature in six sentences
***DOCUMENTATION***
***EXAMPLES***
Input: BACKGROUND Nivolumab ( a programmed death 1 [ PD-1 ] checkpoint inhibitor ) and ipilimumab ( a cytotoxic T-lymphocyte-associated antigen 4 [ CTLA-4 ] checkpoint inhibitor ) have been shown to have complementary activity in metastatic melanoma . In this r and omized , double-blind , phase 3 study , nivolumab alone or nivolumab plus ipilimumab was compared with ipilimumab alone in patients with metastatic melanoma . METHODS We assigned , in a 1:1:1 ratio , 945 previously untreated patients with unresectable stage III or IV melanoma to nivolumab alone , nivolumab plus ipilimumab , or ipilimumab alone . Progression-free survival and overall survival were co primary end points . Results regarding progression-free survival are presented here . RESULTS The median progression-free survival was 11.5 months ( 95 % confidence interval [ CI ] , 8.9 to 16.7 ) with nivolumab plus ipilimumab , as compared with 2.9 months ( 95 % CI , 2.8 to 3.4 ) with ipilimumab ( hazard ratio for death or disease progression , 0.42 ; 99.5 % CI , 0.31 to 0.57 ; P<0.001 ) , and 6.9 months ( 95 % CI , 4.3 to 9.5 ) with nivolumab ( hazard ratio for the comparison with ipilimumab , 0.57 ; 99.5 % CI , 0.43 to 0.76 ; P<0.001 ) . In patients with tumors positive for the PD-1 lig and ( PD-L1 ) , the median progression-free survival was 14.0 months in the nivolumab-plus-ipilimumab group and in the nivolumab group , but in patients with PD-L1-negative tumors , progression-free survival was longer with the combination therapy than with nivolumab alone ( 11.2 months [ 95 % CI , 8.0 to not reached ] vs. 5.3 months [ 95 % CI , 2.8 to 7.1 ] ) . Treatment-related adverse events of grade 3 or 4 occurred in 16.3 % of the patients in the nivolumab group , 55.0 % of those in the nivolumab-plus-ipilimumab group , and 27.3 % of those in the ipilimumab group . CONCLUSIONS Among previously untreated patients with metastatic melanoma , nivolumab alone or combined with ipilimumab result ed in significantly longer progression-free survival than ipilimumab alone . In patients with PD-L1-negative tumors , the combination of PD-1 and CTLA-4 blockade was more effective than either agent alone . ( Funded by Bristol-Myers Squibb ; CheckMate 067 Clinical Trials.gov number , NCT01844505 . ) PURPOSE Nivolumab , a programmed death-1 ( PD-1 ) immune checkpoint inhibitor antibody , has demonstrated improved survival over docetaxel in previously treated advanced non-small-cell lung cancer ( NSCLC ) . First-line monotherapy with nivolumab for advanced NSCLC was evaluated in the phase I , multicohort , Checkmate 012 trial . METHODS Fifty-two patients received nivolumab 3 mg/kg intravenously every 2 weeks until progression or unacceptable toxicity ; postprogression treatment was permitted per protocol . The primary objective was to assess safety ; secondary objectives included objective response rate ( ORR ) and 24-week progression-free survival ( PFS ) rate ; overall survival ( OS ) was an exploratory end point . RESULTS Any- grade treatment-related adverse events ( AEs ) occurred in 71 % of patients , most commonly : fatigue ( 29 % ) , rash ( 19 % ) , nausea ( 14 % ) , diarrhea ( 12 % ) , pruritus ( 12 % ) , and arthralgia ( 10 % ) . Ten patients ( 19 % ) reported grade 3 to 4 treatment-related AEs ; grade 3 rash was the only grade 3 to 4 event occurring in more than one patient ( n = 2 ; 4 % ) . Six patients ( 12 % ) discontinued because of a treatment-related AE . The confirmed ORR was 23 % ( 12 of 52 ) , including four ongoing complete responses . Nine of 12 responses ( 75 % ) occurred by first tumor assessment ( week 11 ) ; eight ( 67 % ) were ongoing ( range , 5.3 + to 25.8 + months ) at the time of data lock . ORR was 28 % ( nine of 32 ) in patients with any degree of tumor PD-lig and 1 expression and 14 % ( two of 14 ) in patients with no PD-lig and 1 expression . Median PFS was 3.6 months , and the 24-week PFS rate was 41 % ( 95 % CI , 27 to 54 ) . Median OS was 19.4 months , and the 1-year and 18-month OS rates were 73 % ( 95 % CI , 59 to 83 ) and 57 % ( 95 % CI , 42 to 70 ) , respectively . CONCLUSION First-line nivolumab monotherapy demonstrated a tolerable safety profile and durable responses in first-line advanced NSCLC PURPOSE Blockade of the programmed death-1 inhibitory cell-surface molecule on immune cells using the fully human immunoglobulin G4 antibody nivolumab mediates tumor regression in a portion of patients with advanced treatment-refractory solid tumors . We report clinical activity , survival , and long-term safety in patients with advanced renal cell carcinoma ( RCC ) treated with nivolumab in a phase I study with expansion cohorts . PATIENTS AND METHODS A total of 34 patients with previously treated advanced RCC , enrolled between 2008 and 2012 , received intravenous nivolumab ( 1 or 10 mg/kg ) in an outpatient setting once every two weeks for up to 96 weeks and were observed for survival and duration of response after treatment discontinuation . RESULTS Ten patients ( 29 % ) achieved objective responses ( according to RECIST [ version 1.0 ] ) , with median response duration of 12.9 months ; nine additional patients ( 27 % ) demonstrated stable disease lasting > 24 weeks . Three of five patients who stopped treatment while in response continued to respond for ≥ 45 weeks . Median overall survival in all patients ( 71 % with two to five prior systemic therapies ) was 22.4 months ; 1- , 2- , and 3-year survival rates were 71 % , 48 % , and 44 % , respectively . Grade 3 to 4 treatment-related adverse events occurred in 18 % of patients ; all were reversible . CONCLUSION Patients with advanced treatment-refractory RCC treated with nivolumab demonstrated durable responses that in some responders persisted after drug discontinuation . Overall survival is encouraging , and toxicities were generally manageable . Ongoing r and omized clinical trials will further assess the impact of nivolumab on overall survival in patients with advanced RCC BACKGROUND The immune checkpoint inhibitor ipilimumab is the st and ard-of-care treatment for patients with advanced melanoma . Pembrolizumab inhibits the programmed cell death 1 ( PD-1 ) immune checkpoint and has antitumor activity in patients with advanced melanoma . METHODS In this r and omized , controlled , phase 3 study , we assigned 834 patients with advanced melanoma in a 1:1:1 ratio to receive pembrolizumab ( at a dose of 10 mg per kilogram of body weight ) every 2 weeks or every 3 weeks or four doses of ipilimumab ( at 3 mg per kilogram ) every 3 weeks . Primary end points were progression-free and overall survival . RESULTS The estimated 6-month progression-free-survival rates were 47.3 % for pembrolizumab every 2 weeks , 46.4 % for pembrolizumab every 3 weeks , and 26.5 % for ipilimumab ( hazard ratio for disease progression , 0.58 ; P<0.001 for both pembrolizumab regimens versus ipilimumab ; 95 % confidence intervals [ CIs ] , 0.46 to 0.72 and 0.47 to 0.72 , respectively ) . Estimated 12-month survival rates were 74.1 % , 68.4 % , and 58.2 % , respectively ( hazard ratio for death for pembrolizumab every 2 weeks , 0.63 ; 95 % CI , 0.47 to 0.83 ; P=0.0005 ; hazard ratio for pembrolizumab every 3 weeks , 0.69 ; 95 % CI , 0.52 to 0.90 ; P=0.0036 ) . The response rate was improved with pembrolizumab administered every 2 weeks ( 33.7 % ) and every 3 weeks ( 32.9 % ) , as compared with ipilimumab ( 11.9 % ) ( P<0.001 for both comparisons ) . Responses were ongoing in 89.4 % , 96.7 % , and 87.9 % of patients , respectively , after a median follow-up of 7.9 months . Efficacy was similar in the two pembrolizumab groups . Rates of treatment-related adverse events of grade 3 to 5 severity were lower in the pembrolizumab groups ( 13.3 % and 10.1 % ) than in the ipilimumab group ( 19.9 % ) . CONCLUSIONS The anti-PD-1 antibody pembrolizumab prolonged progression-free survival and overall survival and had less high- grade toxicity than did ipilimumab in patients with advanced melanoma . ( Funded by Merck Sharp & Dohme ; KEYNOTE-006 Clinical Trials.gov number , NCT01866319 . )
Output:
| These significance s were reflected in the subgroup of melanoma metastases .
Conclusion Based on the trends of our findings , there appears to exist an optimal time window around SRS of which ICI may confer the most survival benefit . |
MS213751 | ***TASK*** the task is to summarize an input biomedical literature in six sentences
***INPUT*** the input is a biomedical literature
***OUTPUT*** the output is the summary of an input biomedical literature in six sentences
***DOCUMENTATION***
***EXAMPLES***
Input: Background and Purpose — Mechanical thrombectomy has the potential to improve recanalization rates and outcomes for patients with ischemic stroke , but potential gains could be offset by procedural complications and costs . We evaluated the cost and utility of combined intravenous ( IV ) tissue-type plasminogen activator ( tPA ) and mechanical thrombectomy compared to IV tPA alone for acute large-vessel ischemic stroke . Methods — We constructed a decision tree for a hypothetical 68-year-old with a large-vessel ischemic stroke who is eligible for IV tPA . The interventional strategy was IV tPA , a cerebral angiogram , and mechanical thrombectomy and thrombolysis if indicated . Recanalization , hemorrhage complications , and outcomes for the interventional strategy were from the Multi-MERCI study . The medical strategy was IV tPA using inputs from a comprehensive systematic review . Costs were estimated from Medicare reimbursements . We modeled lifetime costs and utilities for disability using a Markov model and Monte-Carlo multivariable sensitivity analysis . Results — For the baseline scenario , the recanalization rate was 72.9 % for the interventional strategy and 46.2 % for the medical strategy . For the interventional strategy , the symptomatic hemorrhage rate was 8.6 % with recanalization and 15.4 % without . For the medical strategy , the corresponding rates were 3.6 % and 13.3 % , respectively . The interventional strategy was cost-effective in 97.6 % of simulations ( incremental cost-effectiveness ratio $ 16 001/ quality -adjusted life year ; 95 % CI , $ 2736–$39 232 ) . Conclusions — Based on observational data , the combination of IV tPA and mechanical thrombectomy for large-vessel ischemic stroke appears to be cost-effective compared to IV tPA alone . These findings require additional validation with r and omized trial data Background and Purpose — Clinical trials have demonstrated improved 90-day outcomes for patients with acute ischemic stroke treated with stent retriever thrombectomy plus tissue-type plasminogen activator ( SST+tPA ) compared with tPA . Previous studies suggested that this strategy may be cost-effective , but models were derived from pooled data and older assumptions . Methods — In this prospect i ve economic sub study conducted alongside the SWIFT-PRIME trial ( Solitaire With the Intention for Thrombectomy as Primary Endovascular Treatment for Acute Ischemic Stroke ) , in-trial costs were measured for patients using detailed medical re source utilization and hospital billing data . Utility weights were assessed at 30 and 90 days using the EuroQol-5 dimension question naire . Post-trial costs and life-expectancy were estimated for each surviving patient using a model based on trial data and inputs derived from a contemporary cohort of ischemic stroke survivors . Results — Index hospitalization costs were $ 17 183 per patient higher for SST+tPA than for tPA ( $ 45 761 versus $ 28 578 ; P<0.001 ) , driven by initial procedure costs . Between discharge and 90 days , costs were $ 4904 per patient lower for SST+tPA than for tPA ( $ 11 270 versus $ 16 174 ; P=0.014 ) ; total 90-day costs remained higher with SST+tPA ( $ 57 031 versus $ 44 752 ; P<0.001 ) . Higher utility values for SST+tPA led to higher in-trial quality -adjusted life years ( 0.131 versus 0.105 ; P=0.005 ) . In lifetime projections , SST+tPA was associated with substantial gains in quality -adjusted life years ( 6.79 versus 5.05 ) , cost savings of $ 23 203 per patient and was economically dominant when compared with tPA in 90 % of bootstrap replicates . Conclusions — Among patients with acute ischemic stroke enrolled in the SWIFT-PRIME trial , SST increased initial treatment costs , but was projected to improve quality -adjusted life-expectancy and reduce healthcare costs over a lifetime horizon compared with tPA . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT01657461 Objective : To evaluate the cost-effectiveness of adding endovascular thrombectomy to st and ard care in patients with acute ischemic stroke . Methods : The cost-effectiveness analysis of endovascular thrombectomy in patients with acute ischemic stroke was based on a decision-analytic Markov model . Primary outcomes from ESCAPE , Extending the Time for Thrombolysis in Emergency Neurological Deficits – Intra-Arterial ( EXTEND-IA ) , Multicenter R and omized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherl and s ( MR CLEAN ) , Endovascular Revascularization With Solitaire Device Versus Best Medical Therapy in Anterior Circulation Stroke Within 8 Hours ( REVASCAT ) , and Solitaire with the Intention for Thrombectomy as Primary Endovascular Treatment for Acute Ischemic Stroke ( SWIFT PRIME ) along with data from published studies and registries were used in this analysis . We used a health care payer perspective and a lifelong time horizon to estimate costs and effects . Results : The model showed that adding thrombectomy with stent retrievers to guideline -based care ( including IV thrombolysis ) result ed in a gain of 0.40 life-years and 0.99 quality -adjusted life-years along with a cost savings of approximately $ 221 per patient . The sensitivity analysis showed that the results were not sensitive to changes in uncertain parameters or assumptions . Conclusions : Adding endovascular treatment to st and ard care result ed in substantial clinical benefits at low costs . The results were consistent throughout irrespective of whether data from ESCAPE , EXTEND-IA , MR CLEAN , REVASCAT , or SWIFT PRIME were used in this model OBJECT Mechanical thrombectomy is increasingly being used for the treatment of large-vessel ischemic stroke in patients who arrive outside of the 3-hour tissue plasminogen activator time window . In this study , the authors evaluated the cost and effectiveness of mechanical thrombectomy compared with st and ard medical therapy in patients who are ineligible to receive tissue plasminogen activator . METHODS Clinical outcomes of an open-label study of mechanical thrombectomy were compared with a hypothetical control group with a lower recanalization rate ( 18 vs 60 % ) and a lower rate of symptomatic intracranial hemorrhage ( 0.6 vs 7.8 % ) than the active treatment group . A Markov cost-effectiveness model was built to compare the health benefits and costs associated with mechanical thrombectomy compared with st and ard medical therapy . All probabilities , quality -of-life factors , and costs were estimated from the published literature . Univariate sensitivity analyses were performed to assess how variations in model parameters affect health and economic outcomes . RESULTS Treatment of acute ischemic stroke with mechanical thrombectomy increased survival time by 0.54 quality -adjusted life years ( QALYs ) , compared with st and ard medical therapy ( 2.37 vs 1.83 QALYs ) , at an increased cost of $ 6600 . This yielded an incremental cost-effectiveness ratio ( ICER ) of $ 12,120 per QALY gained , a value generally considered cost-effective . Sensitivity analysis showed that mechanical thrombectomy remained cost-effective ( ICER < $ 50,000 per QALY gained ) for all model inputs varied over a reasonable range , except for age at stroke treatment . For patients older than 82 years of age , the treatment was only borderline cost-effective ( ICER of $ 50,000 - 100,000 per QALY gained ) . CONCLUSIONS The treatment of large-vessel ischemic stroke with mechanical thrombectomy appears to be costeffective . These results require validation when data from a r and omized , controlled trial of mechanical thrombectomy become available Background and Purpose — The objective of this study was to determine the cost-effectiveness of intra-arterial treatment within the 0- to 6-hour window after intravenous tissue-type plasminogen activator within 0- to 4.5-hour compared with intravenous tissue-type plasminogen activator alone , in the US setting and from a social perspective . Methods — A decision analytic model estimated the lifetime costs and outcomes associated with the additional benefit of intra-arterial therapy compared with st and ard treatment with intravenous tissue-type plasminogen activator alone . Model inputs were obtained from published literature , the Multicenter R and omized Clinical Trial of Endovascular Therapy for Acute Ischemic Stroke in the Netherl and s ( MR CLEAN ) study , and cl aims data bases in the United States . Health outcomes were measured in quality -adjusted life years ( QALYs ) . Treatment benefit was assessed by calculating the cost per QALY gained . One-way and probabilistic sensitivity analyses were performed to estimate the overall uncertainty of model results . Results — The addition of intra-arterial therapy compared with st and ard treatment alone yielded a lifetime gain of 0.7 QALY for an additional cost of $ 9911 , which result ed in a cost of $ 14 137 per QALY . Multivariable sensitivity analysis predicted cost-effectiveness ( ⩽$50 000 per QALY ) in 97.6 % of simulation runs . Conclusions — Intra-arterial treatment after intravenous tissue-type plasminogen activator for patients with anterior circulation strokes within the 6-hour window is likely cost-effective . From a societal perspective , increased investment in access to intra-arterial treatment for acute stroke may be justified BACKGROUND AND PURPOSE : It is unclear whether the costs and risks of mechanical therapies make them cost-effective . We examined whether interventions such as mechanical clot removal or disruption with angioplasty are cost-effective for acute ischemic stroke compared with best medical therapy . MATERIAL S AND METHODS : We performed a cost-utility analysis of patients with acute stroke due to large intracranial artery occlusion presenting beyond the 3-hour window for IV tPA . Model inputs for the mechanical arm were derived from Multi MERCI trial data and a recent meta- analysis . For best medical therapy , we used rates of spontaneous recanalization , ICH , and functional outcomes based on a systematic literature review . Discounted QALYs were determined by using the Markov modeling for 65-year-old patients with acute ischemic stroke . RESULTS : On the basis of a systematic literature review , we modeled an 84 % rate of recanalization with mechanical intervention and a 6.3 % rate of symptomatic ICH . For best medical therapy , we modeled a spontaneous recanalization rate of 24 % with a 2 % rate of symptomatic ICH . Mechanical therapies were associated with a $ 7718 net cost and a gain of a 0.82 QALYs for each use , thus yielding a net of $ 9386/QALY gained . In sensitivity analyses , results were dependent on the rates of recanalization , symptomatic ICH rates , and costs of treatment . CONCLUSIONS : On the basis of available data , mechanical therapies in qualified patients with acute stroke beyond the window for IV tPA appear to be cost-effective . However , the inputs are not derived from r and omized trials , and results are sensitive to several assumptions BACKGROUND Thrombolytic therapy for acute ischemic stroke has been approached cautiously because there were high rates of intracerebral hemorrhage in early clinical trials . We performed a r and omized , double-blind trial of intravenous recombinant tissue plasminogen activator ( t-PA ) for ischemic stroke after recent pilot studies suggested that t-PA was beneficial when treatment was begun within three hours of the onset of stroke . METHODS The trial had two parts . Part 1 ( in which 291 patients were enrolled ) tested whether t-PA had clinical activity , as indicated by an improvement of 4 points over base-line values in the score of the National Institutes of Health stroke scale ( NIHSS ) or the resolution of the neurologic deficit within 24 hours of the onset of stroke . Part 2 ( in which 333 patients were enrolled ) used a global test statistic to assess clinical outcome at three months , according to scores on the Barthel index , modified Rankin scale , Glasgow outcome scale , and NIHSS : RESULTS In part 1 , there was no significant difference between the group given t-PA and that given placebo in the percentages of patients with neurologic improvement at 24 hours , although a benefit was observed for the t-PA group at three months for all four outcome measures . In part 2 , the long-term clinical benefit of t-PA predicted by the results of part 1 was confirmed ( global odds ratio for a favorable outcome , 1.7 ; 95 percent confidence interval , 1.2 to 2.6 ) . As compared with patients given placebo , patients treated with t-PA were at least 30 percent more likely to have minimal or no disability at three months on the assessment scales . Symptomatic intracerebral hemorrhage within 36 hours after the onset of stroke occurred in 6.4 percent of patients given t-PA but only 0.6 percent of patients given placebo ( P < 0.001 ) . Mortality at three months was 17 percent in the t-PA group and 21 percent in the placebo group ( P = 0.30 ) . CONCLUSIONS Despite an increased incidence of symptomatic intracerebral hemorrhage , treatment with intraven
Output:
| Conclusions If the outcomes of the trials underpinning the evidence of clinical effectiveness can be replicated , then mechanical thrombectomy is likely to be cost-effective by typical willingness-to-pay thresholds .
This finding holds under the assumption that no investment is required to develop stroke centres to the st and ard required to provide a safe emergency endovascular service and that additional expenditure on timely patient transport is not required |
MS213752 | ***TASK*** the task is to summarize an input biomedical literature in six sentences
***INPUT*** the input is a biomedical literature
***OUTPUT*** the output is the summary of an input biomedical literature in six sentences
***DOCUMENTATION***
***EXAMPLES***
Input: All newborn infants in East Anglia are screened for cystic fibrosis by blood immunoreactive trypsin assay at 7 days . Thirty eight infants with cystic fibrosis were r and omised to treatment with either continuous oral flucloxacillin 250 mg/day ( group P , n = 18 ) or with episodic antimicrobials as clinical ly indicated ( group E , n = 20 ) . Their progress was monitored from diagnosis to 24 months by a nurse coordinator who visited all infants regularly , at home and in hospital , to collect anthropometric , dietary , clinical , and microbiological data . Mean ( range ) age of confirmation of diagnosis was 5.7 weeks ( 1 - 14 weeks ) . There was no significant difference in birth weight , genotype , immunoreactive trypsin concentration , neonatal history , symptoms at diagnosis , pancreatic enzyme supplementation , or parental smoking history between the groups . Infants in group E had more frequent cough and a greater number of Staphylococcus aureus isolates than infants in group P. More infants of group E were admitted to hospital , had higher admission rates during the second year ( 19 v 5 ) , for longer periods ( 6.4 v 2.2 days ) , despite receiving more than double the number of courses of antibiotics than group P infants ( in addition to flucloxacillin ) . Continuous prophylactic flucloxacillin from early diagnosis of cystic fibrosis is associated with improved clinical progress during the first two years of life The nature and timing of lower respiratory infections in infants with cystic fibrosis is largely unknown1 because infants do not produce sputum and throat cultures may not predict lower respiratory pathogens.2 We performed a prospect i ve cross sectional study of an unselected cohort of infants with cystic fibrosis in which bronchoalveolar lavage was used to determine lower respiratory infection and inflammation during the first three months of life . The state of Victoria , Australia ( 66000 births per year ) has a cystic fibrosis screening programme , all patients being managed by one centre . Between February 1992 and September 1994 we recruited 45 ( 27 boys ) of the 52 infants with newly diagnosed disease ; 32 were identified by screening , 12 from meconium ileus , and one by failure to thrive , and all cases were confirmed by sweat testing . Sixteen infants had respiratory symptoms , and seven of them were receiving oral antibiotics when bronchoalveolar lavage was performed at a mean age of 2.6 ( SD 1.6 ) months . Nine otherwise healthy infants ( five boys ) aged ABSTRACT Linezolid is a treatment option for methicillin-resistant Staphylococcus aureus ( MRSA ) infections in cystic fibrosis ( CF ) patients . Little is known , however , about its pharmacokinetics in this population . Eight adults with CF were r and omized to receive intravenous ( i.v . ) and oral linezolid at 600 mg twice daily for 9 doses in a crossover design with a 9-day washout . Plasma sample s were collected after the first and ninth doses of each phase . Population pharmacokinetic analyses were performed by nonlinear mixed-effects modeling using a previously described 2-compartment model with time-dependent clearance inhibition . Monte Carlo simulation was performed to assess the activities of the linezolid dosing regimens against 42 contemporary MRSA isolates recovered from CF patients . The following pharmacokinetic parameter estimates were observed for the population : absorption rate constant , 1.91 h−1 ; clearance , 9.54 liters/h ; volume of central compartment , 26.8 liters ; volume of peripheral compartment , 17.3 liters ; and intercompartmental clearance , 104 liters/h . Linezolid demonstrated nonlinear clearance after 9 doses , which was reduced by a mean of 38.9 % ( range , 28.8 to 59.9 % ) . Mean bioavailability was 85 % ( range , 47 to 131 % ) . At steady state , 600 mg given twice daily produced 93.0 % and 87.2 % probabilities of obtaining the target pharmacodynamic exposure against the MRSA isolates for the i.v . and oral formulations , respectively . Thrice-daily dosing increased the probabilities to 97.0 % and 95.6 % , respectively . Linezolid pharmacokinetics in these adults with CF were well described by a 2-compartment model with time-dependent clearance inhibition . St and ard i.v . and oral dosing regimens should be sufficient to reliably attain pharmacodynamic targets against most MRSA isolates ; however , more frequent dosing may be required for isolates with MICs of ≥2 μg/ml RATIONALE Better underst and ing of evolution of lung function in infants with cystic fibrosis ( CF ) and its association with pulmonary inflammation and infection is crucial in informing both early intervention studies aim ed at limiting lung damage and the role of lung function as outcomes in such studies . OBJECTIVES To describe longitudinal change in lung function in infants with CF and its association with pulmonary infection and inflammation . METHODS Infants diagnosed after newborn screening or clinical presentation were recruited prospect ively . FVC , forced expiratory volume in 0.5 seconds ( FEV(0.5 ) ) , and forced expiratory flows at 75 % of exhaled vital capacity ( FEF(75 ) ) were measured using the raised-volume technique , and z-scores were calculated from published reference equations . Pulmonary infection and inflammation were measured in bronchoalveolar lavage within 48 hours of lung function testing . MEASUREMENTS AND MAIN RESULTS Thirty-seven infants had at least two successful repeat lung function measurements . Mean ( SD ) z-scores for FVC were -0.8 ( 1.0 ) , -0.9 ( 1.1 ) , and -1.7 ( 1.2 ) when measured at the first visit , 1-year visit , or 2-year visit , respectively . Mean ( SD ) z-scores for FEV(0.5 ) were -1.4 ( 1.2 ) , -2.4 ( 1.1 ) , and -4.3 ( 1.6 ) , respectively . In those infants in whom free neutrophil elastase was detected , FVC z-scores were 0.81 lower ( P=0.003 ) , and FEV(0.5 ) z-scores 0.96 lower ( P=0.001 ) , respectively . Significantly greater decline in FEV(0.5 ) z-scores occurred in those infected with Staphylococcus aureus ( P=0.018 ) or Pseudomonas aeruginosa ( P=0.021 ) . CONCLUSIONS In infants with CF , pulmonary inflammation is associated with lower lung function , whereas pulmonary infection is associated with a greater rate of decline in lung function . Strategies targeting pulmonary inflammation and infection are required to prevent early decline in lung function in infants with CF The effect of prophylactic antibiotics on bacterial colonization of the respiratory tract and on general progression of cystic fibrosis was studied in a two-year prospect i ve study of 47 mildly to moderately affected patients . One group of patients received inhaled cephaloridine and the other received no inhaled antibiotic ; both groups received cloxacillin orally . Carriage of Haemophilus influenzae was greater in the group not receiving inhaled antibiotic ( 55 % vs 20 % ) . Rates of carriage of Staphylococcus aureus ( 23 % ) . Pseudomonas aeruginosa ( greater than 90 % ) . Pseudomonas cepacia ( 45 % ) , and other organisms were similar in both groups . There were no significant differences between the two groups in incidence of respiratory tract infections or hospital admissions , clinical scores , radiologic scores , or rate of change of pulmonary function . Although continuous antistaphylococcal antibiotic prophylaxis may be successful in suppressing colonization with S. aureus , it may also contribute to the high rates of carriage of Ps . aeruginosa and Ps . cepacia observed in patients with cystic fibrosis On the basis of their answers to a self-administered question naire , 697 nonsmoking healthy subjects were chosen from a r and omly selected sample representative of the white non-Mexican-American population of Tucson , Arizona , enrolled in a longitudinal study of respiratory health . For each subject , the first satisfactory set of flow-volume data obtained during the first 3 consecutive surveys was selected for analysis . For forced vital capacity ( FVC ) and forced expiratory volume in one second ( FEV1 ) , the single best value for each subject was selected . Other flow-volume measurements were derived from the single test with the best sum FEV , plus FVC . These data were used to derive improved prediction equations for each sex by age group for 5 spirometric and flow-volume variables . The result ing predicted values demonstrate the effects of development , maturation , and senescence on ventilatory function . " Normal " limits are proposed that take into consideration the between-subject variability and non-Gaussian distribution of the various measurements Since 1982 all infants born within the East Anglian Regional Health Authority have been screened for cystic fibrosis . Between April 1985 and April 1992 infants identified in this way have been entered into a r and omised prospect i ve controlled trial of antibiotic prophylaxis . Approximately half the infants received continuous oral flucloxacillin and the remainder received antibiotics when clinical ly indicated . Infants underwent tests of respiratory function at 3 - 4 months and at 1 year of age . Measurements of thoracic gas volume and airway conductance were made with an infant whole body plethysmograph , and maximum expiratory flow by the ' squeeze ' technique . A total of 73 tests was performed of 42 infants . To facilitate comparisons , measurements were expressed as scores . The mean values of the scores for the two groups of infants fell within normal limits . There was no difference between the treatment groups at either age . A reduction in airways conductance was observed between the two tests The effects of oral administration of cephalexin were evaluated in a double-blind , placebo-controlled , crossover study in 17 patients with mild to moderate pulmonary disease due to cystic fibrosis . For two years , four-month periods with cephalexin were alternated with four-month placebo periods . Thus , patients served as their own control subjects . Fungal vulvovaginitis occurred in two patients and a cephalexin-resistant Enterobacter cloacae was acquired in the sputum of another patient during cephalexin therapy . During the 2 years of study , the rate of colonization with mucoid strains of Pseudomonas aeruginosa increased and disease severity deteriorated in patients initially colonized with P. aeruginosa . Short-term courses of sputum culture-specific antibiotics improved the course of some patients with mild to moderate pulmonary disease due to cystic fibrosis . Treatment with cephalexin decreased the frequency of respiratory illnesses , respiratory illnesses requiring antibiotics , and hospitalizations for respiratory illnesses in patients initially colonized with Staphylococcus aureus and /or Haemophilus influenzae , and also reduced colonization with these organisms . Improved weight gain in 16 of 17 patients was associated with periods of cephalexin therapy . Pulmonary function tests remained stable or improved in 10 of 14 patients . Disease severity improved in patients not colonized with P. aeruginosa OBJECTIVES To evaluate whether antistaphylococcal prophylaxis in infants and young children with cystic fibrosis ( CF ) would suppress the acquisition of Staphylococcus aureus and delay the onset of the manifestations of bronchopulmonary disease . STUDY DESIGN A 7-year , multicenter , double-blind , placebo-controlled study of continuous antistaphylococcal therapy . Otherwise healthy children < 2 years of age with CF were r and omly assigned to be treated with daily cephalexin ( 80 - 100 mg/kg/day ) or placebo . Clinical , microbiologic , laboratory , radiographic , and anthropometric outcomes were evaluated . RESULTS Of 209 children enrolled , 119 completed a 5- to 7-year course of therapy . Mean age at enrollment was 15.6 and 14.1 months in the cephalexin and placebo groups , respectively . Respiratory cultures from children treated with cephalexin were significantly less likely to be positive for S aureus ( 6.0 % vs 30.4 % ; P < .001 ) . They were , however , much more likely to be positive for Pseudomonas aeruginosa ( 25.6 % vs 13.5 % ; P < .009 ) . These differences became apparent in the first year after enrollment and persisted over the duration of the study . In contrast to these microbiologic differences , there were no differences in clinical outcome measures , including radiographic ( Brasfield score , 23.4 vs 23.2 ) or anthropometric scores or pulmonary function . CONCLUSIONS Although long-term prophylaxis with cephalexin successfully delayed the acquisition of S aureus , it enhanced colonization with P aeruginosa and did not lead to clinical ly significant improvement in major health outcomes . These data do not support routine antistaphylococcal prophylaxisin otherwise healthy infants and young children with CF [ N PATIENTS with cystic fibrosis , the progression of pulmonary disease following Staphylococcus aureus colonization and the improvement after its
Output:
| Prophylaxis:1 .
There was no significant difference between groups in infant or conventional lung function ( moderate quality evidence ) .
We found no significant effect on nutrition ( low quality evidence ) , hospital admissions , additional courses of antibiotics ( low quality evidence ) or adverse effects ( moderate quality evidence ) .
There was no significant difference in the number of isolates of Pseudomonas aeruginosa between groups ( low quality evidence ) , though there was a trend towards a lower cumulative isolation rate of Pseudomonas aeruginosa in the prophylaxis group at two and three years and towards a higher rate from four to six years .
As the studies review ed lasted six years or less , conclusions can not be drawn about the long-term effects of prophylaxis .
Anti-staphylococcal antibiotic prophylaxis leads to fewer children having isolates of Staphylococcus aureus , when commenced early in infancy and continued up to six years of age . |
MS213753 | ***TASK*** the task is to summarize an input biomedical literature in six sentences
***INPUT*** the input is a biomedical literature
***OUTPUT*** the output is the summary of an input biomedical literature in six sentences
***DOCUMENTATION***
***EXAMPLES***
Input: Treatment of naso-sinus polyposis has been the subject of much controversy . The large number of reports in the literature suggest that role of surgical treatment is on the uprise . There is however general agreement that medical treatment is fundamental although an insufficient number of studies have evaluated its efficacy . The aim of this prospect i ve study was to evaluate results 6 months , 12 months and 2 years after medical treatment of polyposis in 181 patients . Despite a well-coduced information protocol , nearly 19 % of the patients were lost to follow-up . Less than 32 % of the patients have been operated . Patients treated medically were given a st and ard regimen according to a protocol combining short-term oral corticosteroids ( prednisolone ) and steroid nasal spray ( beclometasone ) . Treatment was successful in 68 % of the patients given medical treatment alone . Mean symptom intensity declined by 35 to 80 % at 6 months then remained unchanged to the end of the study ( 2 years follow-up ) . Mean doses of prednisolone and beclomethasone were evaluated . Doses could be tapered off progressively allowing satisfactory nasal comfort . Medical treatment should be the first line therapy for nasal polyposis . Surgery should not be proposed until corticosteroid therapy has been found to be unsuccessful over a mean 6 months of a well-conducted treatment and good patient compliance We started therapy sinusitis of our patients with antibiotics cefuroxime axetil ( Zinnat , GSK ) , clarithromycin ( Klacid Uno , Abbott ) and orally given steroid-prednisone in one group ( A+S ) 56 patients . Second group of 60 patients were cured only with antibiotics ( A ) . We compare effects of this therapy . There were 50 % totally cured patients in the first group ( A+S ) and 46.6 % cured in the second group . Percentage totally cured patients with ( A+S ) is 3.4 % better that cured only with antibiotics in the same time . It is statistically important . We present benefits for patients who were operated in the next step . Post therapy with the use of antibiotics and steroids there were less bleeding from the mucosal membrane , and there was no edema . It is a good method of therapy if patients have no contraindications A r and omized comparison of the usual surgical removal of nasal polyps versus systemic steroid treatment was performed in 53 patients . In all , continuous topical steroid treatment was given during the one year period of observation . In both groups the initial treatment result ed in a continuous increase in mean nasal expiratory peak flow as well as in the sense of smell ; these two parameters showed a temporary statistically significant difference in favour of the medically treated group . In general though , the results in the two treatment groups were alike . Therefore medical treatment is recommended for routine use . Surgical removal should be reserved for those few cases in which the presence of residual or recurrent polyps justifies the inherent risks and discomfort for the patient BACKGROUND There is little scientific evidence to support the current practice of using oral glucocorticosteroids and antibiotics to treat patients with chronic rhinosinusitis and nasal polyps . OBJECTIVE We evaluated the effects of oral glucocorticoids and doxycycline on symptoms and objective clinical and biological parameters in patients with chronic rhinosinusitis and nasal polyps . METHODS In a double-blind , placebo-controlled , multicenter trial , we r and omly assigned 47 participants with bilateral nasal polyps to receive either methylprednisolone in decreasing doses ( 32 - 8 mg once daily ) , doxycycline ( 200 mg on the first day , followed by 100 mg once daily ) , or placebo for 20 days . Participants were followed for 12 weeks . Patients were assessed for nasal peak inspiratory flow and symptoms and by nasal endoscopy . Markers of inflammation such as eosinophilic cationic protein ( ECP ) , IL-5 , myeloperoxidase , matrix metalloproteinase 9 , and IgE were measured in nasal secretions . Concentrations of eosinophils , ECP , and soluble IL-5 receptor alpha were measured in peripheral blood sample s. RESULTS Methylprednisolone and doxycycline each significantly decreased nasal polyp size compared with placebo . The effect of methylprednisolone was maximal at week 3 and lasted until week 8 , whereas the effect of doxycycline was moderate but present for 12 weeks . Methylprednisolone significantly reduced levels of ECP , IL-5 , and IgE in nasal secretions , whereas doxycycline significantly reduced levels of myeloperoxidase , ECP , and matrix metalloproteinase 9 in nasal secretions . CONCLUSION This is the first double-blind , placebo-controlled study to show a significant effect of oral methylprednisolone and doxycycline on size of nasal polyps , nasal symptoms , and mucosal and systemic markers of inflammation Background Although combined oral and nasal steroid therapy is widely used in nasal polyposis , a subset of patients show an unfavorable therapeutic outcome . This study aim ed to evaluate whether oral prednisolone produces any additive effects on subsequent nasal steroid therapy and to evaluate if any clinical variables can predict therapeutic outcome . Methods Using a 3:2 r and omization ratio , 67 patients with nasal polyposis received 50 mg of prednisolone and 47 patients received placebo daily for 2 weeks , followed by mometasone furoate nasal spray ( MFNS ) at 200 micrograms twice daily for 10 weeks . Clinical response was evaluated by nasal symptom score ( NSS ) , peak expiratory flow index ( PEFI ) , and total nasal polyps score ( TNPS ) . Potential predictor variables were assessed by clinical history , nasal endoscopy , allergy skin test , and sinus radiography . Results At the end of the 2-week oral steroid phase , the prednisolone group showed significantly greater improvements in all nasal symptoms , nasal airflow , and polyp size than the placebo group . In the nasal steroid phase , while the MFNS maintained the outcome improvements in the prednisolone group , all outcome variables in the placebo group showed continuing improvements . At the end of the nasal steroid phase , there re no significant differences of most outcome improvements between the two groups , except in hyposmia , PEFI , and TNPS ( p = 0.049 , p = 0.029 , and p = 0.005 , respectively ) . In the prednisolone group , patients with polyps grade 3 and endoscopic signs of meatal discharge showed significantly less improvement in total NSS , PEFI , and TNPS than patients with grade 1–2 size and negative metal discharge . Conclusion In the 12-week treatment evaluation of nasal polyposis , pretreatment with oral steroids had no significant advantage for most nasal symptoms other than earlier relief ; however , combined oral and nasal steroid therapy more effectively improved hyposmia , polyps size , and nasal airflow . Polyps size grade 3 and /or endoscopic signs of meatal discharge predisposed to a poorer treatment outcome BACKGROUND Controlled prospect i ve studies are needed to determine whether surgical treatment in fact has an effect additive to that of medical treatment of nasal polyposis . OBJECTIVE We sought to compare the effect of medical treatment versus combined surgical and medical treatment on olfaction , polyp score , and symptoms in nasal polyposis . METHODS Thirty-two patients with nasal polyposis and symmetrical nasal airways were r and omized to unilateral endoscopic sinus surgery after pretreatment with oral prednisolone for 10 days and local nasal budesonide bilaterally for 1 month . Postoperatively , patients were given local nasal steroids ( budesonide ) . Patients were evaluated with nasal endoscopy , symptom scores , and olfactory thresholds . They were followed for 12 months . RESULTS The sense of smell was improved by the combination of local and oral steroids . Surgery had no additional effect . Symptom scores improved significantly with medical treatment alone , but surgery had additional beneficial effects on nasal obstruction and secretion . After surgery , the polyp score decreased significantly on the operated side but remained the same on the unoperated side . Twenty-five percent of the patients were willing to undergo an operation also on the unoperated side at the end of the study . CONCLUSIONS Medical treatment seems to be sufficient to treat most symptoms of nasal polyposis . When hyposmia is the primary symptom , no additional benefit seems to be gained from surgical treatment . If nasal obstruction is the main problem after steroid treatment , surgical treatment is indicated . Selection of those who will benefit from surgery should be based on the patient 's symptoms and not on the examiner 's polyp score The effects of rhinosinusitis treatment upon asthma are disputed . The first r and omised prospect i ve study of surgical compared with medical therapy of chronic rhinosinusitis in 90 patients with and without nasal polyps was previously reported . Asthma symptoms , control , forced expiratory volume in one second ( FEV1 ) , peak flow , exhaled nitric oxide , medication use and hospitalisation at 6 and 12 months from the start of the study were also monitored . This paper reports these results in 43 of those patients with concomitant asthma . Both medical and surgical treatment of chronic rhinosinusitis were associated with subjective and objective improvements in asthma . Overall asthma control improved significantly following both treatment modalities , but was better maintained after medical therapy , where improvement could also be demonstrated in the subgroup with nasal polyps . Medicine was superior to surgery with respect to a decrease in exhaled nitric oxide and increase in FEV1 in the polyp patients . Two patients noted worsening of asthma post-operatively . Improvement in upper airway symptoms , as assessed using a visual analogue scale , correlated with improvement in asthma symptoms and control . Treatment of chronic rhinosinusitis , medical or surgical , benefits concomitant asthma ; that associated with nasal polyposis benefits more from medical therapy OBJECTIVES /HYPOTHESIS To assess the effect of oral plus intranasal corticosteroids on subjective outcomes ( smell and nasal congestion ) and objective outcomes ( tissue eosinophilia and nitric oxide ) in severe nasal polyposis ( NP ) . STUDY DESIGN After a 4-week steroid washout period ( w0 ) , severe NP were r and omized into a treatment group ( n = 67 ) that receive oral prednisone for 2 weeks ( w2 ) plus intranasal budesonide for 12 weeks ( w12 ) , and a control group ( n = 22 ) that received no steroid treatment . METHODS Barcelona Smell Test 24 ( BAST-24 ) , nasal congestion , tissue eosinophilia , and nasal nitric oxide ( nNO ) were assessed . RESULTS Before treatment , patients showed a significant impairment of smell detection ( 30.7 ± 39.5 % ) , identification ( 7.1 ± 16.1 % ) , and forced choice ( 13.8 ± 23.3 % ) in BAST-24 compared to healthy population . At w2 , the treatment group showed a significant improvement in detection , identification , and forced choice . Positive effect was also seen after 12 weeks of intranasal corticosteroids . A significant reduction of nasal congestion ( 1.17 ± 1.0 vs. 2.73 ± 0.5 ) and polyp tissue eosinophilia ( 10.9 ± 4.2 vs. 41.2 ± 12.2 ) with an increase of nNO ( 650 ± 317 vs. 420 ± 221 ppb ) were observed at w2 compared to w0 and to the control group . These effects were also seen at w12 . CONCLUSIONS Combined oral and intranasal corticosteroids improve smell and nasal congestion and decrease nasal inflammation , as measured by reduced tissue eosinophilia and increased detection of nNO . Severity of smell loss correlates with degree of nasal congestion but not with inflammation , as measured by tissue eosinophilia or nasally exhaled nNO . Our findings suggest that improvement in smell may be related to improved conduction of odorants to the olfactory neuroepithelium OBJECTIVE To investigate endoscopic staging , and nitric oxide levels in the polyp tissue , in patients with nasal polyposis undergoing glucocorticoid therapy . METHODS Nasal polyposis was evaluated using endoscopic staging and measurement of polyp tissue nitric oxide levels ( chemiluminescence method ) . Forty-five nasal polyposis patients received either nasal therapy ( n = 15 ) , oral therapy ( n = 15 ) or combined therapy ( n = 15 ) . Pre-treatment and post-treatment staging and nitric oxide levels were evaluated . RESULTS Endoscopic grading indicated significant post-treatment staging improvements in the oral ( p = 0.016 ) and combined ( p = 0.016 ) groups . Post-treatment staging differed significantly between the three groups ( p = 0.041 ) , with greater improvements in the oral and combined groups . All groups showed significantly lower post-treatment nitric oxide levels , compared with baseline , but post-treatment levels did not differ significantly between groups . A significant association was found between treatment response and nitric oxide level alteration . CONCLUSION This study demonstrates the favourable effects of glucocorticoids on nasal polyposis , and alteration in nitric oxide tissue levels post-treatment . Nitric oxide level in nasal polyp tissue could be an indicator of treatment response
Output:
| At the end of the treatment course ( two to three weeks ) there is an improvement in health-related quality of life and symptom severity in patients with chronic rhinosinusitis with nasal polyps taking oral corticosteroids compared with placebo or no treatment .
At three to six months after the end of the oral steroid treatment period , there is little or no improvement in health-related quality of life or symptom severity for patients taking an initial course of oral steroids compared with placebo or no treatment .
The data on the adverse effects associated with short courses of oral corticosteroids indicate that there may be an increase in insomnia and gastrointestinal disturbances but it is not clear whether there is an increase in mood disturbances .
There is no evidence for oral steroids compared with other treatments |
MS213754 | ***TASK*** the task is to summarize an input biomedical literature in six sentences
***INPUT*** the input is a biomedical literature
***OUTPUT*** the output is the summary of an input biomedical literature in six sentences
***DOCUMENTATION***
***EXAMPLES***
Input: Introduction Previous radiostereometric studies have revealed abnormal anterior-posterior translation of the femur in patients operated with AMK ( DePuy , Johnson and Johnson , Leeds , UK ) total knee arthroplasty ( TKA ) . Based on these observations , we hypothesized that patients with TKA have an abnormal gait pattern , and that there are differences in kinematics depending on the design of the tibial joint area . Method We used a gait analysis system to evaluate the influence of joint area design on the kinematics of the hip and knee during level walking . 39 TKA patients ( 42 knees ) and 18 healthy age-matched controls were studied . Patients with 5 ° varus/valgus alignment or less were r and omized to receive either a relatively flat or a concave tibial insert with retention of the posterior cruciate ligament . Patients who had more than 5 ° varus-valgus alignment and /or extension defect of 10 ° or more were r and omized to receive the concave or a posterior-stabilized tibial component with resection of the posterior cruciate ligament . Results Patients with TKA tended to have less hip and knee extension and decreased knee and hip extension moment than controls . They also tended to walk more slowly . TKA altered the gait pattern , but choice of implant design had little influence . Interpretation In patients with a similar degree of degenerative joint disease and within the limits of the constraints offered by the prostheses under study , the choice of joint area constraint has little influence on the gait pattern OBJECTIVE The aim of this study is to evaluate residual muscle function abnormalities after total knee replacement , with respect to gait kinematics and kinetics . DESIGN Longitudinal study on a follow-up of up to two years . BACKGROUND Gait usually presents an excellent improvement after total knee replacement . Nevertheless , some kinematics and kinetics abnormalities persist even after a long period of time and they might have implication s in long-term prosthesis failure . Additionally , lower limb muscle activity has not been sufficiently studied in the past directly by means of dynamic EMG . METHODS Nine patients who had a posterior cruciate sparing total knee replacement design were evaluated by means of clinical assessment and gait analysis at the end of rehabilitation trials at six , twelve and twenty four months . EMG from trunk and lower limb muscles was registered and elaborated through a statistical detector for the on-off timing . RESULTS Gait analysis showed a slow gait , with a " stiff knee gait pattern " and prolonged muscular co-contractions during stance . CONCLUSIONS Knee kinematics and kinetics abnormalities during loading acceptance after total knee replacement are associated with co-contractions in muscular activation pattern . RELEVANCE Gait pattern at two years after total knee replacement is deemed unphysiological , potentially dangerous for the implant duration in time and responsible for residual disability in patients . Muscular behavior during daily activities provides insight into the integration of the prosthetic biomechanics within the muscular-skeletal system . This information is of relevance to improve prosthetic design , rehabilitation programs and knee motor performance OBJECTIVE Patients with unilateral hip or knee replacements for end-stage osteoarthritis ( OA ) are at high risk for future progression of OA in other joints of the lower extremities , often requiring additional joint replacements . Although the risks of future surgery in the contralateral cognate joints ( i.e. , contralateral hip replacement after an initial hip replacement ) have been evaluated , the evolution of end-stage hip OA to OA involving the knee joints , and vice versa ( i.e. , noncognate progression ) has not been investigated . Because characterization of OA progression in noncognate joints may shed light on the pathogenesis of multijoint OA , we investigated the pattern of evolution of end-stage lower extremity OA in a large , clinical cohort . METHODS Total joint replacement ( TJR ) was selected as a marker of end-stage OA , and a data base comprising all lower extremity TJRs performed at a large referral center between 1981 and 2001 was accessed . Of the 5,894 patients identified , 486 patients with idiopathic OA who underwent hip replacement and 414 who underwent initial knee replacement were analyzed to determine the relative likelihood of subsequent TJRs . Patients with the systemic inflammatory arthropathy , rheumatoid arthritis ( RA ) , were evaluated as a control population because RA progression is not considered to be a primarily mechanically mediated process . RESULTS The contralateral cognate joint was the most common second joint to undergo replacement in both the OA and the RA groups . However , in OA patients for whom the second TJR was in a noncognate joint , that joint was > 2-fold more likely to be on the contralateral limb than on the ipsilateral limb ( hip to knee P < 0.001 ; knee to hip P = 0.013 ) . In contrast , among the RA cohort , the evolution was r and om and no laterality for noncognate TJR was observed at either the hip or the knee ( P = 0.782 ) . CONCLUSION This characterization of end-stage lower extremity OA demonstrates that the disease evolves nonr and omly ; after 1 joint is replaced , the contralateral limb is significantly more likely to show progression of OA than is the ipsilateral limb . Thus , OA in 1 weight-bearing joint appears to influence the evolution of OA in other joints . The absence of such laterality in RA suggests that OA progression may be mediated by extrinsic factors such as altered joint loading Abstract : The objective of this study was to measure three-dimensional knee motion during gait in patients with total knee replacements which either retained the posterior cruciate ligament ( n = 11 ) , or required sacrifice of the posterior cruciate ligament and replacement of its function with a posterior stabilizing articular surface ( n = 9 ) . Clinical ly meaningful translations ( anterior and posterior , medial and lateral , proximal and distal ) and rotations ( flexion and extension , internal and external rotation , abduction and adduction ) were measured using an instrumented spatial linkage . Although patients from both groups were able to achieve passive full extension and a minimum of 95 ° flexion , some of their translations and rotations during free speed walking were consistently less than those in a group of healthy controls . Motion during the swing phase of gait was similar for both knee replacement groups . However , abduction and adduction and proximal and distal translation were larger ( but neither difference was significant ) for the patients with implants with a posterior stabilizing surface , which suggests that the stabilizing surface may not reliably provide as much stability in these directions as does retention of the posterior cruciate ligament BACKGROUND Clarification of the indications for patellar resurfacing in total knee arthroplasty ( TKA ) is still necessary . Few studies of adequate power have evaluated functional differences between total knee arthroplasty with and without patellar resurfacing , in particular walking gait . This study aim ed to identify clinical ly relevant differences in knee kinematic or kinetic parameters during level walking between total knee arthroplasty with and without patellar resurfacing , after controlling for pre-surgery gait parameters . METHODS Kinematic and kinetic gait analysis of level walking was performed on 34 subjects ( 41 knees ) before and 12 - 18 months after total knee arthroplasty with patellar resurfacing performed r and omly . Linear regression analysis was used to examine the influence of patellar resurfacing upon gait variables whilst controlling for the corresponding pre-surgery measure . FINDINGS The pre-surgery value was a moderate to strong significant predictor of all post-surgery temporal-spatial and kinetic gait parameters ( p < 0.001 - 0.008 ) , and most kinematic parameters ( p < 0.001 - 0.066 ) . The addition of patellar resurfacing to the regression models did not improve the predictive power in any case . Only one parameter , knee flexion at heel-strike , displayed a difference near statistical significance between total knee arthroplasty with and without patellar resurfacing ( 10 degrees versus 7 degrees respectively , p = 0.023 ) . INTERPRETATION Pre-surgery gait patterns are an important determinant of post-surgery gait . There are no clinical ly relevant differences in walking gait between total knee arthroplasty performed with or without patellar resurfacing , using the Profix design
Output:
| Studies indicated smaller peak knee flexion during weight acceptance and less knee flexion excursion in total knee arthroplasty subjects compared to controls .
Knee angle at foot strike was generally similar in arthroplasty groups compared to controls .
Maximum external knee flexion moment was generally lower in arthroplasty groups compared to controls .
Conflicting results were found for other knee moments .
Conclusions Peak knee flexion and knee flexion excursion during weight acceptance are smaller in the operated knee following total knee arthroplasty compared to healthy controls .
There may also be a smaller peak knee flexion moment after arthroplasty compared to controls .
Knee mechanics in the operated knee are not normal after total knee arthroplasty .
Abnormal gait mechanics may predispose the individual to further joint degeneration , particularly in the nonoperated knee . |
MS213755 | ***TASK*** the task is to summarize an input biomedical literature in six sentences
***INPUT*** the input is a biomedical literature
***OUTPUT*** the output is the summary of an input biomedical literature in six sentences
***DOCUMENTATION***
***EXAMPLES***
Input: After experimental induction of acute bronchospasm in 8 subjects with clinical ly stable bronchial asthma , effects of 500 mg of smoked marijuana ( 2.0 per cent delta9-tetrahydrocannabinol ) on specific airway conductance and thoracic gas volume were compared with those of 500 mg of smoked placebo marijuana ( 0.0 per cent delta9-tetrahydrocannabinol ) , 0.25 ml of aerosolized saline , and 0.25 ml of aerosolized isoproterenol ( 1,250 mug ) . Bronchospasm was induced on 4 separate occasions , by inhalation of methacholine and , on four other occasions , by exercise on a bicycle ergometer or treadmill . Methacholine and exercise caused average decreases in specific airway conductance of 40 to 55 per cent and 30 to 39 per cent , respectively , and average increases in thoracic gas volume of 35 to 43 per cent and 25 to 35 per cent , respectively . After methacholine-induced bronchospasm , placebo marijuana and saline inhalation produced minimal changes in specific airway conductance and thoracic gas volume , whereas 2.0 per cent marijuana and isoproterenol each caused a prompt correction of the bronchospasm and associated hyperinflation . After exercise-induced bronchospasm , placebo marijuana and saline were followed by gradual recovery during 30 to 60 min , whereas 2.0 per cent marijuana and isoproterenol caused an immediate reversal of exercise-induced asthma and hyperinflation OBJECTIVE : To test the feasibility of creating a valid and reliable checklist with the following features : appropriate for assessing both r and omised and non-r and omised studies ; provision of both an overall score for study quality and a profile of scores not only for the quality of reporting , internal validity ( bias and confounding ) and power , but also for external validity . DESIGN : A pilot version was first developed , based on epidemiological principles , review s , and existing checklists for r and omised studies . Face and content validity were assessed by three experienced review ers and reliability was determined using two raters assessing 10 r and omised and 10 non-r and omised studies . Using different raters , the checklist was revised and tested for internal consistency ( Kuder-Richardson 20 ) , test-retest and inter-rater reliability ( Spearman correlation coefficient and sign rank test ; kappa statistics ) , criterion validity , and respondent burden . MAIN RESULTS : The performance of the checklist improved considerably after revision of a pilot version . The Quality Index had high internal consistency ( KR-20 : 0.89 ) as did the subscales apart from external validity ( KR-20 : 0.54 ) . Test-retest ( r 0.88 ) and inter-rater ( r 0.75 ) reliability of the Quality Index were good . Reliability of the subscales varied from good ( bias ) to poor ( external validity ) . The Quality Index correlated highly with an existing , established instrument for assessing r and omised studies ( r 0.90 ) . There was little difference between its performance with non-r and omised and with r and omised studies . Raters took about 20 minutes to assess each paper ( range 10 to 45 minutes ) . CONCLUSIONS : This study has shown that it is feasible to develop a checklist that can be used to assess the method ological quality not only of r and omised controlled trials but also non-r and omised studies . It has also shown that it is possible to produce a checklist that provides a profile of the paper , alerting review ers to its particular method ological strengths and weaknesses . Further work is required to improve the checklist and the training of raters in the assessment of external validity Abstract Normal volunteers with previous marihuana smoking experience inhaled the total smoke from 3.23 mg per kilogram of marihuana , using a bag-in-box technic . R and omly , nine received marihuana containing a high ( 2.6 per cent ) , and eight a low ( 1.0 per cent ) concentration of delta-9 tetrahydrocannabinol . Physiologic variables were monitored before and for 20 minutes after smoking . In the high-dose group the heart rate increased 28 per cent . Concomitantly , airway resistance , measured in a body plethysmograph , fell 38 per cent ; the functional residual capacity remained unchanged ( ± 50 ml ) throughout , and specific airway conductance increased 44 per cent . Flow-volume loops showed a 45 per cent increase in flow rate at 25 per cent of vital capacity . The low-dose group showed no increase in heart rate but significant , if lesser changes , in airways dynamics . Carbon dioxide sensitivity , measured by rebreathing remained unchanged in both groups . Marihuana smoke , unlike cigarette smoke , causes bronchodilatation Abstract Acute pulmonary physiologic effects of smoked marijuana and oral Δ9-tetrahydrocannabinol were investigated in 32 healthy , experienced male marijuana smokers . After smoking of marijuana ass Ten young , healthy male volunteers smoked a marihuana cigarette with 2.5 % δ9-THC and a THC-exhausted placebo cigarette . The marihuana administration was associated with an increase in heart rate , elevation of systolic blood pressure , conjunctival reddening and specific airway conductance increase ; time perception and Automated Digit Symbol Substitution Test performance were impaired . Diastolic blood pressure and attention measured by the Continuous Performance Task were not affected . The placebo preparation produced a subjective pleasant “ high ” but no physiologic effects nor performance change . The “ high ” induced by the active preparation was often rated as unpleasant Effects on airway dynamics , heart rate , and the central nervous system of various doses of delta9-tetrahydrocannabinol administered in a r and om , double blind fashion using a Freon-propelled , metered-dose nebulizer were evaluated in 11 healthy men and 5 asthmatic subjects . Effects of aerosolized delta9-tetrahydrocannabinol were compared with aerosolized placebo and isoproterenol and with 20 mg of oral and smoked delta9-tetrahydrocannabinol . In the normal subjects , after 5 to 20 mg of aerosolized delta9-tetrahydrocannabinol , specific airway conductance increased immediately , reached a maximum ( 33 to 41 per cent increase ) after 1 to 2 hours , and remained significantly greater than placebo values for 2 to 3 hours . The bronchodilator effect of aerosolized delta9-tetrahydrocannabinol was less than that of isoproterenol after 5 min , but significantly greater than that of isoproterenol after 1 to 3 hours . The magnitude of bronchodilatation after all doses of aerosolized delta9-tetrahydrocannabinol was comparable , but 5 mg of delta9-tetrahydrocannabinol caused a significantly smaller increase in heart rate and level of intoxication than the 20-mg dose . Smoked delta9-tetrahydrocannabinol produced greater cardiac and intoxicating effects than either aerosolized or oral delta9-tetrahydrocannabinol . Side effects of aerosolized delta9-tetrahydrocannabinol included slight cough and /or chest discomfort in 3 of the 11 normal subjects . Aerosolized delta9-tetrahydrocannabinol caused significant bronchodilatation in 3 of 5 asthmatic subjects , but caused moderate to severe bronchoconstriction associated with cough and chest discomfort in the other 2 . These findings indicate that aerosolized delat9-tetrahydrocannabinol , although capable of causing significant bronchodilatation with minimal systemic side effects , has a local irritating effect on the airways , which may make it unsuitable for therapeutic use To assess the possible role of daily smoking of marijuana in the development of chronic obstructive pulmonary disease ( COPD ) , we evaluated the effect of habitual use of marijuana with or without tobacco on the age-related change in lung function ( measured as FEV1 ) in comparison with the effect of nonsmoking and regular tobacco smoking . A convenience sample of 394 healthy young Caucasian adults ( 68 % men ; age : 33 + /- 6 yr ; mean + /- SD ) including , at study entry , 131 heavy , habitual smokers of marijuana alone , 112 smokers of marijuana plus tobacco , 65 regular smokers of tobacco alone , and 86 nonsmokers of either substance were recruited from the greater Los Angeles community . FEV1 was measured in all 394 participants at study entry and in 255 subjects ( 65 % ) on up to six additional occasions at intervals of > or = 1 yr ( 1.7 + /- 1.1 yr ) over a period of 8 yr . R and om-effects models were used to estimate mean rates of decline in FEV1 and to compare these rates between smoking groups . Although men showed a significant effect of tobacco on FEV1 decline ( p < 0.05 ) , in neither men nor women was marijuana smoking associated with greater declines in FEV1 than was nonsmoking , nor was an additive effect of marijuana and tobacco noted , or a significant relationship found between the number of marijuana cigarettes smoked per day and the rate of decline in FEV1 . We conclude that regular tobacco , but not marijuana , smoking is associated with greater annual rates of decline in lung function than is nonsmoking . These findings do not support an association between regular marijuana smoking and chronic COPD but do not exclude the possibility of other adverse respiratory effects
Output:
| Short-term exposure to marijuana is associated with bronchodilation .
Physiologic data were inconclusive regarding an association between long-term marijuana smoking and airflow obstruction measures .
Long-term marijuana smoking is associated with increased respiratory symptoms suggestive of obstructive lung disease |
MS213756 | ***TASK*** the task is to summarize an input biomedical literature in six sentences
***INPUT*** the input is a biomedical literature
***OUTPUT*** the output is the summary of an input biomedical literature in six sentences
***DOCUMENTATION***
***EXAMPLES***
Input: The National Surgical Adjuvant Breast and Bowel Project ( NSABP ) implemented protocol B-15 to compare 2 months of Adriamycin ( doxorubicin ; Adria Laboratories , Columbus , OH ) and cyclophosphamide ( AC ) with 6 months of conventional cyclophosphamide , methotrexate , and fluorouracil ( CMF ) in patients with breast cancer nonresponsive to tamoxifen ( TAM , T ) . A second aim was to determine whether AC followed in 6 months by intravenous ( IV ) CMF was more effective than AC without reinduction therapy . Through 3 years of follow-up , findings from 2,194 patients indicate no significant difference in disease-free survival ( DFS , P = .5 ) , distant disease-free survival ( DDFS , P = .5 ) or survival ( S , P = .8 ) among the three groups . Since the outcome from AC and CMF was almost identical , the issue arises concerning which regimen is more appropriate for the treatment of breast cancer patients . AC seems preferable since , following total mastectomy , AC was completed on day 63 versus day 154 for conventional CMF ; patients visited health professionals three times as often for conventional CMF as for AC ; women on AC received therapy on each of 4 days versus on each of 84 days for conventional CMF ; and nausea-control medication was given for about 84 days to conventional CMF patients versus for about 12 days to patients on AC . The difference in the amount of alopecia between the two treatment groups was less than anticipated . While alopecia was almost universally observed following AC therapy , 71 % of the CMF patients also had hair loss and , in 41 % , the loss was greater than 50 % . This study and NSABP B-16 , which evaluates the worth of AC therapy in TAM-responsive patients , indicate the merit of 2 months of AC therapy for all positive-node breast cancer patients PURPOSE We evaluated the efficacy of cyclophosphamide , methotrexate , and fluorouracil ( CMF ) versus cyclophosphamide , doxorubicin , and fluorouracil ( CAF ) in node-negative breast cancer patients with and without tamoxifen ( TAM ) , overall and by hormone receptor ( HR ) status . PATIENTS AND METHODS Node-negative patients identified by tumor size ( > 2 cm ) , negative HR , or high S-phase fraction ( n = 2,690 ) were r and omly assigned to CMF , CAF , CMF + TAM ( CMFT ) , or CAF + TAM ( CAFT ) . Cox regression evaluated overall survival ( OS ) and disease-free survival ( DFS ) for CAF versus CMF and TAM versus no TAM separately . Two-sided CIs and one-sided P values for planned comparisons were calculated . RESULTS Ten-year estimates indicated that CAF was not significantly better than CMF ( P = .13 ) for the primary outcome of DFS ( 77 % v 75 % ; HR = 1.09 ; 95 % CI , 0.94 to 1.27 ) . CAF had slightly better OS than CMF ( 85 % v 82 % , HR = 1.19 for CMF v CAF ; 95 % CI , 0.99 to 1.43 ) ; values were statistically significant in the planned one-sided test ( P = .03 ) . Toxicity was greater with CAF and did not increase with TAM . Overall , TAM had no benefit ( DFS , P = .16 ; OS , P = .37 ) , but the TAM effect differed by HR groups . For HR-positive patients , TAM was beneficial ( DFS , HR = 1.32 for no TAM v TAM ; 95 % CI , 1.09 to 1.61 ; P = .003 ; OS , HR = 1.26 ; 95 % CI , 0.99 to 1.61 ; P = .03 ) , but not for HR-negative patients ( DFS , HR = 0.81 for no TAM v TAM ; 95 % CI , 0.64 to 1.03 ; OS , HR = 0.79 ; 95 % CI , 0.60 to 1.05 ) . CONCLUSION CAF did not improve DFS compared with CMF ; there was a slight effect on OS . Given greater toxicity , we can not conclude CAF to be superior to CMF . TAM is effective in HR-positive disease , but not in HR-negative disease PURPOSE To determine whether the combination of pegylated liposomal doxorubicin ( PLD ) and docetaxel significantly prolongs time to disease progression compared with docetaxel alone without an increase in cardiac toxicity in women with advanced breast cancer who had experienced relapse at least 1 year after prior adjuvant or neoadjuvant anthracycline therapy . PATIENTS AND METHODS This international , phase III study r and omly assigned 751 patients to receive either docetaxel 75 mg/m(2 ) ( n = 373 ) or PLD 30 mg/m(2 ) followed by docetaxel 60 mg/m(2 ) every 21 days ( n = 378 ) and continued until disease progression or prohibitive toxicity . The primary end point was time to progression ( TTP ) . Secondary end points were overall survival ( OS ) , objective response rate ( ORR ) , cardiac toxicity , and safety . RESULTS Treatment with PLD-docetaxel significantly improved median TTP from 7.0 to 9.8 months ( hazard ratio [ HR ] = 0.65 ; 95 % CI , 0.55 to 0.77 ; P = .000001 ) and the ORR from 26 % to 35 % ( P = .0085 ) . OS was similar between the two groups ( HR = 1.02 ; 95 % CI , 0.86 to 1.22 ) . The incidence of grade 3 or 4 adverse events were similar ( 78 % v 72 % ) , although a higher incidence of h and -foot syndrome ( 24 % v 0 % ) and mucositis/stomatitis ( 12 % v 1 % ) were observed in the PLD-docetaxel combination . Protocol -defined left ventricular ejection fraction decreases and congestive heart failure were reported in 5 % and 1 % in both treatment arms , respectively . CONCLUSION The PLD-docetaxel combination was more effective than docetaxel alone in women with metastatic breast cancer who had experienced relapse at least 1 year after prior adjuvant anthracycline therapy without an increase in cardiac toxicity , although mucocutaneous toxicity was more common Mixed treatment comparison ( MTC ) meta- analysis is a generalization of st and ard pairwise meta- analysis for A vs B trials , to data structures that include , for example , A vs B , B vs C , and A vs C trials . There are two roles for MTC : one is to strengthen inference concerning the relative efficacy of two treatments , by including both ' direct ' and ' indirect ' comparisons . The other is to facilitate simultaneous inference regarding all treatments , in order for example to select the best treatment . In this paper , we present a range of Bayesian hierarchical models using the Markov chain Monte Carlo software WinBUGS . These are multivariate r and om effects models that allow for variation in true treatment effects across trials . We consider models where the between-trials variance is homogeneous across treatment comparisons as well as heterogeneous variance models . We also compare models with fixed ( unconstrained ) baseline study effects with models with r and om baselines drawn from a common distribution . These models are applied to an illustrative data set and posterior parameter distributions are compared . We discuss model critique and model selection , illustrating the role of Bayesian deviance analysis , and node-based model criticism . The assumptions underlying the MTC models and their parameterization are also discussed Background To evaluate activity and tolerability of two anthracycline-containing regimens as first-line treatment for anthracycline-naïve relapsed breast cancer patients . Methods Patients with relapsed breast cancer not previously treated with adjuvant anthracyclines were r and omly assigned to epirubicin/vinorelbine ( arm A : EPI/VNB , EPI 90 mg/m2 on day 1 , VNB 25 mg/m2 on days 1,5 plus G-CSF subcutaneously on days 7 - 12 , with cycles repeated every 21 days ) , or to pegylated liposomal doxorubicin/VNB ( arm B : PLD/VNB , PLD 40 mg/m2 on day 1 , VNB 30 mg/m2 on days 1 , 15 , with cycles repeated every 4 weeks ) . Primary objective was to evaluate the efficacy of the two regimens in terms of response rate , secondarily toxicity , progression free survival and overall survival . Results One hundred and four patients have been enrolled ( arm A 54 , arm B 50 ) : characteristics were well balanced between the 2 arms . Responses were as follows : arm A , 3 ( 5.6 % ) CR , 20 ( 37 % ) PR , ( ORR 42.6 % , 95%CI 29.3%-55.9 % ) ; arm B , 8 ( 16 % ) CR , 18 ( 36 % ) PR , ( ORR 52 % , 95%CI 38.2%-65.8 % ) . Median progression free survival was 10.7 months in arm A ( 95 % CI , 8.7 - 12.6 ) , and 8.8 months in arm B ( 95 % CI , 7.1 - 10.5 ) . Median overall survival was 34.6 months in arm A ( 95%CI , 19.5 - 49.8 ) and 24.8 months in arm B ( 95%CI , 15.7 - 33.9 ) . As toxicity concerns , both treatment regimens were well tolerated ; myelosuppression was the dose-limiting toxicity , with G3 - 4 neutropenia occurring in 18.5 % and 22 % of the patients of arm A and B , respectively . No relevant differences in main toxic effects have been observed between the two arms , except for alopecia , more common in arm A , and cutaneous toxicity , observed only in arm B. No clinical congestive heart failures have been observed , one case of tachyarrhythmia was reported after the last EPI/VNB cycle , and two reversible ≥ 20 % LVEF decreases have been observed in arm A. Conclusions Both anthracycline- containing regimens evaluated in the present study seem to be active and with a satisfactory tolerability in anthracycline-naïve relapsed breast cancer patients The EORTC Breast Cancer Cooperative Group carried out a r and omized trial to compare doxorubicin with epirubicin as second-line chemotherapy in patients with metastatic breast cancer . Two hundred and fifty-nine patients with at least one site of metastatic disease entered this trial , of whom 232 patients were eligible . Treatment consisted of doxorubicin 75 mg m(-2 ) or epirubicin 90 mg m(-2 ) i.v . every 3 weeks . The overall response rates for doxorubicin and epirubicin were 36 % and 28 % respectively ( P = 0.173 ) . The median time to progression was 23 weeks for doxorubicin and 19 weeks for epirubicin ( P = 0.063 ) and the median duration of response was 40 weeks for doxorubicin and 32 weeks for epirubicin ( P = 0.059 ) . The median survival was 47 weeks for doxorubicin and 44 weeks for epirubicin ( P = 0.196 ) . Leucocyte count on retreatment day ( P = 0.011 ) and platelet nadir ( P = 0.031 ) were significantly lower in the doxorubicin-treated group . Also mucositis ( P < 0.001 ) , diarrhoea ( P = 0.005 ) and haemorrhage ( P = 0.048 ) were significantly worse in the doxorubicin arm . Nine patients on doxorubicin and two patients on epirubicin experienced congestive heart failure ( CHF ) . At the dose levels used in this study , no statistical differences in response rate and survival were found between the two treatment arms . Treatment with doxorubicin tended to result in a slightly longer duration of response and time to progression but doxorubicin was more toxic than epirubicin PURPOSE To compare a full-dose epirubicin-cyclophosphamide ( HEC ) regimen with classical cyclophosphamide , methotrexate , and fluorouracil ( CMF ) therapy and with a moderate-dose epirubicin-cyclophosphamide regimen ( EC ) in the adjuvant therapy of node-positive breast cancer . PATIENTS AND METHODS Node-positive breast cancer patients who were aged 70 years or younger were r and omly allocated to one of the following treatments : CMF for six cycles ( oral cyclophosphamide ) ; EC for eight cycles ( epirubicin 60 mg/m(2 ) , cyclophosphamide 500 mg/m(2 ) ; day 1 every 3 weeks ) ; and HEC for eight cycles ( epirubicin 100 mg/m(2 ) , cyclophosphamide 830 mg/m(2 ) ; day 1 every 3 weeks ) . RESULTS Two hundred fifty-five , 267 , and 25
Output:
| INTERPRETATION DOX has higher CE3 rates than NON does .
LD statistically trended to lower cardiac event rates than DOX .
Non-statistical significance among EPI , LD and DOX with regard to cardiac toxicity indicates that avoidance of CE3 should not motivate selection of a particular anthracycline in otherwise healthy women in whom total lifetime anthracycline exposure will likely be limited .
Overall low incidence of CE3 with any type of anthracycline indicates that we can safely use any anthracycline if cumulative dose limits are not exceeded .
While CE3 does not limit our choice of anthracycline LD appears to be the least cardiotoxic . |
MS213757 | ***TASK*** the task is to summarize an input biomedical literature in six sentences
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Input: Purpose Computer-based , patient-reported symptom survey tools have been described for patients undergoing chemotherapy . We hypothesized that patients undergoing radiotherapy might also benefit , so we developed a computer application to acquire symptom ratings from patients and generate summaries for use at point of care office visits and conducted a r and omized , controlled pilot trial to test its feasibility . Methods Subjects were r and omized prior to beginning radiotherapy . Both control and intervention group subjects completed the computerized symptom assessment , but only for the intervention group were printed symptom summaries made available before each weekly office visit . Metrics compared included the Global Distress Index ( GDI ) , concordance of patient-reported symptoms and symptoms discussed by the physician and numbers of new and /or adjusted symptom management medications prescribed . Results One hundred twelve patients completed the study : 54 in the control and 58 in the intervention arms . There were no differences in GDI over time between the control and intervention groups . In the intervention group , more patient-reported symptoms were actually discussed in radiotherapy office visits : 46/202 vs. 19/230 . A sensitivity analysis to account for within-subjects correlation yielded 23.2 vs. 10.3 % ( p = 0.03 ) . Medications were started or adjusted at 15.4 % ( 43/280 ) of control visits compared to 20.4 % ( 65/319 ) of intervention visits ( p = 0.07 ) . Conclusions This computer application is easy to use and makes extensive patient-reported outcome data available at the point of care . Although no differences were seen in symptom trajectory , patients who had printed symptom summaries had improved communication during office visits and a trend towards a more active symptom management during radiotherapy Background The electronic self report assessment - cancer ( ESRA-C ) , has been shown to reduce symptom distress during cancer therapy The purpose of this analysis was to evaluate aspects of how the ESRA-C intervention may have result ed in lower symptom distress ( SD ) . Methods Patients at two cancer centers were r and omized to ESRA-C assessment only ( control ) or the Web-based ESRA-C intervention delivered to patients ’ homes or to a tablet in clinic . The intervention allowed patients to self-monitor symptom and quality of life ( SxQOL ) between visits , receive self-care education and coaching to report SxQOL to clinicians . Summaries of assessment s were delivered to clinicians in both groups . Audio-recordings of clinic visits made 6 weeks after treatment initiation were coded for discussion s of 26 SxQOL issues , focusing on patients ’ /caregivers ’ coached verbal reports of SxQOL severity , pattern , alleviating/aggravating factors and requests for help . Among issues identified as problematic , two measures were defined for each patient : the percent SxQOL reported that included a coached statement , and an index of verbalized coached statements per SxQOL . The Wilcoxon rank test was used to compare measures between groups . Clinician responses to problematic SxQOL were compared . A mediation analysis was conducted , exploring the effect of verbal reports on SD outcomes . Results 517 ( 256 intervention ) clinic visits were audio-recorded . General discussion of problematic SxQOL was similar in both groups . Control group patients reported a median 75 % of problematic SxQOL using any specific coached statement compared to a median 85 % in the intervention group ( p = .0009 ) . The median report index of coached statements was 0.25 for the control group and 0.31 for the intervention group ( p = 0.008 ) . Fatigue , pain and physical function issues were reported significantly more often in the intervention group ( all p < .05 ) . Clinicians ' verbalized responses did not differ between groups . Patients ' verbal reports did not mediate final SD outcomes ( p = .41 ) . Conclusions Adding electronically-delivered , self-care instructions and communication coaching to ESRA-C promoted specific patient descriptions of problematic SxQOL issues compared with ESRA-C assessment alone . However , clinician verbal responses were no different and subsequent symptom distress group differences were not mediated by the patients ' reports . Trial registration NCT00852852 ; 26 Feb PURPOSE Although patient-reported cancer symptoms and quality -of-life issues ( SQLIs ) have been promoted as essential to a comprehensive assessment , efficient and efficacious methods have not been widely tested in clinical setting s. The purpose of this trial was to determine the effect of the Electronic Self-Report Assessment -Cancer ( ESRA-C ) on the likelihood of SQLIs discussed between clinicians and patients with cancer in ambulatory clinic visits . Secondary objectives included comparison of visit duration between groups and usefulness of the ESRA-C as reported by clinicians . PATIENTS AND METHODS This r and omized controlled trial was conducted in 660 patients with various cancer diagnoses and stages at two institutions of a comprehensive cancer center . Patient-reported SQLIs were automatically displayed on a graphical summary and provided to the clinical team before an on-treatment visit ( n = 327 ) ; in the control group , no summary was provided ( n = 333 ) . SQLIs were scored for level of severity or distress . One on-treatment clinic visit was audio recorded for each participant and then scored for discussion of each SQLI . We hypothesized that problematic SQLIs would be discussed more often when the intervention was delivered to the clinicians . RESULTS The likelihood of SQLIs being discussed differed by r and omized group and depended on whether an SQLI was first reported as problematic ( P = .032 ) . Clinic visits were similar with regard to duration between groups , and clinicians reported the summary as useful . CONCLUSION The ESRA-C is the first electronic self-report application to increase discussion of SQLIs in a US r and omized clinical trial PURPOSE This study aim ed to determine whether feeding back patient-reported outcomes ( PROs ) to providers and families of children with advanced cancer improves symptom distress and health-related quality of life ( HRQoL ) . PATIENTS AND METHODS This study was a parallel , multicentered pilot r and omized controlled trial . At most once per week , children age ≥ 2 years old with advanced cancer or their parent completed the computer-based Pediatric Quality of Life and Evaluation of Symptoms Technology ( PediQUEST ) survey consisting of age- and respondent-adapted versions of the Memorial Symptom Assessment Scale ( MSAS ) , Pediatric Quality of Life Inventory 4.0 Generic Core Scales ( PedsQL4.0 ) , and an overall Sickness question . In the intervention group ( n = 51 ) , oncologists and families received printed reports summarizing PROs ; e-mails were sent to oncologists and subspecialists when predetermined scores were exceeded . No feedback was provided in the control group ( n = 53 ) . Primary outcomes included linear trends of MSAS , PedsQL4.0 total and subscale scores , and Sickness scores during 20 weeks of follow-up , along with child , parent , and provider satisfaction with PediQUEST feedback . RESULTS Feedback did not significantly affect average MSAS , PedsQL4.0 , or Sickness score trends . Post hoc subgroup analyses among children age ≥ 8 years who survived 20 weeks showed that feedback improved PedsQL4.0 emotional ( + 8.1 ; 95 % CI , 1.8 to 14.4 ) and Sickness ( -8.2 ; 95 % CI , -14.2 to -2.2 ) scores . PediQUEST reports were valued by children , parents , and providers and contributed at least sometimes to physician initiation of a psychosocial consult ( 56 % ) . CONCLUSION Although routine feedback of PROs did not significantly affect the child 's symptoms or HRQoL , changes were in expected directions and improvements observed in emotional HRQoL through exploratory analyses were encouraging . Importantly , children , parents , and providers value PRO feedback The potential benefits of health-related quality of life ( HRQL ) assessment in oncology clinical practice include better detection of problems , enhanced disease and treatment monitoring and improved care . However , few empirical studies have investigated the effects of incorporating such assessment s into routine clinical care . Recent r and omized studies have reported improved detection of and communication about patients ' concerns , but few have found effects on patient HRQL or satisfaction . This study examined whether offering interpretive assistance of HRQL results would improve these patient outcomes . Two hundred and thirteen participants with metastatic breast , lung or colorectal cancer were r and omly assigned to one of three conditions : usual care ; HRQL assessment or HRQL assessment followed by a structured interview and discussion . Interviews about patients ' assessment responses were conducted by a research nurse , who then presented HRQL information to the treating nurse . HRQL and treatment satisfaction outcomes were assessed at 3 and 6 months . No significant differences were found between study conditions in HRQL or satisfaction . Results suggest that routine HRQL assessment , even with description of results , is insufficient to improve patient HRQL and satisfaction . It is suggested that positive effects may require supplementing assessment results with specific suggestions for clinical management changes PURPOSE There is growing interest to enhance symptom monitoring during routine cancer care using patient-reported outcomes , but evidence of impact on clinical outcomes is limited . METHODS We r and omly assigned patients receiving routine outpatient chemotherapy for advanced solid tumors at Memorial Sloan Kettering Cancer Center to report 12 common symptoms via tablet computers or to receive usual care consisting of symptom monitoring at the discretion of clinicians . Those with home computers received weekly e-mail prompts to report between visits . Treating physicians received symptom printouts at visits , and nurses received e-mail alerts when participants reported severe or worsening symptoms . The primary outcome was change in health-related quality of life ( HRQL ) at 6 months compared with baseline , measured by the EuroQol EQ-5D Index . Secondary endpoints included emergency room ( ER ) visits , hospitalizations , and survival . RESULTS Among 766 patients allocated , HRQL improved among more participants in the intervention group than usual care ( 34 % v 18 % ) and worsened among fewer ( 38 % v 53 % ; P < .001 ) . Overall , mean HRQL declined by less in the intervention group than usual care ( 1.4- v 7.1-point drop ; P < .001 ) . Patients receiving intervention were less frequently admitted to the ER ( 34 % v 41 % ; P = .02 ) or hospitalized ( 45 % v 49 % ; P = .08 ) and remained on chemotherapy longer ( mean , 8.2 v 6.3 months ; P = .002 ) . Although 75 % of the intervention group was alive at 1 year , 69 % with usual care survived the year ( P = .05 ) , with differences also seen in quality -adjusted survival ( mean of 8.7 v. 8.0 months ; P = .004 ) . Benefits were greater for participants lacking prior computer experience . Most patients receiving intervention ( 63 % ) reported severe symptoms during the study . Nurses frequently initiated clinical actions in response to e-mail alerts . CONCLUSION Clinical benefits were associated with symptom self-reporting during cancer care Purpose Monitoring patient-reported symptoms is necessary to adjust and improve supportive care during chemotherapy . Continuing advances in computerized approaches to symptom monitoring can enhance communication about unrelieved symptoms between patients and oncology providers and may facilitate intensified symptom treatment . Methods An automated IT-based telephone monitoring system was developed to enable oncology providers to receive and act on alert reports from patients about unrelieved symptoms during chemotherapy treatment . Daily , 250 participants ( r and omized to treatment or attentional control ) were asked to call the automated system to report presence , severity , and distress for common chemotherapy-related symptoms ( 1–10 scale if present ) . For the treatment group , symptoms exceeding preset thresholds for moderate-to-severe intensity levels generated emailed alert reports to both the patient ’s oncologist and oncology nurse . Results Patients reported high satisfaction and ease of use of the automated system . Over 80 % of providers reported usefulness of the symptom alert reports . Ten monitored symptoms result ed in , on average , nine moderate-to-severe intensity alerts per patient over 45 study days . However , providers rarely contacted patients after receiving alerts . There were no significant differences in change of symptom severity between the two groups ( mean difference = 0.06 , p = 0.58 ) . Conclusion Despite patients ’ use of a daily symptom monitoring system and providers ’ receipt of information about unrelieved symptoms of moderate-to-severe intensity , oncology physicians and nurses did not contact patients to intensify symptom treatment nor did symptoms improve . Further research is indicated to determine if oncology providers initiated follow-up to intensify symptom treatment , whether symptom outcomes would improve This r and omized controlled trial investigated the effect of reporting physical symptoms by using a systematic symptom monitoring instrument , the Symptom Monitor , on symptom prevalence and severity among patients with cancer in the palliative phase . The overall objective was to achieve symptom relief through systematic and regular symptom reporting by patients themselves . One hundred forty-six patients with cancer in the palliative phase were r and omized to either the intervention group ( n = 69 with Symptom Monitor ) or the control group ( n = 77 without Symptom Monitor ) . Ten physical symptoms with regard to prevalence and severity were monitored . After 2 months , the prevalence of symptoms was lower in the intervention group compared to the control group ( prevalent differences 2.1 - 24.3 % ) for 9 out of 10 symptoms ( except coughing ) . The intervention group scored a statistically significantly lower prevalence in constipation and vomiting ( prevalence differences 24.3 % and 18.0 % , respectively ) . In four symptoms ( fatigue , lack of appetite , shortness of breath ,
Output:
| Synthesis of the review ed studies provided evidence of the usefulness of PROs in facilitating patient-clinician communication on a variety of topics .
We identified mechanisms though which PROs influenced patient-clinician communication to include increasing symptom awareness , prompting discussion , streamlining consultations , and facilitating inter-professional communication .
Barriers to PRO use in communication improvement include technical problems impeding its administration and completion , compliance issues due to lack of incentive or forgetfulness , and use of PROs that do not appropriately assess issues relevant to the patient .
Facilitators include increased education on PRO use , using PRO tools that patients find more acceptable , and providing patient data summaries in an easily accessible format for clinicians .
Conclusions Our review suggests that PROs facilitate patient-clinician communication through various mechanisms that could perhaps contribute to improvements in symptom management and survival . |
MS213758 | ***TASK*** the task is to summarize an input biomedical literature in six sentences
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Input: Background Maternal and newborn mortality rates remain unacceptably high , especially where the majority of births occur in home setting s or in facilities with inadequate re sources . The introduction of emergency obstetric and newborn care services has been proposed by several organizations in order to improve pregnancy outcomes . However , the effectiveness of emergency obstetric and neonatal care services has never been proven . Also unproven is the effectiveness of community mobilization and community birth attendant training to improve pregnancy outcomes . Methods / Design We have developed a cluster-r and omized controlled trial to evaluate the impact of a comprehensive intervention of community mobilization , birth attendant training and improvement of quality of care in health facilities on perinatal mortality in low and middle-income countries where the majority of births take place in homes or first level care facilities . This trial will take place in 106 clusters ( 300 - 500 deliveries per year each ) across 7 sites of the Global Network for Women 's and Children 's Health Research in Argentina , Guatemala , India , Kenya , Pakistan and Zambia . The trial intervention has three key elements , community mobilization , home-based life saving skills for communities and birth attendants , and training of providers at obstetric facilities to improve quality of care . The primary outcome of the trial is perinatal mortality . Secondary outcomes include rates of stillbirth , 7-day neonatal mortality , maternal death or severe morbidity ( including obstetric fistula , eclampsia and obstetrical sepsis ) and 28-day neonatal mortality . Discussion In this trial , we are evaluating a combination of interventions including community mobilization and facility training in an attempt to improve pregnancy outcomes . If successful , the results of this trial will provide important information for policy makers and clinicians as they attempt to improve delivery services for pregnant women and newborns in low-income countries . Trial Registration Clinical Trials.gov BACKGROUND Neonatal deaths in developing countries make the largest contribution to global mortality in children younger than 5 years . 90 % of deliveries in the poorest quintile of households happen at home . We postulated that a community-based participatory intervention could significantly reduce neonatal mortality rates . METHODS We pair-matched 42 geopolitical clusters in Makwanpur district , Nepal , selected 12 pairs r and omly , and r and omly assigned one of each pair to intervention or control . In each intervention cluster ( average population 7000 ) , a female facilitator convened nine women 's group meetings every month . The facilitator supported groups through an action-learning cycle in which they identified local perinatal problems and formulated strategies to address them . We monitored birth outcomes in a cohort of 28?931 women , of whom 8 % joined the groups . The primary outcome was neonatal mortality rate . Other outcomes included stillbirths and maternal deaths , uptake of antenatal and delivery services , home care practice s , infant morbidity , and health-care seeking . Analysis was by intention to treat . The study is registered as an International St and ard R and omised Controlled Trial , number IS RCT N31137309 . FINDINGS From 2001 to 2003 , the neonatal mortality rate was 26.2 per 1000 ( 76 deaths per 2899 livebirths ) in intervention clusters compared with 36.9 per 1000 ( 119 deaths per 3226 livebirths ) in controls ( adjusted odds ratio 0.70 [ 95 % CI 0.53 - 0.94 ] ) . Stillbirth rates were similar in both groups . The maternal mortality ratio was 69 per 100000 ( two deaths per 2899 livebirths ) in intervention clusters compared with 341 per 100000 ( 11 deaths per 3226 livebirths ) in control clusters ( 0.22 [ 0.05 - 0.90 ] ) . Women in intervention clusters were more likely to have antenatal care , institutional delivery , trained birth attendance , and hygienic care than were controls . INTERPRETATION Birth outcomes in a poor rural population improved greatly through a low cost , potentially sustainable and scalable , participatory intervention with women 's groups Background Fetal and neonatal mortality rates in low-income countries are at least 10-fold greater than in high-income countries . These differences have been related to poor access to and poor quality of obstetric and neonatal care . Methods This trial tested the hypothesis that teams of health care providers , administrators and local residents can address the problem of limited access to quality obstetric and neonatal care and lead to a reduction in perinatal mortality in intervention compared to control locations . In seven geographic areas in five low-income and one middle-income country , most with high perinatal mortality rates and substantial numbers of home deliveries , we performed a cluster r and omized non-masked trial of a package of interventions that included community mobilization focusing on birth planning and hospital transport , community birth attendant training in problem recognition , and facility staff training in the management of obstetric and neonatal emergencies . The primary outcome was perinatal mortality at ≥28 weeks gestation or birth weight ≥1000 g. Results Despite extensive effort in all sites in each of the three intervention areas , no differences emerged in the primary or any secondary outcome between the intervention and control clusters . In both groups , the mean perinatal mortality was 40.1/1,000 births ( P = 0.9996 ) . Neither were there differences between the two groups in outcomes in the last six months of the project , in the year following intervention cessation , nor in the clusters that best implemented the intervention . Conclusions This cluster r and omized comprehensive , large-scale , multi-sector intervention did not result in detectable impact on the proposed outcomes . While this does not negate the importance of these interventions , we expect that achieving improvement in pregnancy outcomes in these setting s will require substantially more obstetric and neonatal care infrastructure than was available at the sites during this trial , and without them provider training and community mobilization will not be sufficient . Our results highlight the critical importance of evaluating outcomes in r and omized trials , as interventions that should be effective may not be . Trial registration Clinical Trials.gov OBJECTIVE : Poor communication and teamwork may contribute to errors during neonatal resuscitation . Our objective was to evaluate whether interns who received a 2-hour teamwork training intervention with the Neonatal Resuscitation Program ( NRP ) demonstrated more teamwork and higher quality resuscitations than control subjects . METHODS : Participants were noncertified 2007 and 2008 incoming interns for pediatrics , combined pediatrics and internal medicine , family medicine , emergency medicine , and obstetrics and gynecology ( n = 98 ) . Pediatrics and combined pediatrics/internal medicine interns were eligible for 6-month follow-up ( n = 34 ) . A r and omized trial was conducted in which half of the participants in the team training arm practice d NRP skills by using high-fidelity simulators ; the remaining practice d with low-fidelity simulators , as did control subjects . Blinded , trained observers viewed video recordings of high-fidelity – simulated resuscitations for teamwork and resuscitation quality . RESULTS : High-fidelity training ( HFT ) group had higher teamwork frequency than did control subjects ( 12.8 vs 9.0 behaviors per minute ; P < .001 ) . Intervention groups maintained more workload management ( control subjects : 89.3 % ; low-fidelity training [ LFT ] group : 98.0 % [ P < .001 ] ; HFT group : 98.8 % ; HFT group versus control subjects [ P < .001 ] ) and completed resuscitations faster ( control subjects : 10.6 minutes ; LFT group : 8.6 minutes [ P = .040 ] ; HFT group : 7.4 minutes ; HFT group versus control subjects [ P < .001 ] ) . Overall , intervention teams completed the resuscitation an average of 2.6 minutes faster than did control subjects , a time reduction of 24 % ( 95 % confidence interval : 12%–37 % ) . Intervention groups demonstrated more frequent teamwork during 6-month follow-up resuscitations ( 11.8 vs 10.0 behaviors per minute ; P = .030 ) . CONCLUSIONS : Trained participants exhibited more frequent teamwork behaviors ( especially the HFT group ) and better workload management and completed the resuscitation more quickly than did control subjects . The impact on team behaviors persisted for at least 6 months . Incorporating team training into the NRP curriculum is a feasible and effective way to teach interns teamwork skills . It also improves simulated resuscitation quality by shortening the duration BACKGROUND Two recent trials have shown that women 's groups can reduce neonatal mortality in poor communities . We assessed the effectiveness of a scaled-up development programme with women 's groups to address maternal and neonatal care in three rural districts of Bangladesh . METHODS 18 clusters ( with a mean population of 27 953 [ SD 5953 ] ) in three districts were r and omly assigned to either intervention or control ( nine clusters each ) by use of stratified r and omisation . For each district , cluster names were written on pieces of paper , which were folded and placed in a bottle . The first three cluster names drawn from the bottle were allocated to the intervention group and the remaining three to control . All clusters received health services strengthening and basic training of traditional birth attendants . In intervention clusters , a facilitator convened 18 groups every month to support participatory action and learning for women , and to develop and implement strategies to address maternal and neonatal health problems . Women were eligible to participate if they were aged 15 - 49 years , residing in the project area , and had given birth during the study period ( Feb 1 , 2005 , to Dec 31 , 2007 ) . Neither study investigators nor participants were masked to treatment assignment . In a population of 229 195 people ( intervention clusters only ) , 162 women 's groups provided coverage of one group per 1414 population . The primary outcome was neonatal mortality rate ( NMR ) . Analysis was by intention to treat . This trial is registered as an International St and ard R and omised Controlled Trial , number IS RCT N54792066 . FINDINGS We monitored outcomes for 36 113 births ( intervention clusters , n=17 514 ; control clusters , n=18 599 ) in a population of 503 163 over 3 years . From 2005 to 2007 , there were 570 neonatal deaths in the intervention clusters and 656 in the control clusters . Cluster-level mean NMR ( adjusted for stratification and clustering ) was 33.9 deaths per 1000 livebirths in the intervention clusters compared with 36.5 per 1000 in the control clusters ( risk ratio 0.93 , 95 % CI 0.80 - 1.09 ) . INTERPRETATION For participatory women 's groups to have a significant effect on neonatal mortality in rural Bangladesh , detailed attention to programme design and context ual factors , enhanced population coverage , and increased enrolment of newly pregnant women might be needed . FUNDING Women and Children First , the UK Big Lottery Fund , Saving Newborn Lives , and the UK Department for International Development OBJECTIVE To evaluate the effectiveness of an educational intervention on pediatric residents ' resuscitation fund of knowledge , technical skills , confidence , and overall performance . DESIGN Prospect i ve , nonconcurrent , controlled interventional trial . SETTING Urban pediatric tertiary care hospital . PARTICIPANTS An intervention group ( IG ) of 28 pediatric residents graduating in 1997 , and a control group ( CG ) of 30 pediatric residents graduating in 1996 . INTERVENTIONS Resuscitation course with didactic lectures and skills practice stations , as well as a minimum of 3 practice mock resuscitations with immediate feedback throughout postgraduate year 3 . MAIN OUTCOME MEASURES Fund of knowledge , using the Pediatric Advanced Life Support test and short answer test ; technical skills , using the Airway and Vascular Access Skills Assessment ; experience and confidence , using an anonymous survey ; and overall performance , evaluated using a videotaped mock resuscitation test . RESULTS The IG scored better on the short answer test ( P<.001 ) . A larger number of IG residents were successful in the completion of ancillary airway maneuvers and femoral vascular access ( P = .02 ) , as well as endotracheal intubation ( P = .004 ) and intraosseous access ( P = .002 ) . The IG was more confident in their leadership role ( P = .0001 ) and technical skills ( P = .05 ) . Trends toward improved overall performance were noted for the IG mock resuscitations . Residents in the IG were more likely to assess the airway in fewer than 2 minutes ( P = .02 ) , recognize the threat to life in fewer than 5 minutes ( P = .02 ) , and complete the primary survey in a timely fashion ( P = .05 ) . They required fewer prompts ( P = .04 ) and made fewer mistakes ( P = .07 ) . CONCLUSIONS A structured , formal curriculum can improve the necessary fund of knowledge , skills , confidence , and leadership required for resuscitation Objective : To add a team training and human error curriculum to the Neonatal Resuscitation Program ( NRP ) and measure its effect on teamwork . We hypothesized that teams that received the new course would exhibit more teamwork behaviors than those in the st and ard NRP course . Study design : Interns were r and omized to receive NRP with team training or st and ard NRP , then video recorded when they performed simulated resuscitations at the end of the day-long course . Outcomes were assessed by observers blinded to study arm allocation and included the frequency or duration of six
Output:
| Conclusions Findings of this review show that implementation of NRT improves neonatal and perinatal mortality . |
MS213759 | ***TASK*** the task is to summarize an input biomedical literature in six sentences
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Input: CARdiovascular Outcome Trial of LINAgliptin Versus Glimepiride in Type 2 Diabetes ( NCT01243424 ) is an ongoing , r and omized trial in subjects with early type 2 diabetes and increased cardiovascular risk or established complications that will determine the long-term cardiovascular impact of linagliptin versus the sulphonylurea glimepiride . Eligible patients were sulphonylurea-naïve with HbA1c 6.5%–8.5 % or previously exposed to sulphonylurea ( in monotherapy or in a combination regimen < 5 years ) with HbA1c 6.5%–7.5 % . Primary outcome is time to first occurrence of cardiovascular death , non-fatal myocardial infa rct ion , non-fatal stroke or hospitalization for unstable angina . A total of 631 patients with primary outcome events will be required to provide 91 % power to demonstrate non-inferiority in cardiovascular safety by comparing the upper limit of the two-sided 95 % confidence interval as being below 1.3 for a given hazard ratio . Hierarchical testing for superiority will follow , and the trial has 80 % power to demonstrate a 20 % relative cardiovascular risk reduction . A total of 6041 patients were treated with median type 2 diabetes duration 6.2 years , 40.0 % female , mean HbA1c 7.2 % , 66 % on 1 and 24 % on 2 glucose-lowering agents and 34.5 % had previous cardiovascular complications . The results of CARdiovascular Outcome Trial of LINAgliptin Versus Glimepiride in Type 2 Diabetes may influence the decision-making process for selecting a second glucose-lowering agent after metformin in type 2 diabetes BACKGROUND The cardiovascular safety and efficacy of many current antihyperglycemic agents , including saxagliptin , a dipeptidyl peptidase 4 ( DPP-4 ) inhibitor , are unclear . METHODS We r and omly assigned 16,492 patients with type 2 diabetes who had a history of , or were at risk for , cardiovascular events to receive saxagliptin or placebo and followed them for a median of 2.1 years . Physicians were permitted to adjust other medications , including antihyperglycemic agents . The primary end point was a composite of cardiovascular death , myocardial infa rct ion , or ischemic stroke . RESULTS A primary end-point event occurred in 613 patients in the saxagliptin group and in 609 patients in the placebo group ( 7.3 % and 7.2 % , respectively , according to 2-year Kaplan-Meier estimates ; hazard ratio with saxagliptin , 1.00 ; 95 % confidence interval [ CI ] , 0.89 to 1.12 ; P=0.99 for superiority ; P<0.001 for noninferiority ) ; the results were similar in the " on-treatment " analysis ( hazard ratio , 1.03 ; 95 % CI , 0.91 to 1.17 ) . The major secondary end point of a composite of cardiovascular death , myocardial infa rct ion , stroke , hospitalization for unstable angina , coronary revascularization , or heart failure occurred in 1059 patients in the saxagliptin group and in 1034 patients in the placebo group ( 12.8 % and 12.4 % , respectively , according to 2-year Kaplan-Meier estimates ; hazard ratio , 1.02 ; 95 % CI , 0.94 to 1.11 ; P=0.66 ) . More patients in the saxagliptin group than in the placebo group were hospitalized for heart failure ( 3.5 % vs. 2.8 % ; hazard ratio , 1.27 ; 95 % CI , 1.07 to 1.51 ; P=0.007 ) . Rates of adjudicated cases of acute and chronic pancreatitis were similar in the two groups ( acute pancreatitis , 0.3 % in the saxagliptin group and 0.2 % in the placebo group ; chronic pancreatitis , < 0.1 % and 0.1 % in the two groups , respectively ) . CONCLUSIONS DPP-4 inhibition with saxagliptin did not increase or decrease the rate of ischemic events , though the rate of hospitalization for heart failure was increased . Although saxagliptin improves glycemic control , other approaches are necessary to reduce cardiovascular risk in patients with diabetes . ( Funded by AstraZeneca and Bristol-Myers Squibb ; SAVOR-TIMI 53 Clinical Trials.gov number , NCT01107886 . ) OBJECTIVE The epidemic of type 2 diabetes ( T2DM ) threatens to become the major public health problem of this century . However , a comprehensive comparison of the long-term effects of medications to treat T2DM has not been conducted . GRADE , a pragmatic , unmasked clinical trial , aims to compare commonly used diabetes medications , when combined with metformin , on glycemia-lowering effectiveness and patient-centered outcomes . RESEARCH DESIGN AND METHODS GRADE was design ed with support from a U34 planning grant from the National Institute of Diabetes and Digestive and Kidney Diseases ( NIDDK ) . The consensus protocol was approved by NIDDK and the GRADE Research Group . Eligibility criteria for the 5,000 metformin-treated subjects include < 5 years ' diabetes duration , ≥30 years of age at time of diagnosis , and baseline hemoglobin A1c ( A1C ) of 6.8–8.5 % ( 51–69 mmol/mol ) . Medications representing four classes ( sulfonylureas , dipeptidyl peptidase 4 inhibitors , glucagon-like peptide 1 receptor agonists , and insulin ) will be r and omly assigned and added to metformin ( minimum – maximum 1,000–2,000 mg/day ) . The primary metabolic outcome is the time to primary failure defined as an A1C ≥7 % ( 53 mmol/mol ) , subsequently confirmed , over an anticipated mean observation period of 4.8 years ( range 4–7 years ) . Other long-term metabolic outcomes include the need for the addition of basal insulin after a confirmed A1C > 7.5 % ( 58 mmol/mol ) and , ultimately , the need to implement an intensive basal/bolus insulin regimen . The four drugs will also be compared with respect to selected microvascular complications , cardiovascular disease risk factors , adverse effects , tolerability , quality of life , and cost-effectiveness . CONCLUSIONS GRADE will compare the long-term effectiveness of major glycemia-lowering medications and provide guidance to clinicians about the most appropriate medications to treat T2DM . GRADE begins recruitment at 37 centers in the U.S. in 2013 Aims /hypothesisThe aims of this work were to assess glycaemic control in metformin users receiving their first add-on glucose-lowering therapy and to examine the real-life effectiveness of different add-on drugs . Methods We carried out a population -based cohort study using healthcare data bases in northern Denmark during 2000–2012 . We included 4,734 persons who initiated metformin monotherapy and added another glucose-lowering drug within 3 years . Attainment of recommended HbA1c goals within 6 months of add-on was investigated , using Poisson regression analysis adjusted for age , sex , baseline HbA1c , diabetes duration , complications and Charlson Comorbidity Index . Results Median metformin treatment duration at intensification was 12 months ( interquartile range [ IQR ] 4–23 months ) and pre-intensification HbA1c was 8.0 % ( IQR 7.2–9.2 % ) ( 64 [ IQR 55–77 ] mmol/mol ) . Median HbA1c dropped 1.2 % ( 13 mmol/mol ) with a sulfonylurea ( SU ) add-on , 0.8 % ( 9 mmol/mol ) with a dipeptidyl peptidase-4 ( DPP-4 ) inhibitor , 1.3 % ( 14 mmol/mol ) with a glucagon-like peptide-1 ( GLP-1 ) receptor agonist , 0.9 % ( 10 mmol/mol ) with other non-insulin drugs and 2.4 % ( 26 mmol/mol ) with insulin . Compared with SU add-on , attainment of HbA1c < 7 % ( < 53 mmol/mol ) was higher with GLP-1 receptor agonists ( adjusted RR [ aRR ] 1.10 ; 95 % CI 1.01 , 1.19 ) and lower with DPP-4 inhibitors ( aRR 0.94 ; 95 % CI 0.89 , 0.99 ) , other drugs ( aRR 0.86 ; 95 % CI 0.77 , 0.96 ) and insulin ( aRR 0.88 ; 95 % CI 0.77 , 0.99 ) . The proportion of metformin add-on users who attained HbA1c < 7 % ( < 53 mmol/mol ) increased from 46 % in 2000–2003 to 59 % in 2010–2012 , whereas attainment of HbA1c < 6.5 % ( < 48 mmol/mol ) remained 30 % among patients aged < 65 years without comorbidities . Conclusions /interpretationAmong early type 2 diabetes patients receiving their first metformin add-on treatment , HbA1c reduction with different non-insulin drugs is similar to , and comparable with , that observed in r and omised trials , yet 41 % do not achieve HbA1c < 7 % ( < 53 mmol/mol ) within 6 months OBJECTIVE To compare the efficacy and safety of weekly albiglutide with daily sitagliptin , daily glimepiride , and placebo . Research Design And Methods Patients with type 2 diabetes receiving metformin were r and omized to albiglutide ( 30 mg ) , sitagliptin ( 100 mg ) , glimepiride ( 2 mg ) , or placebo . Blinded dose titration for albiglutide ( to 50 mg ) and glimepiride ( to 4 mg ) was based on predefined hyperglycemia criteria . The primary end point was change in HbA1c from baseline at week 104 . Secondary end points included fasting plasma glucose ( FPG ) , weight , and time to hyperglycemic rescue . RESULTS Baseline characteristics were similar among the albiglutide ( n = 302 ) , glimepiride ( n = 307 ) , sitagliptin ( n = 302 ) , and placebo ( n = 101 ) groups . Baseline HbA1c was 8.1 % ( 65.0 mmol/mol ) ; mean age was 54.5 years . The mean doses for albiglutide and glimepiride at week 104 were 40.5 and 3.1 mg , respectively . At week 104 , albiglutide significantly reduced HbA1c compared with placebo ( −0.9 % [ −9.8 mmol/mol ] ; P < 0.0001 ) , sitagliptin ( −0.4 % [ −4.4 mmol/mol ] ; P = 0.0001 ) , and glimepiride ( −0.3 % [ −3.3 mmol/mol ] ; P = 0.0033 ) . Outcomes for FPG and HbA1c were similar . Weight change from baseline for each were as follows : albiglutide −1.21 kg ( 95 % CI −1.68 to −0.74 ) , placebo −1.00 kg ( 95 % CI −1.81 to −0.20 ) , sitagliptin −0.86 kg ( 95 % CI −1.32 to −0.39 ) , glimepiride 1.17 kg ( 95 % CI 0.70–1.63 ) . The difference between albiglutide and glimepiride was statistically significant ( P < 0.0001 ) . Hyperglycemic rescue rate at week 104 was 25.8 % for albiglutide compared with 59.2 % ( P < 0.0001 ) , 36.4 % ( P = 0.0118 ) , and 32.7 % ( P = 0.1504 ) for placebo , sitagliptin , and glimepiride , respectively . Rates of serious adverse events in the albiglutide group were similar to comparison groups . Diarrhea ( albiglutide 12.9 % , other groups 8.6–10.9 % ) and nausea ( albiglutide 10.3 % , other groups 6.2–10.9 % ) were generally the most frequently reported gastrointestinal events . CONCLUSIONS Added to metformin , albiglutide was well tolerated ; produced superior reductions in HbA1c and FPG at week 104 compared with placebo , sitaglipt
Output:
| Similar change was observed across most other effectiveness outcomes reported . |
MS213760 | ***TASK*** the task is to summarize an input biomedical literature in six sentences
***INPUT*** the input is a biomedical literature
***OUTPUT*** the output is the summary of an input biomedical literature in six sentences
***DOCUMENTATION***
***EXAMPLES***
Input: In order for clinicians to effectively manage their practice s , they need to know how much time they spent in carrying out procedures . The provision of two-implant overdentures for edentulous patients is becoming more prevalent as increasing evidence demonstrates their great benefit to patients . The aim of this study was to measure the number of visits and the time required during the surgical phase ( from pre-op examination to preliminary impressions ) of m and ibular two-implant overdenture treatment . Thirty edentulous patients were assigned to receive two root-form implants in the m and ible between the mental foramen , as part of a r and omized controlled clinical trial . All visits and time spent by the oral surgeon , the surgical assistant and the prosthodontist were measured individually . The mean number of scheduled visits with the oral surgeon was four , and the mean time taken was 104 min . The mean time taken by the surgical assistant was 122 min . On average , the prosthodontist was required for two visits , with a total mean time of 36 min . In addition to the scheduled visits , 14 patients solicited additional appointments ( unscheduled visits ) for various problems ( e.g. loose healing cap ) . The average time taken for unscheduled visits was 32 min . Combining scheduled and unscheduled visits , the mean total time taken by the oral surgeon was 109 min . The surgical assistant was needed for a mean total of 125 min , and the prosthodontist spent , on average , 46 min in this phase of treatment . Results from this study will assist clinicians in establishing the total time and number of visits needed for the surgical phase of two-implant m and ibular overdenture treatment Purpose : The aim of this study was to evaluate and compare immediate-loaded implant-retained m and ibular overdentures and delayed-loaded implant-retained m and ibular overdentures . Material s : Ten completely edentulous male patients received 40 dental implants . Patients were r and omly divided into 2 equal groups , 5 patients each . Patients of both groups received conventional maxillary complete denture and had stage 1 surgery for placing 4 dental implant fixtures , 2 on each side anterior to the mental foramina . Group A : One-stage surgical procedure and immediate loading . Patients in this group received m and ibular bar-retained overdenture supported by 4 endosseous implants loaded immediately after implant placement . Group B : The original 2-stage concept and delayed loading . Patients in this group received m and ibular bar-retained overdenture supported by 4 endosseous implants that remained submerged for a period of 4 months before loading . The patients were evaluated clinical ly and radiographically immediately after overdenture delivery and after 6 months , 12 months , 18 months , and 24 months . Results : The results of clinical evaluation showed no statistical significant difference between the 2 groups regarding the effect of treatment . The radiographic assessment showed no statistical significant difference in mesial and distal alveolar bone loss at the different intervals of the follow-up period , except at the 12-month period , where immediately loaded implants showed a decrease in the amount of alveolar bone loss mesially and distally compared to delayed loaded implants . Conclusions : The results suggest that immediate-loaded implants provide promising results compared to delayed-loaded implants and can be a possible alternative procedure in implant dentistry This study was design ed to compare the results of immediate and delayed loading of implants with implant-retained m and ibular overdentures . Ten patients ( test group ) received 40 Brånemark System MKII implants ( 4 per patient ) placed in the interforaminal area of the m and ible . St and ard abutments were immediately screwed to the implants , rigidly connected with a bar , and immediately loaded with an overdenture . Ten patients ( control group ) received the same type and number of implants in the same area , but the implants were left to heal submerged . Four to 8 months later , st and ard abutments were screwed to the implants and the same prosthetic procedure was applied . Each implant was evaluated at the time of prosthetic loading and at 6 , 12 , and 24 months after the initial prosthetic load with the following parameters : modified Plaque Index ( MPI ) , modified Bleeding Index ( MBI ) , probing depth ( PD ) , and Periotest . Peri-implant bone resorption was evaluated on panoramic radiographs taken 12 and 24 months after initial prosthetic loading . No significant differences were found between the 2 groups regarding MPI , MBI , Periotest , peri-implant bone resorption , and PD at 6 and 24 months ( P > .05 ) . The only difference was found regarding PD values on the mesial and lingual sites at 12 months ( P < .05 ) . The cumulative success rate of implants was 97.5 % in both groups . Results from this study showed that immediate loading of endosseous implants rigidly connected with a U-shaped bar does not seem to have any detrimental effect on osseointegration . Conversely , this method significantly shortens the duration of treatment with relevant satisfaction for the patients The aim of this study was to determine the influence of age on peri-implant tissues in patients treated with implant-supported overdentures in the m and ible . A prospect i ve study was carried out with 2 groups of healthy edentulous patients . The mean age of the younger group ( n = 32 ) was 46 years ( range 35 to 50 years ) ; the mean age of the older group ( n = 26 ) was 68 years ( range 60 to 80 years ) . Two dental implants were placed in the interforaminal region of the m and ible , and after a 3-month healing period , overdentures were fabricated . Clinical and radiographic parameters were evaluated immediately after completion of the prosthetic treatment , after 1 year , and after 3 years . The evaluated clinical parameters were implant loss , Plaque Index , Gingival Index , Bleeding Index , and probing depth . Radiographic evaluation was performed using a st and ardized long-cone technique with a direction device . Statistical analysis was carried out with SPSS software . One implant in the older group was lost during the healing period . After 3 years , the mean scores for Plaque Index , Gingival Index , and Bleeding Index were between 0 and 1 for both groups ( out of possible scores of 0 to 3 ) , and the mean probing depth was 3 mm in both groups . The mean bone loss after 3 years was 1.2 mm in the younger group and 0.8 mm in the older group , but this difference was not significant . It was concluded from this study population that the clinical performance of implant-supported overdentures in the m and ible is equally successful in younger and older patients PURPOSE This r and omized controlled clinical trial aim ed to evaluate the efficacy of splinted implants versus unsplinted implants in overdenture therapy over a 10-year period . MATERIAL S AND METHODS The study sample comprised 36 completely edentulous patients , 17 men and 19 women ( mean age 63.7 years ) . In each patient , 2 implants ( Brånemark System , Nobel Biocare , Göteborg , Sweden ) were placed in the interforaminal area . Three to 5 months after placement , they were connected to st and ard abutments . The patients were then rehabilitated with ball-retained overdentures , magnet-retained overdentures , or bar-retained overdentures ( the control group ) . Patients were followed for 4 , 12 , 60 , and 120 months post-abutment connection . Group means as well as linear regression models were fitted with attachment type and time as classification variables and corrected for simultaneous testing ( Tukey ) . RESULTS After 10 years , 9 patients had died and 1 was severely ill . Over 10 years , no implants failed . Mean Plaque Index , Bleeding Index , change in attachment level , Periotest values , and marginal bone level at the end of the follow-up period were not significantly different among the groups . DISCUSSION The annual marginal bone loss , excluding the first months of remodeling , was comparable with that found around healthy natural teeth . CONCLUSION The fact that no implants failed and that overall marginal bone loss after the first year of bone remodeling was limited suggested that implants in a 2-implant m and ibular overdenture concept have an excellent prognosis in this patient population , irrespective of the attachment system used The aim of this study was to compare the success rates after 1 and 2 years of conventionally and early loaded pairs of unsplinted ITI implants supporting m and ibular overdentures in edentulous patients . Twenty-four participants ( age range 55 - 80 years ) were r and omly allocated with maximum concealment to two treatment groups . In the first group , the implants were allowed to heal for 12 weeks before being functionally loaded ( control ) and the second group had 6 weeks of healing with identical loading . All participants had new conventional complete maxillary and m and ibular dentures prior to the study . Two s and blasted large-grit acid-etched ( SLA ) surface ITI implants were placed in the m and ibular interforaminal area , following a st and ardized nonsubmerged surgical protocol . After 6 or 12 weeks of healing , matrices were processed into the fitting surface of the pre-existing m and ibular dentures and the implants loaded . Implant success was determined using mobility tests and radiographs taken at baseline and 52 and 104 weeks after surgery . Clinical peri-implant parameters were also documented . Results showed all implants successfully osseointegrated , according to accepted criteria , after 2 years . Mean loss of crestal bone height after 1 year was 0.35 + /- 0.22 mm ( control ) vs. 0.27 + /- 0.18 mm ( test ) . After 2 years this reduced to 0.09 + /- 0.06 mm ( control ) vs. 0.12 + /- 0.17 mm ( test ) . The mean Periotest value after 1 year was -4.9 ( control ) vs.-3.78 ( test ) . After 2 years , the mean resonance frequency value for the control implants was 6797 Hz [ mean implant stability quotient ( ISQ ) = 64.77 ] and for the test implants 6670 Hz ( mean ISQ = 62.0 ) . Shortened loading periods for these ITI implants did not cause any statistically significant differences in osseointegration or peri-implant parameters . We conclude that pairs of unsplinted SLA-surface ITI implants can be successfully loaded with m and ibular overdentures 6 weeks after surgery BACKGROUND Step-wise reduction in loading protocol s is necessary to evaluate early loading of implants with m and ibular overdentures . PURPOSE To compare the success rates of two different dental implant systems following conventional or early loading protocol s in patients being rehabilitated with m and ibular overdentures . MATERIAL S AND METHODS Forty-eight edentulous participants were r and omly allocated to two different implant systems : one with a machined titanium implant surface ( Sterioss , Nobel Biocare , Yorba Linda , California , USA ) and the other with a roughened titanium surface ( Southern Implants , Irene , South Africa ) . For each system , the participants were further divided into control groups , in whom m and ibular implant overdentures and their respective matrices were inserted following a st and ard 12-week healing period , and test groups , in whom a 6-week healing period was followed prior to identical loading . Two unsplinted implants to support implant overdentures were placed in the anterior m and ible of all participants , using a st and ardized one-stage surgical procedure . Mobility tests and marginal bone levels , as well as peri-implant parameters , were evaluated at each baseline and 52 and 104 weeks after surgery . RESULTS There was no statistically significant difference in the success rates of the two systems in either control or test groups . At the 2-year evaluation , a success rate was found of 87.5 % and 70.8 % for the control and test Sterioss groups , respectively , and 83.3 % and 100 % for the control and test Southern Implants groups were observed . For the Sterioss groups , eight implants were lost at an early stage : seven in the test group and one in the control group . For the Southern Implants control and test groups , no failures were seen at any time interval . There were no significant differences in marginal bone loss , Periotest values , and peri-implant parameters between implant systems or between any of the control or test groups . CONCLUSIONS Early loading , with step-wise reductions in loading protocol s , of unsplinted machined Sterioss and roughened Southern Implants fixtures with m and ibular overdentures is possible for up to 2 years It is unclear whether m and ibular implant overdentures improve the nutritional state of edentulous patients better than conventional dentures . In a r and omized clinical trial , we tested for post-treatment differences in nutritional status between patients with m and ibular two-implant retained overdentures and those with conventional complete dentures . Edentulous subjects ( ages 65–75 yrs ) received two-implant m and ibular overdentures ( IOD , n = 30 ) or conventional dentures ( CD , n = 30 ) . Measures of nutritional state were gathered before and 6 mos after treatment . Significant improvements in anthropometric parameters were detected in the IOD but not in the CD group , for percent body fat ( p = 0.011 ) and skin-fold thickness at the biceps , subscapularis , and abdomen ( p < 0.05 ) , with significant decreases in waist circumference ( p < 0.0001 ) and waist-hip ratio ( p = 0.001 ) . Significant increases were seen in concentrations of serum albumin ( p = 0.015 ) , hemoglobin ( p = 0.01 ) , and B12 ( p = 0.01 ) . No significant between-group differences
Output:
| Considering implant success rates and peri-implant parameters early loading protocol produces equal outcomes as with conventional loading . |
MS213761 | ***TASK*** the task is to summarize an input biomedical literature in six sentences
***INPUT*** the input is a biomedical literature
***OUTPUT*** the output is the summary of an input biomedical literature in six sentences
***DOCUMENTATION***
***EXAMPLES***
Input: OBJECTIVES The purpose of this study was to investigate the physiological and psychological effects of massage on delayed onset muscle soreness ( DOMS ) . METHODS Eighteen volunteers were r and omly assigned to either a massage or control group . DOMS was induced with six sets of eight maximal eccentric contractions of the right hamstring , which were followed 2 h later by 20 min of massage or sham massage ( control ) . Peak torque and mood were assessed at 2 , 6 , 24 , and 48 h postexercise . Range of motion ( ROM ) and intensity and unpleasantness of soreness were assessed at 6 , 24 , and 48 h postexercise . Neutrophil count was assessed at 6 and 24 h postexercise . RESULTS A two factor ANOVA ( treatment v time ) with repeated measures on the second factor showed no significant treatment differences for peak torque , ROM , neutrophils , unpleasantness of soreness , and mood ( p > 0.05 ) . The intensity of soreness , however , was significantly lower in the massage group relative to the control group at 48 h postexercise ( p < 0.05 ) . CONCLUSIONS Massage administered 2 h after exercise induced muscle injury did not improve hamstring function but did reduce the intensity of soreness 48 h after muscle insult Massage therapy is commonly used following endurance running races with the expectation that it will enhance post-run recovery of muscle function and reduce soreness . A limited number of studies have reported little or no influence of massage therapy on post-exercise muscle recovery . However , no studies have been conducted in a field setting to assess the potential for massage to influence muscle recovery following an actual endurance running race . To evaluate the potential for repeated massage therapy interventions to influence recovery of quadriceps and hamstring muscle soreness , recovery of quadriceps and hamstring muscle strength and reduction of upper leg muscle swelling over a two week recovery period following an actual road running race . Twelve adult recreational runners ( 8 male , 4 female ) completed a half marathon ( 21.1 km ) road race . On days 1,4 , 8 , and 11 post-race , subjects received 30 minutes of st and ardized massage therapy performed by a registered massage therapist on a r and omly assigned massage treatment leg , while the other ( control ) leg received no massage treatment . Two days prior to the race ( baseline ) and preceding the treatments on post-race days 1 , 4 , 8 , and 11 the following measures were conducted on each of the massage and control legs : strength of quadriceps and hamstring muscles , leg swelling , and soreness perception . At day 1 , post-race quadriceps peak torque was significantly reduced ( p < 0.05 ) , and soreness and leg circumference significantly elevated ( p < 0.05 ) relative to pre-race values with no difference between legs . This suggested that exercise-induced muscle disruption did occur . Comparing the rate of return to baseline measures between the massaged and control legs , revealed no significant differences ( p > 0.05 ) . All measures had returned to baseline at day 11 . Massage did not affect the recovery of muscles in terms of physiological measures of strength , swelling , or soreness . However , question naires revealed that 7 of the 12 participants perceived that the massaged leg felt better upon recovery . Key PointsMassage does not appear to affect physiological indices of muscle recovery post exercise . Massage does appear to positively influence perceptions of recovery . More research needs to be completed on the purported benefits of massage PURPOSE The intention of this study was to assess the effectiveness of massage on muscle recovery as a function of therapist education in participants who completed a 10-km running race . METHODS Race participants were offered a 12- to 15-min massage immediately post-event . Participants were r and omly assigned to a student therapist with either 450 , 700 , or 950 h of didactic training in massage . Muscle soreness was recorded by question naire using a 0- to 10-point visual scale at time points immediately before and after massage , and 24 and 48 h post-event . Eight hundred ninety-five subjects were recruited , with 317 subjects returning question naires from all time points . RESULTS Race participants who received massage from student therapists with 950 h of didactic training reported significantly greater improvement in muscle soreness across time compared with those who received massage from therapists with 700 or 450 h of education in massage ( P < 0.01 ) . On study entry , there was no difference in muscle soreness ( P = 0.99 ) , with a group mean of 4.4 + /- 0.4 ; at the 24-h measurement , soreness was 2.4 + /- 0.6 , 3.7 + /- 0.5 , and 3.6 + /- 0.9 for the 950- , 700- , and 450-h groups , respectively ( P < 0.01 ) . CONCLUSION Level of therapist training was shown to impact effectiveness of massage as a post-race recovery tool ; greater reduction in muscle soreness was achieved by therapists with 950 h of training as opposed to those with 700 or 450 The physiological adaptations to sauna bathing could enhance endurance performance . We have therefore performed a cross-over study in which six male distance runners completed 3 wk of post-training sauna bathing and 3 wk of control training , with a 3 wk washout . During the sauna period , subjects sat in a humid sauna at 89.9+/-2.0 degrees C ( mean+/-st and ard deviation ) immediately post-exercise for 31+/-5 min on 12.7+/-2.1 occasions . The performance test was a approximately 15 min treadmill run to exhaustion at the runner 's current best speed over 5 km . The test was performed on the 1st and 2nd day following completion of the sauna and control periods , and the times were averaged . Plasma , red-cell and total blood volume were measured via Evans blue dye dilution immediately prior to the first run to exhaustion for each period . Relative to control , sauna bathing increased run time to exhaustion by 32 % ( 90 % confidence limits 21 - 43 % ) , which is equivalent to an enhancement of approximately 1.9 % ( 1.3 - 2.4 % ) in an endurance time trial . Plasma and red-cell volumes increased by 7.1 % ( 5.6 - 8.7 % ) and 3.5 % ( -0.8 % to 8.1 % ) respectively , after sauna relative to control . Change in performance had high correlations with change in plasma volume ( 0.96 , 0.76 - 0.99 ) and total blood volume ( 0.94 , 0.66 - 0.99 ) , but the correlation with change in red cell volume was unclear ( 0.48 , -0.40 to 0.90 ) . We conclude that 3 wk of post-exercise sauna bathing produced a worthwhile enhancement of endurance running performance , probably by increasing blood volume Delayed onset muscle soreness is a common problem that can interfere with rehabilitation as well as activities of daily living . The purpose of this study was to test the impact of therapeutic massage , upper body ergometry , or microcurrent electrical stimulation on muscle soreness and force deficits evident following a high-intensity eccentric exercise bout . Forty untrained , volunteer female subjects were r and omly assigned to one of three treatment groups or to a control group . Exercise consisted of high-intensity eccentric contractions of the elbow flexors . Resistance was reduced as subjects fatigued , until they reached exhaustion . Soreness rating was determined using a visual analog scale . Force deficits were determined by measures of maximal voluntary isometric contraction at 90 degrees of elbow flexion and peak torque for elbow flexion at 60 degrees/sec on a Cybex II isokinetic dynamometer . Maximal voluntary isometric contraction and peak torque were determined at the 0 hour ( before exercise ) and again at 24 and 48 hours postexercise . Treatments were applied immediately following exercise and again at 24 hours after exercise . The control group subjects rested following their exercise bout . Statistical analysis showed significant increases in soreness rating and significant decreases in force generated when the 0 hour was compared with 24- and 48-hour measures . Further analysis indicated no statistically significant differences between massage , microcurrent electrical stimulation , upper body ergometry , and control groups Abstract Objective To evaluate the effectiveness of acupressure in terms of disability , pain scores , and functional status . Design R and omised controlled trial . Setting Orthopaedic clinic in Kaohsiung , Taiwan . Participants 129 patients with chronic low back pain . Intervention Acupressure or physical therapy for one month . Main outcome measures Self administered Chinese versions of st and ard outcome measures for low back pain ( primary outcome : Rol and and Morris disability question naire ) at baseline , after treatment , and at six month follow-up . Results The mean total Rol and and Morris disability question naire score after treatment was significantly lower in the acupressure group than in the physical therapy group regardless of the difference in absolute score ( - 3.8 , 95 % confidence interval - 5.7 to - 1.9 ) or mean change from the baseline ( - 4.64 , - 6.39 to - 2.89 ) . Acupressure conferred an 89 % ( 95 % confidence interval 61 % to 97 % ) reduction in significant disability compared with physical therapy . The improvement in disability score in the acupressure group compared with the physical group remained at six month follow-up . Statistically significant differences also occurred between the two groups for all six domains of the core outcome , pain visual scale , and modified Oswestry disability question naire after treatment and at six month follow-up . Conclusions Acupressure was effective in reducing low back pain in terms of disability , pain scores , and functional status . The benefit was sustained for six months PURPOSE The purpose of the present study was to determine whether activity would affect the recovery of muscle function after high-force eccentric exercise of the elbow flexors . METHODS Twenty-six male volunteers were r and omly assigned to one of three groups for a 4-d treatment period : immobilization ( N = 9 ) , control ( N = 8) , and light exercise ( N = 9 ) . Relaxed arm angle ( RANG ) , flexed arm angle ( FANG ) , maximal isometric force ( MIF ) , and perceived muscle soreness ( SOR ) were obtained for 3 consecutive days pre-exercise ( baseline ) , immediately post-exercise , and for 8 consecutive days after the 4-d treatment period ( recovery ) . During the treatment period , the immobilization group had their arm placed in a cast and supported in a sling at 90 degrees . The control group had no restriction of their arm activity . The light exercise group performed a daily exercise regimen of 50 biceps curls with a 5-lb dumbbell . RESULTS All subjects showed a prolonged decrease in RANG , increase in FANG , loss in MIF , and increase in SOR in the days after eccentric exercise . During recovery , there was no significant interaction observed among groups over time in RANG ( P > 0.05 ) or FANG ( P > 0.05 ) , but there was a significant interaction observed among groups over time in both MIF ( P < 0.01 ) and SOR ( P < 0.01 ) . Recovery of MIF was facilitated by light exercise and immobilization , whereas recovery from SOR was facilitated by light exercise and delayed by immobilization . CONCLUSIONS The recovery of MIF in both the light exercise and immobilization groups suggests that more than one mechanism may be involved in the recovery of isometric force after eccentric exercise Thirteen males and 7 females completed their maximum number of leg extensions against a half maximum load . In a r and omised , crossover study they were exercised to fatigue using an ergonometer , ski-squats and leg extensions followed either by a 6 min massage or rest after which they again completed their maximum number of leg extensions against half maximum load . The process was repeated a few days later with the alternative condition ( rest or massage ) . The results showed that massage after exercise fatigue significantly improved quadriceps performance compared to rest ( p = 0.001 ) . The data was further analysed in relation to age and gender The aim of this study was to examine the acute effects of pre- performance lower limb massage after warm-up on explosive and high-speed motor capacities and flexibility . Twenty-four physically active healthy Caucasian male subjects volunteered to participate in this study . All subjects were from a Physical Education and Sport Department in a large university in Turkey . The study had a counterbalanced crossover design . Each of the subjects applied the following intervention protocol s in a r and omised order ; ( a ) massage , ( b ) stretching , and ( c ) rest . Before ( pre ) and after ( post ) each of the interventions , the 10 meter acceleration ( AS ) , flying start 20 meter sprint ( FS ) , 30 meter sprint from st and ing position ( TS ) , leg reaction time ( LR ) , vertical jump ( VJ ) and sit & reach ( SR ) tests were performed . A Wilcoxon 's signed rank test was used to compare before and after test values within the three interventions ( massage , stretching and rest ) . The data showed a significant worsening , after massage and stretching interventions , in the VJ , LR ( only in stretching intervention ) , AS and TS tests ( p < 0.05 ) , and significant improvement in the SR test ( p < 0.05 ) . In contrast , the rest intervention led only to a significant decrement in TS performance ( p < 0.05 ) . In conclusion , the present findings suggest that performing 10 minute posterior and 5 minute anterior lower limb Swedish massage has an adverse effect on vertical jump , speed , and reaction time , and a positive effect on sit and reach test results . Key pointsPerforming 10 minute posterior and
Output:
| Conclusion The effects of massage on performance recovery are rather small and partly unclear , but can be relevant under appropriate circumstances ( short-term recovery after intensive mixed training ) .
However , it remains question able if the limited effects justify the widespread use of massage as a recovery intervention in competitive athletes |
MS213762 | ***TASK*** the task is to summarize an input biomedical literature in six sentences
***INPUT*** the input is a biomedical literature
***OUTPUT*** the output is the summary of an input biomedical literature in six sentences
***DOCUMENTATION***
***EXAMPLES***
Input: The authors conducted a r and omized , double-blind , 10-week clinical trial of two doses of nortriptyline in eight nursing homes . Sixty-nine patients , average age 79.5 years , were r and omized to receive regular doses ( 60 mg-80 mg/day ) vs. low doses ( 10 mg-13 mg/day ) of nortriptyline . Among the more cognitively intact patients , there was a significant quadratic relationship defining a " therapeutic window " for nortriptyline plasma levels and clinical improvement . There were also significant differences in plasma level-response relationships between depressed patients who were cognitively impaired and those who were more cognitively intact . Depression remains a syndrome that responds to specific treatment , even in frail nursing home patients , and those depressions that occur in patients with significant dementia may represent a treatment-relevant condition with a different plasma level-response relationship than in depression alone A significant drug-placebo difference was found in a double-blind , placebo-controlled study of nortriptyline for treatment of major depression among frail elderly patients living in an institutional setting . This finding confirms the validity of the DSM-III-R diagnosis of major depression and establishes the need for specific psychiatric services for the chronically ill elderly living in nursing homes and congregate housing facilities . The incidence of adverse events requiring early termination of treatment was 34 % , demonstrating the vulnerability of these patients and their need for careful monitoring during treatment . High levels of self-care disability and low levels of serum albumin were both associated with decreased therapeutic responses , demonstrating the need for further research on psychopathology in these setting There has been limited research into defining what constitutes an adequate first-line antidepressant trial in elderly patients . The authors report the outcome of extended , high-dosage sertraline treatment in a sample of nursing home residents experiencing residual significant depressive symptoms after 10 weeks of treatment with sertraline at a final dosage of 100 mg/day . Subjects who had a Hamilton Depression Rating Scale score ≥ 12 after 10 weeks of treatment with sertraline were eligible for the 8-week open-label extension phase , which involved titrating the sertraline dosage to 200 mg/day . The cumulative response rate was 52 % for the extension phase , compared with 37 % for the acute phase . Examining acute phase nonresponders , 39 % responded during the extension phase . Rates of discontinuation due to adverse events were comparable in the 2 phases . Our findings suggest that an extended trial or high dosages of sertraline may benefit some depressed elderly patients with persistent depression after acute treatment . ( J Geriatr Psychiatry Neurol 2003 ; 16:109 - 111 SUMMARY Objective : To evaluate the efficacy and tolerability of mirtazapine orally disintegrating tablets in depressed , elderly nursing home residents , under naturalistic study conditions . Methods : In this open-label 12-week study , mirtazapine orally disintegrating tablets ( 15–45 mg day−1 ) were administered to patients > 70 years old with physician-diagnosed depression and a Mini-Mental State Examination ( MMSE ) score > 10 . Patients with medical comorbidities , cognitive impairment and /or concomitant medications were enrolled if they met study inclusion criteria and had illnesses and /or medication dosages that were considered stable . Assessment s were performed at baseline by physicians and at days 14 , 28 , 56 , and 84 ( or early termination ) by physicians or nurse coordinators using the Clinical Global Impression ( CGI ) scale , the 16-item Hamilton Rating Scale for depression ( Ham-D-16 ( the st and ard 17-item scale minus item 14 ) ) , and the Cornell Scale for Depression in Dementia ( CSDD ) . Tolerability was evaluated based on treatment-emergent adverse events . Results : A total of 119 patients in the intent-to-treat ( ITT ) group were treated with mirtazapine orally disintegrating tablets ( mean daily dose : 19.4 mg ) and evaluated for efficacy . At endpoint , 54 % of patients in the ITT group showed CGI-I response ( defined as a CGI-I score of 1 or 2 ( ' very much ' or ' much ' improved ) and 47 % were Ham-D-16 responders ( defined as decrease from baseline of at least 50 % in Ham-D-16 total score ) . CSDD mean scores and Ham-D-16 mean total scores demonstrated a progressive decrease from baseline to trial completion . The decrease in Ham-D scores from baseline to day 84 was statistically significant ( p < 0.0001 ) . Mean changes from baseline to day 84 were −6.6 ± 6.9 ( CSDD score ) and −7.9 ± 7.4 ( Ham-D-16 total score ) . Ham-D Factor I , Factor VI and item 1 scores also decreased . Fourteen of 124 patients in the all-subjects-treated ( AST ) group ( 11.3 % ) discontinued prematurely due to adverse events . The most frequently occurring adverse events were urinary tract infection ( 19 % ) , accidental injury ( 18 % ) , fall ( 18 % ) , somnolence ( 12 % ) , and upper respiratory infection ( 12 % ) . Mean body weight increased by 0.7 ± 2.25 kg ( 1.54 ± 5 lb ) from baseline to day 28 , and by 1.3 ± 3.36 kg ( 2.86 ± 7.4 lb ) from baseline to day 84 . Conclusions : The results suggest that mirtazapine orally disintegrating tablets provide antidepressant efficacy and are a relatively well-tolerated treatment for depression in this patient population of elderly nursing home residents with medical and cognitive comorbidities Studies have demonstrated that the selective serotonin reuptake inhibitor antidepressants have similar efficacy to other agents , such as tricyclic antidepressants . However , data are limited for direct comparisons with other antidepressants . The authors conducted a contemporaneous comparison of nursing home residents treated with open-label sertraline in doses up to 100 mg/day with nursing home residents treated in a double-blind r and omized study of low vs. regular doses of nortriptyline . There were 97 patients enrolled in the study ( 28 treated with sertraline ) , with an average treatment duration of 55 days . There were no differences in the tolerability of sertraline vs. nortriptyline . However , in this group of frail older adults , sertraline was not as effective as nortriptyline for the treatment of depression Depression is common across a broad spectrum of severity among nursing home residents . Previous research has demonstrated the effectiveness of antidepressants in nursing home residents with major depression , but it is not known whether antidepressants are helpful in residents with less severe forms of depression . We conducted a r and omized double-blind placebo-controlled 8-week trial comparing paroxetine and placebo in very old nursing home residents with non-major depression . The main outcome measure was the primary nurse 's Clinical Impression of Change ( CGI-C ) . Additional outcome measures were improvement on the interview-derived Hamilton Depression Rating Scale ( HDRS ) and Cornell Scale for Depression ( CS ) scores . Twenty-four subjects with a mean age of 87.9 were enrolled and twenty subjects completed the trial . Placebo response was high , and when all subjects were considered , there were no differences in improvement between the paroxetine and placebo groups . Two subjects that received paroxetine developed delirium , and subjects that received paroxetine were more likely to experience a decrease in Mini Mental State Exam scores ( P = .03 ) . There were no differences in serum anticholinergic activity between groups . In a subgroup analysis of 15 subjects with higher baseline HDRS and CS scores , there was a trend toward greater improvement in the paroxetine group in an outcome measure that combined the CGI-C and interview-based measures ( P = .06 ) . Paroxetine is not clearly superior to placebo in this small study of very old nursing home residents with non-major depression , and there is a risk of adverse cognitive effects . Because of the high placebo response and the trend towards improvement in the more severely ill patients , it is possible that a larger study would have demonstrated a significant therapeutic effect for paroxetine as compared with placebo . The study also illustrates the discordance between patient and caregiver ratings , and the difficulties in study ing very elderly patients with mood disorders The authors examined 50 patients , with a mean age of 89 years ( range : 80–98 ) , placed in a prospect i ve , open-label trial of either fluoxetine , sertraline , or paroxetine . At 12-week follow-up , there was a significant overall decline ( 36 % ) in Ham-D scores ; 42 % had at least a 50 % decline in their scores . There were no significant differences in responses to the three antidepressants , and all drugs were well tolerated . However , there were significant differences between diagnostic subgroups in the percentage of persons showing at least a 50 % decrease in their Ham-D scores : major depressive disorder ( MDD ; 93 % ) , Alzheimer 's disease with MDD ( 8 % ) , vascular dementia with MDD ( 6 % ) , and other CNS-related disorders with MDD ( 83 % ) . The findings confirm earlier accounts that antidepressants may be substantially less effective with MDD secondary to dementia in very old patients A sample of 31 female nursing home patients with late-stage Alzheimer 's disease participated in a double-blind clinical trial of the antidepressant medication sertraline . Measures of depression included various objective scales and two measures of facial expressions of emotion coded during a semistructured interview using a facial affect coding system . Repeated- measures ANOVAs at baseline and at the 8-week endpoint indicated that on all measures , both the treatment and placebo groups improved over time , with three of six measures showing a significant time effect . The " knit-brow " facial measure approached significance for a Treatment x Time effect . Thus , sertraline had no significant benefits over placebo . However , if , as we hypothesize , the knit-brow response is more sensitive to signs of depression in advanced dementia , our study justifies the further investigation of the use of sertraline in this population OBJECTIVES Depression in older patients contributes to personal suffering and family disruption and increases disability , medical morbidity , mortality , suicide risk , and healthcare utilization . The majority of clinical trials of antidepressant treatments are conducted in younger patients . For this reason , clinicians often have to extrapolate from studies in population s that do not present the same problems as older patients . For example , older patients often have serious coexisting medical conditions that may contribute to the depression and complicate the choice of treatment . Older patients as a rule need to be on many medications , some of which may contribute to depression and /or interact with antidepressants . Finally , older adults metabolize medications slowly and are more sensitive to side effects than younger patients . Because of these complexities , we conducted a consensus survey of expert opinion on the pharmacotherapy of depressive disorders in older patients to address clinical questions not definitively answered in the research literature . METHOD After review ing the literature and convening a work group of experts , we prepared a written survey with 64 questions that asked about 857 options . 618 of the options were scored using a modified version of the R AND 9-point scale for rating appropriateness of medical decisions . For the other options , the experts were asked to write in answers ( e.g. , average doses ) or to check a box to indicate their preferred answer . We sent the survey to 50 national experts on geriatric depression , all of whom completed it . Consensus on each option was defined as a nonr and om distribution of scores by chi-square " goodness-of-fit " test . We assigned a categorical rank ( first line/preferred choice , second line/alternate choice , third line/usually inappropriate ) to each option based on the 95 % confidence interval around the mean rating . Guideline tables indicating preferred treatment strategies were then developed for key clinical situations . RESULTS The expert panel reached consensus on 89 % of the options rated on the 9-point scale . The experts stress the importance of identifying coexisting medical conditions that may be contributing to the depression or complicate treatment . For unipolar nonpsychotic major depression , the preferred strategy is an antidepressant ( selective serotonin reuptake inhibitor [ SSRI ] or venlafaxine XR preferred ) plus psychotherapy . For unipolar psychotic major depression , the treatment of choice is an antidepressant ( SSRI or venlafaxine XR ) plus one of the newer atypical antipsychotics . Electroconvulsive therapy is also first line . For dysthymic disorder or persistent milder depression , the experts recommend combining an antidepressant ( SSRIs preferred ) and psychotherapy . If the patient has a comorbid medical condition ( e.g. , hypothyroidism ) that is contributing to the depression , the experts recommend treating both the depression and the medical condition from the outset . The SSRIs were the top-rated antidepressants for all types of depression . Among them , the experts gave the highest ratings for efficacy and tolerability to citalopram and sertraline . Paroxetine was another first-line option , and fluoxetine was rated high second line . The preferred psychotherapy techniques for treating depression in older patients are cognitive-behavioral therapy , supportive psychotherapy , problem-solving psychotherapy , and interpersonal psychotherapy . The experts also give strong support to including
Output:
| The limited amount of evidence from r and omized and non-r and omized open-label trials suggests that depressed NH residents have a modest response to antidepressant medications . |
MS213763 | ***TASK*** the task is to summarize an input biomedical literature in six sentences
***INPUT*** the input is a biomedical literature
***OUTPUT*** the output is the summary of an input biomedical literature in six sentences
***DOCUMENTATION***
***EXAMPLES***
Input: Patients over the age of 65 years with clear catch specimens of urine containing organisms sensitive to norfloxacin were blindly r and omised to receive either norfloxacin in a dose of 400 mg twice daily for 7 days or a placebo for the same period . Urine cultures were repeated immediately prior to treatment , at the end of treatment and at 7 days , 1 month and 3 months after treatment . Physical and mental function were assessed by performing a Crighton Behavioural Rating Scale at the same time intervals . Observations were made on 29 each of subjects on norfloxacin and placebo . The proportions of patients abacteriuric at the end of treatment , 7 days and 3 months post- treatment were 16/24 ( 66 % ) , 12/24 ( 50 % ) and 5/24 ( 21 % ) in the norfloxacin group and 10/26 ( 38 % ) , 8/26 ( 31 % ) and 8/25 ( 32 % ) in the placebo group . Percentage calculations ( and denominators ) exclude those patients withdrawn or for whom there were no specimens available at the sampling interval in question . Means and 95 % intervals for the Crighton Behaviour Rating Scales initially and at 3 months in subjects on norfloxacin were 18.1 ( 15.1 - 20.7 ) and 19.1 ( 16.2 - 21.9 ) respectively . The same figures for the placebo group were 15.7 ( 12.6 - 18.8 ) and 16.6 ( 13.7 - 19.5 ) . It is concluded that a 7 day course of norfloxacin for the treatment of asymptomatic bacteriuria had no effect on the physical and mental function of elderly continuing care patients , and that one explanation for this is that there was a high rate of urinary re-infection Urinary incontinence is a multibillion-dollar health problem that afflicts almost 60 % of some 2 million residents of the 20 000 nursing homes in the United States . Bacteriuria is also prevalent in this population , and the two conditions commonly coexist [ 1 ] . Incontinent nursing home residents are frequently prescribed antimicrobial agents for urinary tract infections , but the quality and appropriateness of such prescriptions have been question ed [ 2 - 5 ] . Unnecessary antimicrobial treatment may result in the undesired development of resistant organisms and substantial unnecessary morbidity and health care expenditure . Well- design ed clinical trials have documented that treating asymptomatic bacteriuria in the nursing home population has no significant effects on morbidity and mortality and that it actually leads to the development of strains of bacteria that are resistant to commonly prescribed antimicrobial agents [ 6 , 7 ] . However , no studies have carefully examined the effects of eradicating bacteriuria on the severity of incontinence in this population . In a longitudinal study of a cohort of older women , Boscia and colleagues [ 8 ] found no difference in self-reported symptoms of incontinence in patients with and without bacteriuria . This was , however , a study of bacteriuria and not of incontinence , and the participants had , on average , mild incontinence [ 9 ] . In one study of behavioral therapy for incontinence in nursing home residents , incontinence appeared to worsen in several of the study participants when bacteriuria developed [ 10 ] . Epidemiologic studies from Europe have reached different conclusions about the association between bacteriuria and incontinence in the geriatric population [ 11 , 12 ] . Despite a lack of definitive data on the relation of bacteriuria to the pathogenesis and severity of incontinence in the nursing home population , recently implemented federal guidelines for the care of incontinence in nursing homes ( Resident Assessment Protocol ) [ 13 ] suggest that bacteriuria should be treated only when symptoms of urinary tract infection other than stable incontinence are present . If eradicating bacteriuria makes the bladder less irritable in this patient population , then the severity of incontinence and the use of expensive adult diapers might be reduced [ 14 ] . If , however , eradicating bacteriuria has no effect on the severity of incontinence , no rationale would exist for exposing incontinent nursing home residents with bacteriuria to the potential added morbidity and expense of antimicrobial therapy . We conducted a clinical trial to determine whether eradicating bacteriuria affects the severity of incontinence among nursing home residents . We defined bacteriuria as would a practicing clinician in a nursing home rather than by the strict definition used in most studies of the epidemiology of asymptomatic bacteriuria ( that is , two consecutive cultures with growth of more than 105 colony-forming units [ CFUs ] of the same organism ) . We hypothesized that sterilizing the urine would have no short-term effect on the severity of chronic incontinence in this population . Methods Setting Our study was the first phase of a multifaceted clinical trial addressing the assessment and treatment of incontinence in nursing homes . It was done in one nonprofit and five proprietary nursing homes located close to the offices of the University of California at Los Angeles Borun Center for Gerontological Research at the Jewish Home for the Aging . The nursing homes had a total of 1011 beds ( range , 99 to 256 beds ) and a total of 832 residents . Patients We identified potential patients by asking nursing home staff to identify residents who were incontinent of urine on a regular basis [ that is , several times per week to several times per day ] . Patients were excluded if 1 ) their care was being reimbursed by Medicare [ indicating either short-term rehabilitation or medical instability ] ; 2 ) their prognosis , as determined by the research staff nurse , was so poor that they would probably not live at least 3 to 4 months to complete the protocol ; 3 ) daytime incontinence was not documented by r and om-hour checks for wetness [ described below ] ; 4 ) the resident had a permanent indwelling bladder catheter ; 5 ) the resident failed a cognitive status screening test [ to pass , the resident had to either say their name or reliably point to one of two objects ] ; and 6 ) the resident manifested a severe behavioral disturbance , such as physical aggression or verbal abusiveness , during the wet-checking procedures . Informed consent was obtained from residents who could provide it ( as determined by a facility nurse or social worker ) . If the resident was not capable of consenting , their assent was obtained ( by describing a simple version of the protocol and then observing their cooperation as the protocol was initiated ) , and consent was then obtained from a responsible party . Procedures All patients for whom informed consent was obtained had a focused history , functional status assessment , cognitive assessment with the 30-point Mini-Mental State Examination , targeted physical examination , urinalysis , and urine culture . For the functional assessment , research staff used the Multidimensional Observational Scale for the Elderly Subject [ 15 ] to interview nursing home staff who knew the residents well . ( When our study was implemented , the Minimum Data Set was not yet available . ) Research staff used a st and ardized scale ( Performance on Timed Toileting Instrument [ 16 ] ) to objective ly assess functional status specifically related to toileting skills . The physical examination was done by research staff and a physician coinvestigator and included abdominal , genital , pelvic , rectal , and neurologic examinations . Research staff collected urine from female patients by cleaning the perineal area with Betadine and having them void into a fracture bed pan or measuring hat that had been cleaned with an antiseptic solution . We compared the culture results of urine sample s obtained by this procedure to urine sample s obtained by catheterization in 101 of our female patients [ 17 ] . The prevalence of bacteriuria in the catheterized specimens was 29 % . The sensitivity , specificity , and positive and negative predictive values of this procedure in detecting bacteriuria ( with a catheter specimen used as the criterion st and ard ) are 90 % , 92 % , 81 % , and 95 % , respectively . For men who could not void voluntarily , we used a previously vali date d technique that involved cleaning the glans penis with Betadine , applying a clean condom catheter , and processing the first voided specimen [ 18 ] . Urine specimens were subjected to screening tests done by research staff ( including a dipstick method for leukocyte esterase and nitrite and a rapid enzyme-based test for bacteriuria [ Uriscreen , Ventrex Laboratories , Portl and , Maine ] ) . A bio clinical laboratory used st and ard techniques to do a microscopic urinalysis and a urine culture and sensitivity test . We defined pyuria as the presence of more than 10 leukocytes per high-power field on microscopic examination of spun urine . Cultured specimens that grew more than 50 000 CFUs were considered to have significant growth . If significant growth of one or more urinary pathogens occurred on a second specimen , the patient was considered to be bacteriuric . Patients whose urine had significant growth of organisms that are not typically pathogens ( for example , lactobacillus and -streptococcus ) were not considered to be bacteriuric . Our quantitative definition of bacteriuria differs from the st and ard definition ( presence of more than 100 000 CFUs ) that has been used in most epidemiologic studies and intervention trials . However , there is controversy about the clinical significance of lower levels of growth [ 19 ] , and in some studies in the elderly , bacteriuria has been defined as growth of less than 100 000 CFUs [ 20 , 21 ] . We used the cutoff of 50 000 CFUs because our clinical laboratory reported results at this level , and we believe that most clinicians who practice in nursing homes would consider this to be significant growth when making decisions about treatment . Less than 10 % of our cultures that were considered to have significant bacteriuria had growth of more than 50 000 CFUs . In addition , each patient identified as bacteriuric who had growth of more than 50 000 CFUs on one culture did have a second culture with growth of more than 100 000 CFUs ; the only exceptions were two patients whose urine sample s before treatment were collected by catheterization ( see below ) . Most specimens obtained after antimicrobial treatment were collected by catheterization , which was done for a determination of postvoid residual volume in the second phase of the longer ongoing clinical trial . Six patients whose urine was initially not bacteriuric by the criteria outlined above were considered to be bacteriuric on the basis of the catheterized specimen and were enrolled in the antimicrobial trial . For these patients , follow-up urine sample s were collected by the methods described above rather than by repeat catheterization . Eradication of bacteriuria was documented by culture in all but seven cases ; in these cases , the screening tests were used to document that bacteriuria had been eradicated . We have shown that in our population , the presence of at least two negative results on these screening tests has a negative predictive value of more than 90 % [ 22 ] . Bacteriuric patients were r and omly assigned to receive either immediate treatment or delayed treatment ( which was administered 2 to 3 weeks after the immediate treatment group had been treated ) with a 7-day course of norfloxacin , 400 mg orally twice daily . In three cases , the organism or organisms were not susceptible to norfloxacin , and another antimicrobial agent ( trimethoprim-sulfamethoxazole ) was used on the basis of results of the sensitivity testing . Wet checks , the outcome measure used in our study and described in detail below , In a prospect i ve r and omized study ofloxacin ( 400 mg orally once daily ) versus co-trimoxazole ( 320/1,600 mg orally once daily ) were given for 3 weeks in 30 and 22 elderly semimobile patients respectively , suffering from asymptomatic bacteriuria . From the obtained results it was evident that : ( a ) ofloxacin was superior to co-trimoxazole regarding eradication of bacteriuria ( p less than 0.05 ) particularly in patients with a positive antibody-coated bacteria test ; ( b ) a high rate of superinfections and reinfections with strains resistant to co-trimoxazole was observed in both groups indicative of hidden underlying conditions predisposing to urinary tract infections and ( c ) ofloxacin did not accumulate in serum during prolonged therapy but the half-life ranged between 8.3 and 10.2 BACKGROUND Little is known about the role of asymptomatic bacteriuria ( AB ) treatment in young women affected by recurrent urinary tract infection ( UTI ) . We aim ed to evaluate the impact of AB treatment on the recurrence rate among young women affected by recurrent UTI . METHODS A total of 673 consecutive asymptomatic young women with demonstrated bacteriuria from January 2005 to December 2009 were prospect ively enrolled . Patients were split into 2 groups : not treated ( group A , n = 312 ) and treated ( group B , n = 361 ) . Microbiological and clinical evaluations were performed at 3 , 6 , and 12 months . Quality of life was also measured . Recurrence-free rate at the end of the entire study period was the main outcome measure . RESULTS At baseline , the 2 most commonly isolated pathogens were Escherichia coli ( group A , 38.4 % ; group B , 39.3 % ) and Enterococcus faecalis ( group A ,
Output:
| Although treatment of ASB with antimicrobial therapy may improve short-term microbiologic outcomes , the clinical significance is diminished because the effect is not sustained , there is no measurable improvement in morbidity or mortality , and some data indicate that therapy is deleterious . |
MS213764 | ***TASK*** the task is to summarize an input biomedical literature in six sentences
***INPUT*** the input is a biomedical literature
***OUTPUT*** the output is the summary of an input biomedical literature in six sentences
***DOCUMENTATION***
***EXAMPLES***
Input: Patients with solitary thyroid nodules that are benign on aspiration biopsy are often treated nonsurgically . To find out if thyroxine therapy is effective , 74 patients were r and omized to receive levothyroxine treatment or nothing . There were 8 males and 66 females . Their mean age was 39 years . The mean nodule size was 3.6 cm and the mean nodule duration was 11 months . All patients had normal serum thyroxine and thyroid stimulating hormone ( TSH ) levels , and positive thyrotropin releasing hormone ( TRH ) tests . The dose of thyroxine was adjusted until the TRH test was negative . Patients were followed at 6-month intervals in the first 2 years and yearly thereafter , with measurement of the nodule diameter . The mean follow-up period was 1.5 years . In the 37 patients receiving thyroxine therapy , 8 had disappearance of nodules , 6 had greater than 50 % reduction in nodule size . In 19 , the nodules were unchanged and in 4 , the nodules were enlarged . In the 37 patients receiving no drug , 8 had disappearance of nodules , 5 had greater than a 50 % reduction in nodule size , 17 had nodules unchanged , and 7 had enlarged nodules ( p > 0.9 ) . The mean reduction in nodule diameter at various follow-up periods was greater in the thyroxine group , but the difference did not reach statistical significance . Carcinoma was found in 1 patient in each group and both of them experienced nodule enlargement . We conclude that an adequate suppressive dose of levothyroxine does not alter the natural course of benign solitary thyroid nodules . An enlargement of the nodule or a change in its consistency should be further investigated to exclude malignancy . RésuméLes patients présentant un nodule thyroïdien solitaire bénin à la biopsie par aiguille ne sont souvent pas traités chirurgicalement . Pour évaluer 1'efficacité de la thyroxine dans ces cas , 74 patients ont été r and omisés , recevant de la lévothyroxine ou rien . Il y avait 8 hommes et 66 femmes ; 1'âge moyen était de 39 ans . La taille moyenne du nodule était de 3.6 cm , et 1'évolution moyenne était de 11 mois . Tous les patients avaient un taux sérique de thyroxine et de TSH normal ; le test de la TRH était normal . La thyroxine a été dosée jusqu'à obtenir une réponse négative à la TRH . Les patients étaient suivis à intervalles de 6 mois pendant 2 ans puis une fois par an . Le diamètre du nodule etait mesuré à chaque examen . Le suivi moyen était de 1.5 ans . Pour 37 patients qui recevaient de la thyroxine , le nodule a disparu chez 8 et s'est réduit de plus de 50 % chez 6 . Le nodule était inchangé chez 19 et a continué d'évoluer chez 4 . Parmi les 37 patients n'ayant pas reçu de thyroxine , le nodule a disparu chez 8 , s'est réduit en taille de plus de 50 % chez 5 , est resté inchangé chez 17 et a augmenté de volume chez 7 ( p > 0.9 ) . La réduction moyenne du diamètre du nodule était supérieure chez les patients dans le groupe thyroxine mais cette différence n'était pas statistiquement significative . Dans chaque groupe , il y avait un cancer , et dans les deux cas , le nodule avait grossi . Nous concluons que la lévothyroxine aux doses suppressives ne modifie pas 1'évolution des nodules solitaires de la thyroïde . Une augmentation du volume ou une modification dans sa consistance dem and e des examens complémentaires pour exclure une évolution maligne . ResumenLos pacientes con nódulos tiroideos solitarios que demuestran ser benignos en la biopsia por aspiración frecuentemente reciben tratamiento no operatorio . Con el objeto de determinar si el tratamiento con tiroxina es efectivo , se estudiaron 74 pacientes mediante aleatorización : un grupo recibió levotiroxina y el otro ninguna terapia endocrina . El grupo tuvo 8 hombres y 66 mujeres ; la edad promedio fue 39 años . El tamaño promedio de los nódulos fue 3.6 cm y el promedio de evolución del nódulo fue 11 meses . La totalidad de los pacientes exhibió niveles séricos de tiroxina y de TSH normales , y pruebas normales de TRH . La dosis de tiroxina fue ajustada hasta que la prueba de TRH result ó negativa . Los pacientes fueron seguidos a intervalos de 6 meses en el curso de los primeros 2 años , y anualmente de ahí en adelante , registr and o en cada visita el diámetro del nódulo . El promedio del seguimiento fue 1.5 años . En el grupo de 37 pacientes tratados con tiroxina , 8 exhibieron desaparición de los nódulos y 6 reducción de más del 50 % en el tamaño del nódulo ; en 19 los nódulos no demostraron cambio y en 4 aumentaron de tamaño . En los 37 pacientes que no recibieron terapia , 8 demostraron desaparición del nódulo y 5 reduccción de más del 50 % en su tamaño ; en 17 el nódulo no modificó el tamaño y en 7 el nódulo se agr and ó ( p > 0.9 ) . La reducción promedio en el diámetro del nódulo observada en los diferentes períodos de seguimiento fue mayor en el grupo tratado con tiroxina , pero la diferencia no alcanzó significancia estadística . Se halló carcinoma en un paciente en cada grupo , y ambos mostraron crecimiento del nódulo . Hemos concluído que una dosis supresiva de levotiroxina no altera la evolución natural de los nódulos tiroideos benignos . El crecimiento del nódulo o un cambio en su consistencia debe ser investigado para excluir posible malignidad High-frequency ultrasound examination of the thyroid was performed in 253 subjects ( 130 women and 123 men ; age range , 19 - 50 years ) that were r and omly selected from the population in an area of Finl and where goiter is not endemic . Thyroid echo abnormalities were detected in 69 subjects ( 27.3 % ) . Prevalence of abnormalities increased with age , and women showed more lesions than did men in each of the 3 decades . The abnormality was solitary in 39 subjects ( 57 % ) , multiple in 15 ( 22 % ) , and diffuse in 15 ( 22 % ) . Of the 68 individual nodules , 48 ( 70 % ) were smaller than 1 cm in diameter . Anechoic rounded nodules 1 - 5 mm in diameter were found in 28 subjects . Fine-needle aspiration biopsy was performed in 30 subjects . Cytologic examination revealed no unequivocal malignancies . In eight subjects ( 3.2 % ) with a diffuse echo abnormality , cytologic evaluation indicated lymphocytic thyroiditis . It is concluded that the prevalence of small thyroid echo abnormalities in a r and omly selected adult population is rather high , a fact that supports use of a conservative approach to these types of findings Abstract Objective . Many patients with nonerosive reflux disease ( NERD ) have insufficient relief on proton pump inhibitors ( PPIs ) . Some patients have a hypersensitive esophagus and may respond to transient receptor potential vanilloid 1 ( TRPV1 ) antagonists . Aim . To investigate the effect of the TRPV1 antagonist AZD1386 on experimental esophageal pain in NERD patients . Material and methods . Enrolled patients had NERD and a partial PPI response ( moderate-to-severe heartburn or regurgitation ≥3 days/week before enrolment despite ≥6 weeks ' PPI therapy ) . Fourteen patients ( 21–69 years , 9 women ) were block-r and omized into this placebo-controlled , double-blinded , crossover study examining efficacy of a single dose ( 95 mg ) of AZD1386 . On treatment days , each participant 's esophagus was stimulated with heat , distension , and electrical current at teaching hospitals in Denmark and Sweden . Heat and pressure pain served as somatic control stimuli . Per protocol results were analyzed . Results . Of 14 r and omized patients , 12 were treated with AZD1386 . In the esophagus AZD1386 did not significantly change the moderate pain threshold for heat [ –3 % , 95 % confidence interval ( CI ) , –22;20 % ] , distension ( –11 % , 95 % CI , –28;10 % ) , or electrical current ( 6 % , 95 % CI , –10;25 % ) . Mean cutaneous heat tolerance increased by 4.9 ° C ( 95 % CI , 3.7;6.2 ° C ) . AZD1386 increased the maximum body temperature by a mean of 0.59 ° C ( 95 % CI , 0.40–0.79 ° C ) , normalizing within 4 h. Conclusions . AZD1386 had no analgesic effect on experimental esophageal pain in patients with NERD and a partial PPI response , whereas it increased cutaneous heat tolerance . TRPV1 does not play a major role in heat- , mechanically and electrically evoked esophageal pain in these patients . Clinical Trials.gov identifier : D9127C00002 OBJECTIVE To study the efficacy of levothyroxine suppressive therapy in the management of benign thyroid nodules . METHODS We performed a double-blind clinical trial comparing levothyroxine treatment ( 1.5 to 2.0 mg/kg of body weight daily ) ( N = 32 ) with placebo ( N = 30 ) for a 1-year period in patients with a benign , cold thyroid nodule confirmed by biopsy and 99mTc-pertechnetate scanning , who were r and omly assigned to the treatment or control group . High-resolution sonography was used to measure the size of the nodules before and after the treatment . Suppression of thyrotropin was evaluated by the administration of thyrotropin-releasing hormone to 10 patients r and omly in each group . RESULTS The mean volume of the thyroid nodules decreased significantly after 6 months in both the levothyroxine group ( from 12.8 + /- 11.9 mL to 9.4 + /- 9.8 mL ; P = 0.003 ) and the placebo group ( from 13.2 + /- 10.2 mL to 11.5 + /- 8.0 mL ; P = 0.003 ) . After 12 months , however , the volume of the nodules had increased . Thus , no significant decrease was found in the mean nodule volume in either study group at 1 year in comparison with the mean volume at baseline ( final mean volume : 12.4 + /- 16.7 mL in the levothyroxine group and 11.7 + /- 13.6 mL in the placebo group ) . CONCLUSION Suppressive therapy with levothyroxine for a period of 12 months proved to be ineffective in significantly reducing the size of the thyroid nodules in our patients despite effective suppression of the thyrotropin level OBJECTIVE We examined the effects of l‐thyroxine therapy versus placebo over a 12‐month period on volume of solitary thyroid nodules PURPOSE To prospect ively evaluate the efficacy of additional radiofrequency ( RF ) ablation by comparing the results of one and two sessions . MATERIAL S AND METHODS All patients gave written informed consent to participate in this institutional review board-approved prospect i ve study . From September 2007 to February 2008 , 30 patients with benign predominantly solid thyroid nodules causing pressure symptoms and /or cosmetic problems were r and omly assigned to undergo single-session ( group 1 , n = 15 ) or two-session ( group 2 , n = 15 ) RF ablation . RF ablation was performed by using an 18-gauge internally cooled electrode with ultrasonographic guidance . Nodule volume and cosmetic and symptom scores were evaluated before ablation and at 1 , 3 , and 6 months after initial ablation , and quantitative comparisons of these were performed by using the Mann-Whitney and Wilcoxon signed rank tests ; the Spearman rank test was used for correlation between nodule volume reduction and applied energy . RESULTS At 6-month follow-up , there was significant nodule volume reduction , from 13.3 mL ± 12.9 ( st and ard deviation ) to 3.8 mL ± 4.4 in group 1 ( P = .001 ) , and from 13.0 mL ± 6.8 to 3.0 mL ± 2.2 in group 2 ( P = .001 ) . Each group showed significant improvement in cosmetic ( P < .0001 ) and symptom ( P = .001 ) scores . However , there was no significant difference in volume reduction , cosmetic score , and symptom score between two groups ( P = .078 , P > .99 , and P = .259 , respectively ) . In group 1 , three of four patients who had a pretreatment nodule volume larger than 20 mL underwent additional RF ablation because of unresolved clinical problems after the first session .
Output:
| Pressure symptoms or cosmetic complaints were not investigated in LT4 studies .
Nodule volume reductions were achieved by PEI , LP and RF , and to a lesser extent , by LT4 .
However , the clinical relevance of this outcome measure is doubtful .
PEI , LP and RF led to improvements in pressure symptoms and cosmetic complaints .
Adverse events such as light-to-moderate periprocedural pain were seen after PEI , LP and RF . |
MS213765 | ***TASK*** the task is to summarize an input biomedical literature in six sentences
***INPUT*** the input is a biomedical literature
***OUTPUT*** the output is the summary of an input biomedical literature in six sentences
***DOCUMENTATION***
***EXAMPLES***
Input: PURPOSE In metastatic colorectal cancer , phase III studies have demonstrated the superiority of fluorouracil ( FU ) with leucovorin ( LV ) in combination with irinotecan or oxaliplatin over FU + LV alone . This phase III study investigated two sequences : folinic acid , FU , and irinotecan ( FOLFIRI ) followed by folinic acid , FU , and oxaliplatin ( FOLFOX6 ; arm A ) , and FOLFOX6 followed by FOLFIRI ( arm B ) . PATIENTS AND METHODS Previously untreated patients with assessable disease were r and omly assigned to receive a 2-hour infusion of l-LV 200 mg/m(2 ) or dl-LV 400 mg/m(2 ) followed by a FU bolus 400 mg/m(2 ) and 46-hour infusion 2,400 to 3,000 mg/m(2 ) every 46 hours every 2 weeks , either with irinotecan 180 mg/m(2 ) or with oxaliplatin 100 mg/m(2 ) as a 2-hour infusion on day 1 . At progression , irinotecan was replaced by oxaliplatin ( arm A ) , or oxaliplatin by irinotecan ( arm B ) . RESULT Median survival was 21.5 months in 109 patients allocated to FOLFIRI then FOLFOX6 versus 20.6 months in 111 patients allocated to FOLFOX6 then FOLFIRI ( P = .99 ) . Median second progression-free survival ( PFS ) was 14.2 months in arm A versus 10.9 in arm B ( P = .64 ) . In first-line therapy , FOLFIRI achieved 56 % response rate ( RR ) and 8.5 months median PFS , versus FOLFOX6 which achieved 54 % RR and 8.0 months median PFS ( P = .26 ) . Second-line FOLFIRI achieved 4 % RR and 2.5 months median PFS , versus FOLFOX6 which achieved 15 % RR and 4.2 months PFS . In first-line therapy , National Cancer Institute Common Toxicity Criteria grade 3/4 mucositis , nausea/vomiting , and grade 2 alopecia were more frequent with FOLFIRI , and grade 3/4 neutropenia and neurosensory toxicity were more frequent with FOLFOX6 . CONCLUSION Both sequences achieved a prolonged survival and similar efficacy . The toxicity profiles were different PURPOSE The aim of this r and omised trial was to evaluate the activity and toxicity of a biweekly regimen including 6S-leucovorin-modulated 5-fluorouracil ( LFA-5-FU ) , combined with either irinotecan ( CPT-11 + LFA 5-FU ) or raltitrexed ( Tomudex ) ( TOM + LFA-5-FU ) , in advanced colorectal cancer patients , and to make a preliminary comparison of both these experimental regimens with a biweekly administration of LFA-5-FU modulated by methotrexate ( MTX + LFA-5-FU ) . PATIENTS AND METHODS One hundred fifty-nine patients with advanced colorectal carcinoma previously untreated for the metastatic disease ( 34 of them previously exposed to adjuvant 5-FU ) were r and omly allocated to receive : CPT-11 , 200 mg/m2 i.v . on day 1 , followed on day 2 by LFA , 250 mg/m2 i.v . infusion and 5-FU , 850 mg/m2 s i.v . bolus ( arm A ) ; TOM , 3 mg/m2 i.v . on day 1 , followed on day 2 by LFA , 250 mg/m2 i.v . infusion and 5-FU , 1050 mg/m2 i.v . bolus ( arm B ) ; or MTX , 750 mg/m2 i.v . on day 1 , followed on day 2 by LFA , 250 mg/m2 i.v . infusion and 5-FU , 800 mg/m2 i.v . bolus ( arm C ) . Courses were repeated every two weeks in all arms of the trial . Response rate ( RR ) was evaluated after every four courses . The sample size was defined to have an 80 % power to detect a 35 % RR for each experimental treatment , and to show a difference of at least 4 % in RR with the st and ard treatment if the true difference is 15 % or more . RESULTS The RRs were : 34 % ( 95 % confidence interval ( 95 % , CI ) : 21%-48 % ) in arm A , including 3 complete responses ( CRs ) and 15 partial responses ( PRs ) , 24 % ( 95 % CI : 14%-38 % ) in arm B , including 2 CRs and 11 PRs , and 24 % ( 95 % CI : 14%-38 % ) , with 2 CRs and 11 PRs , in arm C. After a median follow-up time of 62 ( range 18 - 108 ) weeks , the median time to progression was 38 , 25 , and 27 weeks for arm A , B , and C , respectively . With 94 patients still alive , the one-year probability of survival was 61 % , 54 % , and 59 % , respectively . WHO grade 3 or 4 neutropenia and diarrhoea affected 46 % and 16 % , respectively , of patients treated with CPT-11 + LFA 5-FU . Median relative dose intensity over eight cycles ( DI8 ) was 78 % for CPT-11 and 82 % for 5-FU . Severe toxicities of TOM + LFA-5-FU were neutropenia ( 16 % ) and diarrhoea ( 16 % ) , but median relative DI8 was 93 % for TOM , and 82 % for 5-FU . CONCLUSIONS CPT-11 + LFA-5-FU compares favorably in term of activity and toxicity with other combination regimens including CPT-11 and continuous infusional 5-FU . The hypothesis of a RR 15 % higher than the MTX + LFA-5-FU treatment can not be ruled out after this interim analysis . The TOM + LFA 5-FU regimen showed a RR and a toxicity profile very close to the MTX + LFA 5-FU combination , and dose not deserve further evaluation in advanced colorectal cancer patients Elderly patients are recommended to have a reduced starting dose ( 300 mg m−2 once every 3 weeks ) of irinotecan monotherapy . The aims of this analysis are to compare toxicity and survival according to age , performance status ( PS ) , gender and prior radical pelvic radiotherapy ( RT ) . The primary end points were overall survival and an irinotecan-specific toxicity composite end point ( TCE ) defined as the occurrence of grade 3 or 4 diarrhoea , neutropenia , febrile neutropenia , fever , infection or nausea and vomiting . Between 1997 and 2003 , 339 eligible patients with advanced colorectal cancer ( CRC ) progressing on or within 24 weeks of completing fluoropyrimidine-based chemotherapy were prospect ively registered in a multicentre r and omised trial . All patients commenced irinotecan at 350 mg m−2 once every 3 weeks . There were no differences in proportions of patients developing TCE by age ( < 70 vs ⩾70 : 37.8 vs 45.8 % ; P=0.218 ) , PS ( 0–1 vs 2 : 39.3 vs 41.5 % ; P=0.793 ) or prior RT ( RT vs no RT : 45.1 vs 38.5 % ; P=0.377 ) . Males experienced more toxicity than females ( 44.3 vs 32.6 % ; P=0.031 ) , but this was not significant after controlling for other co-variates ( P=0.06 ) . Patients aged ⩾70 had similar objective responses ( 11.1 vs 9 % ; P=0.585 ) and survival ( median 9.4 vs 9 months ; log rank P=0.74 ) compared to younger patients . Elderly patients derive the same benefit without experiencing more toxicity with second-line irinotecan treatment for advanced CRC . Our data do not support the recommendation to reduce the starting dose for the elderly patients BACKGROUND In the non-curative setting , the sequence in which anticancer agents are used , singly or in combination , may be important if patients are to receive the maximum period of disease control with the minimum of adverse effects . We compared sequential and combination chemotherapy strategies in patients with unpretreated advanced or metastatic colorectal cancer , who were regarded as not potentially curable irrespective of response . METHODS We studied patients with advanced colorectal cancer , starting treatment with non-curative intent . 2135 unpretreated patients were r and omly assigned to three treatment strategies in the ratio 1:1:1 . Strategy A ( control group ) was single-agent fluorouracil ( given with levofolinate over 48 h every 2 weeks ) until failure , then single-agent irinotecan . Strategy B was fluorouracil until failure , then combination chemotherapy . Strategy C was combination chemotherapy from the outset . Within strategies B and C , patients were r and omly assigned to receive , as the combination regimen , fluorouracil plus irinotecan ( groups B-ir and C-ir ) or fluorouracil plus oxaliplatin ( groups B-ox and C-ox ) . The primary endpoint was overall survival , analysed by intention to treat . This study is registered as an International St and ard R and omised Controlled Trial , number IS RCT N 79877428 . RESULTS Median survival of patients allocated to control strategy A was 13.9 months . Median survival of each of the other groups was longer ( B-ir 15.0 , B-ox 15.2 , C-ir 16.7 , and C-ox 15.4 months ) . However , log-rank comparison of each group against control showed that only C-ir -- the first-line combination strategy including irinotecan -- satisfied the statistical test for superiority ( p=0.01 ) . Overall comparison of strategy B with strategy C was within the predetermined non-inferiority boundary of HR=1.18 or less ( HR=1.06 , 90 % CI 0.97 - 1.17 ) . INTERPRETATION Our data challenge the assumption that , in this non-curative setting , maximum tolerable treatment must necessarily be used first-line . The staged approach of initial single-agent treatment up grade d to combination when required is not worse than first-line combination , and is an alternative option for discussion with patients PURPOSE Irinotecan given until disease progression is an accepted st and ard treatment for advanced colorectal cancer ( CRC ) resistant to fluoropyrimidines . It is not known whether a predefined period of irinotecan treatment would result in similar duration of disease control . We performed a multicenter phase III trial to compare the two policies of defined- duration versus continuous irinotecan treatment . PATIENTS AND METHODS Three hundred thirty-three eligible patients with advanced CRC progressing on or within 24 weeks of completing fluoropyrimidine-based chemotherapy were prospect ively registered . After receiving eight cycles of irinotecan given at 350 mg/m2 once every 3 weeks , 55 patients with responding or stable disease were r and omly assigned to stop irinotecan ( n = 30 ) or continue until disease progression ( n = 25 ) . Registered patients were not r and omly assigned predominantly due to disease progression ( n = 236 ) and intolerable toxicity ( n = 38 ) . RESULTS From the time of r and om assignment , there were no differences in failure-free survival ( P = .999 ) or overall survival ( P = .11 ) between the two arms . No difference was seen in mean global health status quality -of-life score between the two arms at 12 weeks after r and om assignment . No grade 3 diarrhea and febrile neutropenia was seen in the continue-irinotecan arm after r and om assignment . CONCLUSION For most patients , the decision to continue on irinotecan beyond 24 weeks is influenced by disease progression or treatment-related toxicity . However , for 17 % of patients in whom this decision is clinical ly relevant , there seems to be little benefit from continuing irinotecan , though the drug was well tolerated without any deterioration in quality of life PURPOSE In North America , no effective therapy has been available for patients with progressive metastatic colorectal cancer after front-line treatment with irinotecan , bolus fluorouracil ( FU ) , and leucovorin ( IFL ) . PATIENTS AND METHODS Patients with metastatic colorectal cancer who progressed after IFL therapy were r and omly assigned to bolus and infusional FU and leucovorin ( LV5FU2 ) , single-agent oxaliplatin , or the combination ( FOLFOX4 ) . This planned interim analysis evaluated objective response rate ( RR ) , time to tumor progression ( TTP ) , and alleviation of tumor-related symptoms ( TRS ) in an initial cohort of patients . RESULTS Between November 2000 and September 2001 , 463 patients
Output:
| targeted agents improved the efficacy of conventional chemotherapy both when considered together ( HR for OS : 0.84 , 95 % CI 0.77 to 0.91 ; 6 RCTs ; high- quality evidence ) and when bevacizumab was used alone ( HR for PFS : 0.67 , 95 % CI 0.60 to 0.75 ; 4 RCTs ; high- quality evidence ) .With regard to secondary endpoints , tumour response rates generally paralleled the survival results ; moreover , higher anticancer efficacy was generally associated with worse treatment-related toxicity , with the important exception of bevacizumab-containing regimens , where the addition of the targeted agent to chemotherapy did not result in a significant increase in the rate of SAE .
Finally , we found that oral ( instead of intravenous ) fluoropyrimidines significantly reduced the incidence of adverse effects ( without compromising efficacy ) in people treated with oxaliplatin-based regimens .
Systemic therapy offers a survival benefit to people with metastatic CRC who did not respond to first-line treatment , especially when targeted agents are combined with conventional chemotherapeutic drugs . |
MS213766 | ***TASK*** the task is to summarize an input biomedical literature in six sentences
***INPUT*** the input is a biomedical literature
***OUTPUT*** the output is the summary of an input biomedical literature in six sentences
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Input: Summary Nonspecific placebo factors such as patients ' perceptions of a treatment and expectations toward effect seem to be central to the clinical efficacy of acupuncture analgesia . ABSTRACT It is well known that acupuncture has pain‐relieving effects , but the contribution of specific and especially nonspecific factors to acupuncture analgesia is less clear . One hundred one patients who developed pain of ≥3 on a visual analog scale ( VAS , 0 to 10 ) after third molar surgery were r and omized to receive active acupuncture , placebo acupuncture , or no treatment for 30 min with acupuncture needles with potential for double‐blinding . Patients ' perception of the treatment ( active or placebo ) and expected pain levels ( VAS ) were assessed before and halfway through the treatment . Looking at actual treatment allocation , there was no specific effect of active acupuncture ( P = .240 ) , but there was a large and significant nonspecific effect of placebo acupuncture ( P < .001 ) , which increased over time . Interestingly , however , looking at perceived treatment allocation , there was a significant effect of acupuncture ( P < .001 ) , indicating that patients who believed they received active acupuncture had significantly lower pain levels than those who believed they received placebo acupuncture . Expected pain levels accounted for significant and progressively larger amounts of the variance in pain ratings after both active and placebo acupuncture ( up to 69.8 % ) . This is the first study to show that under optimized blinding conditions , nonspecific factors such as patients ' perception of and expectations toward treatment are central to the efficacy of acupuncture analgesia and that these factors may contribute to self‐reinforcing effects in acupuncture treatment . To obtain an effect of acupuncture in clinical practice , it may therefore be important to incorporate and optimize these factors Summary This multifactorial mixed‐ methods r and omized controlled trial quantified the specific and nonspecific factors of acupuncture , and found that the practitioner , not the treatment , has the strongest effect on outcome . Abstract The nonspecific effects of acupuncture are well documented ; we wished to quantify these factors in osteoarthritic ( OA ) pain , examining needling , the consultation , and the practitioner . In a prospect i ve r and omised , single‐blind , placebo‐controlled , multifactorial , mixed‐ methods trial , 221 patients with OA awaiting joint replacement surgery were recruited . Interventions were acupuncture , Streitberger placebo acupuncture , and mock electrical stimulation , each with empathic or nonempathic consultations . Interventions involved eight 30‐minute treatments over 4 weeks . The primary outcome was pain ( VAS ) at 1 week posttreatment . Face‐to‐face qualitative interviews were conducted ( purposive sample , 27 participants ) . Improvements occurred from baseline for all interventions with no significant differences between real and placebo acupuncture ( mean difference −2.7 mm , 95 % confidence intervals −9.0 to 3.6 ; P = .40 ) or mock stimulation ( −3.9 , −10.4 to 2.7 ; P = .25 ) . Empathic consultations did not affect pain ( 3.0 mm , −2.2 to 8.2 ; P = .26 ) but practitioner 3 achieved greater analgesia than practitioner 2 ( 10.9 , 3.9 to 18.0 ; P = .002 ) . Qualitative analysis indicated that patients ’ beliefs about treatment veracity and confidence in outcomes were reciprocally linked . The supportive nature of the trial attenuated differences between the different consultation styles . Improvements occurred from baseline , but acupuncture has no specific efficacy over either placebo . The individual practitioner and the patient ’s belief had a significant effect on outcome . The 2 placebos were equally as effective and credible as acupuncture . Needle and nonneedle placebos are equivalent . An unknown characteristic of the treating practitioner predicts outcome , as does the patient ’s belief ( independently ) . Beliefs about treatment veracity shape how patients self‐report outcome , complicating and confounding study interpretation The purpose of this study was to investigate the comparative effectiveness of early use of thrust ( TM ) and non-thrust manipulation ( NTM ) in sample of patients with mechanical low back pain ( LBP ) . The r and omized controlled trial included patients with mechanically reproducible LBP , ≥ age 18-years who were r and omized into two treatment groups . The main outcome measures were the Oswestry Disability Index ( ODI ) and a Numeric Pain Rating Scale ( NPRS ) , with secondary measures of Rate of Recovery , total visits and days in care , and the work subscale of the Fears Avoidance Beliefs Question naire work subscale ( FABQ-w ) . A two-way mixed model MANCOVA was used to compare ODI and pain , at baseline , after visit 2 , and at discharge and total visits , days in care , and rate of recovery ( while controlling for patient expectations and clinical equipoise ) . A total of 149 subjects completed the trial and received care over an average of 35 days . There were no significant differences between TM and NTM at the second visit follow-up or at discharge with any of the outcomes categories . Personal equipoise was significantly associated with ODI and pain . The findings suggest that there is no difference between early use of TM or NTM , and secondarily , that personal equipoise affects study outcome . Within-groups changes were significant for both groups Objectives To develop a sham needle device and test its credibility as a control for acupuncture when used in a r and omised controlled trial of myofascial trigger point needling in patients with whiplash associated pain . Methods Sham needles were developed by blunting true acupuncture needles . Whiplash injured patients ( < 16 weeks duration ) were r and omly allocated to receive either true acupuncture or the “ placebo ” sham needle control . The true and sham needling interventions were delivered using the same st and ardised procedure . Patients were informed that they would receive either real or placebo needles , and asked ( i ) to state which treatment they believed they had received ( treatment belief ) ; ( ii ) to complete the four item Borkovec and Nau self- assessment credibility scale . Results were compared between groups and the analysis explored whether a patient 's previous experience of acupuncture was related to their treatment belief . Other outcomes of the study will be reported elsewhere . Results 20 patients received the true acupuncture and 21 received the sham . There was no significant difference between the treatment beliefs of the two groups ( χ 2 = 1.51 ; p>0.2 ) nor in the mean item scores on the Borkovec and Nau credibility scale ( t test , p values ranged from 0.38 to 0.87 ) . Of the patients in the sham acupuncture group who had previous experience of acupuncture , none recorded receiving the sham intervention . Conclusion Within the context of this pilot study , the sham acupuncture intervention was found to be a credible control for acupuncture . This supports its use in a planned , definitive , r and omised controlled trial on a similar whiplash injured population Background Placebo needles that can mask acupuncture practitioners to the type of needle used have been considered almost impossible to develop until now . Methods We design ed a double-blind non-penetrating placebo needle , the needle tip of which simply presses against the skin , and a matched penetrating needle . The needles are encased inside an opaque guide tube and the appearance and feel of the pair are design ed to be indistinguishable . To vali date the masking effect for the practitioner , 10 acupuncturists each applied 23 non-penetrating needles and 17 penetrating needles to the Large Intestine-4 point . After removing each needle , they judged whether the needle was ' penetrating ' , ' non-penetrating ' or ' unidentifiable ' . For the validation of patient masking , an acupuncturist r and omly applied a non-penetrating/penetrating needle pair to the bilateral Sanjiao-5 points in 60 volunteers . When both applications were completed , we asked them to write down anything that they noticed regarding the needle application and associated sensations . Results The mean ± SD of correct/unidentifiable/incorrect answers given by the 10 acupuncturists were 17.0 ± 4.1/6.4 ± 3.6/16.6 ± 3.0 , respectively . Regarding patient masking , none of the subjects commented in the question naire that they had received a non-penetrating needle . Of 60 penetrating and 60 non-penetrating needle applications , 48 ( 80.0 % ) and 25 ( 41.7 % ) applications elicited skin penetration sensation and 48 ( 80.0 % ) and 20 ( 33.3 % ) applications elicited de qi , respectively . Conclusion These needles have the potential to mask both practitioners and patients from the type of needle used in acupuncture research Blinding protects against bias but the success of blinding is seldom assessed and reported in clinical trials including studies of acupuncture where blinding represents a major challenge . Recently , needles with the potential for double-blinding were developed , so we tested if acupuncture can be double-blinded in a r and omized study of sixty-seven patients with acute pain ≥ 3 ( 0 - 10 scale following third molar removal ) who received active acupuncture with a penetrating needle or placebo acupuncture with a non-penetrating needle . To test if acupuncture was administered double-blind , patients and acupuncturists were asked about perceived treatment allocation at the end of the study . To test if there were clues which led to identification of the treatment , deep dull pain associated with needle application and rotation ( termed “ de qi ” in East Asian medicine ) , and patients ’ pain levels were assessed . Perceived treatment allocation depended on actual group allocation ( p < 0.015 ) for both patients and acupuncturists , indicating that the needles were not successful in double-blinding . Up to 68 % of patients and 83 % of acupuncturists correctly identified the treatment , but for patients the distribution was not far from 50/50 . Also , there was a significant interaction between actual or perceived treatment and the experience of de qi ( p = 0.027 ) , suggesting that the experience of de qi and possible non-verbal clues contributed to correct identification of the treatment . Yet , of the patients who perceived the treatment as active or placebo , 50 % and 23 % , respectively , reported de qi . Patients ’ acute pain levels did not influence the perceived treatment . In conclusion , acupuncture treatment was not fully double-blinded which is similar to observations in pharmacological studies . Still , the non-penetrating needle is the only needle that allows some degree of practitioner blinding . The study raises questions about alternatives to double-blind r and omized clinical trials in the assessment of acupuncture treatment Clinicians cl aim that myofascial trigger points ( MTrPs ) are a primary cause of pain in whiplash injured patients . Pain from MTrPs is often treated by needling , with or without injection . We conducted a placebo controlled study to test the feasibility of a phase III r and omised controlled trial investigating the efficacy of MTrP needling in patients with whiplash associated pain . Forty-one patients referred for physiotherapy with a recent whiplash injury , were recruited . Patients were r and omised to receive st and ardised physiotherapy plus either acupuncture or a sham needle control . A trial was judged feasible if : i ) the majority of eligible patients were willing to participate ; ii ) the majority of patients had MTrPs ; iii ) at least 75 % of patients provided completed self- assessment data ; iv ) no serious adverse events were reported and v ) the end of treatment attrition rate was less than 20 % . 70 % of those patients eligible to participate volunteered to do so ; all participants had clinical ly identified MTrPs ; a 100 % completion rate was achieved for recorded self- assessment data ; no serious adverse events were reported as a result of either intervention ; and the end of treatment attrition rate was 17 % . A phase III study is both feasible and clinical ly relevant . This study is currently being planned Background Plantar heel pain can be managed with dry needling of myofascial trigger points ; however , there is only poor- quality evidence supporting its use . Objective The purpose of this study was to evaluate the effectiveness of dry needling for plantar heel pain . Design The study was a parallel-group , participant-blinded , r and omized controlled trial . Setting The study was conducted in a university health sciences clinic . Patients Study participants were 84 patients with plantar heel pain of at least 1 month 's duration . Intervention Participants were r and omly assigned to receive real or sham trigger point dry needling . The intervention consisted of 1 treatment per week for 6 weeks . Participants were followed for 12 weeks . Measurements Primary outcome measures included first-step pain , as measured with a visual analog scale ( VAS ) , and foot pain , as measured with the pain subscale of the Foot Health Status Question naire ( FHSQ ) . The primary end point for predicting the effectiveness of dry needling for plantar heel pain was 6 weeks . Results At the primary end point , significant effects favored real dry needling over sham dry needling for pain ( adjusted mean difference : VAS first-step pain=−14.4 mm , 95 % confidence interval [ 95 % CI]=−23.5 to −5.2 ; FHSQ foot pain=10.0 points , 95 % CI=1.0 to 19.1 ) , although the between-group difference was lower than the minimal important difference . The number needed to treat at 6 weeks was 4 ( 95 % CI=2 to 12 ) . The frequency of minor transitory adverse events was significantly greater in the real dry needling group ( 70 real dry needling appointments [ 32 % ] compared with only 1 sham dry needling appointment [ < 1 % ] )
Output:
| There was no evidence of a moderating effect of blinding index on pain .
For short-term and long-term pain assessment s pooled effects for inadequately blinded trials were statistically significant in favour of active dry needling , whereas there was no evidence of a difference between active and sham groups for adequately blinded trials .
However , with the caveats of small sample size , generally unclear risk of bias , statistical heterogeneity , potential publication bias , and the limitations of subgroup analyses , the available evidence suggests that inadequate blinding procedures could lead to exaggerated intervention effects in dry needling trials |
MS213767 | ***TASK*** the task is to summarize an input biomedical literature in six sentences
***INPUT*** the input is a biomedical literature
***OUTPUT*** the output is the summary of an input biomedical literature in six sentences
***DOCUMENTATION***
***EXAMPLES***
Input: Evidence -based practice involves the use of evidence from systematic review s and r and omised controlled trials , but the extent of this evidence in physiotherapy has not previously been surveyed . The aim of this survey is to describe the quantity and quality of r and omised controlled trials and the quantity of systematic review s relevant to physiotherapy . The Physiotherapy Evidence Data base ( PEDro ) was search ed . The quality of trials was assessed with the PEDro scale . The search identified a total of 2,376 r and omised controlled trials and 332 systematic review s. The first trial was published in 1955 and the first review was published in 1982 . Since that time , the number of trials and review s has grown exponentially . The mean PEDro quality score has increased from 2.8 in trials published between 1955 and 1959 to 5.0 for trials published between 1995 and 1999 . There is a substantial body of evidence about the effects of physiotherapy . However , there remains scope for improvements in the quality of the conduct and reporting of clinical trials Abstract Thirty-seven adults with spinal-cord injury and chronic pain were r and omly assigned to receive 10 sessions of self-hypnosis ( HYP ) or EMG biofeedback relaxation ( BIO ) training for pain management . Participants in both treatment conditions reported substantial , but similar , decreases in pain intensity from before to after the treatment sessions . However , participants in the HYP condition , but not the BIO condition , reported statistically significant decreases in daily average pain pre- to posttreatment . These pre- to posttreatment decreases in pain reported by the HYP participants were maintained at 3-month follow-up . Participants in the HYP condition , but not the BIO condition , also reported significant pre- to posttreatment increases in perceived control over pain , but this change was not maintained at the 3-month follow-up Sickle cell disease ( SCD ) is the most common genetic disease in African-Americans , characterized by recurrent painful vaso-occlusive crises . Medical therapies for controlling or preventing crises are limited because of efficacy and /or toxicity . This is a r and omized , controlled , single-crossover protocol of hypnosis for managing pain in SCD patients . Participants receive hypnosis from a trained hypnosis therapist followed by six weeks of self-hypnosis using digital media . Those in the control arm receive SCD education followed by a six-week waiting period before crossing over to the hypnosis arm of the study . Outcome measures include assessment s of pain ( frequency , intensity and quality ) , anxiety , coping strategies , sleep , depression , and health care utilization . To date , there are no published r and omized , controlled trials evaluating the efficacy of hypnosis on SCD pain modulation in adults . Self-hypnosis for pain management may be helpful in modulating chronic pain , improving sleep quality , and decreasing use of narcotics in patients with SCD . TRIAL REGISTRATION Clinical Trials.gov : Tension headaches can form a chronic ( very long duration ) condition . EMG biofeedback , relaxation training and analgesia by hypnotic suggestion can reduce the pain . So far , no differences have been demonstrated between the effects of various psychological treatments . In a constructively design ed study , we firstly compared an abbreviated form of autogenic training to a form of hypnotherapy ( future oriented hypnotic imagery ) which was not presented as hypnosis and secondly we compared both treatments to the same future oriented hypnotic imagery , but this time explicitly presented as hypnosis . The three treatments were equally effective at post-treatment , but after a 6-month follow-up period , the future oriented hypnotic imagery which had been explicitly presented as hypnosis was superior to autogenic training . Contrary to common belief , it could be demonstrated that the therapists were as effective with the treatment modality they preferred as with the treatment modality they felt to be less remedial Objective Postpr and ial symptoms in irritable bowel syndrome are common and relate to an exaggerated motor and sensory component of the gastrocolonic response . We investigated whether this response can be affected by hypnotherapy . Methods We included 28 patients with irritable bowel syndrome refractory to other treatments . They were r and omized to receive gut-directed hypnotherapy 1 hour per week for 12 weeks ( N = 14 ) or were provided with supportive therapy ( control group ; N = 14 ) . Before r and omization and after 3 months , all patients underwent a colonic distension trial before and after a 1-hour duodenal lipid infusion . Colonic sensory thresholds and tonic and phasic motor activity were assessed . Results Before r and omization , reduced thresholds after vs. before lipid infusion were seen in both groups for all studied sensations . At 3 months , the colonic sensitivity before duodenal lipids did not differ between groups . Controls reduced their thresholds after duodenal lipids for gas ( 22 ± 1.7 mm Hg vs. 16 ± 1.6 mm Hg , p < .01 ) , discomfort ( 29 ± 2.9 mm Hg vs. 22 ± 2.6 mm Hg , p < .01 ) , and pain ( 33 ± 2.7 mm Hg vs. 26 ± 3.3 mm Hg , p < .01 ) , whereas the hypnotherapy group reduced their thresholds after lipids only for pain ( 35 ± 4.0 mm Hg vs. 29 ± 4.7 mm Hg , p < .01 ) . The colonic balloon volumes and tone response at r and omization were similar in both groups . At 3 months , baseline balloon volumes were lower in the hypnotherapy group than in controls ( 83 ± 14 ml vs. 141 ± 15 ml , p < .01 ) . In the control group , reduced balloon volumes during lipid infusion were seen ( 141 ± 15 ml vs. 111 ± 19 ml , p < .05 ) , but not after hypnotherapy ( 83 ± 14 ml vs. 80 ± 16 ml , p > .20 ) . Conclusion Hypnotherapy reduces the sensory and motor component of the gastrocolonic response in patients with irritable bowel syndrome . These effects may be involved in the clinical efficacy of hypnotherapy in IBS The main aims of this experimental study are : ( 1 ) to compare the relative effects of analgesia suggestions and relaxation suggestions on clinical pain , and ( 2 ) to compare the relative effect of relaxation suggestions when they are presented as “ hypnosis ” and as “ relaxation training ” . Forty‐five patients with fibromyalgia were r and omly assigned to one of the following experimental conditions : ( a ) hypnosis with relaxation suggestions ; ( b ) hypnosis with analgesia suggestions ; ( c ) relaxation . Before and after the experimental session , the pain intensity was measured using a visual analogue scale ( VAS ) and the sensory and affective dimensions were measured with the McGill Pain Question naire . The results showed : ( 1 ) that hypnosis followed by analgesia suggestions has a greater effect on the intensity of pain and on the sensory dimension of pain than hypnosis followed by relaxation suggestions ; ( 2 ) that the effect of hypnosis followed by relaxation suggestions is not greater than relaxation . We discuss the implication s of the study on our underst and ing of the importance of suggestions used in hypnosis and of the differences and similarities between hypnotic relaxation and relaxation training In a controlled study , 40 patients with refractory fibromyalgia were r and omly allocated to treatment with either hypnotherapy or physical therapy for 12 weeks with followup at 24 weeks . Compared with the patients in the physical therapy group , the patients in the hypnotherapy group showed a significantly better outcome with respect to their pain experience , fatigue on awakening , sleep pattern and global assessment at 12 and 24 weeks , but this was not reflected in an improvement of the total myalgic score measured by a dolorimeter . At baseline most patients in both groups had strong feelings of somatic and psychic discomfort as measured by the Hopkins Symptom Checklist . These feelings showed a significant decrease in patients treated by hypnotherapy compared with physical therapy , but they remained abnormally strong in many cases . We conclude hypnotherapy may be useful in relieving symptoms in patients with refractory fibromyalgia BACKGROUND In western population s irritable bowel syndrome ( IBS ) affects between 10 % and 30 % of the population and has a significant effect on quality of life . It generates a substantial workload in both primary and secondary care and has significant cost implication s. Gut-directed hypnotherapy has been demonstrated to alleviate symptoms and improve quality of life but has not been assessed outside of secondary and tertiary referral centres . AIM To assess the effectiveness of gut-directed hypnotherapy as a complementary therapy in the management of IBS . DESIGN OF STUDY R and omised controlled trial . SETTING Primary care patients aged 18 - 65 years inclusive , with a diagnosis of IBS of greater than 6 weeks ' duration and having failed conventional management , located in South Staffordshire and North Birmingham , UK . METHOD Intervention patients received five sessions of hypnotherapy in addition to their usual management . Control patients received usual management alone . Data regarding symptoms and quality of life were collected at baseline and again 3 , 6 , and 12 months post-r and omisation . RESULTS Both groups demonstrated a significant improvement in all symptom dimensions and quality of life over 12 months . At 3 months the intervention group had significantly greater improvements in pain , diarrhoea and overall symptom scores ( P<0.05 ) . No significant differences between groups in quality of life were identified . No differences were maintained over time . Intervention patients , however , were significantly less likely to require medication , and the majority described an improvement in their condition . CONCLUSIONS Gut-directed hypnotherapy benefits patients via symptom reduction and reduced medication usage , although the lack of significant difference between groups beyond 3 months prohibits its general introduction without additional evidence . A large trial incorporating robust economic analysis is , therefore , urgently recommended This article both summarizes the previous review s of r and omized , controlled trials of hypnotic analgesia for the treatment of chronic and acute pain in adults , and review s similar trials which have recently been published in the scientific literature . The results indicate that for both chronic and acute pain conditions : ( 1 ) hypnotic analgesia consistently results in greater decreases in a variety of pain outcomes compared to no treatment/st and ard care ; ( 2 ) hypnosis frequently out-performs non-hypnotic interventions ( e.g. education , supportive therapy ) in terms of reductions in pain-related outcomes ; and ( 3 ) hypnosis performs similarly to treatments that contain hypnotic elements ( such as progressive muscle relaxation ) , but is not surpassed in efficacy by these alternative treatments . Factors that may influence the efficacy of hypnotic analgesia interventions are discussed , including , but not limited to , the patient 's level of suggestibility , treatment outcome expectancy , and provider expertise . Based upon this body of literature , suggestions are offered for practitioners who are using , or would like to use , hypnosis for the amelioration of pain problems in their patients or clients We investigated the effectiveness of a special hypnotherapy technique in the treatment of chronic tension-type headache . A waitinglist control group was used to control for the changes in headache activity due to the passage of time . The results showed significant reductions in the number of headache days ( p less than 0.05 ) , the number of headache hours ( p less than 0.05 ) and headache intensity ( p less than 0.05 ) . The improvement was confirmed by the subjective evaluation data gathered with the use of a question naire and by a significant reduction in anxiety scores ( p less than 0.01 ) & NA ; The aims of this study were to(a ) investigate the efficacy of autogenic training ( AT ) and cognitive self‐hypnosis training ( CSH ) for the treatment of chronic headaches in comparison with a waiting‐list control ( WLC ) condition,(b ) investigate the influence of subject recruitment on treatment outcome ( c ) explore whether the level of hypnotizability is related to therapy outcome . Three different subjects groups ( group 1 , patients ( n = 58 ) who were referred by a neurological outpatient clinic ; group 2 , members ( n = 48 ) of the community who responded to an advertisement in a newspaper ; and group 3 , students ( n = 40 ) who responded to an advertisement in a university newspaper ) were allocated at r and om to a therapy or WLC condition . During treatment , there was a significant reduction in the Headache Index scores of the subjects in contrast with the controls . At post‐treatment and follow‐up almost no significant differences were observed between the 2 treatment conditions or the 3 referral sources regarding the Headache Index , psychological distress ( SCL‐90 ) scores and medication use . Follow‐up measurements indicated that therapeutic improvement was maintained . In both treatment conditions , the high‐hypnotizable subjects achieved a greater reduction in headache pain at post‐treatment and follow‐up than did the low‐hypnotizable subjects . It is concluded that a relatively simple and highly structured relaxation technique for the treatment of chronic headache subjects may be preferable to more complex cognitive hypnotherapeutic procedures , irrespective of the source of recruitment . The level of hypnotic susceptibility seems to be a subject characteristic which is associated with a more favourable outcome in subjects treated with AT or CSH Abstract Twenty-two patients with multiple sclerosis ( MS ) and chronic pain we recruited into a quasi-experimental trial comparing the effects of self-hypnosis training ( HYP ) with progressive muscle relaxation ( PMR ) on pain intensity and pain interference ; 8 received HYP and the remaining 14 participants were r and omly assigned to receive either HYP or PMR . HYP-condition participants reported significantly greater pre- to postsession as well as pre- to posttreatment decreases in pain and pain interference than PMR-condition participants , and gains were maintained
Output:
| This study demonstrates that hypnotherapy and relaxation techniques are effective in reducing short- and long-term headache activity in migraine sufferers |
MS213768 | ***TASK*** the task is to summarize an input biomedical literature in six sentences
***INPUT*** the input is a biomedical literature
***OUTPUT*** the output is the summary of an input biomedical literature in six sentences
***DOCUMENTATION***
***EXAMPLES***
Input: Background Methotrexate is the most efficient anticancer drug in osteosarcoma . It requires individual exposure monitoring because of the high doses used , its wide interpatient pharmacokinetic variability and the existence of demonstrated relationships between efficacy , toxicity and serum drug concentrations . Objective To develop a maximum a posteriori ( MAP ) Bayesian estimator able to predict individual pharmacokinetic parameters and exposure indices such as area under the curve ( AUC ) for methotrexate from a few blood sample s , in order to prevent toxicity and facilitate further studies of the relationships between efficacy and exposure . Methods Methotrexate population pharmacokinetics were estimated by a retrospective analysis of concentration data from 40 children and young adults by using the nonparametric expectation maximisation method NPEM . A linear two-compartment model with elimination from the central compartment was assumed . Individual pharmacokinetic parameters and AUC were subsequently estimated in 30 other young patients , using MAP Bayesian estimation as implemented in two programs , ADAPT II and an inhouse program Winphar ® . Results The pharmacokinetic parameters used in the model were the volume of the central compartment ( V1 ) and the transfer constants ( k10 , k12 and k21 ) . The mean values ( with percentage coefficient of variation ) obtained were : 18.24L ( 54.1 % ) and 0.41 ( 42.3 % ) , 0.0168 ( 68.7 % ) , and 0.1069 ( 61.3 % ) h-1 , respectively . Bayesian forecasting enabled nonbiased estimation of AUC and systemic clearance using a schedule with two sampling times ( 6 and 24 hours after the beginning of the infusion ) and either program . Collection of a third sample at 4 hours improved the precision . Conclusion The Bayesian adaptive method developed herein allows accurate estimation of individual exposure to methotrexate and can easily be used in clinical practice OBJECTIVE To evaluate the safety and activity of an immunoconjugate of ricin A chain and anti-CD5 monoclonal antibody ( anti-CD5 IC ) , with and without concomitant methotrexate and /or azathioprine , in the treatment of rheumatoid arthritis ( RA ) . METHODS Seventy-nine patients with active RA were enrolled in 2 prospect i ve open-label protocol s. RESULTS Using composite criteria , response rates were 50 - 68 % at 1 month and 22 - 25 % at 6 months . Transient depletion of CD3/CD5 T cells was observed on days 2 and 5 of treatment , with reconstitution on day 15 or day 29 . Treatment-associated adverse effects were common but resolved rapidly without sequelae . CONCLUSION These findings suggest activity of anti-CD5 IC in active RA and warrant confirmation in a multicenter r and omized study ( currently underway ) Objectives The aim of this 12-week Phase IIb study was to assess the efficacy and safety of olokizumab ( OKZ ) , a humanised anti-IL6 monoclonal antibody , in patients with rheumatoid arthritis ( RA ) with moderate-to-severe disease activity who had previously failed tumour necrosis factor ( TNF ) inhibitor therapy . The dose-exposure-response relationship for OKZ was also investigated . Methods Patients were r and omised to one of nine treatment arms receiving placebo ( PBO ) or OKZ ( 60 , 120 or 240 mg ) every 4 weeks ( Q4W ) or every 2 weeks ( Q2W ) , or 8 mg/kg tocilizumab ( TCZ ) Q4W . The primary endpoint was change from baseline in DAS28(C-reactive protein , CRP ) at Week 12 . Secondary efficacy endpoints were American College of Rheumatology 20 ( ACR20 ) , ACR50 and ACR70 response rates at Week 12 . Exploratory analyses included comparisons of OKZ efficacy with TCZ . Results Across 221 r and omised patients , OKZ treatment produced significantly greater reductions in DAS28(CRP ) from baseline levels at Week 12 , compared to PBO ( p<0.001 ) , at all the OKZ doses tested ( 60 mg OKZ p=0.0001 , 120 and 240 mg OKZ p<0.0001 ) . Additionally , ACR20 and ACR50 responses were numerically higher for OKZ than PBO ( ACR20 : PBO=17.1–29.9 % , OKZ=32.5–60.7 % ; ACR50 : PBO=1.3–4.9 % , OKZ=11.5–33.2 % ) . OKZ treatment , at several doses , demonstrated similar efficacy to TCZ across multiple endpoints . Most adverse events were mild or moderate and comparable between OKZ and TCZ treatment groups . Pharmacokinetic/pharmacodynamic modelling demonstrated a shallow dose/exposure response relationship in terms of percentage of patients with DAS28(CRP ) < 2.6 . Conclusions OKZ produced significantly greater reductions in DAS28(CRP ) from baseline at Week 12 compared with PBO . Reported AEs were consistent with the safety profile expected of this class of drug , with no new safety signals identified . Trial register number : NCT01242488 OBJECTIVE To investigate the safety , tolerability , pharmacokinetics , and efficacy of apilimod mesylate , an oral interleukin-12 (IL-12)/IL-23 inhibitor , in patients with rheumatoid arthritis ( RA ) . METHODS We performed a phase IIa , r and omized , double-blind , placebo-controlled proof-of-concept study of apilimod , in combination with methotrexate , in 29 patients with active RA ( 3:1 ratio of apilimod-treated to placebo-treated patients ) in 3 stages . Patients received apilimod 100 mg/day or placebo for 4 weeks ( stage 1 ) or 8 weeks ( stage 2 ) . In stage 3 , patients received apilimod 100 mg twice a day or placebo for 8 weeks , with an optional extension of 4 weeks . Clinical response ( Disease Activity Score in 28 joints [ DAS28 ] and American College of Rheumatology [ ACR ] criteria ) was assessed throughout ; synovial tissue sample s collected at baseline and on day 29 ( stages 1 and 2 ) or day 57 ( stage 3 ) were stained for cellular markers and cytokines for immunohistochemistry analysis . RESULTS While only mild adverse events were observed in stages 1 and 2 , in stage 3 , all patients experienced headache and /or nausea . Among apilimod-treated patients ( 100 mg/day ) , there was a small , but significant , reduction in the DAS28 on day 29 and day 57 compared with baseline . ACR20 response was reached in only 6 % of patients on day 29 and 25 % of patients on day 57 , similar to the percentage of responders in the placebo group . Increasing the dosage ( 100 mg twice a day ) did not improve clinical efficacy . Consistent with clinical results , apilimod did not have an effect on expression of synovial biomarkers . Of importance , we also did not observe an effect of apilimod on synovial IL-12 and IL-23 expression . CONCLUSION Our results do not support the notion that IL-12/IL-23 inhibition by apilimod is able to induce robust clinical improvement in RA Objective To evaluate the efficacy and safety of golimumab 50 and 100 mg monotherapy in Japanese patients with active rheumatoid arthritis ( RA ) despite treatment with disease-modifying antirheumatic drugs ( DMARDs ) . Methods A total of 316 patients were r and omised to receive subcutaneous injections every 4 weeks of placebo ( group 1 ) , golimumab 50 mg ( group 2 ) or golimumab 100 mg ( group 3 ) ; group 1 crossed over to golimumab 50 mg at week 16 . The primary end point was the proportion of patients achieving ≥20 % improvement in the American College of Rheumatology criteria ( ACR20 ) at week 14 . ACR50 and ACR70 response rates were also measured . Adverse events ( AEs ) were monitored throughout the study . Results Demographics were similar across groups ; the mean age was 52 years and 81.8 % of patients ( 252/308 ) were female . Week 14 ACR20 response rates were significantly greater in groups 2 ( 51/101 ( 50.5 % ) ) and 3 ( 60/102 ( 58.8 % ) ) than in group 1 ( 20/105 ( 19.0 % ) ; p<0.0001 for both ) , as were ACR50 and ACR70 response rates . After placebo crossover at week 16 , week 24 ACR response rates were similar in groups 1 and 2 . Through week 16 , 63.8 % of patients in group 1 , 62.4 % in group 2 and 60.8 % in group 3 had AEs and 1.9 % , 1.0 % and 2.0 % had serious AEs . After week 16 , one malignancy was reported ( breast cancer , group 3 ) . Infections were the most common AEs . No deaths or cases of tuberculosis were reported through week 24 . Conclusions Golimumab monotherapy ( 50 and 100 mg ) was effective in reducing the signs and symptoms of RA in Japanese patients with active disease despite DMARD treatment Infliximab , a chimeric anti-TNF alpha antibody , showed in two double-blind placebo-controlled trials efficacy in combination with methotrexate ( MTX ) in patients with severe rheumatoid arthritis ( RA ) . Whereas in the first trial low-dose MTX or placebo was compared to infliximab alone and in combination , the second trial compared infliximab to placebo in patients with active RA despite maximal tolerated MTX treatment . Infliximab showed synergistic effects in combination with MTX . The immunogenicity of infliximab was reduced by the combination . Infliximab in combination with high-dose MTX is effective and safe in long-term treatment up to 54 weeks BACKGROUND Tumor necrosis factor ( TNF ) is an important mediator of cachexia , and its blockade prevents catabolism in animal models . However , little evidence shows that anti-TNF therapy is effective in treating cachexia in humans . OBJECTIVE The main aim of this study was to investigate the effect of etanercept , a synthetic soluble TNF receptor , on body composition in patients with early rheumatoid arthritis ( RA ) . DESIGN Twenty-six patients were r and omly assigned to 24 wk of treatment with etanercept or methotrexate ; the latter is the first-line therapy for RA . Body composition , physical function , disease activity , systemic inflammation , and the circulating insulin-like growth factor ( IGF ) system were measured at baseline ( week 0 ) and at follow-up ( weeks 12 and 24 ) . Twelve patients in each treatment group ( 9 F , 3 M ) completed the study . RESULTS Overall , no important changes in body composition were observed , despite a transient increase in IGF-I at week 12 ( P < 0.01 ) . However , the secondary analysis of those patients ( 6/treatment group ) who gained weight during follow-up showed a significant effect of etanercept on the composition of the weight gained : 44 % of weight gained in the etanercept group was fat-free mass , as compared with only 14 % in the methotrexate group ( P = 0.04 ) . Etanercept and methotrexate were equally effective in controlling the disease and improving physical function . CONCLUSIONS Anti-TNF therapy with etanercept is not superior to that with methotrexate for the treatment of rheumatoid cachexia over a period of 6 mo . However , TNF blockade seems to normalize the anabolic response to overfeeding and , if these findings are confirmed , may be useful in conditions characterized by anorexia and weight loss OBJECTIVE Induction of immune tolerance to maintain clinical control with a minimal drug regimen is a current research focus in rheumatoid arthritis ( RA ) . Accordingly , we are developing a tolerization approach to dnaJP1 , a peptide part of a pathogenic mechanism that contributes to autoimmune inflammation in RA . We undertook this study to test 2 hypotheses : 1 ) that mucosal induction of immune tolerance to dnaJP1 would lead to a qualitative change from a proinflammatory phenotype to a more tolerogenic functional phenotype , and 2 ) that immune deviation of responses to an inflammatory epitope might translate into clinical improvement . METHODS One hundred sixty patients with active RA and with immunologic reactivity to dnaJP1 were enrolled in a pilot phase II trial . They received oral doses of 25 mg of dnaJP1 or placebo daily for 6 months . RESULTS The dnaJP1 peptide was safe and well-tolerated . In response to treatment with dnaJP1 , there was a significant reduction in the percentage of T cells producing tumor necrosis factor alpha and a corresponding trend toward an increased percentage of T cells producing interleukin-10 . Coexpression of a cluster of molecules ( programmed death 1 and its lig and s ) associated with T cell regulation was also
Output:
| Conclusion The one adaptive design review ed here , and a simulation study found in the search , both indicate that adaptive design s can be applied to early phase trials in RA . |
MS213769 | ***TASK*** the task is to summarize an input biomedical literature in six sentences
***INPUT*** the input is a biomedical literature
***OUTPUT*** the output is the summary of an input biomedical literature in six sentences
***DOCUMENTATION***
***EXAMPLES***
Input: & NA ; • STUDY DESIGN : Controlled laboratory study . • BACKGROUND : Spinal manipulation ( SM ) can trigger a cascade of responses involving multiple systems , including the sympathetic nervous system and the endocrine system , specifically , the hypothalamic‐pituitary axis . However , no manual therapy study has investigated the neuroendocrine response to SM ( ie , sympathetic nervous system‐hypothalamic‐pituitary axis ) in the same trial . • OBJECTIVE : To determine short‐term changes in sympathetic nervous system activity , heart rate variability , and endocrine activity ( cortisol , testosterone , and testosterone‐cortisol [ T/C ] ratio ) following a thoracic SM . • METHODS : Twenty‐four healthy men aged between 18 and 45 years were r and omized into 2 groups : thoracic SM ( n = 12 ) and sham ( n = 12 ) . Outcome measures were salivary cortisol ( micrograms per deciliter ) , salivary testosterone ( picograms per milliliter ) , T/C ratio , heart rate variability , and changes in oxyhemoglobin concentration of the right calf muscle ( micromoles per liter ) . Measurements were done before and at 5 minutes , 30 minutes , and approximately 6 hours after intervention . • RESULTS : A statistically significant group‐by‐time interaction was noted for T/C ratio ( P<.05 ) and salivary cortisol ( P<.01 ) concentrations . Significant between‐group differences were noted for salivary cortisol concentration at 5 minutes ( mean difference , 0.35 ; 95 % confidence interval : 0.12 , 0.6 ; interaction : P<.01 ) and for T/C ratio at 6 hours postintervention ( mean difference , ‐0.09 ; 95 % confidence interval : ‐0.16 , ‐0.04 ; P = .02 ) . However , SM did not differentially alter oxyhemoglobin , testosterone , or heart rate variability relative to responses in the sham group . • CONCLUSION : Thoracic SM result ed in an immediate decrease in salivary cortisol concentration and reduced T/C ratio 6 hours after intervention . A pattern of immediate sympathetic excitation was also observed in the SM group . • KEY WORDS : autonomic nervous system , cortisol , spinal manipulation , sympathetic nervous system , BACKGROUND Some normotensive patients can have a spike in resting systolic blood pressure ( SBP ) in response to acute neck pain . Applying the typical dosage of mobilization may potentially result in a sympatho-excitatory response , further increasing resting SBP . Therefore , there is a need to explore other dosage regimens that could result in a decrease in SBP . OBJECTIVES To compare the blood pressure ( BP ) and heart rate ( HR ) response of pain-free , normotensive adults when receiving unilateral posterior-to-anterior mobilization ( PA ) applied to the neck versus its corresponding placebo ( PA-P ) . STUDY DESIGN Double-Blind , R and omized Clinical Trial . METHODS 44 ( 18 females ) healthy , pain-free participants ( mean age , 23.8 ± 3.04 years ) were r and omly allocated to 1 of 2 groups . Group 1 received a PA-P in which light touch was applied to the right 6th cervical vertebra . Group 2 received a PA to the same location . BP and HR were measured prior to , during , and after the application of PA or PA-P. A mixed-effect model of repeated measure analysis was used for statistical analysis . RESULTS During-intervention , the PA group had a significant reduction in SBP , while the placebo group had an increase in SBP . The change in SBP during-intervention was significantly different between the PA and the placebo group ( p-value = 0.003 ) . There were no significant between-group differences found for HR and diastolic BP ( DBP ) . The overall group-by-time interaction was statistically significant for SBP ( p-value = 0.01 ) . CONCLUSIONS When compared to placebo , the dosage of applied PA result ed in a small , short-lived drop in SBP not exceeding the minimal detectable change . Trial registered at Germanctr.de ( DRKS00005095 ) Overwhelming evidence shows the quality of reporting of r and omised controlled trials ( RCTs ) is not optimal . Without transparent reporting , readers can not judge the reliability and validity of trial findings nor extract information for systematic review s. Recent method ological analyses indicate that inadequate reporting and design are associated with biased estimates of treatment effects . Such systematic error is seriously damaging to RCTs , which are considered the gold st and ard for evaluating interventions because of their ability to minimise or avoid bias . A group of scientists and editors developed the CONSORT ( Consoli date d St and ards of Reporting Trials ) statement to improve the quality of reporting of RCTs . It was first published in 1996 and up date d in 2001 . The statement consists of a checklist and flow diagram that authors can use for reporting an RCT . Many leading medical journals and major international editorial groups have endorsed the CONSORT statement . The statement facilitates critical appraisal and interpretation of RCTs . During the 2001 CONSORT revision , it became clear that explanation and elaboration of the principles underlying the CONSORT statement would help investigators and others to write or appraise trial reports . A CONSORT explanation and elaboration article was published in 2001 alongside the 2001 version of the CONSORT statement . After an expert meeting in January 2007 , the CONSORT statement has been further revised and is published as the CONSORT 2010 Statement . This up date improves the wording and clarity of the previous checklist and incorporates recommendations related to topics that have only recently received recognition , such as selective outcome reporting bias . This explanatory and elaboration document-intended to enhance the use , underst and ing , and dissemination of the CONSORT statement-has also been extensively revised . It presents the meaning and rationale for each new and up date d checklist item providing examples of good reporting and , where possible , references to relevant empirical studies . Several examples of flow diagrams are included . The CONSORT 2010 Statement , this revised explanatory and elaboration document , and the associated website ( www.consort-statement.org ) should be helpful re sources to improve reporting of r and omised trials Background This systematic review up date d and extended the " UK evidence report " by Bronfort et al. ( Chiropr Osteopath 18:3 , 2010 ) with respect to conditions/ interventions that received an ' inconclusive ’ or ' negative ’ evidence rating or were not covered in the report . Methods A literature search of more than 10 general medical and specialised data bases was conducted in August 2011 and up date d in March 2013 . Systematic review s , primary comparative studies and qualitative studies of patients with musculoskeletal or non-musculoskeletal conditions treated with manual therapy and reporting clinical outcomes were included . Study quality was assessed using st and ardised instruments , studies were summarised , and the results were compared against the evidence ratings of Bronfort . These were either confirmed , up date d , or new categories not assessed by Bronfort were added . Results 25,539 records were found ; 178 new and additional studies were identified , of which 72 were systematic review s , 96 were r and omised controlled trials , and 10 were non-r and omised primary studies . Most ' inconclusive ’ or ' moderate ’ evidence ratings of the UK evidence report were confirmed . Evidence ratings changed in a positive direction from inconclusive to moderate evidence ratings in only three cases ( manipulation/mobilisation [ with exercise ] for rotator cuff disorder ; spinal mobilisation for cervicogenic headache ; and mobilisation for miscellaneous headache ) . In addition , evidence was identified on a large number of non-musculoskeletal conditions not previously considered ; most of this evidence was rated as inconclusive . Conclusions Overall , there was limited high quality evidence for the effectiveness of manual therapy . Most review ed evidence was of low to moderate quality and inconsistent due to substantial method ological and clinical diversity . Areas requiring further research are highlighted Joint mobilisation to the T4 vertebra has been advocated as a treatment for T4 syndrome . To date no controlled studies have investigated the effects of thoracic spinal manual therapy ( SMT ) applied to T4 on sympathetic activity in the h and s. This study investigated whether a grade III postero-anterior rotatory joint mobilisation technique applied to the T4 vertebra at a frequency of 0.5 Hz had demonstrably greater effects than a vali date d placebo intervention on skin conductance ( SC ) in the h and s of healthy subjects . A power analysis calculation was performed and using a double blind , placebo-controlled , independent groups design , 36 healthy subjects ( 18 - 35 years ) were r and omly assigned to two groups ( placebo intervention or treatment intervention ) . A BioPac unit recorded continuous SC measures before , during and after each experimental intervention . An exit question naire was used to vali date the expectancy effects of the placebo intervention . Results demonstrated a significant difference between groups in SC in the right h and during the post-treatment rest period ( F = 4.888 , p = 0.034 ) ; with the treatment intervention being sympathoexcitatory in nature . A trend towards a significant difference between groups was also demonstrated in the left h and during the rest period ( F = 4.072 , p = 0.052 ) . This study provides preliminary evidence that joint mobilisation applied to the T4 vertebra at a frequency of 0.5 Hz can produce sympathoexcitatory effects in the h and . Further research is recommended in a patient population Blinding refers to the concealment of group allocation from one or more individuals involved in a clinical research study , most commonly a r and omized controlled trial ( RCT ) . Although r and omization minimizes differences between treatment groups at the outset of the trial , it does nothing to prevent differential treatment of the groups later in the trial or the differential assessment of outcomes , either of which may result in biased estimates of treatment effects . The optimal strategy to minimize the likelihood of differential treatment or assessment s of outcomes is to blind as many individuals as possible in a trial . R and omized controlled trials of surgical interventions are frequently more difficult to blind than RCTs of medications , which typically achieve blinding with placebos . However , imaginative techniques may make blinding more feasible in surgical trials than is commonly believed by many research ers . In this article we discuss the importance of blinding and provide practical suggestions to research ers who wish to incorporate blinding into their surgical studies Spinal manipulative therapy techniques are commonly employed by physiotherapists in the clinical setting for the management of neuromusculoskeletal pain and dysfunction , although their underlying mechanism is not fully understood . Mulligan 's sustained natural apophyseal glides ( SNAGs ) constitute one of these techniques . This preliminary investigation was undertaken to investigate the relationship between the application of cervical SNAGs to the C5/6 intervertebral joint ( with cervical right rotation ) and indirect measures of sympathetic nervous system ( SNS ) activity . Previous investigations have suggested that cervical manipulative therapy techniques , separate to cervical SNAGs , result in a sympatheoexcitatory effect and that this may be instrumental in producing an analgesic response . Sixteen asymptomatic subjects participated in a laboratory-based experiment . A single blind , r and omized , within subject , repeated measures study design which included control , placebo and treatment comparisons was used . Measures of skin conductance ( SC ) and skin temperature ( ST ) in the right and left upper limbs were used as indicators of SNS activity . The cervical SNAG technique produced a sympathoexcitatory response demonstrated by a significant increase in SC during application of the treatment intervention ( P<0.0005 ) and for a 2-min period after the intervention ( P=0.001 ) compared with control . There was also a significant increase in SC for the placebo condition , both during intervention ( P=0.015 ) and after intervention ( P=0.011 ) compared with control . There was a statistically significant difference in SC between placebo and treatment conditions for the 2-min period after the intervention had been applied ( P=0.01 ) . A trend did emerge for ST change , illustrating a decrease in ST for the treatment and placebo conditions compared with control , however this did not reach statistically significant levels . There were no apparent left/right upper limb differences for SC and ST for each condition . The results of this study suggest that cervical SNAG techniques , performed on naïve asymptomatic subjects , have a sympathoexcitatory effect as measured by changes in SC and ST . The importance of this sympathoexcitatory effect in relation to potential mechanisms for manipulation induced analgesia are discussed , and further areas of research proposed Background Neuromechanical responses to spinal manipulation therapy ( SMT ) have been shown to be modulated through the variation of SMT biomechanical parameters : peak force , time to peak force , and preload force . Although rate of force application was modulated by the variation of these parameters , the assumption that neuromuscular responses are modulated by the rate of force application remains to be confirmed . Therefore , the purpose of the present study was to evaluate the effect of a constant rate of force application in neuromechanical responses to SMT in healthy adults . Methods Four SMT force-time profiles presenting different time to peak force and peak force , but with a constant rate of force application were applied on 25 healthy participants ’ T7 transverse processes . Muscular responses were recorded through surface electromyography electrodes ( T6 and T8 levels ) , while vertebral displacements were assessed through pasted kinematic markers on T6 to T8 spinous processes . Effects of SMT force-time profiles on neuromechanical responses were assessed using repeated- measures ANOVAs . Results There was no main effect of SMT force-time profile modulation on muscular responses ( ps > .05 ) except for the left T8 ( F ( 3 , 72 ) = 3.23 , p = .03 ) and left T6 ( F ( 3
Output:
| Mobilizations ( oscillatory technique ) probably produce an immediate and short-term , bilateral increase in skin sympathetic nerve activity ( reflected by an increase in skin conductance ) regardless of the area treated ( moderate-certainty evidence ) .
It is uncertain whether the sympathetic arousal also explains an increase in respiratory rate ( very low-certainty evidence ) .
Our evaluation of the literature suggests that spinal sustained apophyseal glides ( SNAGs ) mobilization and HVLA manipulation of the spine may have no acute effect on the studied markers of ANS activity ( very low- to low-certainty evidence ) .
ConclusionS ome types of mobilizations probably produce an immediate and short-term , statistically significant increase in skin sympathetic nerve activity when compared to a sham procedure , whereas spinal SNAGs and spinal HVLA techniques may have no acute effect on the studied markers of ANS activity .
No region-specific results were noted .
Il y a des preuves de certitude modérée que les mobilisations ( avec une technique d’oscillation ) produisent une augmentation bilatérale , immédiate et à court terme de l’activité sympathique cutanée , indépendamment de la région mobilisée .
Conclusion Certaines techniques de mobilisation articulaire produisent probablement une augmentation ( statistiquement significative ) immédiate et à court terme de l’activité sympathique cutanée comparées à une procédure placebo .
Les manipulations spinales ( HVLA ) pourraient ne pas avoir d’effet immédiat sur l’activité autonome étudiée .
Nous n’avons pas remarqué d’effet spécifique en fonction de la zone du traitement . |
MS213770 | ***TASK*** the task is to summarize an input biomedical literature in six sentences
***INPUT*** the input is a biomedical literature
***OUTPUT*** the output is the summary of an input biomedical literature in six sentences
***DOCUMENTATION***
***EXAMPLES***
Input: PURPOSE The objective of this research was to test the hypothesis that 3-unit fixed partial dentures ( FPDs ) made from a moderately high-strength core ceramic will adequately resist fracture in posterior regions if fabricated with a minimal connector size of 4 mm . MATERIAL S AND METHODS Thirty ceramic FPD core frameworks were prepared using a hot-pressing technique and a lithia disilicate-based core ceramic . The maximum occlusal force was measured for each patient prior to tooth preparation . Connector heights and widths were measured for each FPD . Patients were recalled annually after cementation for 4 years and evaluated using 11 clinical criteria . All FPDs were examined by 2 independent clinicians , and rankings for each criterion were made from 1 to 4 ( 4 = excellent ; 1 = unacceptable ) . RESULTS The fracture rate was approximately 3 % per year , and the proportion of good overall ratings in the nonfractured FPDs was reduced by more than 6 % per year , where a good overall rating was defined to be a rank of 3 or 4 in all 11 criteria . There was little evidence that the use of either resin-reinforced glass-ionomer cement ( Protec CEM ) or dual-cure resin cement ( Variolink II ) made any difference in terms of fracture rate or overall rating ( P= .30 , .63 , .97 , and .71 for the 4 years , respectively ) . From a fracture resistance perspective , 4 of the 30 ceramic FPDs fractured within the 4-year evaluation period , representing an 86.7 % success rate . Another FPD was replaced because of a caries lesion on 1 abutment tooth away from the margin . One FPD fracture was associated with the subject having the greatest occlusal force ( 1,031 N ) . The other 2 fractures were associated with FPDs that exhibited connector heights of less than 3 mm . All criteria were ranked good to excellent during the 4-year period for the remaining FPDs . CONCLUSION Fractured FPDs were associated with a connector height of less than 4 mm ; thus , the hypothesis was accepted PURPOSE The aim of this prospect i ve study was to evaluate the clinical efficacy and long-term survival rate of three-unit fixed partial dentures ( FPDs ) made from lithium disilicate-based core ceramic . MATERIAL S AND METHODS Twenty-one three-unit FPDs were placed in 19 patients to replace single lost teeth in the esthetic area , following a study protocol that took clinical , esthetic , and radiologic aspects into consideration . Each case was review ed at 1 week following placement , at 6 months , and then annually for 10 years . Statistical analysis was performed using Kaplan-Meier survival analysis . RESULTS Out of the 19 patients , 14.3 % presented reversible postoperative sensitivity . Recession was observed in 24 % of dental posts , and 7.1 % presented marginal discoloration . Treatment did not increase either Bleeding or Plaque Index scores at prepared teeth ; secondary caries did not appear either . The restorations ' survival rate at the 10-year follow-up was 71.4 % ; six FPDs had fractured and one debonded . CONCLUSIONS Fracture failure rate was 28.6 % after 10 years ; a high percentage corresponded to connector fractures and occurred during the first 5 years . Lithium disilicate glass-ceramic FPDs present a higher risk of fracture than st and ard therapies ( metal-ceramic ) or other more recently developed ceramic material s. The prognosis for survival improves for Class I occlusion and nonparafunctional patients This clinical study evaluated posterior three-unit fixed dental prostheses ( FDPs ) made of zirconia substructures veneered with pressable glass – ceramic . Nineteen patients received 21 FDPs replacing either the second premolar , first molar , or second molar . The FDPs were cemented with glass ionomer . Recall examinations were performed every 12 months . The mean service time of the FDP was 40 months . At 30 months , one maxillary FDP exhibited zirconia framework fracture at a thinned occlusal area of the abutment . Loss of retention led to the removal of one FDP after 38 months . The Kaplan – Meier survival probability was 90.5 % after 40 months for all types of failures and 95.2 % concerning framework fractures . The overpressing technique appears to be reliable in terms of the veneering material . However , one framework fracture was observed in this study PURPOSE This study prospect ively evaluated the clinical performance of posterior zirconium-oxide-based all-ceramic fixed partial dentures ( FPDs ) . METHODS Forty-two abutments of 21 Cercon FPDs were fitted in 20 patients at the Tsurumi University Dental Hospital from August 2005 to August 2006 . The performance of these FPDs was evaluated using the California Dental Association ( CDA ) quality assessment system at baseline and at all follow-up examinations . RESULTS All FPDs were examined after a mean observation period of 28.1 ( + /-3.4 ) months . During the observation period , no fracturing of FPDs was seen . All of the FPDs examined were rated as satisfactory with regard to all factors at the follow-up examinations based on the CDA quality assessment criteria . CONCLUSION Within the limitations of this short-term clinical study , no core framework fractures were seen . According to the CDA criteria , 100 % of the FPDs were rated as satisfactory during this observation period The clinical question at issue , whether it is possible to combine implants and natural teeth via fixed bridges , is of current interest . The treatment of the subjects of this prospect i ve study was performed between June 1984 and December 1986 . This article presents the 5-year results of the study . The consecutive patient material comprised 23 patients with Applegate Kennedy Class I residual dentition in the m and ible and a complete maxillary denture . All 23 patients were provided with implants ad modum Brånemark in each m and ibular quadrant . One side was r and omized to rehabilitation with fixed bridge between the distal tooth of the residual dentition and an implant ; the other side received a free-st and ang bridge on 2 implants . The fixture survival rate was 88 % . No difference was found between the two sides . Bridge stability was 89 % for the implant bridges and 91 % for the combination bridges . The change in marginal bone level at the implants was small during the 5-year follow up period ( on average 0.1 - 0.3 mm ) and with no difference between the two sides . In conclusion , it was not possible to demonstrate any higher risk of implant or prosthetic failure for tooth-implant fixed bridges compared with implant-supported bridges OBJECTIVE To evaluate the clinical performance of zirconia-based cantilever fixed dental prostheses ( FDPs ) . METHOD AND MATERIAL S Twenty-one cantilever FDPs with three or four units were design ed to replace one premolar or incisor ( no canines ) . The FDPs were divided into 11 zirconia cantilever FDPs ( test group ) and 10 metal-ceramic cantilever FDPs ( control group ) and r and omly assigned to patients . The results documented included failures , complications , plaque accumulation , and esthetic performance . Statistical analysis was performed using the Mann-Whitney U and chi-square tests . RESULTS During the 2-year observation period , a total of five clinical ly relevant complications in four patients occurred : three endodontic problems ( two in the test group and one in the control group ) and two veneer chippings ( both in the test group ) . Plaque accumulation on the abutment teeth was not significantly different among groups . The esthetic performance of all FDPs was acceptable . CONCLUSION Stability and esthetic performance were acceptable for all-ceramic cantilever FDPs fabricated with zirconia . A longer observation period and larger sample size are necessary to make valid predictions about the longevity of these restorations This study aim ed to evaluate three- and four-unit posterior fixed partial dentures ( FPDs ) with zirconia frameworks after 5 years of function . Of the initial 30 subjects , 25 patients with 25 FPDs were examined after a mean follow-up period of 62.1 months . Five patients were not available for recall visits . Two FPDs failed before the 60-month evaluation because of framework fracture or delamination of the veneering ceramic after endodontic treatment . The 5-year survival rate was 92 % . Based on these results , it can be suggested that zirconia frameworks have sufficient mechanical requirements for use in the stress-bearing posterior region . Major fracture of the ceramic veneer could be related to inadequate framework design or bruxism The aim of this r and omized controlled trial was to evaluate the clinical performance of lithium disilicate fixed partial dentures ( FPDs ) . Eighteen patients received lithium disilicate FPDs ( study group ) , and 19 patients received porcelain-fused-to-metal FPDs ( control ) . After 6 years , the survival probabilities were found to be 63 % in the study group and 95 % in the control group ( log-rank test , P = .028 ) . The data suggest that strict conditions should be considered before the use of lithium disilicate glass-ceramic for FPDs OBJECTIVES The purpose of this prospect i ve study was to evaluate the clinical outcome of crown-retained fixed dental prostheses ( FDPs ) made from a lithium-disilicate glass-ceramic ( IPS e.max Press , Ivoclar-Vivadent ) . METHODS Thirty-six three-unit FDPs were placed in 28 patients . The FDPs replaced teeth in the anterior ( 16 % ) and posterior ( 84 % ) regions . All teeth were prepared following a st and ardized protocol . The size of the proximal connector of the FDPs was 12 mm2 ( anterior ) or 16 mm2 ( posterior ) . FDPs were cemented either with glass-ionomer cement ( n=19 ) or composite resin ( n=17 ) . The following parameters were evaluated at baseline , 6 months after cementation and then annually ( at abutment and contralateral teeth ) : probing pocket depth , plaque index , bleeding on probing , and tooth vitality . RESULTS Three FDPs were defined as drop-out . The mean observation period of the remaining 33 FDPs was 86 months ( range : 67 - 98 months ) : two FDPs in two patients had to be replaced ( 6 % ) because of fractures . The 8-year survival rate according to Kaplan-Meier was 93 % . In addition , chipping of the veneering material was found in two FDPs ( 6 % ) . Two abutments ( 3 % ) of two restorations had to be treated endodontically ; and two FDPs ( 6 % ) lost retention and had to be recemented . These complications did not affect the function of the involved restorations clinical ly . There were no significant differences between the periodontal parameters of the test and control teeth . SIGNIFICANCE Short-span crown-retained three-unit FDPs made from lithium-disilicate glass-ceramic can be used clinical ly irrespective of an adhesive or conventional cementation STATEMENT OF PROBLEM A new method for fabrication of crowns and fixed partial dentures ( Procera system ) that involves electric discharge machining and copy milling has been developed . The metal used is unalloyed titanium , which can be processed as a single coping or multiple units joined to a pontic by laser welding . PURPOSE The single-unit coping or the fixed partial denture ( FPD ) substructure is then veneered with a low-fusing porcelain . MATERIAL AND METHODS In this article the clinical application of this technique was evaluated by six major universities in the United States . A total of 114 patients participated in this study , which involved 126 restorations ( 55 maxillary and 71 m and ibular prostheses ) . There were 179 abutments , of which 73 were crowns and 53 were three-unit FPDs . Surface and color , anatomic form , and margin integrity were assessed 1 month after cementation and at 1 year with the California Dental Association ( CDA ) quality assessment evaluation system . RESULTS No statistically significant differences in CDA scores between the 1 month evaluations and the 1 year assessment s were found for surface and color ( p = 0.68 ) , anatomic form ( p > 0.99 ) , or margin integrity ( p = 0.57 ) . By use of the lowest ranking in the three categories as the overall quality of the restoration , only 3.3 % ( two crowns and two FPDs ) were not acceptable at the 1-month visit and 4.5 % ( two crowns and three FPDs ) were not acceptable at the 1-year evaluation . At-the 1-month visit 96.6 % ( 114 ) of the restorations were considered to be satisfactory , whereas 95.5 % ( 107 restorations ) were evaluated similarly at the 1-year evaluation . CONCLUSIONS The Procera system demonstrated , by use of the CDA criteria , its capability to produce quality prostheses that were rated satisfactory more than 95 % of the time after insertion and maintained this high rating at least for 1 year OBJECTIVES To report the results at year three of an evaluation of fixed-fixed all-ceramic bridges , constructed in a yttria oxide stabilized tetragonal zirconium oxide polycrystal ( Y-TZP ) substructure , placed in adult patients in UK general dental practice s and luted using a self-adhesive resin-based c
Output:
| Both treatments show an almost equally low complication rate , but there is a low level of reporting of hard and soft tissue conditions and PROM .
It is concluded that implant-supported 3-unit FDPs seem to be a reliable treatment with survival rates not significantly different from the results of teeth-supported 3-unit FDPs |
MS213771 | ***TASK*** the task is to summarize an input biomedical literature in six sentences
***INPUT*** the input is a biomedical literature
***OUTPUT*** the output is the summary of an input biomedical literature in six sentences
***DOCUMENTATION***
***EXAMPLES***
Input: Background and Purpose Population -based patient material s have not been used earlier in assessing the effects of neurosurgical treatment on survival and functional outcome of subarachnoid hemorrhage . Moreover , the proportion of all subarachnoid hemorrhage patients who might be c and i date s for neurosurgical treatment has not been estimated . Methods We compared the survival and functional outcome of two population -based patient material s from Central Finl and in 1976 through 1978 ( n=146 ) and 1980 through 1987 ( n=351 ) . The most important basic characteristics of both material s were similar . In the 1970s , only patients aged < 60 years with carotid territory aneurysms were operated on after an interval of 2 weeks from the bleeding . In the 1980s , early surgery was attempted , and the other exclusion criteria were ab and oned . Allocation to medical or surgical treatment was not r and omized . Results During the 1970s , only 14 % of the patients had surgical treatment , with a median delay of 15 days after the bleeding ; in the 1980s , the corresponding figures were 46 % and 4 days . Despite these fundamental changes in the treatment policy , the survival up to 3 years in the 1980s was only marginally improved compared with the 1970s . Conversely , the functional outcome at 4 years after the bleeding was significantly better in the 1980s than the 1970s , with 82 % and 64 % of the survivors , respectively , being independent in the activities of daily living ( P=.002 ) . We estimated that 60 % of all patients with subarachnoid hemorrhage might be c and i date s for neurosurgical treatment , provided that there are no delays in admission or evaluation . Conclusions An active treatment policy of subarachnoid hemorrhage including early surgery only marginally improves survival , but the quality of life of the survivors is significantly better . Only 60 % of all patients in the population with subarachnoid hemorrhage can , at least theoretically , benefit from surgical treatment . ( Stroke . 1993;24:1649 - 1654 . A controlled clinical trial of epsilon-aminocaproic acid ( E.A.C.A. ) , 36 g/day , was undertaken to assess its effectiveness in reducing immediate recurrence in patients with spontaneous subarachnoid haemorrhage ( S.A.H. ) proved by lumbar puncture . Of 83 patients treated with E.A.C.A. , 3 ( 4 % ) had recurrent haemorrhage , and 1 ( 33 % ) of these died . Of 82 control patients who were not given any antifibrinolytic drug , 22 ( 26 % ) had recurrent haemorrhage , and 10 ( 45 % ) of these patients died . E.A.C.A. produced a striking reduction in the early recurrence of S.A.H. No serious side-effect result ed Summary Tranexamic acid as an antifibrinolytic agent has been investigated in a controlled study in patients with recent subarachnoid haemorrhage . It is concluded that tranexamic acid improves neither rebleeding rates , nor mortality . Predominantly thrombotic complications have been noted as a more serious side effect of tranexamic acid OBJECTIVE --To audit the outcome in patients with subarachnoid haemorrhage ( SAH ) after a change in management strategy . METHODS --A retrospective analysis of patients with aneurysmal subarachnoid haemorrhage over a 20 month period ( phase 1 ) was followed by a prospect i ve analysis of patients presenting during the next 20 months ( phase 2 ) in which a protocol driven management regime of immediate intravenous fluid resuscitation and earlier surgery was pursued . Patients in this phase were grouped into those receiving early ( within four days of subarachnoid haemorrhage ) and late ( after four days of subarachnoid haemorrhage ) surgery . In phase 1 , 75 out of a total of 92 patients underwent surgery on ( median ) day 12 . From phase 2 , 109 patients out of a total of 129 underwent surgery on ( median ) day 4 , 58 of which had their surgery within 4 days of the subarachnoid haemorrhage . Patients in each phase/group were well matched for demographic features , site of aneurysm , and severity of subarachnoid haemorrhage . RESULTS --The surgical morbidity and mortality were no different in the two phases ( P < 0.92 ; chi2 test ) . The management outcomes in the two phases of the study were also no different ( P < 0.52 ) . However , there was a significant reduction in the rebleed rate in patients undergoing surgery within four days of the subarachnoid haemorrhage in phase 2 ( P < 0.0001 ) with an associated trend towards reduced incidence of postoperative ischaemia ( P = 0.06 ) and mortality ( P = 0.11 ) . Operating earlier in phase 2 of the trial result ed in a lower total hospital inpatient stay of 15.8 ( 95 % CI 13.1 - 18.5 ) days for survivors compared with 25.7 ( 95 % CI 21.6 - 29.8 ) days in the late group ( P < 0.00001 ; t test ) . CONCLUSIONS --surgical morbidity and mortality seemed independent of the timing of aneurysm surgery . Early surgery within four days was associated with a highly significant reduction in rebleed rate , and in the duration of total hospital inpatient stay The outcome of treatment with an antifibrinolytic agent ( tranexamic acid ) for six weeks after rupture of an intracranial aneurysm was assessed in a r and omised controlled trial . Twenty-two out of 25 ( 88 % ) treated patients survived at follow-up of three to 33 months compared with 14 out of 25 ( 56 % ) control patients . Among the patients who did not undergo operation the survival rate was 81 % ( 13 out of 16 ) in treated patients and 42 % ( 8 out of 19 ) in controls . Antifibrinolytic treatment has so far been assumed merely to postpone rebleeding and has been used to enable surgery to be deferred . These findings suggest that tranexamic acid may actually prevent rebleeding without operation . Prolonged antifibrinolysis may therefore prove useful in those patients in good condition whose aneurysms do not lend themselves to surgical obliteration Objective : To investigate whether antifibrinolytics in combination with treatment to prevent cerebral ischemia improve outcome in patients with subarachnoid hemorrhage ( SAH ) in whom occlusion of the aneurysm is delayed . Background : Antifibrinolytic treatment reduces rebleeding , but outcome does not improve because of a concurrent increase in the occurrence of cerebral ischemia . Because treatment of ischemia has improved , antifibrinolytics might now have a beneficial effect . Methods : A prospect i ve , double-blind , placebo-controlled multicenter clinical trial was performed . R and omized were 462 patients ( 229 received tranexamic acid , 233 placebo ) admitted within 96 hours after onset of SAH , in whom treatment of the aneurysm was delayed beyond 48 hours after SAH . All patients were treated with calcium antagonists and hypervolemia . At 3 months , outcome was assessed with the Glasgow Outcome Scale . The occurrence of cerebral ischemia and other complications were recorded , and the effects of treatment were related to the clinical condition on admission . Results : Antifibrinolytic treatment had no beneficial effect on outcome ( relative risk [ RR ] , 1.10 ; 95 % confidence limits [ CL ] , 0.91–1.34 ) . Antifibrinolytics significantly reduced the occurrence of rebleeding ( RR , 0.58 ; 95 % CL , 0.42–0.80 ) ; the occurrence of ischemic and other complications was the same in the two groups . Conclusion : Antifibrinolytic treatment combined with treatment to prevent cerebral ischemia does not improve outcome A prospect i ve , observational clinical trial was conducted by the International Cooperative Study on the Timing of Aneurysm Surgery to determine the best time in relation to the hemorrhage for surgical treatment of ruptured intracranial aneurysms . Sixty-eight centers contributed 3521 patients in a 2 1/2-year period beginning in December , 1980 . Analysis by a prespecified " planned " surgery interval demonstrated that there was no difference in early ( 0 to 3 days after the bleed ) or late surgery ( 11 to 14 days ) . Outcome was worse if surgery was performed in the 7 to 10-day post-bleed interval . Surgical results were better for patients operated on after 10 days . Patients alert on admission fared best ; however , alert patients had a mortality rate of 10 % to 12 % when undergoing surgery prior to Day 11 compared with 3 % to 5 % when surgery was performed after Day 10 . Patients drowsy on admission had a 21 % to 25 % mortality rate when operated on up to Day 11 and 7 % to 10 % with surgery thereafter . Overall , early surgery was neither more hazardous nor beneficial than delayed surgery . The postoperative risk following early surgery is equivalent to the risk of rebleeding and vasospasm in patients waiting for delayed surgery Summary One hundred patients with a verified subarachnoid haemorrhage were studied in a double blind , placebo-controlled trial at a single centre to determine the value and relative risks of tranexamic acid ( TXA ) in the management of ruptured intracranial aneurysms . The incidence of recurrent haemorrhage between active and placebo groups was identical ( 12 % ) and the mortality from recurrent haemorrhage was 7 % and 5 % , respectively . The overall incidence of cerebral infa rct ion before surgery , at discharge and at 6 months follow-up was greater in the TXA group ( 27 % ) than in the control group ( 11 % ) . Post-operative cerebral ischaemia was significantly more frequent in the active , 18 of 29 as compared to 6 of 32 patients , in the placebo group . In a fifth of the patients in whom cerebral blood flow was estimated there was a significant reduction of cerebral blood flow ( CBF ) on the side of the ruptured aneurysm in the TXA treated group . It is suggested that this may be the cause of the increased incidence of cerebral ischaemia in this group . There was no significant difference in the incidence of cerebral vasospasm , hydrocephalus , visual disturbances and gastrointestinal disturbances . More fatalities were encountered from ischaemia and recurrent haemorrhage in the TXA group but these differences did not reach statistical significance at the 5 % level . Given that disability was due to either vasospasm or recurrent haemorrhage then a patient under TXA treatment was significantly more likely to have disability due to vasospasm ( p<0.04 ) ; the reverse was true for the placebo patient ( p<0.05 ) In a series of 176 prospect ively studied patients who survived for at least 24 hours after aneurysmal subarachnoid hemorrhage , 39 had at least one computerized tomography (CT)-proven rebleed within 4 weeks after the first rupture . There were peaks in the incidence of rebleeding at the end of the 2nd and 3rd weeks . Sudden loss of consciousness occurred in 35 patients , preceded in one-third of them by headache . A sudden increase in headache was a symptom of rebleeding in only one patient . Loss of brain-stem reflexes was recorded in 13 patients , respiratory arrest in six , and both symptoms in eight patients . Apnea was temporary in 11 patients . Rebleeding occurred as gross intraventricular hemorrhage in 20 patients , as a space-occupying hematoma in four , as both types of hemorrhage in three , and as a purely subarachnoid hemorrhage in 12 . The location of the rebleed could not be inferred from the clinical features . Rebleeding was fatal in 51 % of cases ( two of 12 patients with a purely subarachnoid hemorrhage , and 18 of the other 27 patients ( p less than 0.005 ) ) . The risk of rebleeding could not be predicted from the patients ' clinical condition on admission or from the amount of subarachnoid blood identified on the initial CT scan . The risk of further rebleeding was significantly increased in survivors of a first rebleed ( 47 % : p less than 0.01 ) . Only seven ( 18 % ) of the 39 patients with rebleeding had survived at 3 months after the initial hemorrhage A r and omized controlled clinical trial was carried out to study the effect of tranexamic acid ( AMCA , Cyklokapron ; AB Kabi , Stockholm , Sweden ) in the prevention of early rebleeding after the rupture of an intracranial aneurysm . The incidence of vasospasm , hydrocephalus , cerebral ischemic and thromboembolic complications , morbidity , and mortality was also evaluated . The series comprises 59 patients , 30 treated with tranexamic acid and 29 controls . The treatment was stopped if there was rebleeding , operation , or discharge from the hospital . There were 6 recurrent hemorrhages in 6 patients in the tranexamic acid-treated group and 11 recurrences in 7 patients in the control group . Recurrent hemorrhages occurred later in tranexamic acid-treated patients than in controls . Five patients in each group died from rebleeding
Output:
| Short-term use of AF ( 72 h or less ) associated with medical prevention of ischemic deficit seems to yield better results on functional outcome than long-term use of AF , especially if not associated with a medical prevention of ischemic deficit .
The risk of cerebral infa rct ion is not increased by the short-term use of AF and the risk of rebleeding is decreased independently of the length of AF use .
Conclusions The use of AF should be reconsidered in the setting of modern-era treatment strategies , as the short-term use associated with medical prevention of ischemic deficit decreases the rate of rebleeding and does not increase the risk of cerebral infa rct ion , thus potentially yielding better protection against poor functional outcome |
MS213772 | ***TASK*** the task is to summarize an input biomedical literature in six sentences
***INPUT*** the input is a biomedical literature
***OUTPUT*** the output is the summary of an input biomedical literature in six sentences
***DOCUMENTATION***
***EXAMPLES***
Input: BACKGROUND The effect of treatment with β-blockers on the prognosis of patients newly diagnosed with heart failure with preserved ejection fraction ( HFpEF ) is unknown . OBJECTIVE To analyze the relationship of commencing treatment with the β-blockers bisoprolol or carvedilol ( CT-βB ) with the prognosis of newly diagnosed HFpEF . METHODS Prospect i ve study over 10years on 2704 patients with HFpEF . Main outcomes were mortality ( all-cause and cardiovascular ) , hospitalizations for HF worsening , and visits . The independent relationship between CT-βB and the prognosis , stratifying patients for cardiovascular co-morbidity after propensity score-matching ( 985 patients CT-βB vs. another 985 patients non-CT-βB ) , was analyzed . RESULTS During a median follow-up of 1877.4days ( interquartile range , 1 - 3651.2 ) 1600 died ( 81.2 % ) , and 1702 were hospitalized ( 86.4 % ) . CT-βB was associated with a lower risk of mortality ( all-cause : HR [ CI 95 % ] 0.78 [ 0.71 to 0.85 ] , and cardiovascular : 0.75 [ 0.69 to 0.82 ] ) , a lower hospitalization rate ( per 100 persons-year ) , 15.8 vs. 19.2 , and a lower 30-day readmission rate ( per 100 persons-year ) , 4.0 vs. 5.8 , ( P<0.001 in all cases ) , even after adjustment for the propensity to take β-blockers or other medications , comorbidities , and other potential confounders . These effects of CT-βB were independent of gender , and were observed in both patients taking high dose βB ( over the median dose ) and lower dose βB ( under or equal to the median dose ) . CONCLUSIONS In this propensity matched study , commencing treatment with bisoprolol or carvedilol , both at high and at lower doses , is associated with an improved prognosis of patients newly diagnosed with HFpEF Fifteen elderly patients with normal left ventricular ( LV ) systolic function and New York Heart Association functional class II-III were studied . The effect of verapamil on LV diastolic function was assessed by congestive heart failure ( CHF ) score , treadmill exercise test , and Doppler echocardiography at baseline , and after each three-month treatment period ( placebo or verapamil 120 mg once daily ) , separated by a one-week washout period before crossover . Blood pressure , heart rate , LV ejection fraction , LV mass , and cardiac output were unaltered by placebo or verapamil . Verapamil treatment significantly improved CHF score at 3 months ( 3.5 + /- 0.5 , p<0.05 ) compared with baseline ( 5.6 + /- 0.5 ) or placebo ( 5.5 + /- 0.5 ) . The exercise time was similar at baseline ( 7.4 + /- 1.2 min ) and after placebo ( 7.4 + /- 1.3 min ) treatment but significantly ( p<0.05 ) increased after verapamil ( 8.3 + /- 1.2 min ) treatment . The ratio of mitral A wave duration /pulmonary venous atrial systolic reversal duration increased after verapamil ( 1.11 + /- 0.08 ) treatment compared with placebo ( 0.91 + /- 0.07 , p<0.05 ) and baseline ( 0.89 + /- 0.08 ) which had similar duration s. The isovolumic relaxation time was significantly ( p<0.05 ) decreased from 84 + /- 12 ms at baseline and 86 + /- 13 ms with placebo to 73 + /- 9 ms with verapamil . The results of this study suggest that in elderly patients with Doppler evidence of diastolic dysfunction as the cause of CHF , three months treatment with verapamil can improve CHF , increase exercise tolerance and improve LV diastolic function Background — Heart failure ( HF ) developing in hypertensive patients may occur with preserved or reduced left ventricular ejection fraction ( PEF [ ≥50 % ] or REF [ < 50 % ] ) . In the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial ( ALLHAT ) , 42 418 high-risk hypertensive patients were r and omized to chlorthalidone , amlodipine , lisinopril , or doxazosin , providing an opportunity to compare these treatments with regard to occurrence of hospitalized HFPEF or HFREF . Methods and Results — HF diagnostic criteria were prespecified in the ALLHAT protocol . EF estimated by contrast ventriculography , echocardiography , or radionuclide study was available in 910 of 1367 patients ( 66.6 % ) with hospitalized events meeting ALLHAT criteria . Cox regression models adjusted for baseline characteristics were used to examine treatment differences for HF ( overall and by PEF and REF ) . HF case fatality rates were examined . Of those with EF data , 44.4 % had HFPEF and 55.6 % had HFREF . Chlorthalidone reduced the risk of HFPEF compared with amlodipine , lisinopril , or doxazosin ; the hazard ratios were 0.69 ( 95 % confidence interval [ CI ] , 0.53 to 0.91 ; P=0.009 ) , 0.74 ( 95 % CI , 0.56 to 0.97 ; P=0.032 ) , and 0.53 ( 95 % CI , 0.38 to 0.73 ; P<0.001 ) , respectively . Chlorthalidone reduced the risk of HFREF compared with amlodipine or doxazosin ; the hazard ratios were 0.74 ( 95 % CI , 0.59 to 0.94 ; P=0.013 ) and 0.61 ( 95 % CI , 0.47 to 0.79 ; P<0.001 ) , respectively . Chlorthalidone was similar to lisinopril with regard to incidence of HFREF ( hazard ratio , 1.07 ; 95 % CI , 0.82 to 1.40 ; P=0.596 ) . After HF onset , death occurred in 29.2 % of participants ( chlorthalidone/amlodipine/lisinopril ) with new-onset HFPEF versus 41.9 % in those with HFREF ( P<0.001 ; median follow-up , 1.74 years ) ; and in the chlorthalidone/doxazosin comparison that was terminated early , 20.0 % of HFPEF and 26.0 % of HFREF patients died ( P=0.185 ; median follow-up , 1.55 years ) . Conclusions — In ALLHAT , with adjudicated outcomes , chlorthalidone significantly reduced the occurrence of new-onset hospitalized HFPEF and HFREF compared with amlodipine and doxazosin . Chlorthalidone also reduced the incidence of new-onset HFPEF compared with lisinopril . Among high-risk hypertensive men and women , HFPEF has a better prognosis than HFREF Background — Patients with heart failure are at increased risk of sudden death and death attributed to progressive pump failure . We assessed the effect of c and esartan on cause-specific mortality in patients enrolled in the C and esartan in Heart failure Assessment of Reduction in Mortality and morbidity ( CHARM ) program . Methods and Results —The CHARM program consisted of 3 component trials that enrolled patients with symptomatic heart failure : CHARM-Alternative ( n=2028 ; LVEF=40 % and ACE intolerant ) , CHARM-Added ( n=2548 ; LVEF=40 % , already on ACE inhibitors ) , and CHARM-Preserved ( n=3023 ; LVEF > 40 % ) . Patients were r and omized to c and esartan , titrated to 32 mg QD , or placebo and were followed up for a median of 37.7 months . All deaths were review ed by a blinded adjudication committee and categorized according to prespecified definitions on the basis of a narrative and source documentation . The number and rate of deaths by cause were calculated for each of the component trials and the overall program . Of all the patients , 8.5 % died suddenly , and 6.2 % died of progressive heart failure . C and esartan reduced both sudden death ( HR 0.85 [ 0.73 to 0.99 ] , P=0.036 ) and death from worsening heart failure ( HR 0.78 [ 0.65 to 0.94 ] , P=0.008 ) . These reductions were most apparent in the patients with LVEF=40 % . Conclusions —C and esartan reduced sudden death and death from worsening heart failure in patients with symptomatic heart failure , although this reduction was most apparent in patients with systolic dysfunction AIMS To determine the effects of digoxin on all-cause mortality and heart failure ( HF ) hospitalizations , regardless of ejection fraction , accounting for serum digoxin concentration ( SDC ) . METHODS AND RESULTS This comprehensive post-hoc analysis of the r and omized controlled Digitalis Investigation Group trial ( n=7788 ) focuses on 5548 patients : 1687 with SDC , drawn r and omly at 1 month , and 3861 placebo patients , alive at 1 month . Overall , 33 % died and 31 % had HF hospitalizations during a 40-month median follow-up . Compared with placebo , SDC 0.5 - 0.9 ng/mL was associated with lower mortality [ 29 vs. 33 % placebo ; adjusted hazard ratio ( AHR ) , 0.77 ; 95 % confidence interval ( CI ) , 0.67 - 0.89 ] , all-cause hospitalizations ( 64 vs. 67 % placebo ; AHR , 0.85 ; 95 % CI , 0.78 - 0.92 ) and HF hospitalizations ( 23 vs. 33 % placebo ; AHR , 0.62 ; 95 % CI , 0.54 - 0.72 ) . SDC > or = 1.0 ng/mL was associated with lower HF hospitalizations ( 29 vs. 33 % placebo ; AHR , 0.68 ; 95 % CI , 0.59 - 0.79 ) , without any effect on mortality . SDC 0.5 - 0.9 reduced mortality in a wide spectrum of HF patients and had no interaction with ejection fraction > 45 % ( P=0.834 ) or sex ( P=0.917 ) . CONCLUSIONS Digoxin at SDC 0.5 - 0.9 ng/mL reduces mortality and hospitalizations in all HF patients , including those with preserved systolic function . At higher SDC , digoxin reduces HF hospitalization but has no effect on mortality or all-cause hospitalizations Background —Exercise intolerance is the primary symptom in older patients with heart failure and preserved ejection fraction ( HFPEF ) ; however , little is known regarding its mechanisms and therapy . Methods and Results —Seventy-one stable elderly ( 70±1 years ) patients ( 80 % women ) with compensated HFPEF and controlled blood pressure were r and omized into a 12-month follow-up double-blind trial of enalapril 20 mg/d versus placebo . Assessment s were peak exercise oxygen consumption ; 6-minute walk test ; Minnesota Living with HF Question naire ; MRI ; Doppler echocardiography ; and vascular ultrasound . Compliance by pill count was excellent ( 94 % ) . Twenty-five patients in the enalapril group versus 34 in the placebo group completed the 12-month follow-up . During follow-up , there was no difference in the primary outcome of peak exercise oxygen consumption ( enalapril , 14.5±3.2 mL/kg/min ; placebo , 14.3±3.4 mL/kg/min ; P=0.99 ) , or in 6-minute walk distance , aortic distensibility ( the primary mechanistic outcome ) , left ventricle mass , or neurohormonal profile . The effect size of enalapril on peak exercise oxygen consumption was small ( 0.7 % ; 95 % CI , 4.2 % to 5.6 % ) . There was a trend toward improved Minnesota Living with HF Question naire total score ( P=0.07 ) , a modest reduction in systolic blood pressure at peak exercise ( P=0.02 ) , and a marginal improvement in carotid arterial distensibility ( P=0.04 ) . Conclusions —In stable , older patients with compensated HFPEF and controlled blood pressure , 12 months of enalapril did not improve exercise capacity or aortic distensibility . These data , combined with those from large clinical event trials , suggest that angiotensin inhibition does not substantially improve key long-term clinical outcomes in this group of patients . This finding contrasts sharply with observations in HF with reduced EF and highlights our incomplete underst and ing of this important and common disorder Background —The Minnesota Living with Heart Failure Question naire ( MLHFQ ) was used in a large
Output:
| There was no effect seen with ACE inhibitors , aldosterone receptor blockers , mineralocorticoid receptor antagonists and other drug classes , compared with placebo .
Similar results were observed for cardiovascular mortality .
No single drug class reduced heart failure hospitalisation compared with placebo .
Conclusion The efficacy of treatments in patients with heart failure and an LV ejection fraction≥40 % differ depending on the type of therapy , with beta-blockers demonstrating reductions in all-cause and cardiovascular mortality . |
MS213773 | ***TASK*** the task is to summarize an input biomedical literature in six sentences
***INPUT*** the input is a biomedical literature
***OUTPUT*** the output is the summary of an input biomedical literature in six sentences
***DOCUMENTATION***
***EXAMPLES***
Input: BACKGROUND Previous studies found that medication errors result from lack of sufficient information during the prescribing step . Therefore , it is proposed that having a pharmacist available when patients are evaluated during the rounding process may reduce the likelihood of preventable adverse drug events ( ADEs ) . The objectives of this study were to evaluate the impact of having a pharmacist participate with a physician rounding team on preventable ADEs in general medicine units and to document pharmacist interventions made during the rounding process . METHODS A single-blind , st and ard care-controlled study design was used to compare patients receiving care from a rounding team including a pharmacist with patients receiving st and ard care ( no pharmacist on rounding team ) . Patients admitted to and discharged from the same general medicine unit were included in the study . The main outcome measure of this study was preventable ADEs . Patient records were r and omly selected and evaluated by a blinded process involving independent senior pharmacist specialists and a senior staff physician . Interventions made by the pharmacists in the treatment group were documented . RESULTS The rate of preventable ADEs was reduced by 78 % , from 26.5 per 1000 hospital days to 5.7 per 1000 hospital days . There were 150 documented interventions recommended during the rounding process , 147 of which were accepted by the team . The most common interventions were ( 1 ) dosing-related changes and ( 2 ) recommendations to add a drug to therapy . CONCLUSION Pharmacist participation with the medical rounding team on a general medicine unit contributes to a significant reduction in preventable ADEs BACKGROUND There is evidence that pharmacist interventions improve clinical outcomes . The few studies that address economic outcomes ( a ) often report estimated instead of actual medical costs , ( b ) report only medication costs , or ( c ) have been conducted in setting s that are not typical of community-based primary care . OBJECTIVES To ( a ) determine whether a clinical pharmacist 's recommendations to physicians regarding optimizing medication therapy are related to medical costs in capitated patients in an internal medicine practice , and ( b ) compare what primary care physicians ( PCPs ) in a comparison group actually did proactively to optimize medication therapy versus what a clinical pharmacist would have recommended to them . METHODS This was a prospect i ve , controlled study comparing 2 internal medicine practice s. Study enrollment was performed using a screening process carried out every 1 - 2 weeks on a rolling basis for 1 year from July 2001 through June 2002 . Eligibility criteria for prospect i ve enrollment were ( a ) 1 or more risk factors : at least 1 chronic disease or an event ( e.g. , emergency room visit , adverse drug reaction , medication nonadherence ) or aged 50 years or older , ( b ) a scheduled visit to see a PCP within 2 weeks from the screening date or a diagnosis of diabetes without a PCP visit during the first 6 months of the study , ( c ) need for optimization of medication therapy as determined by a clinical pharmacist on the screening date , and ( d ) 12 months of continuous insurance eligibility before enrollment in the study . For inclusion in the final study analyses , patients were also required to have continuous insurance eligibility through 12 months from study enrollment . One clinical pharmacist made recommendations to optimize medication therapy in the intervention group . For the comparison group , the same pharmacist proposed recommendations that remained concealed from the physicians . The primary outcome measure was per patient per year ( PPPY ) medical cost , based on plan liability ( gross allowable costs minus patient costs ) , excluding prescription drug cost . Additional outcome measures included numbers of outpatient visits , hospital admissions , emergency room ( ER ) visits per 1,000 patients , and hospital days ; and percent of recommendations that were accepted by the PCPs . Changes in outcome measures from the pre-intervention to postintervention period were compared across study groups in a difference-indifference analysis , using the Student 's t-test for normally distributed data and the Mann-Whitney U-test ( nonparametric ) for skewed data . RESULTS There were 127 and 216 adult patients in the intervention and comparison groups , respectively . The primary outcome , change in mean PPPY medical ( excluding pharmacy ) cost , did not differ significantly between the groups ( P = 0.711 ) . The between-group difference in the change in ER visits per 1,000 patients approached statistical significance ( P = 0.054 ) . Intervention group patients were more likely than comparison group patients to have the following issues addressed : medication nonadherence ( 85.7 % vs. 40.0 % , respectively ; P = 0.032 ) , untreated indication ( 72.6 % vs. 11.5 % , P < 0.001 ) , suboptimal medication choice ( 60.0 % vs. 5.9 % , P < 0.001 ) and cost-ineffective drug therapies ( 72.1 % vs. 6.5 % , P < 0.001 ) . Of the estimated number of actionable opportunities identified for the comparison group ( but concealed from the physicians ) , 23.5 % were adopted by comparison group physicians without any assistance from a clinical pharmacist . CONCLUSION Compared with patients of PCPs who received no input from a clinical pharmacist , patients of PCPs who received clinical pharmacist recommendations were more likely to have several medication-related issues addressed , including medication nonadherence , untreated indications , suboptimal medication choices , and cost-ineffective drug therapies . However , total medical ( excluding pharmacy ) costs for the intervention and comparison groups were not significantly different Background : Hospital discharge is an interlace of care when patients are at a high risk of medication discrepancies as they transition from hospital to home . These discrepancies are important , as they may contribute to drug-related problems , medication errors , and adverse drug events . Objective : To Identify , characterize , and assess the clinical impact of unintentional medication discrepancies at hospital discharge . Methods : All consecutive general internal medicine patients admitted for at least 72 hours to a tertiary care teaching hospital were prospect ively assessed . Patients were excluded if they were discharged with verbal prescriptions ; died during hospitalization ; or transferred from or to a nursing home , another institution , or another unit within the same hospital . The primary endpoint was to determine the number of patients with at least one unintended medication discrepancy on hospital discharge . Medication discrepancies were assessed through comparison of a best possible medication discharge list with the actual discharge prescriptions . Secondary objectives were to characterize and assess the potential clinical impact of the unintentional discrepancies . Results : From March 14,2006 , to June 2,2006,430 patients were screened for eligibility ; 150 patients were included in the study . Overall , 106 ( 70.7 % ) patients had at least one actual or potential unintentional discrepancy . Sixty-two patients ( 41.3 % ) had at least one actual unintentional medication discrepancy al hospital discharge and 83 patients ( 55.3 % ) had at least one potential unintentional discrepancy . The most common unintentional discrepancies were an incomplete prescription requiring clarification , which could result in a patient delay in obtaining medications ( 49.5 % ) , and the omission of medications ( 22.9 % ) . Of the 105 unintentional discrepancies , 31 ( 29.5 % ) had the potential to cause possible or probable patient discomfort and /or clinical deterioration . Conclusions : Medication discrepancies occur commonly on hospital discharge . Underst and ing the type and frequency of discrepancies can help clinicians better underst and ways to prevent them . Structured medication reconciliation may help to prevent discharge medication discrepancies Background : Medication errors at the time of hospital admission and discharge are common and can lead to preventable adverse drug events . The objective of this study was to describe the potential impact of a medication reconciliation process to identify and rectify medication errors at the time of hospital admission and discharge . Methods : Sixty r and omly selected patients were prospect ively enrolled at the time of admission to a Canadian community hospital . At admission , patients ’ medication orders were compared with pre-admission medication use based on medication vials and interviews with patients , caregivers , and /or outpatient healthcare providers . At discharge , pre-admission and in-patient medications were compared with discharge orders and written instructions . All variances were discussed with the prescribing physician and classified as intended or unintended ; unintended variances were considered to be medication errors . An internist classified the clinical importance of each unintended variance . Results : Overall , 60 % ( 95 % CI 48 to 72 ) of patients had at least one unintended variance and 18 % ( 95 % CI 9 to 28 ) had at least one clinical ly important unintended variance . None of the variances had been detected by usual clinical practice before reconciliation was conducted . Of the 20 clinical ly important variances , 75 % ( 95 % CI 56 to 94 ) were intercepted by medication reconciliation before patients were harmed . Discussion : Unintended medication variances at the time of hospital admission and discharge are common and clinical ly important . The medication reconciliation process identified and addressed most of these unintended variances before harm occurred . In this small study , medication reconciliation was a useful method for identifying and rectifying medication errors at times of transition . Reconciliation warrants broader evaluation BACKGROUND Prior studies suggest that unintended medication discrepancies that represent errors are common at the time of hospital admission . These errors are particularly worthy of attention because they are not likely to be detected by computerized physician order entry systems . METHODS We prospect ively studied patients reporting the use of at least 4 regular prescription medications who were admitted to general internal medicine clinical teaching units . The primary outcome was unintended discrepancies ( errors ) between the physicians ' admission medication orders and a comprehensive medication history obtained through interview . We also evaluated the potential seriousness of these discrepancies . All discrepancies were review ed with the medical team to determine if they were intentional or unintentional . All unintended discrepancies were rated for their potential to cause patient harm . RESULTS After screening 523 admissions , 151 patients were enrolled based on the inclusion criteria . Eighty-one patients ( 53.6 % ; 95 % confidence interval , 45.7%-61.6 % ) had at least 1 unintended discrepancy . The most common error ( 46.4 % ) was omission of a regularly used medication . Most ( 61.4 % ) of the discrepancies were judged to have no potential to cause serious harm . However , 38.6 % of the discrepancies had the potential to cause moderate to severe discomfort or clinical deterioration . CONCLUSIONS Medication errors at the time of hospital admission are common , and some have the potential to cause harm . Better methods of ensuring an accurate medication history at the time of hospital admission are needed OBJECTIVES to investigate the effectiveness of a pharmacy discharge plan in elderly hospitalized patients . DESIGN r and omized controlled trial . SUBJECTS AND SETTING S we r and omized patients aged 75 years and older on four or more medicines who had been discharged from three acute general and one long-stay hospital to a pharmacy intervention or usual care . INTERVENTIONS the hospital pharmacist developed discharge plans which gave details of medication and support required by the patient . A copy was given to the patient and to all relevant professionals and carers . This was followed by a domiciliary assessment by a community pharmacist . In the control group , patients were discharged from hospital following st and ard procedures that included a discharge letter to the general practitioner listing current medications . OUTCOMES the primary outcome was re-admission to hospital within 6 months . Secondary outcomes included the number of deaths , attendance at hospital outpatient clinics and general practice and proportion of days in hospital over the follow-up period , together with patients ' general well-being , satisfaction with the service and knowledge of and adherence to prescribed medication . RESULTS we recruited 362 patients , of whom 181 were r and omized to each group . We collected hospital and general practice data on at least 91 and 72 % of patients respectively at each follow-up point and interviewed between 43 and 90 % of the study subjects . There were no significant differences between the groups in the proportion of patients re-admitted to hospital between baseline and 3 months or 3 and 6 months . There were no significant differences in any of the secondary outcomes . CONCLUSIONS we found no evidence to suggest that the co-ordinated hospital and community pharmacy care discharge plans in elderly patients in this study influence outcomes Introduction : Care home residents are at particular risk from medication errors , and our objective was to determine the prevalence and potential harm of prescribing , monitoring , dispensing and administration errors in UK care homes , and to identify their causes . Methods : A prospect i ve study of a r and om sample of residents within a purposive sample of homes in three areas . Errors were identified by patient interview , note review , observation of practice and examination of dispensed items . Causes were understood by observation and from theoretically framed interviews with home staff , doctors and pharmacists . Potential harm from errors was assessed by expert judgement . Results : The 256 residents recruited in 55 homes were taking a mean of 8.0 medicines . One hundred and seventy-eight ( 69.5 % ) of residents had one or more errors . The mean number per resident was 1.9 errors . The mean potential harm from prescribing , monitoring , administration and dispensing errors was 2.6 , 3.7 , 2.1 and 2.0 ( 0 = no harm , 10 = death ) , respectively . Contrib
Output:
| There is limited evidence of the potential of these discrepancies to cause harm .
The studies reported conflicting findings regarding the impact of medication review on length of stays , readmissions , and mortality .
Conclusions : The evidence demonstrates that medication reconciliation has the potential to identify many medication discrepancies and reduce potential harm , but the impact on clinical outcomes is less clear .
Similarly , medication review can detect medication-related problems in many patients , but evidence of clinical impact is scant .
Overall , there is limited evidence that medication reconciliation and medication review processes , as currently performed , significantly improve clinical outcomes , such as reductions in hospital readmissions |
MS213774 | ***TASK*** the task is to summarize an input biomedical literature in six sentences
***INPUT*** the input is a biomedical literature
***OUTPUT*** the output is the summary of an input biomedical literature in six sentences
***DOCUMENTATION***
***EXAMPLES***
Input: The purpose of this study was to test the torque generating capabilities of three commercially available neuromuscular electrical stimulators ( NMES ) having different current characteristics . Twenty healthy adults were positioned in sitting on an isokinetic dynamometer . Maximum voluntary isometric knee extension torque was determined . Subsequently , two 10-sec , maximally tolerated contractions were elicited with each machine . The order of stimulation was r and omized and there were 2-minute rest periods between contractions . Electrically elicited torque values were expressed as a percentage of the maximal voluntary isometric torque ( % MVIT ) . Analysis of variance with one repeated measure showed a significant difference among % MVIT produced by the stimulators . NMES 2 ( Nemectrodyn 7 ) produced significantly less % MVIT than either NMES 1 ( Electrostim 180 - 2 ) or NMES 3 ( Chattanooga VMS ) . In all but three cases , NMES 2 's maximal current output was reached . Although all three devices were capable of producing % MVIT that has been shown to be sufficient for strengthening , it appears that NMES 2 does not have the capacity to provide " overload " as strength increases . J Orthop Sports Phys Ther 1989;10(8):297 - 301 The aim of the study was to investigate the uniformity of the muscle motor point location for lower limb muscles in healthy subjects . Fifty-three subjects of both genders ( age range : 18–50 years ) were recruited . The muscle motor points were identified for the following ten muscles of the lower limb ( dominant side ) : vastus medialis , rectus femoris , and vastus lateralis of the quadriceps femoris , biceps femoris , semitendinosus , and semimembranosus of the hamstring muscles , tibialis anterior , peroneus longus , lateral and medial gastrocnemius . The muscle motor point was identified by scanning the skin surface with a stimulation pen electrode and corresponded to the location of the skin area above the muscle in which an electrical pulse evoked a muscle twitch with the least injected current . For each investigated muscle , 0.15 ms square pulses were delivered through the pen electrode at low current amplitude ( < 10 mA ) and frequency ( 2 Hz ) . 16 motor points were identified in the 10 investigated muscles of almost all subjects : 3 motor points for the vastus lateralis , 2 motor points for rectus femoris , vastus medialis , biceps femoris , and tibialis anterior , 1 motor point for the remaining muscles . An important inter-individual variability was observed for the position of the following 4 out of 16 motor points : vastus lateralis ( proximal ) , biceps femoris ( short head ) , semimembranosus , and medial gastrocnemius . Possible implication s for electrical stimulation procedures and electrode positioning different from those commonly applied for thigh and leg muscles are discussed This study compared between alternating and pulsed current electrical muscle stimulation ( EMS ) for muscle oxygenation and blood volume during isometric contractions . Nine healthy men ( 23–48 years ) received alternating current EMS ( 2500 Hz ) modulated at 75 Hz on the knee extensors of one leg , and pulsed current EMS ( 75 Hz ) for the other leg separated by 2 weeks in a r and omised , counter-balanced order . Pulse duration ( 400 μs ) , on – off ratio ( 5–15 s ) and other stimulation parameters were matched between conditions and 30 isometric contractions were induced at the knee joint angle of 100 ° ( 0 ° full extension ) . Changes in tissue oxygenation index ( ∆TOI ) and total hemoglobin volume ( ∆tHb ) of vastus lateralis and medialis muscles over 30 contractions were assessed by a near-infrared spectroscopy , and were compared between conditions by a two-way repeated measures ANOVA . Peak torque produced during EMS increased over 30 contractions in response to the increase in the stimulation intensity for pulsed current , but not for the alternating current EMS . The torque during each isometric contraction was less stable in alternating than pulsed current EMS . The changes in ∆TOI amplitude during relaxation phases and ∆tHb amplitude were not significantly different between conditions . However , the decreases in ∆TOI amplitude during contraction phases from baseline were significantly ( P < 0.05 ) greater for the pulsed current than alternating current from the 18th contraction ( −15.6 ± 2.3 vs. −8.9 ± 1.8 % ) to 30th contraction ( −10.7 ± 1.8 vs. −4.8 ± 1.5 % ) . These results suggest that the muscles were less activated in the alternating current EMS when compared with the pulsed current EMS BACKGROUND AND PURPOSE Neuromuscular electrical stimulation is used by physical therapists to improve muscle performance . Optimal forms of stimulation setting s are yet to be determined , as are possible sex-related differences in responsiveness to electrical stimulation . The objectives of the study were : ( 1 ) to compare the ability of 3 different waveforms to generate isometric contractions of the quadriceps femoris muscles of individuals without known impairments , ( 2 ) to compare muscle fatigue caused by repeated contractions induced by these same waveforms , and ( 3 ) to examine the effect of sex on muscle force production and fatigue induced by electrical stimulation . SUBJECTS Fifteen women and 15 men ( mean age=29.5 years , SD=5.4 , range=22 - 38 ) participated in the study . METHODS A portable battery-operated stimulator was used to generate either a monophasic or biphasic rectangular waveform . A stimulator that was plugged into an electrical outlet was used to generate a 2,500-Hz alternating current . Phase duration , frequency , and on-off ratios were kept identical for both stimulators . Participants did not know the type of waveform being used . Torque was measured using a computerized dynamometer . A maximal voluntary isometric contraction ( MVIC ) of the right quadriceps femoris muscle set at 60 degrees of knee flexion was determined during the first session . In each of the 3 testing sessions , torque of contraction and fatigue elicited by one waveform were measured . Order of testing was r and omized . Torque elicited by electrical stimulation was expressed as a percentage of average MVIC . A mixed-model analysis of variance was used to determine the effect of stimulation and sex on strength of contraction and fatigue . Bonferroni-corrected post hoc tests were used to further distinguish between the effects of the 3 stimulus waveforms . RESULTS The results indicated that the monophasic and biphasic waveforms generated contractions with greater torque than the polyphasic waveform . These 2 waveforms also were less fatiguing . The torques from the maximally tolerated electrically elicited contractions were greater for the male subjects than for the female subjects . DISCUSSION AND CONCLUSION Muscle torque and fatigue of electrically induced contractions depend on the waveform used to stimulate the contraction , with monophasic and biphasic waveforms having an advantage over the polyphasic waveform . All tested waveforms elicited , on average , stronger contractions in male subjects than in female subjects when measured as a percentage of MVIC Objective The aim of this study was to investigate the effect of neuromuscular electrical stimulation burst duty cycle ( BDC ) and current type ( sinusoidal alternating current [ sAC ] vs. rectangular alternating current [ rAC ] ) on the electrically induced isometric torque ( EIT ) and discomfort . Pulsed current ( PC ) stimulation , which corresponds to one pulse rAC , was included in testing . Design A repeated- measures design was used . The left quadriceps of 22 healthy subjects ( mean ± SD age , 33 ± 8 yrs ) were stimulated alternately with sAC and rAC current bursts ( 4-kHz carrier frequency ; 71 bursts per second burst frequency ) to produce isometric contractions . A range of BDCs were tested for sAC ( 7%–50 % ) and rAC ( 2%–18 % ) stimulation at fixed intensities while EIT and discomfort were recorded . BDC presentation order was r and omized . Results Overall , both current types elicited peak EIT at ∼14 % BDC ( range , 7%–21 % ) . Significantly more EIT was produced by rAC than by sAC stimulation ( P < 0.005 ) . Discomfort increased with BDC and was similar for both current types . Conclusions The study confirmed previous findings that conventional sAC stimulation ( 50 % BDC ) and pulsed current stimulation ( rAC with 2 % BDC ) used in sports and rehabilitation produce similar EIT levels . However , rAC stimulation at low BDC ( 7%–18 % ) was more effective ( + 35 % torque produced with similar discomfort ) than pulsed current or conventional sAC Background and Purpose . A r and omized controlled trial to compare 2 forms of monophasic pulsed currents with 2 forms of burst-modulated , kilohertz-frequency alternating current ( “ Russian current ” and “ Aussie current ” ) was conducted to establish whether different amounts of wrist extensor torque were produced and whether discomfort varied with stimulus type . Subjects . The 32 subjects were adults who were healthy and were drawn from a population of staff and students at La Trobe University . Methods . Each subject received all 4 currents . Maximal electrically induced torque ( MEIT ) of the wrist extensors was measured for each stimulus type . Relative discomfort of stimulation also was assessed . Results . Russian current elicited lower mean torque than those elicited by Aussie current and monophasic pulsed currents . The Russian and Aussie currents elicited significantly less discomfort than the 2 monophasic pulsed currents . Discussion and Conclusion . When force production and relative discomfort were jointly used as the criteria , Aussie current was found to be more effective than either of the monophasic pulsed currents or Russian current stimulation In the GRADE approach , r and omized trials start as high- quality evidence and observational studies as low- quality evidence , but both can be rated down if a body of evidence is associated with a high risk of publication bias . Even when individual studies included in best- evidence summaries have a low risk of bias , publication bias can result in substantial overestimates of effect . Authors should suspect publication bias when available evidence comes from a number of small studies , most of which have been commercially funded . A number of approaches based on examination of the pattern of data are available to help assess publication bias . The most popular of these is the funnel plot ; all , however , have substantial limitations . Publication bias is likely frequent , and caution in the face of early results , particularly with small sample size and number of events , is warranted The aim of the study was to investigate the influence of two different transcutaneous neuromuscular electrical stimulation procedures on evoked muscle torque and local tissue oxygenation . In the first one ( MP mode ) , the cathode was facing the muscle main motor point and stimulus amplitude was set to the level eliciting the maximal myoelectrical activation according to the amplitude of the evoked electromyogram ( EMG ) ; in the second one ( RC mode ) , the electrodes were positioned following common reference charts for electrode placement while stimulus amplitude was set according to subject tolerance . Tibialis Anterior ( TA ) and Vastus Lateralis ( VL ) muscles of 10 subjects ( 28.4 ± 8.2 years ) were tested in specific dynamometers to measure the evoked isometric torque . The EMG and near-infrared spectroscopy probes were placed on muscle belly to detect the electrical activity and local metabolic modifications of the stimulated muscle , respectively . The stimulation protocol consisted of a gradually increasing frequency ramp from 2 to 50 Hz in 7.5 s. Compared to RC mode , in MP mode the contractile parameters ( peak twitch , tetanic torque , area under the torque build-up ) and the metabolic solicitation ( oxygen consumption and hyperemia due to metabolites accumulation ) result ed significantly higher for both TA and VL muscles . MP mode result ed also to be more comfortable for the subjects . Based on the assumption that proper mechanical and metabolic stimuli are necessary to induce muscle strengthening , our results witness the importance of an optimized , i.e. , comfortable and effective , stimulation to promote the aforementioned muscle adaptive modifications OBJECTIVE : To test the feasibility of creating a valid and reliable checklist with the following features : appropriate for assessing both r and omised and non-r and omised studies ; provision of both an overall score for study quality and a profile of scores not only for the quality of reporting , internal validity ( bias and confounding ) and power , but also for external validity . DESIGN : A pilot version was first developed , based on epidemiological principles , review s , and existing checklists for r and omised studies . Face and content validity were assessed by three experienced review ers and reliability was determined using two raters assessing 10 r and omised and 10 non-r and omised studies . Using different raters , the checklist was revised and tested for internal consistency ( Kuder-Richardson 20 ) , test-retest and inter-rater reliability ( Spearman correlation coefficient and sign rank test ; kappa statistics ) , criterion validity , and respondent burden . MAIN RESULTS : The performance of the checklist improved considerably after revision of a pilot version . The Quality Index had high internal consistency ( KR-20 : 0.89 ) as did the subscales apart from external validity ( KR-20 : 0.54 ) . Test-retest ( r 0.88 ) and inter-rater ( r 0.75 ) reliability of the Quality Index were good . Reliability of the subscales varied from good ( bias ) to poor ( external validity ) . The Quality Index correlated highly with an existing , established instrument for assessing r and omised studies ( r 0.90 ) . There was little difference between its performance with non
Output:
| Conclusions This meta- analysis does not establish that KFAC is superior to PC in increasing muscle-evoked torque and lessening discomfort level . |
MS213775 | ***TASK*** the task is to summarize an input biomedical literature in six sentences
***INPUT*** the input is a biomedical literature
***OUTPUT*** the output is the summary of an input biomedical literature in six sentences
***DOCUMENTATION***
***EXAMPLES***
Input: PURPOSE Recent studies have suggested an alpha/beta ratio in prostate cancer of 1.5 - 3 Gy , which is lower than that assumed for late-responsive normal tissues . Therefore the administration of a single , intraoperative dose of irradiation should represent a convenient irradiation modality in prostate cancer . MATERIAL S AND METHODS Between February 2002 and June 2004 , 34 patients with localized prostate cancer with only one risk factor ( Gleason score > or = 7 , Clinical Stage [ cT ] > or = 2c , or prostate-specific antigen [ PSA ] of 11 - 20 ng/mL ) and without clinical evidence of lymph node metastases were treated with radical prostatectomy ( RP ) and intraoperative radiotherapy on the tumor bed . A dose-finding procedure based on the Fibonacci method was employed . Dose levels of 16 , 18 , and 20 Gy were selected , which are biologically equivalent to total doses of about 60 - 80 Gy administered with conventional fractionation , using an alpha/beta ratio value of 3 . RESULTS At a median follow-up of 41 months , 24 ( 71 % ) patients were alive with an undetectable PSA value . No patients died from disease , whereas 2 patients died from other malignancies . Locoregional failures were detected in 3 ( 9 % ) patients , 2 in the prostate bed and 1 in the common iliac node chain outside the radiation field . A PSA rise without local or distant disease was observed in 7 ( 21 % ) cases . The overall 3-year biochemical progression-free survival rate was 77.3 % . CONCLUSIONS Our dose-finding study demonstrated the feasibility of intraoperative radiotherapy in prostate cancer also at the highest administered dose PURPOSE We evaluated patients at our institution who underwent radical prostatectomy for clinical stage T3 prostate cancer to determine their long-term clinical outcomes . MATERIAL S AND METHODS We review ed our prospect i ve surgical data base and identified 176 men who underwent radical retropubic prostatectomy for clinical stage T3 prostate cancer from 1983 to 2003 . Clinical and pathological data were review ed and evaluated in a Cox proportional hazards model to determine preoperative predictors of biochemical recurrence . Clinical progression following biochemical recurrence was evaluated and clinical failure was defined as the development of clinical metastases or progression to hormone refractory prostate cancer . RESULTS Of the 176 patients with cT3 prostate cancer 64 ( 36 % ) received neoadjuvant hormonal therapy . At a mean followup of 6.4 years 84 ( 48 % ) patients had disease recurrence with a median time to biochemical recurrence of 4.6 years . The actuarial 10-year probability of freedom from recurrence was 44 % . On multivariate analysis biopsy Gleason score , pretreatment serum prostate specific antigen and year of surgery were independent predictors of biochemical recurrence . Neoadjuvant hormonal therapy was not a significant predictor of biochemical recurrence . Following biochemical recurrence clinical failure developed in 30 of 84 ( 36 % ) men with a median time of 11 years . Overall the 5 , 10 and 15-year probabilities of death from prostate cancer were 6 % , 15 % and 24 % , respectively . CONCLUSIONS More than half ( 52 % ) of our patients remained free of disease recurrence following radical prostatectomy . In our series neoadjuvant hormonal therapy offered no advantage with respect to disease recurrence . Radical prostatectomy remains an integral component in the treatment of select patients with clinical stage T3 prostate cancer BACKGROUND To present the technique and dose distribution of intraoperative radiotherapy ( IORT ) for prostate cancer . PATIENTS AND METHODS Pelvic lymphadenectomy , prostate IORT and radical retropubic prostatectomy was performed in 11 prostate cancer patients . Prostate thickness and rectum depth were measured with intraoperative ultrasound . IORT was delivered by a mobile linear accelerator in the operating room ( electron beam , 12 Gy at 90 % isodose ) . RESULTS The mean preoperative probability of organ-confined disease was 10 % ( Memorial Sloan Kettering Cancer Center nomograms ) . Mean prostate thickness , width and length were 3.4 cm , 4.6 and 4.9 cm , respectively . Mean rectum depth was 3.3 cm . Mean doses to the posterior prostate capsule , 5-mm lateral prostate margins and at the subsequent uretheral stump area were 4.6 Gy , 8 . 7 Gy and 11.3 Gy , respectively . Maximum mean rectal dose was 4.9 Gy . CONCLUSION IORT appeared a feasible approach for prostate cancer , showing a satisfactory dose coverage to the prostate bed with relatively low rectal dose . However , high variability in dose distribution calls for further study of patient selection criteria and dosimetry Radiotherapy and and rogen deprivation in combination after local surgery ( RADICALS ) : A new Medical Research Council/National Cancer Institute of Canada phase III trial of adjuvant treatment after radical prostatectomy Chris Parker , Matthew R. Sydes 1 , Charles Catton 2 , Howard Kynaston 3 , John Logue , Claire Murphy 1 , Rachel C. Morgan 1 , Kilian Mellon 5 , Chris Morash 6 , Wendy Parulekar 7 , Mahesh K.B. Parmar 1 , Heather Payne 8 , Colleen Savage 7 , Jim Stansfeld 9 and Noel W. Clarke 10 ( The RADICALS Trial Management Group ) Academic Unit of Radiotherapy & Oncology , Institute of Cancer Research and the Royal , Marsden NHS Foundation Trust , Sutton , Surrey , 1 Medical Research Council ( MRC ) Clinical Trials Unit , London , UK , 2 Princess Margaret Hospital , Toronto , Ontario , Canada , 3 Department of Urology , University Hospital of Wales , Heath Park , Cardiff , 4 Christie Hospital NHS Trust , Manchester , UK , 5 Urology Section , University of Leicester , UK , 6 University of Ottawa , The Ottawa Hospital General Campus , Ottawa , 7 National Cancer Institute of Canada ( NCIC ) Clinical Trials Group , Kingston , Ontario , Canada , 8 Department of Oncology , University College Hospital , London , UK , 9 Hon . Treasurer , PCaSO Prostate Cancer Network , Emsworth , Hants , UK , 10 Salford Royal Hospitals NHS Trust , Salford , BACKGROUND We did a r and omised phase III trial comparing external irradiation alone and external irradiation combined with an analogue of luteinising-hormone releasing hormone ( LHRH ) to investigate the added value of long-term and rogen suppression in locally advanced prostate cancer . METHODS Between 1987 and 1995 , 415 patients were r and omly assigned radiotherapy alone or radiotherapy plus immediate and rogen suppression . Eligible patients had T1 - 2 tumours of WHO grade 3 or T3 - 4 N0 - 1 M0 tumours ; the median age of participants was 71 years ( range 51 - 80 ) . In both treatment groups , 50 Gy radiation was delivered to the pelvis over 5 weeks , and 20 Gy over 2 weeks as a prostatic boost . Goserelin ( 3.6 mg subcutaneously every 4 weeks ) was started on the first day of irradiation and continued for 3 years ; cyproterone acetate ( 150 mg orally ) was given for 1 month starting 1 week before the first goserelin injection . The primary endpoint was clinical disease-free survival . Analyses were by intention to treat . FINDINGS 412 patients had evaluable data , with median follow-up of 66 months ( range 1 - 126 ) . 5-year clinical disease-free survival was 40 % ( 95 % CI 32 - 48 ) in the radiotherapy-alone group and 74 % ( 67 - 81 ) in the combined-treatment group ( p=0.0001 ) . 5-year overall survival was 62 % ( 52 - 72 ) and 78 % ( 72 - 84 ) , respectively ( p=0.0002 ) and 5-year specific survival 79 % ( 72 - 86 ) and 94 % ( 90 - 98 ) . INTERPRETATION Immediate and rogen suppression with an LHRH analogue given during and for 3 years after external irradiation improves disease-free and overall survival of patients with locally advanced prostate cancer CONTEXT Despite a stage-shift to earlier cancer stages and lower tumor volumes for prostate cancer , pathologically advanced disease is detected at radical prostatectomy in 38 % to 52 % of patients . However , the optimal management of these patients after radical prostatectomy is unknown . OBJECTIVE To determine whether adjuvant radiotherapy improves metastasis-free survival in patients with stage pT3 N0 M0 prostate cancer . DESIGN , SETTING , AND PATIENTS R and omized , prospect i ve , multi-institutional , US clinical trial with enrollment between August 15 , 1988 , and January 1 , 1997 ( with data base frozen for statistical analysis on September 21 , 2005 ) . Patients were 425 men with pathologically advanced prostate cancer who had undergone radical prostatectomy . INTERVENTION Men were r and omly assigned to receive 60 to 64 Gy of external beam radiotherapy delivered to the prostatic fossa ( n = 214 ) or usual care plus observation ( n = 211 ) . MAIN OUTCOME MEASURES Primary outcome was metastasis-free survival , defined as time to first occurrence of metastatic disease or death due to any cause . Secondary outcomes included prostate-specific antigen ( PSA ) relapse , recurrence-free survival , overall survival , freedom from hormonal therapy , and postoperative complications . RESULTS Among the 425 men , median follow-up was 10.6 years ( interquartile range , 9.2 - 12.7 years ) . For metastasis-free survival , 76 ( 35.5 % ) of 214 men in the adjuvant radiotherapy group were diagnosed with metastatic disease or died ( median metastasis-free estimate , 14.7 years ) , compared with 91 ( 43.1 % ) of 211 ( median metastasis-free estimate , 13.2 years ) of those in the observation group ( hazard ratio [ HR ] , 0.75 ; 95 % CI , 0.55 - 1.02 ; P = .06 ) . There were no significant between-group differences for overall survival ( 71 deaths , median survival of 14.7 years for radiotherapy vs 83 deaths , median survival of 13.8 years for observation ; HR , 0.80 ; 95 % CI , 0.58 - 1.09 ; P = .16 ) . PSA relapse ( median PSA relapse-free survival , 10.3 years for radiotherapy vs 3.1 years for observation ; HR , 0.43 ; 95 % CI , 0.31 - 0.58 ; P<.001 ) and disease recurrence ( median recurrence-free survival , 13.8 years for radiotherapy vs 9.9 years for observation ; HR , 0.62 ; 95 % CI , 0.46 - 0.82 ; P = .001 ) were both significantly reduced with radiotherapy . Adverse effects were more common with radiotherapy vs observation ( 23.8 % vs 11.9 % ) , including rectal complications ( 3.3 % vs 0 % ) , urethral strictures ( 17.8 % vs 9.5 % ) , and total urinary incontinence ( 6.5 % vs 2.8 % ) . CONCLUSIONS In men who had undergone radical prostatectomy for pathologically advanced prostate cancer , adjuvant radiotherapy result ed in significantly reduced risk of PSA relapse and disease recurrence , although the improvements in metastasis-free survival and overall survival were not statistically significant . Trial Registration clinical trials.gov Identifier : NCT00394511
Output:
| IOERT represents a feasible technique with acceptable surgical time and minimal toxicity . |
MS213776 | ***TASK*** the task is to summarize an input biomedical literature in six sentences
***INPUT*** the input is a biomedical literature
***OUTPUT*** the output is the summary of an input biomedical literature in six sentences
***DOCUMENTATION***
***EXAMPLES***
Input: O(6)-methylguanine DNA-methyltransferase ( MGMT ) promoter methylation status is a prognostic factor in newly diagnosed glioblastoma patients . However , it is not yet clear whether , and if so how , MGMT methylation status may change . Moreover , it is unknown whether the prognostic role of this epigenetic feature is retained during the disease course . A retrospective analysis was made using a data base of 614 glioblastoma patients treated prospect ively from January 2000 to August 2008 . We evaluated only patients who met the following inclusion criteria : age > or = 18 years ; performance status 0 - 2 ; histological diagnosis of glioblastoma at both first and second surgery for recurrence ; postoperative treatment consisting of : ( i ) radiotherapy ( RT ) followed by adjuvant temozolomide ( TMZ ) until 2005 and ( ii ) TMZ concurrent with and adjuvant to RT after 2005 ; a time interval > or = 3 months between first and second surgery . MGMT status was evaluated at first and second surgery in all 44 patients ( M : F 32:12 , median age : 49 years , range : 27 - 67 years ) . In 38 patients ( 86.4 % ) , MGMT promoter status was assessable at both first and second surgery . MGMT methylation status , changed in 14 patients ( 37 % ) of second surgery sample s and more frequently in methylated than in unmethylated patients ( 61.5 % vs 24 % , P = .03 ) . The median survival was significantly influenced only by MGMT methylation status determined at first surgery ( P = .04 ) . Significant changes in MGMT methylation status during the course of GBM occur more frequently in MGMT methylated than unmethylated cases . MGMT methylation status determined at first surgery appears to be of prognostic value ; however , it is not predictive of outcome following second surgery Hypermethylation in the promoter region of the MGMT gene encoding the DNA repair protein O6-methylguanine-DNA methyltransferase is among the most important prognostic factors for patients with glioblastoma and predicts response to treatment with alkylating agents like temozolomide . Hence , the MGMT status is widely determined in most clinical trials and frequently requested in routine diagnostics of glioblastoma . Since various different techniques are available for MGMT promoter methylation analysis , a generally accepted consensus as to the most suitable diagnostic method remains an unmet need . Here , we assessed methylation-specific polymerase chain reaction ( MSP ) as a qualitative and semi-quantitative method , pyrosequencing ( PSQ ) as a quantitative method , and methylation-specific multiplex ligation-dependent probe amplification ( MS-MLPA ) as a semi-quantitative method in a series of 35 formalin-fixed , paraffin-embedded glioblastoma tissues derived from patients treated in a prospect i ve clinical phase II trial that tested up-front chemoradiotherapy with dose-intensified temozolomide ( UKT-05 ) . Our goal was to determine which of these three diagnostic methods provides the most accurate prediction of progression-free survival ( PFS ) . The MGMT promoter methylation status was assessable by each method in almost all cases ( n = 33/35 for MSP ; n = 35/35 for PSQ ; n = 34/35 for MS-MLPA ) . We were able to calculate significant cut-points for the continuous methylation signals at each CpG site analysed by PSQ ( range , 11.5 to 44.9 % ) and at one CpG site assessed by MS-MLPA ( 3.6 % ) indicating that a dichotomisation of continuous methylation data as a prerequisite for comparative survival analyses is feasible . Our results show that , unlike MS-MLPA , MSP and PSQ provide a significant improvement of predicting PFS compared with established clinical prognostic factors alone ( likelihood ratio tests : p<0.001 ) . Conclusively , taking into consideration prognostic value , cost effectiveness and ease of use , we recommend pyrosequencing for analyses of MGMT promoter methylation in high-throughput setting s and MSP for clinical routine diagnostics with low sample numbers BACKGROUND A r and omised trial published by the European Organisation for Research and Treatment of Cancer ( EORTC ) and the National Cancer Institute of Canada ( NCIC ) Clinical Trials Group ( trial 26981 - 22981/CE.3 ) showed that addition of temozolomide to radiotherapy in the treatment of patients with newly diagnosed glioblastoma significantly improved survival . We aim ed to undertake an exploratory sub analysis of the EORTC and NCIC data to confirm or identify new prognostic factors for survival in adult patients with glioblastoma , derive nomograms that predict an individual patient 's prognosis , and suggest stratification factors for future trials . METHODS Data from 573 patients with newly diagnosed glioblastoma who were r and omly assigned to radiotherapy alone or to the same radiotherapy plus temozolomide in the EORTC and NCIC trial were included in this sub analysis . Survival modelling was done in three patient population s : intention-to-treat population of all r and omised patients ( population 1 ) ; patients assigned temozolomide and radiotherapy ( population 2 , n=287 ) ; and patients assigned temozolomide and radiotherapy who had assessment of MGMT promoter methylation status and who had undergone tumour resection ( population 3 , n=103 ) . Cox proportional hazards models were fitted with and without O6-methylguanine-DNA methyltransferase ( MGMT ) promoter methylation status . Nomograms were developed to predict an individual patient 's median and 2-year survival probabilities . No nomogram was developed in the radiotherapy-alone group because combined treatment is now the new st and ard of care . FINDINGS Independent of the MGMT promoter methylation status , analysis in all r and omised patients ( population 1 ) identified combined treatment with temozolomide , more extensive tumour resection , younger age , Mini-Mental State Examination ( MMSE ) score of 27 or higher , and no corticosteroid treatment at baseline as independent prognostic factors correlated with improved survival outcome . In patients assigned temozolomide and radiotherapy ( population 2 ) , younger age , better performance status , more extensive tumour resection , and MMSE score of 27 or higher were associated with better survival . In patients who had tumours resected , who were assigned temozolomide and radiotherapy , and who had available MGMT promoter methylation status ( population 3 ) , methylated MGMT , better performance status , and MMSE score of 27 or higher were associated with improved survival . Nomograms were developed and are available at http://www.eortc.be/tools/g bmc alculator . INTERPRETATION MGMT promoter methylation status , age , performance status , extent of resection , and MMSE are suggested as eligibility or stratification factors for future trials in patients with newly diagnosed glioblastoma . Stratifying by MGMT promoter methylation status should be m and atory in all glioblastoma trials that use alkylating chemotherapy . Nomograms can be used to predict an individual patient 's prognosis , and they integrate pertinent molecular information that is consistent with a paradigm shift towards individualised patient management PURPOSE O6-methylguanine-methyltransferase ( MGMT ) promoter methylation has been shown to predict survival of patients with glioblastomas if temozolomide is added to radiotherapy ( RT ) . It is unknown if MGMT promoter methylation is also predictive to outcome to RT followed by adjuvant procarbazine , lomustine , and vincristine ( PCV ) chemotherapy in patients with anaplastic oligodendroglial tumors ( AOT ) . PATIENTS AND METHODS In the European Organisation for the Research and Treatment of Cancer study 26951 , 368 patients with AOT were r and omly assigned to either RT alone or to RT followed by adjuvant PCV . From 165 patients of this study , formalin-fixed , paraffin-embedded tumor tissue was available for MGMT promoter methylation analysis . This was investigated with methylation specific multiplex ligation-dependent probe amplification . RESULTS In 152 cases , an MGMT result was obtained , in 121 ( 80 % ) cases MGMT promoter methylation was observed . Methylation strongly correlated with combined loss of chromosome 1p and 19q loss ( P = .00043 ) . In multivariate analysis , MGMT promoter methylation , 1p/19q codeletion , tumor necrosis , and extent of resection were independent prognostic factors . The prognostic significance of MGMT promoter methylation was equally strong in the RT arm and the RT/PCV arm for both progression-free survival and overall survival . In tumors diagnosed at central pathology review as glioblastoma , no prognostic effect of MGMT promoter methylation was observed . CONCLUSION In this study , on patients with AOT MGMT promoter methylation was of prognostic significance and did not have predictive significance for outcome to adjuvant PCV chemotherapy . The biologic effect of MGMT promoter methylation or pathogenetic features associated with MGMT promoter methylation may be different for AOT compared with glioblastoma In 2011 , we reported a predominant prognostic/predictive role of MGMT promoter methylation status on progression-free survival ( PFS ) in unresectable glioblastoma patients undergoing upfront radiotherapy plus concomitant and maintenance temozolomide ( RTX/TMZ → TMZ ) . We , here , present the final results of this prospect i ve study focussing on the prognostic/predictive value of MGMT promoter methylation status for death risk stratification . Overall , 56 adult patients with unresectable , biopsy proven glioblastoma were prospect ively assigned to upfront RTX/TMZ → TMZ treatment between March 2006 and August 2008 . Last follow-up was performed in June 2016 . MGMT promoter methylation was determined using methylation-specific PCR ( MSP ) and sodium bisulfite sequencing . Analyses were done by intention to treat . Prognostic factors were obtained from proportional hazard models . At the time of the final analysis 55 patients showed progressive disease and 53 patients had died . MGMT promoter was methylated ( unmethylated ) in 30 ( 26 ) patients . Methylation of the MGMT promoter was the strongest favorable predictor for overall survival ( OS , median : 20.3 vs. 7.3 months , p < 0.001 , HR 0.30 , 95 % CI 0.16–0.55 ) , and PFS ( median : 15.0 vs. 6.1 months , p < 0.001 , HR 0.31 , 95 % CI 0.17–0.57 ) and was also associated with higher frequencies of treatment response and prolonged post-recurrence survival ( PRS , median : 4.5 vs. 1.4 months , p < 0.002 , HR 0.39 , 95 % CI 0.21–0.71 ) . Knowledge of MGMT promoter methylation status is essential for patients ’ counseling , prognostic evaluation , and for the design of future trials dealing with unresectable glioblastomas PURPOSE Glioblastomas are notorious for resistance to therapy , which has been attributed to DNA-repair proficiency , a multitude of deregulated molecular pathways , and , more recently , to the particular biologic behavior of tumor stem-like cells . Here , we aim ed to identify molecular profiles specific for treatment resistance to the current st and ard of care of concomitant chemoradiotherapy with the alkylating agent temozolomide . PATIENTS AND METHODS Gene expression profiles of 80 glioblastomas were interrogated for associations with resistance to therapy . Patients were treated within clinical trials testing the addition of concomitant and adjuvant temozolomide to radiotherapy . RESULTS An expression signature dominated by HOX genes , which comprises Prominin-1 ( CD133 ) , emerged as a predictor for poor survival in patients treated with concomitant chemoradiotherapy ( n = 42 ; hazard ratio = 2.69 ; 95 % CI , 1.38 to 5.26 ; P = .004 ) . This association could be vali date d in an independent data set . Provocatively , the HOX cluster was reminiscent of a " self-renewal " signature ( P = .008 ; Gene Set Enrichment Analysis ) recently characterized in a mouse leukemia model . The HOX signature and EGFR expression were independent prognostic factors in multivariate analysis , adjusted for the O-6-methylguanine-DNA methyltransferase ( MGMT ) methylation status , a known predictive factor for benefit from temozolomide , and age . Better outcome was associated with gene clusters characterizing features of tumor-host interaction including tumor vascularization and cell adhesion , and innate immune response . CONCLUSION This study provides first clinical evidence for the implication of a " glioma stem cell " or " self-renewal " phenotype in treatment resistance of glioblastoma . Biologic mechanisms identified here to be relevant for resistance will guide future targeted therapies and
Output:
| In each subgroup divided by areas , the prognostic significance still remained highly significant .
The proportion of methylation in each group was in inverse proportion to the corresponding HR in the univariate and multivariate analyses of PFS .
However , from the perspective of OS , compared with data from Europe and the US , higher methylation rates in Asia did not bring better returns |
MS213777 | ***TASK*** the task is to summarize an input biomedical literature in six sentences
***INPUT*** the input is a biomedical literature
***OUTPUT*** the output is the summary of an input biomedical literature in six sentences
***DOCUMENTATION***
***EXAMPLES***
Input: Purpose To evaluate the efficacy and safety of the combination of gemcitabine ( GEM ) and S-1 ( GS ) in comparison to GEM alone ( G ) for unresectable pancreatic cancer . Methods In this multicenter r and omized phase II study , we r and omly assigned unresectable pancreatic cancer patients to either the GS group or the G group . The GS group regimen consists of intravenous 1,000 mg/m2 GEM during 30 min on days 1 and 8 , combined with 80 mg/m2 oral S-1 twice daily on days 1–14 , repeated every 3 weeks . On the other h and , the G group regimen consists of intravenous 1,000 mg/m2 GEM on days 1 , 8 , and 15 , repeated every 4 weeks . The primary endpoint was objective response rate ( ORR ) . Secondary end points included treatment toxicity , clinical response benefit , progression-free survival ( PFS ) , and overall survival . Results We registered 117 patients from 16 institutions between June 2007 and August , 2010 . The ORR of the GS group was 28.3 % , whereas that of the G group was 6.8 % . This difference was statistically significant ( P = 0.005 ) . The disease control rate was 64.2 % in the GS group and 44.1 % in the G group . Median PFS was 6.15 months in the GS group and 3.78 month in the G group . This was also statistically significant ( P = 0.0007 ) . Moreover , the median overall survival ( OS ) of the GS group was significantly longer than that of the G group ( 13.7 months vs. 8.0 months ; P = 0.035 ) . The major grade 3–4 adverse events were neutropenia ( 54.7 % in the GS group and 22.0 % in the G group ) , thrombocytopenia ( 15.1 % in the GS group and 5.1 % in the G group ) , and skin rash ( 9.4 % in the GS group ) . Conclusions The GS group showed stronger anticancer activity than the G group , suggesting the need for a large r and omized phase III study to confirm GS advantages in a specific subset Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more Background : This r and omised phase II trial compared gemcitabine alone vs gemcitabine and S-1 combination therapy in advanced pancreatic cancer . Methods : Patients were r and omly assigned to 4-week treatment with gemcitabine alone ( 1000 , mg m−2 gemcitabine by 30-min infusion on days 1 , 8 , and 15 ) or gemcitabine and S-1 combination therapy ( 1000 , mg m−2 gemcitabine by 30-min infusion on days 1 and 15 and 40 mg m−2 S-1 orally twice daily on days 1–15 ) . The primary end point was progression-free survival ( PFS ) . Results : Between July 2006 and February 2009 , 106 patients were enrolled . The PFS in gemcitabine and S-1 combination arm was significantly longer than in gemcitabine arm ( 5.4 vs 3.6 months ) , with a hazard ratio of 0.64 ( P=0.036 ) . Overall survival ( OS ) for gemcitabine and S-1 combination was longer than that for gemcitabine monotherapy ( 13.5 vs 8.8 months ) , with a hazard ratio of 0.72 ( P=0.104 ) . Overall , grade 3 or 4 adverse events were similar in both arms . Conclusion : Gemcitabine and S-1 combination therapy demonstrated longer PFS in advanced pancreatic cancer . Improved OS duration of 4.7 months was found for gemcitabine and S-1 combination therapy , though this was not statistically significant Abstract Purpose To evaluate the efficacy and safety of combined gemcitabine and S-1 as first-line chemotherapy for patients with locally advanced or metastatic pancreatic cancer . Methods This study included patients who had been diagnosed with unresectable , locally advanced or metastatic adenocarcinoma arising from the pancreas , which was histologically or cytologically confirmed and involved at least 1 unidimensionally measurable lesion . The regimen consisted of intravenous 1,000 mg/m2 gemcitabine on day 1 and 8 combined with oral S-1 on days 1–14 every 21 days . The dosage of S-1 was based on the body surface area ( BSA ) as follows : 40 mg bid ( total 80 mg/day ) for a BSA of < 1.25 , 50 mg bid ( total 100 mg/day ) for a BSA of ≥1.25 but < 1.5 , and 60 mg bid ( total 120 mg/day ) for a BSA of ≥1.5 . Treatment consisted of at least 2 courses unless rapid disease progression was noted . The primary end points were the response and disease control rates , and the secondary end points were toxicity and survival . Results Thirty-seven patients were enrolled between August 2005 and December 2010 . The median number of chemotherapy cycles was 4 ( range 1–28 cycles ) . Response to treatment could be evaluated in 31 patients . None of the patients showed complete response , but 5 achieved partial response . The response rate was thus 13.5 % [ 95 % confidence interval ( CI ) 2.7–24.3 % ] in the intent-to-treat population . Sixteen patients ( 43.2 % ; 95 % CI 27–59.5 % ) showed stable disease , and the overall disease control rate was 56.8 % ( 95 % CI 40.6–72.9 % ) . For all 37 patients , the median progression-free survival was 4.6 months ( 95 % CI 1.8–7.6 month ) , and the median overall survival was 9.4 month ( 95 % CI 5.8–12.6 month ) . Chemotherapy-related grade 3/4 hematological toxicities were neutropenia ( 36.1 % ) , leucopenia ( 22.2 % ) , and anemia ( 13.9 % ) . The non-hematological toxicities were generally mild . Conclusions Combination chemotherapy with gemcitabine and S-1 was effective , convenient , and safe in patients with advanced pancreatic cancer PURPOSE The purpose of this trial was to evaluate the role of radiation therapy with concurrent gemcitabine ( GEM ) compared with GEM alone in patients with localized unresectable pancreatic cancer . PATIENTS AND METHODS Patients with localized unresectable adenocarcinoma of the pancreas were r and omly assigned to receive GEM alone ( at 1,000 mg/m(2)/wk for weeks 1 to 6 , followed by 1 week rest , then for 3 of 4 weeks ) or GEM ( 600 mg/m(2)/wk for weeks 1 to 5 , then 4 weeks later 1,000 mg/m(2 ) for 3 of 4 weeks ) plus radiotherapy ( starting on day 1 , 1.8 Gy/Fx for total of 50.4 Gy ) . Measurement of quality of life using the Functional Assessment of Cancer Therapy-Hepatobiliary question naire was also performed . RESULTS Of 74 patients entered on trial and r and omly assigned to receive GEM alone ( arm A ; n = 37 ) or GEM plus radiation ( arm B ; n = 34 ) , patients in arm B had greater incidence of grade s 4 and 5 toxicities ( 41 % v 9 % ) , but grade s 3 and 4 toxicities combined were similar ( 77 % in A v 79 % in B ) . No statistical differences were seen in quality of life measurements at 6 , 15 to 16 , and 36 weeks . The primary end point was survival , which was 9.2 months ( 95 % CI , 7.9 to 11.4 months ) and 11.1 months ( 95 % CI , 7.6 to 15.5 months ) for arms A and B , respectively ( one-sided P = .017 by stratified log-rank test ) . CONCLUSION This trial demonstrates improved overall survival with the addition of radiation therapy to GEM in patients with localized unresectable pancreatic cancer , with acceptable toxicity Purpose The aim of this study was to evaluate efficacy and safety of gemcitabine plus S-1 ( GS ) combination chemotherapy in patients with unresectable pancreatic cancer . Methods Patients were r and omly assigned to receive GS ( oral S-1 60 mg/m2 daily on days 1–15 every 3 weeks and gemcitabine 1,000 mg/m2 on days 8 and 15 ) or gemcitabine ( 1,000 mg/m2 on days 1 , 8 , and 15 every 4 weeks ) . The primary endpoint was progression-free survival ( PFS ) . Results One hundred and one patients were r and omly assigned . PFS was significantly longer in the GS arm with an estimated hazard ratio ( HR ) of 0.65 ( 95 % CI 0.43–0.98 ; P = 0.039 ; median 5.3 vs 3.8 months ) . Objective response rate ( ORR ) was also better in the GS arm ( 21.6 vs 6 % , P = 0.048 ) . Median survival was 8.6 months for GS and 8.6 months for GEM ( HR 0.93 ; 95 % CI 0.61–1.41 ; P = 0.714 ) . Grade 3–4 neutropenia ( 44 vs 19.6 % , P = 0.011 ) and thrombocytopenia ( 26 vs 8.7 % , P = 0.051 ) were more frequent in the GS arm . Conclusions GS therapy improved PFS and ORR with acceptable toxicity profile in patients with unresectable pancreatic cancer PURPOSE Most patients with advanced pancreas cancer experience pain and must limit their daily activities because of tumor-related symptoms . To date , no treatment has had a significant impact on the disease . In early studies with gemcitabine , patients with pancreas cancer experienced an improvement in disease-related symptoms . Based on those findings , a definitive trial was performed to assess the effectiveness of gemcitabine in patients with newly diagnosed advanced pancreas cancer . PATIENTS AND METHODS One hundred twenty-six patients with advanced symptomatic pancreas cancer completed a lead-in period to characterize and stabilize pain and were r and omized to receive either gemcitabine 1,000 mg/m2 weekly x 7 followed by 1 week of rest , then weekly x 3 every 4 weeks thereafter ( 63 patients ) , or to fluorouracil ( 5-FU ) 600 mg/m2 once weekly ( 63 patients ) . The primary efficacy measure was clinical benefit response , which was a composite of measurements of pain ( analgesic consumption and pain intensity ) , Karnofsky performance status , and weight . Clinical benefit required a sustained ( > or = 4 weeks ) improvement in at least one parameter without worsening in any others . Other measures of efficacy included response rate , time to progressive disease , and survival . RESULTS Clinical benefit response was experienced by 23.8 % of gemcitabine-treated patients compared with 4.8 % of 5-FU-treated patients ( P = .0022 ) . The median survival duration s were 5.65 and 4.41 months for gemcitabine-treated and 5-FU-treated patients , respectively ( P = .0025 ) . The survival rate at 12 months was 18 % for gemcitabine patients and 2 % for 5-FU patients . Treatment was well tolerated . CONCLUSION This study demonstrates that gemcitabine is more effective than 5-FU in alleviation of some disease-related symptoms in patients with advanced , symptomatic pancreas cancer . Gemcitabine also confers a modest survival advantage over treatment with 5-FU BACKGROUND The long-term prognosis for localized pancreatic cancer ( PC ) remains poor . Three r and omized trials ( GEST phase III , JACCRO PC-01 phase II and GEMSAP phase II ) evaluated gemcitabine ( Gem ) with or without S-1 for patients with metastatic and locally advanced PC . A pooled analysis based on published data examined whether Gem with S-1 ( GS ) is superior to Gem alone in overall survival ( OS ) in patients with locally advanced PC . METHODS Data were extracted on 193 patients : 31 ( JACCRO ) , 28 ( GEMSAP ) , and 134 ( GEST ) . OS was used for primary endpoint and progression-free survival ( PFS ) was used for secondary endpoint . A general variance-based method was used to estimate the pooled HR and 95 % CI between GS ( n = 96 ) and Gem ( n = 97 ) . RESULTS Meta- analysis demonstrated that the overall risk of death was significantly different between the two chemotherapies ( hazard ratio = 0.673 , 95 % confidence interval : 0.488 - 0.929 , P = 0.016 ) . The median PFSs for GS and GEM in the JACCRO , GEMSAP , and GEST studies
Output:
| Discussion : Overall response rate and disease control rate as well as 1-year survival rate in patients who received GS were superior to those treated with GEM alone .
Combination chemotherapy with GEM and S-1 may offer greater benefits in the treatment of pancreatic cancer than GEM alone , although the GS group had higher haematological toxicities .
Combination chemotherapy with GEM and S-1 might be an option of first-line chemotherapy for pancreatic cancer patients , at least in Asia .
Mini Abstract : This systematic review analysing r and omized controlled trials ( RCTs ) comparing S-1 combination chemotherapy versus GEM alone for locally advanced and metastatic pancreatic cancer demonstrated greater efficacy for S-1 combination in term of response , disease control and 1-year survival proportion |
MS213778 | ***TASK*** the task is to summarize an input biomedical literature in six sentences
***INPUT*** the input is a biomedical literature
***OUTPUT*** the output is the summary of an input biomedical literature in six sentences
***DOCUMENTATION***
***EXAMPLES***
Input: PURPOSE To perform a r and omized trial comparing 70 and 80 Gy radiotherapy for prostate cancer . PATIENTS AND METHODS A total of 306 patients with localized prostate cancer were r and omized . No and rogen deprivation was allowed . The primary endpoint was biochemical relapse according to the modified 1997-American Society for Therapeutic Radiology and Oncology and Phoenix definitions . Toxicity was grade d using the Radiation Therapy Oncology Group 1991 criteria and the late effects on normal tissues-subjective , objective , management , analytic scales ( LENT-SOMA ) scales . The patients ' quality of life was scored using the European Organization for Research and Treatment of Cancer Quality of Life Question naire 30-item cancer-specific and 25-item prostate-specific modules . RESULTS The median follow-up was 61 months . According to the 1997-American Society for Therapeutic Radiology and Oncology definition , the 5-year biochemical relapse rate was 39 % and 28 % in the 70- and 80-Gy arms , respectively ( p = .036 ) . Using the Phoenix definition , the 5-year biochemical relapse rate was 32 % and 23.5 % , respectively ( p = .09 ) . The subgroup analysis showed a better biochemical outcome for the higher dose group with an initial prostate-specific antigen level > 15 ng/mL. At the last follow-up date , 26 patients had died , 10 of their disease and none of toxicity , with no differences between the two arms . According to the Radiation Therapy Oncology Group scale , the Grade 2 or greater rectal toxicity rate was 14 % and 19.5 % for the 70- and 80-Gy arms ( p = .22 ) , respectively . The Grade 2 or greater urinary toxicity was 10 % at 70 Gy and 17.5 % at 80 Gy ( p = .046 ) . Similar results were observed using the LENT-SOMA scale . Bladder toxicity was more frequent at 80 Gy than at 70 Gy ( p = .039 ) . The quality -of-life question naire results before and 5 years after treatment were available for 103 patients with no differences found between the 70- and 80-Gy arms . CONCLUSION High-dose radiotherapy provided a better 5-year biochemical outcome with slightly greater toxicity PURPOSE To evaluate the acute toxicities of hypofractionated accelerated radiotherapy ( RT ) using a concomitant intensity-modulated RT boost in conjunction with elective pelvic nodal irradiation for high-risk prostate cancer . METHODS AND MATERIAL S This report focused on 66 patients entered into this prospect i ve Phase I study . The eligible patients had clinical ly localized prostate cancer with at least one of the following high-risk features ( Stage T3 , Gleason score > or=8 , or prostate-specific antigen level > 20 ng/mL ) . Patients were treated with 45 Gy in 25 fractions to the pelvic lymph nodes using a conventional four-field technique . A concomitant intensity-modulated radiotherapy boost of 22.5 Gy in 25 fractions was delivered to the prostate . Thus , the prostate received 67.5 Gy in 25 fractions within 5 weeks . Next , the patients underwent 3 years of adjuvant and rogen ablative therapy . Acute toxicities were assessed using the Common Terminology Criteria for Adverse Events , version 3.0 , weekly during treatment and at 3 months after RT . RESULTS The median patient age was 71 years . The median pretreatment prostate-specific antigen level and Gleason score was 18.7 ng/L and 8 , respectively . Grade 1 - 2 genitourinary and gastrointestinal toxicities were common during RT but most had settled at 3 months after treatment . Only 5 patients had acute Grade 3 genitourinary toxicity , in the form of urinary incontinence ( n = 1 ) , urinary frequency/urgency ( n = 3 ) , and urinary retention ( n = 1 ) . None of the patients developed Grade 3 or greater gastrointestinal or Grade 4 or greater genitourinary toxicity . CONCLUSION The results of the present study have indicated that hypofractionated accelerated RT with a concomitant intensity-modulated RT boost and pelvic nodal irradiation is feasible with acceptable acute toxicity The objectives of this study were to evaluate dosimetric quality and acute toxicity of volumetric-modulated arc therapy ( VMAT ) and daily image guidance in high-risk prostate cancer patients . A total of 100 consecutive high-risk prostate cancer patients treated with definitive VMAT with prophylactic whole-pelvic radiotherapy ( WPRT ) were enrolled . All patients were treated with a double-arc VMAT plan delivering 52 Gy to the prostate planning target volume ( PTV ) , while simultaneously delivering 46.8 Gy to the pelvic nodal PTV in 26 fractions , followed by a single-arc VMAT plan delivering 26 Gy to the prostate PTV in 13 fractions . Image-guided RT was performed with daily cone-beam computed tomography . Dose – volume parameters for the PTV and the organs at risk ( OARs ) , total number of monitor units ( MUs ) and treatment time were evaluated . Acute toxicity was assessed using the Common Terminology Criteria for Adverse Events , version 4.0 . All dosimetric parameters met the present plan acceptance criteria . Mean MU and treatment time were 471 and 146 s for double-arc VMAT , respectively , and were 520 and 76 s for single-arc VMAT , respectively . No Grade 3 or higher acute toxicity was reported . Acute Grade 2 proctitis , diarrhea , and genitourinary toxicity occurred in 12 patients ( 12 % ) , 6 patients ( 6 % ) and 13 patients ( 13 % ) , respectively . The present study demonstrated that VMAT for WPRT in prostate cancer results in favorable PTV coverage and OAR sparing with short treatment time and an acceptable rate of acute toxicity . These findings support the use of VMAT for delivering WPRT to high-risk prostate cancer patients PURPOSE To report acute toxicity result ing from radiotherapy ( RT ) dose escalation and hypofractionation using intensity-modulated RT ( IMRT ) treatment combined with and rogen suppression in high-risk prostate cancer patients . METHODS AND MATERIAL S Sixty patients with a histological diagnosis of high-risk prostatic adenocarcinoma ( having either a clinical Stage of > or = T3a or an initial prostate-specific antigen [ PSA ] level of > or = 20 ng/ml or a Gleason score of 8 to 10 or a combination of a PSA concentration of > 15 ng/ml and a Gleason score of 7 ) were enrolled . RT prescription was 68 Gy in 25 fractions ( 2.72 Gy/fraction ) over 5 weeks to the prostate and proximal seminal vesicles . The pelvic lymph nodes and distal seminal vesicles concurrently received 45 Gy in 25 fractions . The patients were treated with helical TomoTherapy-based IMRT and underwent daily megavoltage CT image-guided verification prior to each treatment . Acute toxicity scores were recorded weekly during RT and at 3 months post-RT , using Radiation Therapy Oncology Group acute toxicity scales . RESULTS All patients completed RT and follow up for 3 months . The maximum acute toxicity scores were as follows : 21 ( 35 % ) patients had Grade 2 gastrointestinal ( GI ) toxicity ; 4 ( 6.67 % ) patients had Grade 3 genitourinary ( GU ) toxicity ; and 30 ( 33.33 % ) patients had Grade 2 GU toxicity . These toxicity scores were reduced after RT ; there were only 8 ( 13.6 % ) patients with Grade 1 GI toxicity , 11 ( 18.97 % ) with Grade 1 GU toxicity , and 5 ( 8.62 % ) with Grade 2 GU toxicity at 3 months follow up . Only the V60 to the rectum correlated with the GI toxicity . CONCLUSION Dose escalation using a hypofractionated schedule to the prostate with concurrent pelvic lymph node RT and long-term and rogen suppression therapy is well tolerated acutely . Longer follow up for outcome and late toxicity is required OBJECTIVE Accuracy of biopsy scheme depends on different parameters . Prostate-specific antigen ( PSA ) level and digital rectal examination ( DRE ) influenced the detection rate and suggested the biopsy scheme to approach each patient . Another parameter is the prostate volume . Sampling accuracy tends to decrease progressively with an increasing prostate volume . We prospect ively observed detection cancer rate in suspicious prostate cancer ( PCa ) and improved by applying a protocol biopsy according to prostate volume ( PV ) . PATIENTS AND METHODS Clinical data and pathological features of these 1356 patients were analysed and included in this study . This protocol is a combined scheme that includes transrectal ( TR ) 12-core PBx ( TR12PBx ) for PV ≤ 30 cc , TR 14-core PBx ( TR14PBx ) for PV > 30 cc but < 60 cc , TR 18-core PBx ( TR18PBx ) for PV ≥ 60 cc . RESULTS Out of a total of 1356 patients , in 111 ( 8.2 % ) PCa was identified through TR12PBx scheme , in 198 ( 14.6 % ) through TR14PBx scheme and in 253 ( 18.6 % ) through TR18PBx scheme . The PCa detection rate was increased by 44 % by adding two TZ cores ( TR14PBx scheme ) . The TR18PBx scheme increased this rate by 21.7 % vs. TR14PBx scheme . The diagnostic yield offered by TR18PBx was statistically significant compared to the detection rate offered by the TR14PBx scheme ( p < 0.003 ) . The biopsy Gleason score and the percentage of core involvement were comparable between PCa detected by the TR14PBx scheme diagnostic yield and those detected by the TR18PBx scheme ( p = 0.362 ) . CONCLUSIONS The only PV parameter , in our opinion , can be significant in choosing the best biopsy scheme to approach in a first setting of biopsies increasing PCa detection rate Abstract Background A prospect i ve clinical trial was conducted to evaluate the feasibility of a novel approach to the treatment of patients with high risk prostate cancer ( HRPC ) through the use of a nomogram to tailor radiotherapy target volumes . Methods Twenty seven subjects with HRPC were treated with a mildly hypofractionated radiotherapy regimen using image-guided IMRT technique between Jun/2013-Jan/2015.A set of vali date d prognostic factors were inputted into the Memorial-Sloan-Kettering Cancer Center ( MSKCC ) prostate cancer nomogram to estimate risk of loco-regional spread ( LRS ) . The nomogram risk estimates for extra-capsular extension ( ECE ) , seminal vesicles involvement ( SVI ) , and pelvic lymph nodes involvement ( LNI ) were used to adapt radiotherapy treatment volumes based on a risk threshold of ≥15 % in all cases . A planning guide was used to delineate target volumes and organs at risk ( OAR ) . Up to three dose levels were administered over 28 fractions ; 70Gy for gross disease in the prostate + /− seminal vesicles ( 2.5Gy/fraction ) , 61.6Gy for sub clinical peri-prostatic disease ( 2.2Gy/fraction ) and 50.4Gy to pelvic nodes ( 1.8Gy/fraction ) . Data regarding protocol adherence , nomogram use , radiotherapy dose distribution , and acute toxicity were collected . Results Nomogram use 100 % of patients were treated for ECE , 88.9 % for SVI , and 70.4 % for LNI . The three areas at risk of LRS were appropriately treated according to the study protocol in 98.8 % cases . The MSKCC nomogram estimates for LRS differed significantly between the time of recruitment and analysis . Contouring protocol compliance Compliance with the trial contouring protocol for up to seven target volumes was 93.0 % ( 159/171 ) . Compliance with protocol for small bowel contouring was poor ( 59.3 % ) . Dose constraints compliance Compliance with dose constraints for target volumes was 97.4 % ( 191/196 ) . Compliance with dose constraints for OAR was 88.2 % ( 285/323 ) . Acute toxicity There were no grade 3 acute toxicities observed . 20/27 ( 74.1 % ) and 6/27 ( 22.2 % ) patients experienced a grade 2 genitourinary and gastrointestinal toxicity respectively . Conclusions We have demonstrated the feasibility of this novel risk-adapted radiation treatment protocol for HRPC . This study has identified key learning points regarding this approach , including the importance of st and ardization and updating of risk quantification tools , and the utility of an observer to verify their correct use . Trial registration ClincialTrials.gov identifier NCT01418040.Hunter New Engl and Human Research Ethics Committee ( HNEHREC ) reference number Background Definitive , percutaneous irradiation of the prostate and the pelvic lymph nodes in high-
Output:
| In order to perform odds ratio we observed a decrease in late gastrointestinal toxicity for patients treated with hypofractionated schemes compared to CV treated ones .
Among patients who underwent conventional treatment , SIB seemed to decrease acute genitourinary side effects ; SIB-Hypo treated patients suffered less toxicity than patients treated with hypofractionated- sequential boost schemes .
Hypo-SIB schemes would seem less toxic in terms of acute gastrointestinal and late genitourinary side effects than CV-SIB . |
MS213779 | ***TASK*** the task is to summarize an input biomedical literature in six sentences
***INPUT*** the input is a biomedical literature
***OUTPUT*** the output is the summary of an input biomedical literature in six sentences
***DOCUMENTATION***
***EXAMPLES***
Input: OBJECTIVES This r and omised , controlled multicentre trial aim ed at comparing two versions of a variable-thread dental implant design to a st and ard tapered dental implant design in cases of immediate functional loading for 36 months after loading . MATERIAL S AND METHODS 177 patients ( 325 implants ) were included at 12 study centres and r and omly allocated into one of three treatment groups : NAI ( variable-thread design , NobelActive internal connection ) , NAE ( variable-thread design , NobelActive external connection ) and , as control , NR ( st and ard tapered design , NobelReplace tapered groovy ) . Inclusion criteria concerned healed bony implant sites and feasibility for immediate loading . Clinical and radiographic examinations were performed at implant placement and after 3 , 6 , 12 , 24 and 36 months . The outcome measures were marginal bone remodelling ( primary outcome ) , implant survival and success , papilla score , plaque accumulation , and bleeding on probing . RESULTS 127 patients ( NAI : 45 , NAE : 41 , NR : 41 ) were followed-up and evaluated after 36 months . No significant differences in cumulative survival rates were seen for the groups ( NAI : 95.7 % ; NAE : 96.3 % ; NR : 96.6 % ) . In all groups , bone remodelling occurred during the first 3 months , with stable or even increasing bone levels after the initial remodelling period . The bone remodelling from insertion to 36 months for the NAI group ( -0.89 ± 1.65 mm ) was comparable ( P = 0.98 ) to that of the NR group ( -0.85 ± 1.32 mm ) . The NAE group showed comparable bone remodelling during the first year , with an increase in following years result ing in significantly less overall bone loss ( -0.16 ± 1.06 mm ) ( P = 0.041 ) . Overall improvement in papilla size was observed in all treatment groups . CONCLUSIONS Over 36 months , the results show stable or improving bone levels for all treatment groups after the initial bone remodelling seen during the first 3 months after placement . The variable- thread implants showed results comparable to those of st and ard tapered implants in cases of immediate function , and therefore can be considered as a treatment option for immediate loading OBJECTIVES The aim of this prospect i ve study was to assess the effects of abutment removal after 6 months on bone healing after the subcrestal placement of immediately restored , tapered implants in cases of partial posterior m and ibular edentulism . MATERIAL AND METHODS Each of the 24 patients with partial posterior m and ibular edentulism was consecutively treated with two immediately restored 3.5 mm diameter tapered implants . A total of 48 implants were placed in healed sites and immediately splinted with a temporary restoration , which was placed in such a way as to avoid occlusal contact . Twenty-four weeks after surgery , 12 patients underwent the st and ard prosthetic protocol : the abutments were removed and impressions were made directly on the implant platform . Twelve patients underwent the " one abutment at one time " protocol : impressions were made of the abutments using snap-on abutment copies . The final restoration was delivered approximately 6 months after implant insertion . Vertical and horizontal bone changes were assessed using periapical radiographs immediately after surgery and at 6- , 12- , 24- and 36-month follow-up examinations . RESULTS All implants osseointegrated and were clinical ly stable at the 6-month follow-up . No statistically significant difference was evidence d between the two groups regarding the measurement of vertical bone healing . A small but significant horizontal bone loss was evidence d in the hard tissue portion over the implant platform in the period of time between the 6-month and 1-year follow-up in the control group . CONCLUSIONS The non-removal of an abutment placed at the time of surgery results in a statistically significant reduction of the horizontal bone remodeling around the immediately restored , subcrestally placed , tapered implant in cases of partial posterior m and ibular edentulism PURPOSE To compare the clinical and radiological outcomes of two implant design s with different prosthetic interfaces and neck configurations . MATERIAL S AND METHODS Thirty-four partially edentate patients r and omly received at least one NobelActive implant ( Nobel Biocare , Göteborg , Sweden ) with back-tapered collar , internal conical connection and platform shifting design , and one NobelSpeedy implant ( Nobel Biocare ) with external hexagon and flat-to-flat implant-abutment interface according to a split-mouth design . Follow-up continued to 3 years post-loading . The primary outcome measures were the success rates of the implants and prostheses , and the occurrence of any surgical and prosthetic complications during the entire follow-up . Secondary outcome measures were : horizontal and vertical peri-implant marginal bone level ( MBL ) changes , resonance frequency analysis values at implant placement and loading ( 4 months ) , sulcus bleeding index ( SBI ) and plaque score ( PS ) . RESULTS No drop-out occurred . No implants and prostheses failures were observed to the 3-year follow-up . MBL changes were statistically significant different with better results for the NobelActive implants for both horizontal and vertical measurements ( P = 0.000 ) . After 3 years post-loading , the NobelActive implants underwent a mean vertical bone resorption of 0.66 mm , compared with 1.25 mm for the NobelSpeedy Groovy implants ( P = 0.000 ) ; the mean horizontal bone resorption was 0.19 mm for the NobelActive implants and 0.60 mm for the NobelSpeedy Groovy implants ( P = 0.000 ) . A high ISQ value was found for both implants , and no statistically significant difference was found for ISQ mean values between interventions ( P = 0.941 at baseline ; P = 0.454 at implantabutment connection ; P = 0.120 at prosthesis delivery ) . All implants showed good periodontal health at the 3-year-in-function visit , with no significant differences between groups . CONCLUSION The results of this research suggest that in well-maintained patients , the MBL changes could be affected by the different implant design . After 4 months of unloaded healing , as well as after 3 years in function , both implants provided good results , however vertical and horizontal bone loss had statistically significant differences between the two groups ( difference of 0.58 ± 0.10 mm for the vertical MBL , and 0.4 ± 0.05 mm for the horizontal MBL ) , with lower values in the Nobel Active implants , compared to the NobelSpeedy Groovy implants OBJECTIVE To carry out a comparative study of two implants with different neck features and prostheses platform connection ( machined with external connection and rough-surfaced with switching platform ) upon peri-implant marginal bone loss , before and after functional loading . MATERIAL AND METHODS A r and omized , prospect i ve radiological study was made . Eighteen totally edentulous patients were selected . Subjects were divided into two groups according to the type of implant neck used : ( a ) Osseous ( ® ) , with machined surface , without microthreads , external connection , and without platform switching ; and ( b ) Inhex ( ® ) , with treated surface , microthreads , internal connection , and platform switching . Mesial and distal marginal bone loss was measured . Implant success was assessed according to the criteria of Buser . Control timepoints were as follows : ( a ) at implant placement ; ( b ) at prosthesis placement ; ( c ) 6 months after loading ; ( d ) 12 months after loading . RESULTS Fifteen patients that received 120 dental implants were included : 47 % Osseous ( ® ) group and 53 % Inhex ( ® ) group . Global mean marginal bone loss with Osseous ( ® ) was 0.27 ± 0.43 mm and 0.38 ± 0.51 mm as determined 6 and 12 months after prosthetic loading , respectively , whereas in the case of Inhex ( ® ) was 0.07 ± 0.13 and 0.12 ± 0.17 mm . These differences were statistically significant ( P = 0.047 ) . Difference between Osseous ( ® ) and Inhex ( ® ) in maxilla ( P = 0.272 ) and m and ibular ( P = 0.462 ) bone loss were not statistically significant . CONCLUSIONS Bone loss after 6 and 12 months proved statistically significant between two groups , with comparatively greater loss in the case of Osseous ( ® ) implants vs. Inhex ( ® ) implants . Regardless the heterogeneity of the two groups ( neck shape , microthreads , surface texture ) , the implant-abutment connection appears to be a significant factor on peri-implant crestal bone levels . Anyway , in both groups , the values obtained were within normal ranges described in the literature BACKGROUND Peri-implant bone loss seems to occur following implant placement/loading regardless of all the efforts to eliminate it . Several factors , including surgical trauma , biologic width establishment , lack of passive fit of the superstructures , implant-abutment microgap , and occlusal overloading , may increase peri-implant bone loss . Over the years , new interface design s were introduced and clinical studies suggest that internal conical connection and platform shifting may be advantageous for marginal bone preservation . PURPOSE To compare clinical and radiological outcomes of two implant design s with different prosthetic interfaces and neck configurations in a r and omized , controlled , split-mouth clinical trial . MATERIAL S AND METHODS Thirty-four partially edentate patients r and omly received at least one internal conical connection with back-tapered collar and platform shifting design or external-hexagon implants with flat-to-flat implant-abutment interface . Primary end point was peri-implant bone level changes at different time points , failures of implants and /or prosthesis , any complications , implant stability quotient ( ISQ ) values , and periodontal parameters . RESULTS No dropout occurred . Marginal bone changes were statistically significantly different with better results for the internal conical connection . No implants and prosthesis failures have been observed , yielding a cumulative survival rate of 100 % . A high ISQ value was found for both implants , and no statistically significant difference was found for ISQ mean values between interventions at each time point ( p > .05 ) . All implants showed no bleeding on probing and a very slight amount of plaque at the 1-year-in-function visit . CONCLUSIONS Both implant design s investigated performed similarly in terms of failure rates , providing successful results up to 1 year after loading . The back-tapered neck configuration with conical connection and built-in platform shifting showed statistically lower marginal bone loss than straight neck configuration with flat-to-flat implant-abutment interface and external-hexagonal connection PURPOSE To evaluate advantages and disadvantages of identical implants with internal or external connections . MATERIAL S AND METHODS One hundred and twenty patients with any type of edentulism ( single tooth , partial and total edentulism ) , requiring one implant-supported prosthesis were r and omly allocated in two equal groups to receive either implants with an external connection ( EC ) or implants of the same type with an internal connection ( IC ) ( EZ Plus , MegaGen Implant , Gyeongbuk , South Korea ) , at four centres . Due to slight differences in implant design and components , IC implants were platformswitched while EC were not . Patients were followed for 5 years after initial loading . Outcome measures were prosthesis/implant failures , any complication , marginal bone level changes and clinician preference , assessed by blinded outcome assessors . RESULTS Sixty patients received 96 EC implants and 60 patients received 107 IC implants . Three patients dropped out with four EC implants and five patients with ten IC implants , but all remaining patients were followed up to 5-year post-loading . One prosthesis supported by EC implants and two by IC implants failed ( P = 0.615 , difference = -0.02 , 95 % CI : -0.08 to 0.04 ) . One EC implant failed versus three IC implants in two patients ( P = 0.615 , difference = -0.02 , 95 % CI : -0.08 to 0.04 ) . Ten complications occurred in 10 EC patients versus nine complications in 9 IC patients ( P = 1.000 , difference = 0.01 , 95 % CI : -0.13 to 0.15 ) . There were no statistically significant differences for prosthesis and implant failures and complications between the different connection types . Five years after loading , there were no statistically significant differences in marginal bone level estimates between the two groups ( difference = 0.14 mm , 95 % CI : -0.28 to 0.56 , P ( ancova ) = 0.505 ) and both groups lost bone from implant placement in a statistically significant way : 1.13 mm for the EC implants and 1.21 mm for the IC implants . Two operators had no preference and two preferred IC implants . CONCLUSIONS Within the limitations given by the difference in neck design and platform switching between EC and IC implants , 5-year post-loading data did not show any statistically significant differences between the two connection types , therefore clinicians could choose whichever they preferred BACKGROUND Today , implants are placed using both non-submerged and submerged approaches , and in 1- and 2-piece configurations . Previous work has demonstrated that peri-implant crestal bone reactions differ radiographically under such conditions and are dependent on a rough/smooth implant border in 1-piece implants and on the location of the interface ( microgap ) between the implant and abutment/restoration in 2-pie
Output:
| The network meta- analysis ( NMA ) suggested a significant difference between the external and the conical connections ; this was less evident for the internal and conical ones .
Platform-switching ( PS ) seemed to positively affect bone levels , non-regarding the implant-connection it was applied to .
Within the limitations of this systematic review , it can be concluded that crestal bone levels are better maintained in the short-medium term when internal kinds of interface are adopted . |
MS213780 | ***TASK*** the task is to summarize an input biomedical literature in six sentences
***INPUT*** the input is a biomedical literature
***OUTPUT*** the output is the summary of an input biomedical literature in six sentences
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Input: This 48-week , r and omized , placebo-controlled phase 3 study ( DMD114044 ; NCT01254019 ) evaluated efficacy and safety of subcutaneous drisapersen 6 mg/kg/week in 186 ambulant boys aged ≥5 years , with Duchenne muscular dystrophy ( DMD ) result ing from an exon 51 skipping amenable mutation . Drisapersen was generally well tolerated , with injection-site reactions and renal events as most commonly reported adverse events . A nonsignificant treatment difference ( P = 0.415 ) in the change from baseline in six-minute walk distance ( 6MWD ; primary efficacy endpoint ) of 10.3 meters in favor of drisapersen was observed at week 48 . Key secondary efficacy endpoints ( North Star Ambulatory Assessment , 4-stair climb ascent velocity , and 10-meter walk/run velocity ) gave consistent findings . Lack of statistical significance was thought to be largely due to greater data variability and subgroup heterogeneity . The increased st and ard deviation alone , due to less stringent inclusion /exclusion criteria , reduced the statistical power from pre-specified 90 % to actual 53 % . Therefore , a post-hoc analysis was performed in 80 subjects with a baseline 6MWD 300 - 400 meters and ability to rise from floor . A statistically significant improvement in 6MWD of 35.4 meters ( P = 0.039 ) in favor of drisapersen was observed in this sub population . Results suggest that drisapersen could have benefit in a less impaired population of DMD subjects Summary Background We report clinical safety and biochemical efficacy from a dose-ranging study of intravenously administered AVI-4658 phosphorodiami date morpholino oligomer ( PMO ) in patients with Duchenne muscular dystrophy . Method We undertook an open-label , phase 2 , dose-escalation study ( 0·5 , 1·0 , 2·0 , 4·0 , 10·0 , and 20·0 mg/kg bodyweight ) in ambulant patients with Duchenne muscular dystrophy aged 5–15 years with amenable deletions in DMD . Participants had a muscle biopsy before starting treatment and after 12 weekly intravenous infusions of AVI-4658 . The primary study objective was to assess safety and tolerability of AVI-4658 . The secondary objectives were pharmacokinetic properties and the ability of AVI-4658 to induce exon 51 skipping and dystrophin restoration by RT-PCR , immunohistochemistry , and immunoblotting . The study is registered , number NCT00844597 . Findings 19 patients took part in the study . AVI-4658 was well tolerated with no drug-related serious adverse events . AVI-4658 induced exon 51 skipping in all cohorts and new dystrophin protein expression in a significant dose-dependent ( p=0·0203 ) , but variable , manner in boys from cohort 3 ( dose 2 mg/kg ) onwards . Seven patients responded to treatment , in whom mean dystrophin fluorescence intensity increased from 8·9 % ( 95 % CI 7·1–10·6 ) to 16·4 % ( 10·8–22·0 ) of normal control after treatment ( p=0·0287 ) . The three patients with the greatest responses to treatment had 21 % , 15 % , and 55 % dystrophin-positive fibres after treatment and these findings were confirmed with western blot , which showed an increase after treatment of protein levels from 2 % to 18 % , from 0·9 % to 17 % , and from 0 % to 7·7 % of normal muscle , respectively . The dystrophin-associated proteins α-sarcoglycan and neuronal nitric oxide synthase were also restored at the sarcolemma . Analysis of the inflammatory infiltrate indicated a reduction of cytotoxic T cells in the post-treatment muscle biopsies in the two high-dose cohorts . Interpretation The safety and biochemical efficacy that we present show the potential of AVI-4658 to become a disease-modifying drug for Duchenne muscular dystrophy . Funding UK Medical Research Council ; AVI BioPharma BACKGROUND Cardiorespiratory failure is the leading cause of death in Duchenne muscular dystrophy . Based on pre clinical and phase 2 evidence , we assessed the efficacy and safety of idebenone in young patients with Duchenne muscular dystrophy who were not taking concomitant glucocorticoids . METHODS In a multicentre phase 3 trial in Belgium , Germany , the Netherl and s , Switzerl and , France , Sweden , Austria , Italy , Spain , and the USA , patients ( age 10 - 18 years old ) with Duchenne muscular dystrophy were r and omly assigned in a one-to-one ratio with a central interactive web response system with a permuted block design with four patients per block to receive idebenone ( 300 mg three times a day ) or matching placebo orally for 52 weeks . Study personnel and patients were masked to treatment assignment . The primary endpoint was change in peak expiratory flow ( PEF ) as percentage predicted ( PEF%p ) from baseline to week 52 , measured with spirometry . Analysis was by intention to treat ( ITT ) and a modified ITT ( mITT ) , which was prospect ively defined to exclude patients with at least 20 % difference in the yearly change in PEF%p , measured with hospital-based and weekly home-based spirometry . This study is registered with Clinical Trials.gov , number NCT01027884 . FINDINGS 31 patients in the idebenone group and 33 in the placebo group comprised the ITT population , and 30 and 27 comprised the mITT population . Idebenone significantly attenuated the fall in PEF%p from baseline to week 52 in the mITT ( -3·05%p [ 95 % CI -7·08 to 0·97 ] , p=0·134 , vs placebo -9·01%p [ -13·18 to -4·84 ] , p=0·0001 ; difference 5·96%p [ 0·16 to 11·76 ] , p=0·044 ) and ITT population s ( -2·57%p [ -6·68 to 1·54 ] , p=0·215 , vs -8·84%p [ -12·73 to -4·95 ] , p<0·0001 ; difference 6·27%p [ 0·61 to 11·93 ] , p=0·031 ) . Idebenone also had a significant effect on PEF ( L/min ) , weekly home-based PEF , FVC , and FEV1 . The effect of idebenone on respiratory function outcomes was similar between patients with previous corticosteroid use and steroid-naive patients . Treatment with idebenone was safe and well tolerated with adverse event rates were similar in both groups . Nasopharyngitis and headache were the most common adverse events ( idebenone , eight [ 25 % ] and six [ 19 % ] of 32 patients ; placebo , nine [ 26 % ] and seven [ 21 % ] of 34 patients ) . Transient and mild diarrhoea was more common in the idebenone group than in the placebo group ( eight [ 25 % ] vs four [ 12 % ] patients ) . INTERPRETATION Idebenone reduced the loss of respiratory function and represents a new treatment option for patients with Duchenne muscular dystrophy . FUNDING Santhera Pharmaceuticals BACKGROUND Local intramuscular administration of the antisense oligonucleotide PRO051 in patients with Duchenne 's muscular dystrophy with relevant mutations was previously reported to induce the skipping of exon 51 during pre-messenger RNA splicing of the dystrophin gene and to facilitate new dystrophin expression in muscle-fiber membranes . The present phase 1 - 2a study aim ed to assess the safety , pharmacokinetics , and molecular and clinical effects of systemically administered PRO051 . METHODS We administered weekly abdominal subcutaneous injections of PRO051 for 5 weeks in 12 patients , with each of four possible doses ( 0.5 , 2.0 , 4.0 , and 6.0 mg per kilogram of body weight ) given to 3 patients . Changes in RNA splicing and protein levels in the tibialis anterior muscle were assessed at two time points . All patients subsequently entered a 12-week open-label extension phase , during which they all received PRO051 at a dose of 6.0 mg per kilogram per week . Safety , pharmacokinetics , serum creatine kinase levels , and muscle strength and function were assessed . RESULTS The most common adverse events were irritation at the administration site and , during the extension phase , mild and variable proteinuria and increased urinary α(1)-microglobulin levels ; there were no serious adverse events . The mean terminal half-life of PRO051 in the circulation was 29 days . PRO051 induced detectable , specific exon-51 skipping at doses of 2.0 mg or more per kilogram . New dystrophin expression was observed between approximately 60 % and 100 % of muscle fibers in 10 of the 12 patients , as measured on post-treatment biopsy , which increased in a dose-dependent manner to up to 15.6 % of the expression in healthy muscle . After the 12-week extension phase , there was a mean ( ±SD ) improvement of 35.2±28.7 m ( from the baseline of 384±121 m ) on the 6-minute walk test . CONCLUSIONS Systemically administered PRO051 showed dose-dependent molecular efficacy in patients with Duchenne 's muscular dystrophy , with a modest improvement in the 6-minute walk test after 12 weeks of extended treatment . ( Funded by Prosensa Therapeutics ; Netherl and s National Trial Register number , NTR1241 . ) Despite long-st and ing critiques of the conduct of underpowered clinical trials , the practice not only remains widespread , but also has garnered increasing support . Patients and healthy volunteers continue to participate in research that may be of limited clinical value , and authors recently have offered 2 related arguments to support the validity and value of underpowered clinical trials : that meta- analysis may " save " small studies by providing a means to combine the results with those of other similar studies to enable estimates of an intervention 's efficacy , and that although small studies may not provide a good basis for testing hypotheses , they may provide valuable estimates of treatment effects using confidence intervals . In this article , we examine these arguments in light of the distinctive moral issues associated with the conduct of underpowered trials , the disclosures that are owed to potential participants in underpowered trials so they may make autonomous enrollment decisions , and the circumstances in which the prospect s for future meta-analyses may justify individually underpowered trials . We conclude that underpowered trials are ethical in only 2 situations : small trials of interventions for rare diseases in which investigators document explicit plans for including their results with those of similar trials in a prospect i ve meta- analysis , and early-phase trials in the development of drugs or devices , provided they are adequately powered for defined purpose s other than r and omized treatment comparisons . In both cases , investigators must inform prospect i ve subjects that their participation may only indirectly contribute to future health care benefits Objective : We aim ed to perform an observational study of age at loss of independent ambulation ( LoA ) and side-effect profiles associated with different glucocorticoid corticosteroid ( GC ) regimens in Duchenne muscular dystrophy ( DMD ) . Methods : We studied 340 participants in the Cooperative International Neuromuscular Research Group Duchenne Natural History Study ( CINRG-DNHS ) . LoA was defined as continuous wheelchair use . Effects of prednisone or prednisolone (PRED)/deflazacort ( DFZ ) , administration frequency , and dose were analyzed by time-varying Cox regression . Side-effect frequencies were compared using χ2 test . Results : Participants treated ≥1 year while ambulatory ( n = 252/340 ) showed a 3-year median delay in LoA ( p < 0.001 ) . Fourteen different regimens were observed . Nondaily treatment was common for PRED ( 37 % ) and rare for DFZ ( 3 % ) . DFZ was associated with later LoA than PRED ( hazard ratio 0.294 ± 0.053 vs 0.490 ± 0.08 , p = 0.003 ; 2-year difference in median LoA with daily administration , p < 0.001 ) . Average dose was lower for daily PRED ( 0.56 mg/kg/d , 75 % of recommended ) than daily DFZ ( 0.75 mg/kg/d , 83 % of recommended , p < 0.001 ) . DFZ showed higher frequencies of growth delay ( p < 0.001 ) , cushingoid appearance ( p = 0.002 ) , and cataracts ( p < 0.001 ) , but not weight gain . Conclusions : Use of DFZ was associated with later LoA and increased frequency of side effects . Differences in st and ards of care and dosing complicate interpretation of this finding , but stratification by PRED/DFZ might be considered in clinical trials . This study emphasizes the necessity of a r and omized , blinded trial of GC regimens in DMD . Classification of evidence
Output:
| Conclusions Current available data do not show evidence that exon-skipping drugs are effective in DMD .
Despite potential effectiveness when used at a specific dose , significant side effects were reported with drisapersen . |
MS213781 | ***TASK*** the task is to summarize an input biomedical literature in six sentences
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Input: Background Although several studies have found probiotics encouraging in prevention of gestational diabetes mellitus ( GDM ) , the evidence for the use of probiotics in diagnosed GDM is largely limited . The aim of this study was to assess the effect of a probiotic supplement capsule containing four bacterial strains on glucose metabolism indices and weight changes in women with newly diagnosed GDM . Methods Sixty-four pregnant women with GDM were enrolled into a double-blind placebo-controlled r and omized clinical trial . They were r and omly assigned to receive either a probiotic or placebo capsule along with dietary advice for eight consecutive weeks . The trend of weight gain along with glucose metabolism indices was assayed . Results During the first 6 weeks of the study , the weight gain trend was similar between the groups . However , in the last 2 weeks of the study , the weight gain in the probiotic group was significantly lower than in the placebo group ( p < 0.05 ) . Fasting blood sugar ( FBS ) decreased in both intervention ( from 103.7 to 88.4 mg/dl ) and control ( from 100.9 to 93.6 mg/dl ) groups significantly , and the decrease in the probiotic group was significantly higher than in the placebo group ( p < 0.05 ) . Insulin resistance index in the probiotic group had 6.74 % reduction over the study period ( p < 0.05 ) . In the placebo group , however , there was an increase in insulin resistance index ( 6.45 % ) , but the observed change in insulin resistance was not statistically significant . Insulin sensitivity index was increased in both groups . The post-intervention insulin sensitivity index in the probiotic group was not significantly different from placebo when adjusted for the baseline levels . Conclusions The probiotic supplement appeared to affect glucose metabolism and weight gain among pregnant women with GDM . This needs to be confirmed in other setting s before a therapeutic value could be approved The study aims to assess whether supplementation with the probiotic Lactobacillus rhamnosus HN001 ( HN001 ) can reduce the prevalence of gestational diabetes mellitus ( GDM ) . A double-blind , r and omised , placebo-controlled parallel trial was conducted in New Zeal and ( NZ ) ( Wellington and Auckl and ) . Pregnant women with a personal or partner history of atopic disease were r and omised at 14–16 weeks ’ gestation to receive HN001 ( 6 × 109 colony-forming units ) ( n 212 ) or placebo ( n 211 ) daily . GDM at 24–30 weeks was assessed using the definition of the International Association of Diabetes and Pregnancy Study Groups ( IADPSG ) ( fasting plasma glucose ≥5·1 mmol/l , or 1 h post 75 g glucose level at ≥10 mmol/l or at 2 h ≥8·5 mmol/l ) and NZ definition ( fasting plasma glucose ≥5·5 mmol/l or 2 h post 75 g glucose at ≥9 mmol/l ) . All analyses were intention-to-treat . A total of 184 ( 87 % ) women took HN001 and 189 ( 90 % ) women took placebo . There was a trend towards lower relative rates ( RR ) of GDM ( IADPSG definition ) in the HN001 group , 0·59 ( 95 % CI 0·32 , 1·08 ) ( P=0·08 ) . HN001 was associated with lower rates of GDM in women aged ≥35 years ( RR 0·31 ; 95 % CI 0·12 , 0·81 , P=0·009 ) and women with a history of GDM ( RR 0·00 ; 95 % CI 0·00 , 0·66 , P=0·004 ) . These rates did not differ significantly from those of women without these characteristics . Using the NZ definition , GDM prevalence was significantly lower in the HN001 group , 2·1 % ( 95 % CI 0·6 , 5·2 ) , v. 6·5 % ( 95 % CI 3·5 , 10·9 ) in the placebo group ( P=0·03 ) . HN001 supplementation from 14 to 16 weeks ’ gestation may reduce GDM prevalence , particularly among older women and those with previous GDM Objective . This trial aims to examine the effects of a Probiotic Mixture ( VSL#3 ) on glycemic status and inflammatory markers , in women with GDM . Material s and Methods . Over a period of 8 weeks , 82 women with gestational diabetes were r and omly assigned to either an intervention group ( n = 41 ) which were given VSL#3 capsule or to a control group which were given placebo capsule ( n = 41 ) . Fasting plasma glucose , homeostatic model assessment of insulin resistance , glycosylated hemoglobin , high-sensitivity C-reactive protein , tumor necrosis factor-α , interleukin-6 , Interferon gamma , and interleukin-10 were measured before and after the intervention . Results . After 8 wk of supplementation FPG , HbA1c , HOMA-IR , and insulin levels remained unchanged in the probiotic and placebo groups . The comparison between the two groups showed no significant differences with FPG and HbA1c , but there were significant differences in insulin levels and HOMA-IR ( 16.6 ± 5.9 ; 3.7 ± 1.5 , resp . ) . Unlike the levels of IFN-g ( 19.21 ± 16.6 ) , there was a significant decrease in levels of IL-6 ( 3.81 ± 0.7 ) , TNF-α ( 3.10 ± 1.1 ) , and hs-CRP ( 4927.4 ± 924.6 ) . No significant increase was observed in IL-10 ( 3.11 ± 5.7 ) in the intervention group as compared with the control group . Conclusions . In women with GDM , supplementation with probiotics ( VSL#3 ) may help to modulate some inflammatory markers and may have benefits on glycemic control Background / objectives : Owing to excess body weight and increased secretion of inflammatory cytokines primarily during the third trimester , pregnancy is associated with elevated insulin resistance . To our knowledge , no report is available indicating the effects of probiotic yoghurt consumption on serum insulin levels in pregnant women . This study was design ed to determine the effects of daily consumption of probiotic yoghurt on insulin resistance and serum insulin levels of Iranian pregnant women . Subjects/ methods : In this r and omized controlled clinical trial , 70 primigravida pregnant women with singleton pregnancy at their third trimester were participated . We r and omly assigned participants to consume 200 g per day of conventional ( n=33 ) or the probiotic group ( n=37 ) for 9 weeks . The probiotic yoghurt was a commercially available product prepared with the starter cultures of Streptococcus thermophilus and Lactobacillus bulgaricus , enriched with probiotic culture of two strains of lactobacilli ( Lactobacillus acidophilus LA5 ) and bifidobacteria ( Bifidobacterium animalis BB12 ) with a total of min 1 × 107 colony-forming units . Fasting blood sample s were taken at baseline and after 9-week intervention to measure fasting plasma glucose and serum insulin levels . Homeostatic model assessment of insulin resistance ( HOMA-IR ) was used to calculate insulin resistance score . Results : Although consumption of probiotic yogurt for 9 weeks did not affect serum insulin levels and HOMA-IR score , significant differences were found comparing changes in these variables between probiotic and conventional yogurts ( changes from baseline in serum insulin levels : + 1.2±1.2 vs + 5.0±1.1 μIU/ml , respectively , P=0.02 ; and in HOMA-IR score : −0.2±0.3 vs 0.7±0.2 , respectively , P=0.01 ) . Conclusions : It is concluded that in contrast to conventional yogurt , daily consumption of probiotic yogurt for 9 weeks maintains serum insulin levels and might help pregnant women prevent developing insulin resistance Objectives To explore the predictive power of measuring the abdominal fetal fat layer ( FFL ) as a soft tissue marker at 31 , 34 , and 37 weeks ’ gestation to improve the detection of fetal macrosomia in pregnant women with GDM , in addition to the biometric values with close monitoring of maternal blood sugar level and BMI changes . Methods We conducted a prospect i ve observational study at the Department of Obstetrics , University Hospitals , Campus Kiel , Germany , in collaboration with diabetic clinic staff . Participants underwent a third-trimester scan and extra FFL measurements were performed at 31 , 34 , and 37 weeks of gestation . The clinical outcomes of pregnancy and birth weight were collected from the obstetric record . All of the enrolled women had an early pregnancy ultrasound scan to confirm gestational age . Results The FFL at 34 and 37 weeks , with respective cutoff values of > 0.48 cm and > 0.59 cm , showed a very good sensitivity of 60 % for both gestational points , and specificity of 89.3 and 90.6 % , respectively . The probability of fetal macrosomia could be more than doubled if the FFL at 34 weeks was more than 0.48 cm . However , the probability of macrosomia dropped to 16 % if the FFL was ≤0.48 cm . The median FFLs of macrosomic fetuses at 34 and 37 weeks were 0.50 ( IQR 0.10 ) and 0.60 ( IQR 0.25 ) cm , respectively . The mean age of the study population ( n = 80 ) was 32.26 ( SD = 5.06 ) years . In our study population , ten newborns were born with birth weight > 4000 g. The body mass index ( BMI ) for the mothers of later-onset macrosomic newborns showed higher median values of 30 ( IQR 8) , 32 ( IQR 5 ) , and 33 ( IQR 9 ) at 31 , 34 , and 37 weeks , respectively , in comparison to mothers of non-macrosomic newborn . However , the BMI did not show any statistically significant difference from those with normal-weight newborn and did not show any specific sensitivity for predicting macrosomia . Conclusion Measuring the FFL at 34 and 37 weeks of gestation , in addition to the st and ard measurement , might be useful for predicting macrosomia and is worth further evaluation Abstract The human gut microbiome can modulate metabolic health and affect insulin resistance , and it may play an important role in the etiology of gestational diabetes mellitus ( GDM ) . Here , we compared the gut microbial composition of 43 GDM patients and 81 healthy pregnant women via whole-metagenome shotgun sequencing of their fecal sample s , collected at 21–29 weeks , to explore associations between GDM and the composition of microbial taxonomic units and functional genes . A metagenome-wide association study identified 154 837 genes , which clustered into 129 metagenome linkage groups ( MLGs ) for species description , with significant relative abundance differences between the 2 cohorts . Parabacteroides distasonis , Klebsiella variicola , etc . , were enriched in GDM patients , whereas Methanobrevibacter smithii , Alistipes spp . , Bifidobacterium spp . , and Eubacterium spp . were enriched in controls . The ratios of the gross abundances of GDM-enriched MLGs to control-enriched MLGs were positively correlated with blood glucose levels . A r and om forest model shows that fecal MLGs have excellent discriminatory power to predict GDM status . Our study discovered novel relationships between the gut microbiome and GDM status and suggests that changes in microbial composition may potentially be used to identify individuals at risk for GDM BACKGROUND Recent studies have reported beneficial effects of probiotics on maternal glycemia in healthy pregnant women . Obesity significantly increases risk of impaired glucose tolerance in pregnancy , but glycemic effects of probiotics in this specific obstetric group require additional investigation . OBJECTIVE The aim of the Probiotics in Pregnancy Study was to investigate the effect of a probiotic capsule on maternal fasting glucose in obese pregnant women . DESIGN In this placebo-controlled , double-blind , r and omized trial , 175 pregnant women with an early pregnancy body mass index ( BMI ; in kg/m² ) from 30.0 to 39.9 were recruited from antenatal clinics at the National Maternity Hospital , Dublin , Irel and . Exclusion criteria were BMI < 30.0 or > 39.9 , prepregnancy or gestational diabetes , age < 18 y , multiple pregnancy , and fetal anomaly . Women were r and omly assigned to receive either a daily probiotic or a placebo capsule from 24 to 28 wk of gestation in addition to routine antenatal care . The primary outcome was the change in fasting glucose between groups from preintervention to postintervention . Secondary outcomes were the incidence of gestational diabetes and neonatal anthropometric measures . R
Output:
| Results demonstrated that probiotics used during pregnancy in women with GDM may improve glycaemic control and reduce VDL cholesterol , triglycerides , and inflammatory markers .
Conclusions The present systematic review highlights the importance of probiotics for glycemic control and decrease of inflammatory markers in GDM . |
MS213782 | ***TASK*** the task is to summarize an input biomedical literature in six sentences
***INPUT*** the input is a biomedical literature
***OUTPUT*** the output is the summary of an input biomedical literature in six sentences
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Input: Introduction In the emergency department setting , it is essential to rapidly and accurately confirm correct endotracheal tube ( ETT ) placement . Ultrasound is an increasingly studied modality for identifying ETT location . However , there has been significant variation in techniques between studies , with some using the dynamic technique , while others use a static approach . This study compared the static and dynamic techniques to determine which was more accurate for ETT identification . Methods We performed this study in a cadaver lab using three different cadavers to represent variations in neck circumference . Cadavers were r and omized to either tracheal or esophageal intubation in equal proportions . Blinded sonographers then assessed the location of the ETT using either static or dynamic sonography . We assessed accuracy of sonographer identification of ETT location , time to identification , and operator confidence . Results A total of 120 intubations were performed : 62 tracheal intubations and 58 esophageal intubations . The static technique was 93.6 % ( 95 % confidence interval [ CI ] [ 84.3 % to 98.2 % ] ) sensitive and 98.3 % specific ( 95 % CI [ 90.8 % to 99.9 % ] ) . The dynamic technique was 92.1 % ( 95 % CI [ 82.4 % to 97.4 % ] ) sensitive and 91.2 % specific ( 95 % CI [ 80.7 % to 97.1 % ] ) . The mean time to identification was 6.72 seconds ( 95 % CI [ 5.53 to 7.9 ] seconds ) in the static technique and 6.4 seconds ( 95 % CI [ 5.65 to 7.16 ] seconds ) in the dynamic technique . Operator confidence was 4.9/5.0 ( 95 % CI [ 4.83 to 4.97 ] ) in the static technique and 4.86/5.0 ( 95 % CI [ 4.78 to 4.94 ] ) in the dynamic technique . There was no statistically significant difference between groups for any of the outcomes . Conclusion This study demonstrated that both the static and dynamic sonography approaches were rapid and accurate for confirming ETT location with no statistically significant difference between modalities . Further studies are recommended to compare these techniques in ED patients and with more novice sonographers Introduction : Confirmation of proper endotracheal tube placement is one of the most important and lifesaving issues of tracheal intubation . The present study was aim ed to evaluate the accuracy of tracheal ultrasonography by emergency residents in this regard . Method : This was a prospect i ve , cross sectional study for evaluating the diagnostic accuracy of ultrasonography in endotracheal tube placement confirmation compared to a combination of 4 clinical confirmation methods of chest and epigastric auscultation , direct laryngoscopy , aspiration of the tube , and pulse oximetry ( as reference test ) . Results : 150 patients with the mean age of 58.52 ± 1.73 years were included ( 56.6 % male ) . Sensitivity , specificity , positive predictive value , negative predictive value , and positive and negative likelihood ratio of tracheal ultrasonography in endotracheal tube confirmation were 96 ( 95 % CI : 92 - 99 ) , 88 ( 95 % CI : 62 - 97 ) , 98 ( 95 % CI : 94 - 99 ) , 78 ( 95 % CI : 53 - 93 ) , 64 ( 95 % CI : 16 - 255 ) , and 0.2 ( 95 % CI : 0.1 - 0.6 ) , respectively . Conclusion : The present study showed that tracheal ultrasonography by trained emergency medicine residents had excellent sensitivity ( > 90 % ) and good specificity ( 80 - 90 ) for confirming endotracheal tube placement . Therefore , it seems that ultrasonography is a proper screening tool in determining endotracheal tube placement Background In emergency setting s , verification of endotracheal tube ( ETT ) location is important for critically ill patients . Ignorance of oesophageal intubation can be disastrous . Many methods are used for verification of the endotracheal tube location ; none are ideal . Quantitative waveform capnography is considered the st and ard of care for this purpose but is not always available and is expensive . Therefore , this feasibility study is conducted to compare a cheaper alternative , bedside upper airway ultrasonography to waveform capnography , for verification of endotracheal tube location after intubation . Methods This was a prospect i ve , single-centre , observational study , conducted at the HRPB , Ipoh . It included patients who were intubated in the emergency department from 28 March 2012 to 17 August 2012 . A waiver of consent had been obtained from the Medical Research Ethics Committee . Bedside upper airway ultrasonography was performed after intubation and compared to waveform capnography . Specificity , sensitivity , positive and negative predictive value and likelihood ratio are calculated . Results A sample of 107 patients were analysed , and 6 ( 5.6 % ) had oesophageal intubations . The overall accuracy of bedside upper airway ultrasonography was 98.1 % ( 95 % confidence interval ( CI ) 93.0 % to 100.0 % ) . The kappa value ( Κ ) was 0.85 , indicating a very good agreement between the bedside upper airway ultrasonography and waveform capnography . Thus , bedside upper airway ultrasonography is in concordance with waveform capnography . The sensitivity , specificity , positive predictive value and negative predictive value of bedside upper airway ultrasonography were 98.0 % ( 95 % CI 93.0 % to 99.8 % ) , 100 % ( 95 % CI 54.1 % to 100.0 % ) , 100 % ( 95 % CI 96.3 % to 100.0 % ) and 75.0 % ( 95 % CI 34.9 % to 96.8 % ) . The likelihood ratio of a positive test is infinite and the likelihood ratio of a negative test is 0.0198 ( 95 % CI 0.005 to 0.0781 ) . The mean confirmation time by ultrasound is 16.4 s. No adverse effects were recorded . Conclusions Our study shows that ultrasonography can replace waveform capnography in confirming ETT placement in centres without capnography . This can reduce incidence of unrecognised oesophageal intubation and prevent morbidity and mortality . Trial registration National Medical Research Register NMRR11100810230 Introduction Recent research has investigated the use of ultrasound ( US ) for confirming endotracheal tube ( ETT ) placement with varying techniques , accuracies , and challenges . Our objective was to evaluate the accuracy of a novel , simplified , four-step ( 4S ) technique . Methods We conducted a blinded , r and omized trial of the 4S technique utilizing an adult human cadaver model . ETT placement was r and omized to tracheal or esophageal location . Three US experts and 45 emergency medicine residents ( EMR ) performed a total of 150 scans . The primary outcome was the overall sensitivity and specificity of both experts and EMRs to detect location of ETT placement . Secondary outcomes included a priori subgroup comparison of experts and EMRs for thin and obese cadavers , time to detection , and level of operator confidence . Results Experts had a sensitivity of 100 % ( 95 % CI = 72 % to 100 % ) and specificity of 100 % ( 95 % CI = 77 % to 100 % ) on thin , and a sensitivity of 93 % ( 95 % CI = 66 % to 100 % ) and specificity of 100 % ( 95 % CI = 75 % to 100 % ) on obese cadavers . EMRs had a sensitivity of 91 % ( 95 % CI = 69 % to 98 % ) and of specificity 96 % ( 95 % CI = 76 % to 100 % ) on thin , and a sensitivity of 100 % ( 95 % CI = 82 % to 100 % ) specificity of 48 % ( 95 % CI = 27 % to 69 % ) on obese cadavers . The overall mean time to detection was 17 seconds ( 95 % CI = 13 seconds to 20 seconds , range : 2 to 63 seconds ) for US experts and 29 seconds ( 95 % CI = 25 seconds to 33 seconds ; range : 6 to 120 seconds ) for EMRs . There was a statistically significant decrease in the specificity of this technique on obese cadavers when comparing the EMRs and experts , as well as an increased overall time to detection among the EMRs . Conclusion The simplified 4S technique was accurate and rapid for US experts . Among novices , the 4S technique was accurate in thin , but appears less accurate in obese cadavers . Further studies will determine optimal teaching time and accuracy in emergency department patients OBJECTIVES This study aim ed to assess the diagnostic accuracy and timeliness of using tracheal ultrasound to examine endotracheal tube placement during emergency intubation . METHODS This was a prospect i ve , observational study , conducted at the emergency department of a national university teaching hospital . Patients received emergency intubation because of impending respiratory failure , cardiac arrest , or severe trauma . The tracheal rapid ultrasound exam ( T.R.U.E. ) was performed during emergency intubation with the transducer placed transversely at the trachea over the suprasternal notch . Quantitative waveform capnography was used as the criterion st and ard for confirmation of tracheal intubation . The main outcome was the concordance between the T.R.U.E. and the capnography . RESULTS A total of 112 patients were included in the analysis , and 17 ( 15.2 % ) had esophageal intubations . The overall accuracy of the T.R.U.E. was 98.2 % ( 95 % confidence interval [ CI ] : 93.7 - 99.5 % ) . The kappa ( κ ) value was 0.93 ( 95 % CI : 0.84 - 1.00 ) , indicating a high degree of agreement between the T.R.U.E. and capnography . The sensitivity , specificity , positive predictive value , and negative predictive value of the T.R.U.E. were 98.9 % ( 95 % CI : 94.3 - 99.8 % ) , 94.1 % ( 95 % CI : 73.0 - 99.0 % ) , 98.9 % ( 95 % CI : 94.3 - 99.8 % ) and 94.1 % ( 95 % CI : 73.0 - 99.0 % ) . The median operating time of the T.R.U.E. was 9.0s ( interquartile range [ IQR ] : 6.0 , 14.0 ) . CONCLUSIONS The application of the T.R.U.E. to examine endotracheal tube placement during emergency intubation is feasible , and can be rapidly performed Background Unrecognized esophageal intubations are associated with significant patient morbidity and mortality . No single confirmatory device has been shown to be 100 % accurate at ruling out esophageal intubations in the emergency department . Recent studies have demonstrated that point-of-care ultrasound ( POCUS ) may be a useful adjunct for confirming endotracheal tube placement ; however , the amount of practice required to become proficient at this technique is unclear . The purpose of this study is to determine the amount of practice required by emergency physicians to become proficient at interpreting ultrasound video clips of esophageal and endotracheal intubations . Methods Emergency physicians and emergency medicine residents completed a baseline interpretation test followed by a 10 min online tutorial . They then interpreted POCUS clips of esophageal and endotracheal intubations in a r and omly selected order . If an incorrect response was provided , the participant completed another practice session with feedback . This process continued until they correctly interpreted ten consecutive ultrasound clips . Descriptive statistics were used to summarize the data . Results Of the 87 eligible physicians , 66 ( 75.9 % ) completed the study . The mean score on the baseline test was 42.9 % ( SD 32.7 % ) . After the tutorial , 90.9 % ( 60/66 ) of the participants achieved proficiency after one practice attempt and 100 % achieved proficiency after two practice attempts . Six intubation ultrasound clips were misinterpreted , for a total error rate of 0.9 % ( 6/684 ) . Overall , the participants had a sensitivity of 98.3 % ( 95 % CI 96.3–99.4 % ) and specificity of 100 % ( 95 % CI 98.9–100 % ) for detecting correct tube location . Scans were interpreted within an average of 4 s ( SD 2.9 s ) of the intubation . Conclusions After a brief online tutorial and only two practice attempts , emergency physicians were able to quickly and accurately interpret ultrasound intubation clips of esophageal and endotracheal intubations STUDY OBJECTIVE Visualization of the vocal cords and end-tidal capnography are the usual st and ards in confirming endotracheal tube placement . Vocal cord visualization is , however , not always possible , and capnography is not 100 % reliable and requires ventilation of the lungs to confirm placement . The goal of this study is to determine the accuracy of ultrason
Output:
| Conclusion : Transtracheal sonography is rapid to perform , with an acceptable degree of sensitivity and specificity for the confirmation of endotracheal intubation . |
MS213783 | ***TASK*** the task is to summarize an input biomedical literature in six sentences
***INPUT*** the input is a biomedical literature
***OUTPUT*** the output is the summary of an input biomedical literature in six sentences
***DOCUMENTATION***
***EXAMPLES***
Input: Background : Social anxiety disorder ( SAD ) is characterized by distorted self-views . The goal of this study was to examine whether mindfulness-based stress reduction ( MBSR ) alters behavioral and brain measures of negative and positive self-views . Methods : Fifty-six adult patients with generalized SAD were r and omly assigned to MBSR or a comparison aerobic exercise ( AE ) program . A self-referential encoding task was administered at baseline and post-intervention to examine changes in behavioral and neural responses in the self-referential brain network during functional magnetic resonance imaging . Patients were cued to decide whether positive and negative social trait adjectives were self-descriptive or in upper case font . Results : Behaviorally , compared to AE , MBSR produced greater decreases in negative self-views , and equivalent increases in positive self-views . Neurally , during negative self versus case , compared to AE , MBSR led to increased brain responses in the posterior cingulate cortex ( PCC ) . There were no differential changes for positive self versus case . Secondary analyses showed that changes in endorsement of negative and positive self-views were associated with decreased social anxiety symptom severity for MBSR , but not AE . Additionally , MBSR-related increases in dorsomedial prefrontal cortex ( DMPFC ) activity during negative self-view versus case were associated with decreased social anxiety related disability and increased mindfulness . Analysis of neural temporal dynamics revealed MBSR-related changes in the timing of neural responses in the DMPFC and PCC for negative self-view versus case . Conclusion : These findings suggest that MBSR attenuates maladaptive habitual self-views by facilitating automatic ( i.e. , uninstructed ) recruitment of cognitive and attention regulation neural networks . This highlights potentially important links between self-referential and cognitive-attention regulation systems and suggests that MBSR may enhance more adaptive social self-referential processes in patients with SAD Decentering has been proposed as a potential mechanism of mindfulness-based interventions but has received limited empirical examination to date in experimental studies comparing mindfulness meditation to active comparison conditions . In the present study , we compared the immediate effects of mindful breathing ( MB ) to two alternative stress-management techniques : progressive muscle relaxation ( PMR ) and loving-kindness meditation ( LKM ) to test whether decentering is unique to mindfulness meditation or common across approaches . Novice meditators ( 190 female undergraduates ) were r and omly assigned to complete one of three 15-min stress-management exercises ( MB , PMR , or LKM ) presented by audio recording . Immediately after the exercise , participants completed measures of decentering , frequency of repetitive thoughts during the exercise , and degree of negative reaction to thoughts . As predicted , participants in the MB condition reported greater decentering relative to the other two conditions . The association between frequency of repetitive thought and negative reactions to thoughts was relatively weaker in the MB condition than in the PMR and LKM conditions , in which these two variables were strongly and positively correlated . Consistent with the construct of decentering , the relative independence between these two variables in the MB condition suggests that mindful breathing may help to reduce reactivity to repetitive thoughts . Taken together , results help to provide further evidence of decentering as a potential mechanism that distinguishes mindfulness practice from other credible stress-management approaches Mindfulness meditation is a set of attention-based , regulatory , and self-inquiry training regimes . Although the impact of mindfulness training ( MT ) on self-regulation is well established , the neural mechanisms supporting such plasticity are poorly understood . MT is thought to act through interoceptive salience and attentional control mechanisms , but until now conflicting evidence from behavioral and neural measures renders difficult distinguishing their respective roles . To resolve this question we conducted a fully r and omized 6 week longitudinal trial of MT , explicitly controlling for cognitive and treatment effects with an active-control group . We measured behavioral metacognition and whole-brain blood oxygenation level-dependent ( BOLD ) signals using functional MRI during an affective Stroop task before and after intervention in healthy human subjects . Although both groups improved significantly on a response-inhibition task , only the MT group showed reduced affective Stroop conflict . Moreover , the MT group displayed greater dorsolateral prefrontal cortex responses during executive processing , consistent with increased recruitment of top-down mechanisms to resolve conflict . In contrast , we did not observe overall group-by-time interactions on negative affect-related reaction times or BOLD responses . However , only participants with the greatest amount of MT practice showed improvements in response inhibition and increased recruitment of dorsal anterior cingulate cortex , medial prefrontal cortex , and right anterior insula during negative valence processing . Our findings highlight the importance of active control in MT research , indicate unique neural mechanisms for progressive stages of mindfulness training , and suggest that optimal application of MT may differ depending on context , contrary to a one-size-fits-all approach Mindfulness-based stress reduction ( MBSR ) is thought to reduce emotional reactivity and enhance emotion regulation in patients with social anxiety disorder ( SAD ) . The goal of this study was to examine the neural correlates of deploying attention to regulate responses to negative self-beliefs using functional magnetic resonance imaging . Participants were 56 patients with generalized SAD in a r and omized controlled trial who were assigned to MBSR or a comparison aerobic exercise ( AE ) stress reduction program . Compared to AE , MBSR yielded greater ( i ) reductions in negative emotion when implementing regulation and ( ii ) increases in attention-related parietal cortical regions . Meditation practice was associated with decreases in negative emotion and social anxiety symptom severity , and increases in attention-related parietal cortex neural responses when implementing attention regulation of negative self-beliefs . Changes in attention regulation during MBSR may be an important psychological factor that helps to explain how mindfulness meditation training benefits patients with anxiety disorders Mindfulness training aims to impact emotion regulation . Generalized anxiety disorder ( GAD ) symptoms can be successfully addressed through mindfulness-based interventions . This preliminary study is the first to investigate neural mechanisms of symptom improvements in GAD following mindfulness training . Furthermore , we compared brain activation between GAD patients and healthy participants at baseline . 26 patients with a current DSM-IV GAD diagnosis were r and omized to an 8-week Mindfulness Based Stress Reduction ( MBSR , N = 15 ) or a stress management education ( SME , N = 11 ) active control program . 26 healthy participants were included for baseline comparisons . BOLD response was assessed with fMRI during affect labeling of angry and neutral facial expressions . At baseline , GAD patients showed higher amygdala activation than healthy participants in response to neutral , but not angry faces , suggesting that ambiguous stimuli reveal stronger reactivity in GAD patients . In patients , amygdala activation in response to neutral faces decreased following both interventions . BOLD response in ventrolateral prefrontal regions ( VLPFC ) showed greater increase in MBSR than SME participants . Functional connectivity between amygdala and PFC regions increased significantly pre- to post-intervention within the MBSR , but not SME group . Both , change in VLPFC activation and amygdala – prefrontal connectivity were correlated with change in Beck Anxiety Inventory ( BAI ) scores , suggesting clinical relevance of these changes . Amygdala – prefrontal connectivity turned from negative coupling ( typically seen in down-regulation of emotions ) , to positive coupling ; potentially suggesting a unique mechanism of mindfulness . Findings suggest that in GAD , mindfulness training leads to changes in fronto-limbic areas crucial for the regulation of emotion ; these changes correspond with reported symptom improvements Cardiovascular fitness is thought to offset declines in cognitive performance , but little is known about the cortical mechanisms that underlie these changes in humans . Research using animal models shows that aerobic training increases cortical capillary supplies , the number of synaptic connections , and the development of new neurons . The end result is a brain that is more efficient , plastic , and adaptive , which translates into better performance in aging animals . Here , in two separate experiments , we demonstrate for the first time to our knowledge , in humans that increases in cardiovascular fitness results in increased functioning of key aspects of the attentional network of the brain during a cognitively challenging task . Specifically , highly fit ( Study 1 ) or aerobically trained ( Study 2 ) persons show greater task-related activity in regions of the prefrontal and parietal cortices that are involved in spatial selection and inhibitory functioning , when compared with low-fit ( Study 1 ) or nonaerobic control ( Study 2 ) participants . Additionally , in both studies there exist groupwise differences in activation of the anterior cingulate cortex , which is thought to monitor for conflict in the attentional system , and signal the need for adaptation in the attentional network . These data suggest that increased cardiovascular fitness can affect improvements in the plasticity of the aging human brain , and may serve to reduce both biological and cognitive senescence in humans Mindfulness-based stress reduction ( MBSR ) is an established program shown to reduce symptoms of stress , anxiety , and depression . MBSR is believed to alter emotional responding by modifying cognitive-affective processes . Given that social anxiety disorder ( SAD ) is characterized by emotional and attentional biases as well as distorted negative self-beliefs , we examined MBSR-related changes in the brain-behavior indices of emotional reactivity and regulation of negative self-beliefs in patients with SAD . Sixteen patients underwent functional MRI while reacting to negative self-beliefs and while regulating negative emotions using 2 types of attention deployment emotion regulation-breath-focused attention and distraction-focused attention . Post-MBSR , 14 patients completed neuroimaging assessment s. Compared with baseline , MBSR completers showed improvement in anxiety and depression symptoms and self-esteem . During the breath-focused attention task ( but not the distraction-focused attention task ) , they also showed ( a ) decreased negative emotion experience , ( b ) reduced amygdala activity , and ( c ) increased activity in brain regions implicated in attentional deployment . MBSR training in patients with SAD may reduce emotional reactivity while enhancing emotion regulation . These changes might facilitate reduction in SAD-related avoidance behaviors , clinical symptoms , and automatic emotional reactivity to negative self-beliefs in adults with SAD Inhibitory control and error detection are among the highest evolved human self-monitoring functions . Attempts in functional neuroimaging to effectively isolate inhibitory motor control from other cognitive functions have met with limited success . Different brain regions in inferior , mesial , and dorsolateral prefrontal cortices and parietal and temporal lobes have been related to inhibitory control in go/no-go and stop tasks . The widespread activation reflects the fact that the design s used so far have comeasured additional noninhibitory cognitive functions such as selective attention , response competition , decision making , target detection , and inhibition failure . Here we use rapid , mixed trial , event-related functional magnetic resonance imaging to correlate brain activation with an extremely difficult situation of inhibitory control in a challenging stop task that controls for noninhibitory functions . The difficulty of the stop task , requiring withholding of a triggered motor response , was assured by an algorithm that adjusted the task individually so that each subject only succeeded on half of all stop trials , failing on the other half . This design allowed to elegantly separate brain activation related to successful motor response inhibition and to inhibition failure or error detection . Brain activation correlating with successful inhibitory control in 20 healthy volunteers could be isolated in right inferior prefrontal cortex . Failure to inhibit was associated with activation in mesial frontopolar and bilateral inferior parietal cortices , presumably reflecting an attention network for error detection
Output:
| Results showed a predominance of greater prefrontal/frontal activity related to meditation , which might indicate the increased recruitment of cognitive/attentional control re sources in naïve and long-term meditators .
This increased frontal activity was also observed when participants were asked to simply react to negative stimuli .
Findings from emotion-related areas were scarce but suggested increased insular activity in meditators , potentially indicating that meditation might be associated with greater bodily awareness .
Conclusions : Meditation practice prompts regulatory mechanisms when participants face aversive stimuli , even without an explicit request .
Moreover , some studies reported increased insular activity in meditators , consistent with the hypothesis that meditation helps foster an interoceptive awareness of bodily and emotional states |
MS213784 | ***TASK*** the task is to summarize an input biomedical literature in six sentences
***INPUT*** the input is a biomedical literature
***OUTPUT*** the output is the summary of an input biomedical literature in six sentences
***DOCUMENTATION***
***EXAMPLES***
Input: Background We planned to compare the effect of intravenous oxycodone and fentanyl on post-operative pain after laparoscopic hysterectomy . Methods We examined 60 patients were r and omized to postoperative pain treatment with either oxycodone ( n = 30 , Group O ) or fentanyl ( n = 30 , Group F ) . The patients received 10 mg oxycodone/100 µg fentanyl with ketorolac 30 mg before the end of anesthesia and then continued with patient-controlled analgesia for 48 h postoperatively . Results The accumulated oxycodone consumption was less than fentanyl during 8 , 24 and 48 h postoperatively . Numeric rating score of Group O showed significantly lower than that of Group F during 30 min , 2 , 4 , 8 and 24 h postoperatively . The incidences of adverse reactions were similar in the two groups , though the incidence of nausea was higher in the Group O during the 24 and 48 h postoperative period . Conclusions Oxycodone IV-PCA was more advantageous than fentanyl IV-PCA for laparoscopic hysterectomy in view of accumulated oxycodone consumption , pain control and cost beneficial effect . However , patient satisfaction was not good in the group O compared to group Intravenous morphine and oxycodone were given double blind in doses of 0.05 mg/kg after major abdominal surgery to 39 patients . The dosing interval was 5 min , until the patient did not want any further analgesics . Less oxycodone was needed than morphine , both to achieve the “ first state of pain relief ” ( 13.2 mg vs. 24.9 mg ) and during the whole 2‐h study period ( 21.8 mg vs. 34.2 mg ) . The “ first state of pain relief ” was achieved faster ( 28 min vs. 46 min ) and lasted longer ( 39 min vs. 27 min ) with oxycodone than morphine . Morphine caused more sedation and a greater decrease in the mean arterial blood pressure than oxycodone . In other respects the two opioids were comparable Objectives Oxycodone is semi-synthetic opioid , oral and parenteral preparations have been widely used for acute and chronic pain . The aim of this study was to assess the efficacy and side effects of oxycodone and fentanyl in patient controlled analgesia ( PCA ) after laparoscopic cholecystectomy . Methods A prospect i ve , r and omized , double-blind study was conducted . 81 patients were r and omly divided into two groups ; fentanyl ( 10 mcg fentanyl and 1.5 mg ketorolac ) and oxycodone group ( 1 mg oxycodone and 1.5 mg ketorolac ) . After the operation , a blinded observer assessed pain using a numerical rating scale ( NRS ) , infused PCA dose , side effects , sedation levels , and satisfaction . Results Cumulative PCA dose of oxycodone group at 48 h ( 31.4 ± 16.0 ml ) was significantly less than that of fentanyl group ( 43.8 ± 23.1 ml , P = 0.009 ) . Oxycodone group showed more nausea at 6 - 24 h after the operation ( P = 0.001 ) , but there was no difference in satisfaction score ( P = 0.073 ) . There were no significant differences in other side effects , sedation and NRS scores between two groups . Conclusion Oxycodone showed comparable effects for pain relief compared to fentanyl in spite of less cumulative PCA dose . Based on these results , we could conclude that oxycodone may be useful as an alternative to fentanyl for PCA after laparoscopic cholecystectomy Background Opioids are widely used in boluses and patient-controlled analgesia ( PCA ) for postoperative pain control . In this study , we compared the effects of oxycodone and fentanyl on postoperative pain in patients with intravenous patient-controlled analgesia ( IV-PCA ) after laparoscopic gynecological surgery . Methods Seventy-four patients undergoing elective total laparoscopic hysterectomy or laparoscopic myomectomy were r and omly assigned to the administration of either fentanyl or oxycodone using IV-PCA ( potency ratio 1 : 60 ) . The cumulative dose administered in the patient-controlled mode during the initial 48 hours after the operation was measured . Patients were also assessed for postoperative pain severity , adverse effects , and patient satisfaction . Results No significant differences were observed in patient satisfaction with the analgesia during the postoperative period . Patients in the oxycodone group experienced significantly more dizziness compared to the fentanyl group . Patients in the oxycodone group showed significantly lower consumption of opioid in the patient-controlled mode ( 10.1 ± 8.5 ml vs. 16.6 ± 12.0 ml , P = 0.013 ) . Conclusions Our data suggest that oxycodone and fentanyl demonstrated similar effects , and therefore oxycodone may be a good alternative to fentanyl in postoperative pain management . Further studies in various clinical setting s will be needed to determine the adequate potency ratio The single-dose pharmacokinetics and pharmacodynamics of oxycodone administered by the intravenous and rectal routes were determined in 12 adult cancer patients with moderate to severe cancer pain ( visual analog scale [ VAS ] score , approximately 5 ) . Oxycodone was administered by the intravenous and rectal routes with open drug administration and a cross-over design . After single-dose intravenous administration ( 7.9 + /- 1.5 mg , mean + /- SD ) , the mean ( + /- SD ) terminal half-life was 3.4 h ( + /- 1.1 ) , the mean ( + /- SD ) plasma clearance was 45.4 L/h ( + /- 10.1 ) , and the mean ( + /- SD ) volume of distribution in the terminal phase was 3.0 L/kg ( + /- 1.1 ) . After rectal oxycodone ( 30 mg ) , the mean ( + /- SD ) absorption lag time was 0.52 h ( + /- 0.29 ) and the mean ( + /- SD ) absolute bioavailability was 61.6 % ( + /- 30.2 % ) . Intravenous oxycodone was associated with a rapid onset of pain relief ( 5 - 8 min ) in contrast to the 0.5- to 1.0-h delay observed after rectal administration . However , rectal oxycodone provided analgesia of much longer duration ( approximate equals 8 - 12 h ) than did intravenous oxycodone ( approximate equals 4 h ) . There were no significant differences ( P > 0.05 ) in the incidence and severity of side effects between intravenous and rectal oxycodone . The marked interindividual variation observed in the pharmacokinetics and pharmacodynamics of oxycodone in this study emphasizes the need for individualized dosing regimens . ( Anesth Analg 1995;80:296 - 302 Abstract Visceral pain can be difficult to treat with classical & mgr;‐opioid agonists and it has been suggested to use opioids with distinct pharmacological profiles . In animal experiments , oxycodone has shown different effects compared to morphine , and clinical observations have shown that oxycodone may occasionally be superior to , e.g. , morphine in the treatment of visceral pain . In the current study , we r and omised 24 healthy subjects to treatment with either morphine ( 30 mg ) , oxycodone ( 15 mg ) or placebo in a crossover study . The experimental pain model involved multi‐modal ( mechanical , thermal and electrical ) pain tests in the skin , muscles and viscera . The pain tests were carried out at baseline and 30 , 60 and 90 min after oral administration of the drugs . The model showed effect of the two opioids compared to placebo on all stimulus modalities in all three types of tissues ( all P values < 0.001 ) . Both opioids attenuated the sensory response mainly to painful stimulations . Morphine and oxycodone were equipotent in pain modulation of the skin and muscles , but oxycodone had superior analgesic effect to both morphine and placebo on the mechanical ( P < 0.001 ) and thermal ( P < 0.001 ) stimulations of the oesophagus . In conclusion , the multi‐modal and tissue‐differentiated pain model could link findings from animal experiments to clinical findings . A different pharmacological profile of oxycodone compared to that of morphine was shown , and thus oxycodone may be a useful alternative to morphine in the treatment of visceral pain syndromes According to previous studies oxycodone might have some advantages over morphine in the treatment of visceral pain . This study investigated the opioid consumption ( primary outcome ) , pain relief and side effects ( secondary outcomes ) of morphine versus oxycodone after percutaneous nephrolithotomy using a method where the somatic pain component was minimized . Forty-four adult patients were studied . The patients were r and omised to receive either morphine or oxycodone intravenously as postoperative pain treatment . During the first 4 h after surgery the opioid consumption , pain scores and side effects ( nausea , dizziness , sedation , respiratory effects and itching ) were registered . The postoperative opioid consumption varied considerably between the patients but the mean opioid consumption in the morphine and oxycodone group was comparable ( 18.93 mg versus 16.15 mg , P = 0.7 ) . Nausea was significantly less frequent with morphine ( P = 0.03 ) . In this study morphine and oxycodone produced similar analgesia the first 4 h after surgery but the frequency of nausea was significantly less patient-reported with morphine . The hypothesis that oxycodone would be superior in the treatment of visceral pain after percutaneous kidney stone operation was not confirmed Background : Morphine has been the st and ard opioid in patient‐controlled analgesia ( PCA ) . Oxycodone , the analgesic potency of which in i.v . administration has been suggested to be slightly greater than that of morphine , has not yet been studied for its efficacy in PCA
Output:
| Higher incidences of adverse effects were associated with IV oxycodone .
Conclusions : IV oxycodone can be considered as effective analgesia for acute postoperative pain with careful regards to its adverse effects |
MS213785 | ***TASK*** the task is to summarize an input biomedical literature in six sentences
***INPUT*** the input is a biomedical literature
***OUTPUT*** the output is the summary of an input biomedical literature in six sentences
***DOCUMENTATION***
***EXAMPLES***
Input: Adults with type 2 diabetes mellitus often struggle with their antihyperglycemic medication regimens . To improve medication management , providers must ensure that their patients underst and potential benefits , harms , and burdens of available options and elicit patients ' preferences and barriers to taking medications . Patients who are actively involved in treatment decision making tend to be more satisfied with their health care , be more adherent to treatment , and have improved clinical outcomes ( 13 ) . Such discussion s , however , can be too time-consuming for clinic visits . For inner-city low-income African American and Latino adults , low health literacy and limited English proficiency are often additional barriers ( 4 ) that reduce the exchange of information and decrease patient participation during primary care visits ( 58 ) . This contributes to less optimal treatment decisions and lower patient satisfaction , leading to poor medication adherence and outcomes ( 3 , 911 ) . There is therefore an urgent need for cost-effective approaches to enable low-re source health systems to help these high-risk population s gain information and decision support so that they can more actively participate in and improve satisfaction with their treatment decision making . Since 2000 , the REACH ( Racial and Ethnic Approaches to Community Health 2010 ) Detroit Partnership , a coalition of community , health system , and academic partners , has used community-based participatory research principles to guide development , implementation , and evaluation of interventions to meet this need among African American and Latino adults with diabetes in Detroit , Michigan . These interventions have built on evidence that community health workers ( CHWs ) are effective in improving diabetes outcomes , particularly among racial and ethnic minority communities ( 12 ) . CHW interventions train community members to work as bridges between their ethnic , cultural , or geographic communities and health care providers ( 13 ) . Two cohorts of participants in our previous CHW-led diabetes self-management support interventions improved hemoglobin A1c ( HbA1c ) levels and diabetes distress compared with usual care ( 14 , 15 ) . An important next step in increasing the potential effect of CHWs and other lay health care workers is to develop and test effective tools they can use to better present evidence -based information to patients and to help patients make better self-management decisions ( 16 ) . Little is known about the effectiveness of different approaches for nontraditional care providers , such as CHWs , to deliver health information to ethnic minority and low-literacy population s ( 17 ) . By definition , CHWs and other lay workers do not have medical expertise and thus rely on effectively sharing printed educational and support material s with patients as part of their coaching and counseling efforts . Decision aids can increase satisfaction with treatment decisions and result in treatments that better reflect patients ' preferences ( 18 , 19 ) . There is also evidence that tailored health messages are more effective than generic group messages ( 20 , 21 ) , including for patients with diabetes ( 22 , 23 ) . Tailoring individualizes information and behavior change strategies to reach each person based on characteristics unique to that person derived from an individual assessment and related to the outcome of interest ( 24 ) . Software programs that are being developed to automatically embed tailored content into portable e-health Web applications show promise in improving health behaviors and outcomes ( 25 , 26 ) . To date , however , most e-health applications have been design ed for use by patients with relatively high literacy and the skills to navigate them ( 27 ) . Do more sophisticated , tailored , interactive e-health tools increase the effectiveness of CHW outreach with underserved patients compared with reliance on printed educational material s alone ? We addressed this question by developing and evaluating a personally tailored , interactive diabetes medication decision aid ( iDecide [ in English ] or iDecido [ in Spanish ] ) design ed for CHWs to deliver on tablet computers with 3 G wireless access to African American and Latino adults with diabetes and low health literacy . We then evaluated the effectiveness of iDecide in improving key diabetes outcomes compared with CHW delivery of the same evidence -based information , without tailoring , through print consumer booklets developed by the Agency for Healthcare Research and Quality ( AHRQ ) . Methods Setting This study was developed and implemented by using community-based participatory research principles ( 28 ) in partnership with the REACH Detroit Partnership and the Community Health and Social Services Center ( CHASS ) , a federally qualified health center in Southwest Detroit serving more than 13000 patients with 47099 visits in 2012 ( 29 ) . The University of Michigan and CHASS institutional review boards approved the study . Content of AHRQ Consumer Guides The AHRQ guides ( Pills for Type 2 Diabetes and Premixed Insulin for Type 2 Diabetes ) ( 30 , 31 ) provide information on diabetes and summarize the effectiveness of currently available medication classes ( oral and insulin ) on HbA1c . They also provide information on administration methods , costs , medication adverse effects , risks for diabetes complications , suggested questions to discuss with health care providers , and prompts to make notes of any questions for the doctor . The booklets include pictures of patients and tables and graphs summarizing information . Content of iDecide The development process and content of the iDecide program have been described in detail elsewhere ( 32 ) . Briefly , we used community-based participatory research and user-centered design ( 33 , 34 ) principles to iteratively develop and refine the iDecide tool . iDecide is available in English and Spanish , can be delivered via tablet computers , and enables navigation by the CHW and participant to selectively explore issues most important to the participant . The iDecide program is organized into 4 main sections and includes the same content as the AHRQ consumer guides . However , its information is presented in a more graphical style suited to patients with low literacy . Table 1 summarizes key differences between the presentation of information in iDecide and the printed material s. The first section illustrates , through animations , how diabetes affects the way glucose is processed in the body and how different medication classes , foods , and physical activity affect blood glucose . The second section includes pictographs showing participants ' own risk for diabetes complications ( tailored according to their baseline HbA1c ) and enabling participants to explore how their risk for different complications changes with their HbA1c levels . In the third section , participants review their current diabetes medications and barriers to taking the medications they had reported on the baseline survey . This section includes an interactive issue card approach to help elicit patient preferences and priorities about different medication characteristics ( for example , cost , adverse effects , effects on weight , and dosing schedules ) ( 22 , 35 ) . The fourth section prompts participants to set goals and develop specific action plans to address identified barriers or other concerns and identify specific questions and concerns to discuss with their doctor about their medications or making lifestyle changes . Personal information from the baseline assessment is interwoven throughout the program ( high-depth tailoring within sentences ) . Motivational interviewingbased , tailored discussion prompts encourage autonomy-supportive CHWpatient interactions at key points with open-ended questions and values exploration to help participants discover their motivation , overcome barriers to change , and develop an action plan ( 36 ) . Table 1 . Comparison of Content and Mode of Delivery Between the iDecide Study Group and the Printed Material s Group Recruitment and R and omization From September 2011 to August 2012 , potentially eligible participants were identified from a computer-generated list of CHASS patients with physician-diagnosed type 2 diabetes . Inclusion criteria required a HbA1c value greater than 7.5 % in the previous 6 months or expressed concerns about current diabetes medications during the screening assessment . Exclusion criteria were age younger than 21 years , terminal health conditions , self-reported alcohol or drug abuse , and conditions ( such as blindness and dementia ) that would impede meaningful participation . Pregnant women and individuals who reported that they could not be contacted by telephone were also excluded . Introductory letters were sent in timed batches . Research staff then telephoned patients and screened them for eligibility . Interested eligible patients met with research staff , who facilitated completion of written informed consent , administered baseline surveys in English or Spanish , and measured HbA1c and blood pressure . Participants received a stipend of $ 20 after each assessment . Within 1 to 14 days , participants were scheduled for a visit with a CHW ( at home , the clinic , or another agreed-upon place ) . At the beginning of the CHW visits , participants were registered into the iDecide program and r and omly assigned by the computer program , through use of a r and om-sequence algorithm , into 1 of 2 study groups . There were no differences between the steps to participate in either study group . Patients , research staff , and CHWs were blinded to r and omization results through completion of all baseline measures up to the start of the intervention . Data assessors remained blinded to group assignment throughout the study . CHW Intervention for Both Study Groups All participants received an initial one-on-one , face-to-face session with a CHW and a copy of the printed material s to take home . The iDecide sessions lasted approximately 2 hours , and the sessions using printed material s lasted OBJECTIVE To compare glycemic control and secondary outcomes of a 4-month telephonic couples behavioral intervention to individual intervention , and to education , for adults with type 2 diabetes . RESEARCH DESIGN AND METHODS A r and omized trial with the following three arms : couples calls ( CC ) ( n = 104 ) ; individual calls ( IC ) ( n = 94 ) ; and diabetes education ( DE ) ( n = 82 ) . All arms had self-management education ( two calls ) . CC and IC had 10 additional behavior change calls . CC addressed collaboration and relationships/communication . Participants consisted of 280 couples , among whom one partner had type 2 diabetes and an A1C level ≥7.5 % . Blinded assessment s occurred at 4 , 8 , and 12 months . The primary outcome was change in A1C ; and secondary outcomes were BMI , waist circumference , blood pressure , depressive symptoms , diabetes self-efficacy , and diabetes distress . RESULTS Patients had a mean age of 56.8 years ; 61.6 % were male , and 30.4 % were minorities . The baseline mean A1C level was 9.1 % . Intention-to-treat analyses found significant A1C reductions for all ( 12 months : CC −0.47 % , IC −0.52 % , DE −0.57 % ) , with no differences between arms . Preplanned within-arm analyses were stratified by baseline A1C tertiles : lowest tertile ( 7.5–8.2 % ) , no change from baseline ; middle tertile ( 8.3–9.2 % ) , only CC led to significantly lower A1C level ; and highest tertile ( ≥9.3 % ) , significant improvement for all interventions . For BMI , CC showed significant improvement , and CC and DE led to decreased waist circumference . The IC group showed greater blood pressure improvement . Results for secondary psychosocial outcomes favored the CC group . CONCLUSIONS In adults with poorly controlled type 2 diabetes , a collaborative couples intervention result ed in significant , lasting improvement in A1C levels , obesity measures , and some psychosocial outcomes . For those with exceedingly high A1C levels , education alone was beneficial , but additional intervention is needed to achieve glycemic targets OBJECTIVE To determine the concurrent , prospect i ve , and time-concordant relationships among major depressive disorder ( MDD ) , depressive symptoms , and diabetes distress with glycemic control . RESEARCH DESIGN AND METHODS In a noninterventional study , we assessed 506 type 2 diabetic patients for MDD ( Composite International Diagnostic Interview ) , for depressive symptoms ( Center for Epidemiological Studies -Depression ) , and for diabetes distress ( Diabetes Distress Scale ) , along with self-management , stress , demographics , and diabetes status , at baseline and 9 and 18 months later . Using multilevel modeling ( MLM ) , we explored the cross-sectional relationships of the three affective variables with A1C , the prospect i ve relationships of baseline variables with change in A1C over time , and the time-concordant relationships with A1C . RESULTS All three affective variables were moderately intercorrelated , although the relationship between depressive symptoms and diabetes distress was greater than the relationship of either with MDD . In the cross-sectional MLM , only diabetes distress but not MDD or depressive symptoms was significantly associated with A1C . None of the three affective variables were linked with A1C in prospect i ve analyses . Only diabetes distress displayed significant time-concordant relationships with A1C . CONCLUSIONS We found no concurrent or longitudinal association between MDD or depressive symptoms with A1C , whereas both concurrent and time-concordant relationships were found between diabetes distress and A1C . What has been called “ depression ” among type 2 diabetic patients may really be two conditions , MDD and diabetes distress , with only the latter displaying significant associations with A1C . Ongoing evaluation of both diabetes distress and MDD may be helpful in clinical setting Technology and improved care coordination models can help diabetes educators and providers meet national care st and ards and provide culturally sensitive diabetes education that may improve diabetes outcomes . The purpose of the study was to evaluate the clinical usefulness of a nurse-led diabetes care program ( Comprehensive Diabetes Management Program , CDMP ) for poorly controlled Hispanic type 2 diabetes ( T2DM ) patients in an urban community health center setting . Patients were r and omized to the intervention condition ( IC ; n = 21 ) or an attention control condition ( AC ; n = 18 ) . IC and AC conditions were compared on rates of adherence to national clinical practice guidelines ( blood glucose , blood pressure , foot exam , eye exam ) , and levels of diabetes distress , depression , and treatment satisfaction . IC patients had a significant improvement
Output:
| The effect on depression was small , while there was no effect on health-related quality of life .
Exploratory subgroup analyses suggested that interventions using motivational interviewing and individual interventions were associated with incremental effects on DD .
Likewise , intensive interventions were associated with significant reductions in both DD and HbA1c |
MS213786 | ***TASK*** the task is to summarize an input biomedical literature in six sentences
***INPUT*** the input is a biomedical literature
***OUTPUT*** the output is the summary of an input biomedical literature in six sentences
***DOCUMENTATION***
***EXAMPLES***
Input: Four treatments for sciatic symptoms -- traction , exercises , manipulation , and corset -- were assessed in a r and omised controlled trial in 322 out patients . The design was factorial . There were thus sixteen treatment groups , enabling a comparison of combinations of methods as well as of individual methods . Treatment lasted for four weeks . Patients were review ed at the end of this period and at four and sixteen months after entry to the trial . Progress was measured by the patient 's account of symptomatic improvement or deterioration and by return to work or normal activities . At four weeks each of the treatments was associated with a small degree of benefit over and above the high rate of spontaneous improvement . For manipulation , the benefit was statistically significant on one of the scales used to measure progress . There was a significant increase in symptomatic improvement with increasing numbers of treatments used in combination . This was complemented by a clear tendency for those who had received fewer types of treatment during the trial to have further treatment in the ensuing three months . There were no beneficial effects of treatment detectable at four or sixteen months . In the short-term , active physiotherapy with several treatments appears to be of value in the outpatient management of patients with sciatic symptoms , but it does not seem to confer any longer-term benefit BACKGROUND AND PURPOSE Since the release of acute low back pain management guidelines in 1994 , little was known about the effect of these guidelines on clinical practice . The purpose of this study was to examine physical therapists ' reported management of acute and subacute lumbar impairment . SUBJECTS One in 10 registered physical therapists who were r and omly selected from southern Ontario , Canada , ( n=454 ) and all registered physical therapists from northern Ontario ( n=331 ) were surveyed . METHODS In the question naire , case scenarios covered 3 areas related to the management of lumbar impairment : ( 1 ) physical examination , ( 2 ) treatment and recommendations , and ( 3 ) therapists ' beliefs regarding its management . RESULTS Five hundred sixty-nine question naires were returned ( response rate=72.5 % ) . Only data obtained for therapists ( n=274 ) whose weekly workload included more than 10 % of people with lumbar impairment were used in the analysis . Overall , patient education , exercise , and electrotherapeutic and thermal modalities were the preferred interventions for acute lumbar impairment ( symptom onset of less than 5 weeks ) with or without sciatica , whereas exercise and work modification were preferred for subacute lumbar impairment ( symptom onset of 5 weeks or longer ) . There was a trend of using electrotherapeutic and thermal modalities with uncertain effectiveness . Only 46.3 % of the therapists agreed or strongly agreed that practice guidelines were useful for managing lumbar impairment . DISCUSSION AND CONCLUSION Although the physical therapists surveyed , in general , followed the guidelines in managing acute lumbar impairment , they felt uncertain regarding the value of practice guidelines . Future research should focus on identifying effective treatment approaches and exploring the effectiveness of practice guidelines STUDY DESIGN A descriptive question naire of chartered physiotherapists . OBJECTIVE To investigate current physiotherapeutic management of low back pain throughout Britain and Irel and . SUMMARY OF BACKGROUND DATA Physiotherapists play a key role in low back pain management . Although clinical guidelines for best practice have been developed recently , there has been no large-scale attempt to describe current physiotherapeutic treatment approaches within Britain or Irel and . METHODS After semi-structured interviews ( n = 6 ) and two pilot studies ( n = 77 ) were done , postal question naires were distributed to four regional cluster sample s of the membership of two physiotherapy professional organizations ( n = 2654 ) . After two mailings , a r and om sample of 90 nonresponders were followed up . Data were analyzed using the Statistical Package for the Social Sciences ( SPSS Ltd. , Woking , Surrey , UK ) , and precision of the survey estimates was assessed by calculation of sampling errors and intraclass correlation coefficients for cluster sampling . RESULTS Results were received from 1548 therapists ( total response rate , 58.3 % ) ; of these , 813 reported that they were practicing in setting s in which they treated patients with low back pain . Analysis of the results indicated the overall popularity of the Maitl and mobilization and McKenzie approaches among physiotherapists . Although exercise per se was mentioned frequently by respondents , a marked difference in opinion among therapists regarding the optimal type of exercise for low back pain was obvious . Little evidence was demonstrated of the use of manipulation , fitness programs , or multidisciplinary efforts involving behavioral and physical aspects of treatment . Commonly used methods of electrotherapy were interferential therapy , ultrasound , pulsed short-wave diathermy , and transcutaneous electrical nerve stimulation . CONCLUSIONS The results of this study emphasize the need to evaluate further and improve the dissemination of findings regarding the effectiveness of specific physiotherapy approaches for low back pain management Traction therapy for low back pain with sciatica has been evaluated in a double blind study . 60 patients hospitalized for sciatica with or without signs of sensory or motor deficiency were r and omized to 3 treatment groups : " placebo traction " ( 5 kg ) , " light traction " ( 15 kg ) and " normal traction " ( 50 kg ) . Clinical evaluation after 4 , 8 and 12 traction sessions showed no difference between the three groups Four treatment regimens for patients with specified combinations of low back pain and sciatica were evaluated . The largest group studied had low back pain with limited straight-leg raising ( SLR ) and in them the beneficial effect of manipulation in hastening pain relief was highly significant . In similar patients without limitation of SLR , the effect was of borderline significance . In all the other groups , treated patients also recovered more quickly than their controls . Traction , for patients with low back pain and sciatica , and epidural injections when a root palsy was present also produced some significant pain relief . The effect of sclerosants for back pain was less clear STUDY DESIGN A r and omized trial design ed to compare interferential therapy with motorized lumbar traction and massage management for low back pain in a primary care setting . OBJECTIVE To measure and compare the outcome of interferential therapy and management by motorized lumbar traction and massage . SUMMARY OF BACKGROUND DATA Management of low back pain by interferential therapy and motorized lumbar traction and massage is common in Germany . No reports of previous r and omized trials for the outcome from interferential therapy were found . METHODS Consenting patients were r and omly assigned into one of two groups . A pretreatment interview was performed by the patient using a computer-based question naire . It also incorporated the Oswestry Disability Index and a pain visual analog scale . Management consisted of six sessions over a 2- to 3-week period . Oswestry Disability Indexes and pain visual analog scale scores also were obtained immediately after and at 3 months after treatment . RESULTS A total of 152 patients were recruited . The two treatment groups had similar demographic and clinical baseline characteristics . The mean Oswestry Disability Index before treatment was 30 for both groups ( n = 147 ) . After treatment , this had dropped to 25 , and , at 3 months , were 21 ( interferential therapy ) and 22 ( motorized lumbar traction and massage ) . The mean pain visual analog scale score before treatment was 50 ( interferential therapy ) and 51 ( motorized lumbar traction and massage ) . This had dropped , respectively , to 46 and 44 after treatment and to 42 and 39 at 3 months . CONCLUSIONS This study shows a progressive fall in Oswestry Disability Index and pain visual analog scale scores in patients with low back pain treated with either-interferential therapy or motorized lumbar traction and massage . There was no difference in the improvement between the two groups at the end of treatment . Although there is evidence from several trials that traction alone is ineffective in the management of low back pain , this study could not exclude some effect from the concomitant massage Previous trials to assess the efficacy of lumbar traction for back pain have been method ologically flawed . To avoid these shortcomings , we conducted a r and omised controlled trial in which high-dose traction was compared with sham traction . The sham traction was given with a specially developed brace that tightens in the back during traction . To the patient , the experience is that of traction . The patients and outcome assessor were blinded for the assigned treatment . 151 patients with at least six weeks of non-specific low back pain were r and omised . Intention to treat analysis showed no differences between the groups on all outcome measures ( patients ' global perceived effect , severity of main complaints , functional status and pain ) ; all 95 % confidence intervals included the value zero . The number of withdrawals from treatment , loss to follow-up , and protocol deviations was low . Consequently , the per- protocol analysis showed results similar to the intention to treat analysis . Subgroup analyses did not show any group for which traction might seem promising . Our data do not support the cl aim that traction is effective for patients with low back pain Autotraction ( AT ) is a treatment for low-back pain syndrome of benign etiology that uses a specially design ed traction table divided into two movable sections . While lying on the table , the pelvis secured , the patient controls the traction forces by grasping and pulling the bars at the head of the table . There are controls for the therapist to apply , through movable sections of the table , rotation and bending forces to help restore mobility to the lumbar spine without inducing pain . The present study is based upon a r and omized treatment trial comparing conventional passive traction ( PT ) to AT . The following outcome indicators were used : ( 1 ) subjective response concerning overall improvement , ( 2 ) pain intensity ( visual analog scale , 0 - 100 ) , ( 3 ) qualitative pain severity ( McGill Pain Question naire , short-form , 0 - 45 ) , and ( 4 ) pain related disability ( Oswestry Low Back Pain Disability Score , 0 - 100 ) . The favorable response to AT was 75 % ( 30 of the 40 patients ) versus the 22 % ( 6 of 27 patients ) to PT ( p < 0.001 ) . After 3 months , 19 of the 30 responders to AT ( 63 % ) reported continued improvement . In these patients , pain ratings remained stable and the disability scores decreased to 0 to 23 % of the pretreatment value ( median and mean respectively , p < 0.001 ) Forty-nine patients with lumbago-sciatica and prolapsed lumbar intervertebral discs , comparable concerning anamnestical and clinical data were r and omized for autotraction and manual traction given by the same therapist for a period of one week while strict bed rest was prescribed . A blind overall assessment performed immediately after the traction period , after two weeks follow-up training and three months after hospitalization showed that the two traction modalities are equally efficient . As treatment for hospitalized patients with lumbar intervertebral disc prolapses the relatively simple manual traction variety should be preferred , if any . Traction is suggested to be used as a prognostical aid . Pain intensity was significantly reduced in all body parts . About one fourth of patients avoided operation . After two years there was no recurrence of symptoms Study Design A clinical study was conducted on 39 patients with acute , first‐episode , unilateral low back pain and unilateral , segmental inhibition of the multifidus muscle . Patients were allocated r and omly to a control or treatment group . Objectives To document the natural course of lumbar multifidus recovery and to evaluate the effectiveness of specific , localized , exercise therapy on muscle recovery . Summary of Background Data Acute low back pain usually resolves spontaneously , but the recurrence rate is high . Inhibition of multifidus occurs with acute , first‐episode , low back pain , and pathologic changes in this muscle have been linked with poor outcome and recurrence of symptoms . Methods Patients in group 1 received medical treatment only . Patients in group 2 received medical treatment and specific , localized , exercise therapy . Outcome measures for both groups included 4 weekly assessment s of pain , disability , range of motion , and size of the multifidus cross‐sectional area . Independent examiners were blinded to group allocation . Patients were reassessed at a 10‐week follow‐up examination . Results Multifidus muscle recovery was not spontaneous on remission of painful symptoms in patients in group 1 . Muscle recovery was more rapid and more complete in patients in group 2 who received exercise therapy ( P = 0.0001 ) . Other outcome measurements were similar for the two groups at the 4‐week examination . Although they resumed normal levels of activity , patients in group 1 still had decreased multifidus muscle size at the 10‐week follow‐up examination . Conclusions Multifidus muscle recovery is not spontaneous on remission of painful symptoms . Lack of localized , muscle support may be one reason for the high recurrence rate of low back pain following the initial episode A double-blind control study of lumbar traction for sciatica has been carried out . Although there is a tendency for traction to produce improvement in pain and straight-leg raise the extent does not achieve statistical significance . Changing ' control ' patients to ' treatment ' seemed to produce worthwhile relief of pain for all who were not already improving . It is suggested that a large trial using more discriminating criteria might delineate a group of patients susceptible to help by traction This study investigates whether there is a difference in electromyographic activity in the lumbar sacrospinalis musculature during continuous and intermittent pelvic traction . Twenty-nine normal subjects were r and omly assigned to a control group , a continuous traction group , or an intermittent traction group . Electromyographic activity was recorded at specific timed intervals . Myoelectric activity increased with the onset of either type of traction , but by the third recording both groups had returned to their normal initial resting myoelectric recordings . The myoelectric patterns over time were similar for the two treatment groups . No significant difference in electromyographic activity of the lumbar sacrospinalis
Output:
| The evidence for the use of traction in LBP remains inconclusive because of the continued lack of method ologic rigor and the limited application of clinical parameters as used in clinical practice . |
MS213787 | ***TASK*** the task is to summarize an input biomedical literature in six sentences
***INPUT*** the input is a biomedical literature
***OUTPUT*** the output is the summary of an input biomedical literature in six sentences
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Input: Reports of cluster r and omised trials require additional information to allow readers to interpret them accurately The effective reporting of r and omised controlled trials has received useful attention in recent years . Many journals now require that reports conform to the guidelines in the Consoli date d St and ards of Reporting Trials ( CONSORT ) statement , first published in 1996 and revised in 2001 . The statement includes a checklist of items that should be included in the trial report . These items are evidence based whenever possible and are regularly review ed . The statement also recommends including a flow diagram to show the flow of participants from group assignment through to the final analysis . The CONSORT statement focused on reporting parallel group r and omised trials in which individual participants are r and omly assigned to study groups . However , in some situations it is preferable to r and omly assign groups of individuals ( such as families or medical practice s ) rather than individuals . Reasons include the threat of contamination of some interventions ( such as dietary interventions ) if individual r and omisation is used . 5 Also , in certain setting s r and omisation by group may be the only feasible method of conducting a trial . Trials with this design are variously known as field trials , community based trials , place based trials , or ( as in this paper ) cluster r and omised trials . In an earlier discussion paper we considered the implication s of the CONSORT statement for the reporting of cluster r and omised trials . Here we present up date d guidance , based on the 2001 revision of the CONSORT statement This article describes and evaluates a K-6 child sexual abuse prevention curriculum that was piloted in a large northwestern school district 1986–89 . Paired t-tests using pre-test and post-test scores from a r and om sample of 1,391 K-6 students indicates that significant learning occurred at all grade levels . Analysis of variance results suggest that , overall , learning is not related to students ' gender or to the school 's socioeconomic level . Responses by 197 teachers concerning their evaluations of curriculum material s and training were positive . Study limitations and future research plans and needs are discussed The authors evaluated a coeducational program for teenagers on preventing sexual coercion in dating situations . Students examined individual and social attitudes underlying coercive sexual behavior and learned communication skills aim ed at preventing or dealing with unwanted sexual advances . Instruction was enhanced by video and an interactive video " virtual date . " Outcomes were assessed using sexual attitude scales with a sample of 458 high school students . Student health education classes were r and omly assigned to either a treatment or a control condition . Findings , based on a latent variable model of differential effectiveness , showed that students in the treatment group with initial coercive attitude scores at or above the mean benefited significantly more than students with the same range of scores in the control group This paper reports the outcome of an attempt to teach children in grade s 5 and 6 about child abuse and neglect . The Child Abuse Component of the Human Relations Program described and evaluated here is a unique effort to provide children with an opportunity to discuss and learn about this aspect of family violence . An impact assessment was conducted by documenting possible changes in student knowledge and attitudes regarding child abuse as a result of exposure to the Child Abuse Component of the Human Relations Program . The test group of children consisted of 315 boys and girls in grade s 5 and 6 . A comparison group of 298 children was closely matched with the test group on the basis of age and sex . These groups were formed by r and omly selecting 12 teachers from all teachers agreeing to use the Component and 10 teachers choosing not to employ the Component . The students in the classrooms of these teachers received the same curriculum for their grade level with the exception of the field-test group additionally receiving the Component . Selected child abuse knowledge , attitude , and personality ( security ) measures were given all subjects in a post-test with comparison group research design . Teacher knowledge and attitude were also assessed . The results of the data analysis , teacher , and special observer reports suggest that the Component was effective in meeting its objectives and was not disturbing to test subjects . Apparently , the test children profited by experiencing the Component mainly because of the opportunity it provided for class discussion . Moreover , the knowledge levels and interest of the children in both groups was seriously underestimated Young children ( ages 4 and 5 ) and school-aged children ( 6 to 10 ) from a day-care center were r and omly assigned to a sexual abuse prevention training group and a wait-list control group . Children in the prevention training group were exposed to a three-hour program teaching common sexual abuse prevention concepts ( e.g. , the difference between OK and not-OK touches ) . Children in both groups were given a structured interview before and after the prevention group received training . Results of a repeated measures multivariate analysis of variance indicate that children in the prevention training group significantly increased their knowledge of prevention concepts while children in the control group did not . Older children learned more than younger children . Both younger and older children had greater difficulty learning prevention concepts of an abstract nature than concepts of a specific nature OBJECTIVES This study assessed the effects of the Safe Date s program on the primary and secondary prevention of adolescent dating violence . METHODS Fourteen schools were r and omly allocated to treatment conditions . Eighty percent ( n=1886 ) of the eighth and ninth grade rs in a rural county completed baseline question naires , and 1700 ( 90 % ) completed follow-up question naires . RESULTS Treatment and control groups were comparable at baseline . In the full sample at follow-up , less psychological abuse , sexual violence , and violence perpetrated against the current dating partner were reported in treatment than in control schools . In a sub sample of adolescents reporting no dating violence at baseline ( a primary prevention sub sample ) , there was less initiation of psychological abuse in treatment than in control schools . In a sub sample of adolescents reporting dating violence at baseline ( a secondary prevention sub sample ) , there was less psychological abuse and sexual violence perpetration reported at follow-up in treatment than in control schools . Most program effects were explained by changes in dating violence norms , gender stereotyping , and awareness of services . CONCLUSIONS The Safe Date s program shows promise for preventing dating violence among adolescents OBJECTIVE The research evaluated a sexual abuse prevention program for elementary school-aged children . Although other evaluations of similar programs have demonstrated significant improvements in knowledge and skills , a number of key questions with respect to their efficacy remain . METHOD 231 children were r and omly assigned ( matched by age ) to participate in the program ( N = 117 ) or in a wait-list control condition ( N = 114 ) . Knowledge of abuse prevention concepts were tested using the 33-item Children 's Knowledge of Abuse Question naire-Revised ( CKAQ-R ) , a st and ardized measure with strong psychometric properties ( Tutty , 1995 ) , with a new subscale on Appropriate Touch . RESULTS An analysis of covariance showed that children who received the program increased their knowledge levels of both Inappropriate Touch ( p = .000 ) and Appropriate Touch ( p = .012 ) to a significantly greater degree than children in the control group . Age also significantly differentiated the knowledge levels regarding Inappropriate Touch , with younger children knowing fewer concepts both at pretest and posttest ( p = .000 ) . Parallel results apply to the Appropriate Touch subscale ( p = .04 ) . CONCLUSIONS The results are consistent with other evaluations of child sexual abuse prevention programs , however the statistically significant though small gains suggest that the programs need to be presented in a more powerful manner OBJECTIVE The purpose of this study was to describe the extent to which childhood abuse and neglect increase a person 's risk for subsequent posttraumatic stress disorder ( PTSD ) and to determine whether the relationship to PTSD persists despite controls for family , individual , and lifestyle characteristics associated with both childhood victimization and PTSD . METHOD Victims of substantiated child abuse and neglect from 1967 to 1971 in a Midwestern metropolitan county area were matched on the basis of age , race , sex , and approximate family socioeconomic class with a group of nonabused and nonneglected children and followed prospect ively into young adulthood . Subjects ( N = 1,196 ) were located and administered a 2-hour interview that included the National Institute of Mental Health Diagnostic Interview Schedule to assess PTSD . RESULTS Childhood victimization was associated with increased risk for lifetime and current PTSD . Slightly more than a third of the childhood victims of sexual abuse ( 37.5 % ) , 32.7 % of those physically abused , and 30.6 % of victims of childhood neglect met DSM-III-R criteria for lifetime PTSD . The relationship between childhood victimization and number of PTSD symptoms persisted despite the introduction of covariates associated with risk for both . CONCLUSIONS Victims of child abuse ( sexual and physical ) and neglect are at increased risk for developing PTSD , but childhood victimization is not a sufficient condition . Family , individual , and lifestyle variables also place individuals at risk and contribute to the symptoms of PTSD This paper presents results from a third grade sexual abuse prevention program . A 24-item question naire was administered as a pretest and post-test to an experimental group ( n = 236 ) and a control group ( n = 195 ) of third grade students . Those receiving the sexual abuse prevention program significantly increased their sexual abuse knowledge scores from pretest to post-test . In addition , differences in knowledge were significantly higher in the experimental compared to the control group . Students who received the sexual abuse curriculum significantly improved from pretest to post-test on their behavioral intention scores . Results from this evaluation indicated a modest improvement can be obtained through use of this two-hour sexual abuse prevention curriculum In this experiment , 123 sixth and seventh grade classrooms from Clevel and area schools were r and omly assigned to one of two five-session curricula addressing gender violence/sexual harassment ( GV/SH ) or to a no-treatment control . Three-student surveys were administered . Students in the law and justice curricula , compared to the control group , had significantly improved outcomes in awareness of their abusive behaviors , attitudes toward GV/SH and personal space , and knowledge . Students in the interaction curricula experienced lower rates of victimization , increased awareness of abusive behaviors , and improved attitudes toward personal space . Neither curricula affected perpetration or victimization of sexual harassment . While the intervention appeared to reduce peer violence victimization and perpetration , a conflicting finding emerged — the intervention may have increased dating violence perpetration ( or at least the reporting of it ) but not dating violence victimization PURPOSE Dating violence (DV)--physical , sexual , and psychological aggression in adolescent romantic relationships -- is prevalent among youth . Despite broad calls for primary prevention , few programs with demonstrated effectiveness exist . This cluster-r and omized trial examined the effectiveness of a DV perpetration prevention program targeting coaches and high school male athletes . METHODS The unit of r and omization was the high school ( 16 schools ) , and the unit of analysis was the athlete ( N = 2,006 students ) . Primary outcomes were intentions to intervene , recognition of abusive behaviors , and gender-equitable attitudes . Secondary outcomes explored byst and er behaviors and abuse perpetration . Regression models for clustered , longitudinal data assessed between-arm differences in over-time changes in mean levels of continuous outcomes in 1,798 athletes followed up at 3 months . RESULTS Intervention athletes ' changes in intentions to intervene were positive compared with control subjects , result ing in an estimated intervention effect of .12 ( 95 % CI : .003 , .24 ) . Intervention athletes also reported higher levels of positive byst and er intervention behavior than control subjects ( .25 , 95 % CI : .13 , .38 ) . Changes in gender-equitable attitudes , recognition of abusive behaviors , and DV perpetration were not significant . Secondary analyses estimated intervention impacts according to intensity of program implementation . Compared with control subjects , athletes exposed to full-intensity implementation of the intervention demonstrated improvements in intentions to intervene ( .16 , 95 % CI : .04 , .27 ) , recognition of abusive behaviors ( .13 , 95 % CI : .003 , .25 ) , and positive byst and er intervention ( .28 , 95 % CI : .14 , .41 ) . CONCLUSION This cluster-r and omized controlled trial supports the effectiveness of a school athletics-based prevention program as one promising strategy to reduce DV perpetration BACKGROUND Perpetration of physical , sexual , and psychological abuse is prevalent in adolescent relationships . One strategy for reducing such violence is to increase the likelihood that youth will intervene when they see peers engaging in disrespectful and abusive behaviors . PURPOSE This 12-month follow-up of a cluster RCT examined the longer-term effectiveness of Coaching Boys Into Men , a dating violence prevention program targeting high school male athletes . DESIGN This cluster RCT was conducted from 2009 to 2011 . The unit of r and omization was the school , and the unit of analysis was the athlete . Data were analyzed in 2012 . SETTING / PARTICIPANTS Participants were male athletes in Grade s 9 - 11 ( N=1513 ) participating in athletics in 16 high schools . INTERVENTION The intervention consisted of training athletic coaches to integrate violence prevention messages into coaching activities through brief , weekly , scripted discussion s with athletes . MAIN OUTCOME MEASURES Primary outcomes were intentions to intervene , recognition of abusive behaviors , and gender-equitable attitudes . Secondary outcomes included byst and er behaviors and abuse perpetration . Intervention effects were expressed as adjusted mean between-arm differences in changes in outcomes over time , estimated via regression models for clustered , longitudinal data . RESULTS Perpetration of dating violence in the past 3 months was less prevalent among intervention athletes relative to control athletes , result ing in an estimated intervention effect of -0.15 ( 95 % CI=-0.
Output:
| The studies included in this review show evidence of improvements in protective behaviours and knowledge among children exposed to school-based programmes , regardless of the type of programme .
There is evidence that children 's knowledge does not deteriorate over time , although this requires further research with longer-term follow-up .
Programme participation does not generate increased or decreased child anxiety or fear , however there is a need for ongoing monitoring of both positive and negative short- and long-term effects .
The results show that programme participation may increase the odds of disclosure , however there is a need for more programme evaluations to routinely collect such data . |
MS213788 | ***TASK*** the task is to summarize an input biomedical literature in six sentences
***INPUT*** the input is a biomedical literature
***OUTPUT*** the output is the summary of an input biomedical literature in six sentences
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Input: BACKGROUND There is no completely satisfactory treatment for multiple actinic keratoses ( AKs ) . OBJECTIVE To evaluate the efficacy of short incubation , broad-area application of delta-aminolevulinic acid followed by exposure to activating light-photodynamic therapy ( delta-ALA/PDT ) for treatment of AKs and background photodamage . The benefit of pretreatment with 40 % urea cream to enhance penetration and the use of topical 3 % lidocaine hydrochloride to decrease discomfort were also evaluated . METHODS Eighteen patients with at least 4 nonhypertrophic facial AKs and mild to moderate diffuse facial photodamage were enrolled in the study . For 7 days , 40 % urea cream or vehicle was applied to half of the treatment area , and then delta-ALA was applied to the entire area for 1 , 2 , or 3 hours . Lidocaine hydrochloride ( 3 % ) or vehicle cream was also applied to the entire area 45 minutes before exposure to 10 J/cm(2 ) of blue light . Pain , phototoxic reactions , AK counts , and photodamage improvement were evaluated 1 day , 1 week , and 1 month after treatment in all patients and after 5 months in 10 patients . RESULTS All patients experienced mild to moderate discomfort during treatment and moderate phototoxic effects for 1 week . At 1 and 5 months there was significant reduction in AKs in all groups and significant improvement of several photodamage parameters . Different delta-ALA application times and pretreatment with urea cream or lidocaine had no significant effect on the results . CONCLUSIONS This delta-ALA/PDT protocol is safe and effective for AK treatment as well as for improving photodamage . Further studies with a larger cohort , longer follow-up , and histologic confirmation of the clinical data would be of value This double-blind , vehicle-controlled , multicenter study evaluated the efficacy and safety of a new topical antineoplastic agent , masoprocol , in the treatment of actinic keratoses of the head and neck . Of the 113 patients who applied topical masoprocol twice a day for 14 to 28 days , there was a mean decrease in actinic keratoses from 15.0 to 5.4 and a median percent reduction from baseline actinic keratosis count of 71.4 % at the 1-month follow-up visit . Comparable numbers for the vehicle-treated group were 13.4 to 11.1 actinic keratoses and 4.3 % median percent reduction . Irritation , as manifested by erythema or flaking , occurred in 61.5 % of topical masoprocol-treated patients versus 26.7 % of those treated with vehicle and did not correlate with clinical response . Topical masoprocol appears to be useful in the treatment of actinic keratoses The efficacy of photodynamic therapy ( PDT ) using broad area treatment with 5-aminolevulinic acid ( ALA ) has not been compared to topical 5-fluorouracil ( 5-FU ) in the treatment of actinic keratoses ( AK ) . The purpose of this study was to compare the efficacy and tolerability of PDT using short incubation time , broad area treatment with ALA plus activation with either blue light or laser light to topical 5-FU in the treatment of AK of the face and scalp . Thirty-six subjects with AK of either the face or scalp were r and omized to receive either application of ALA for 1 hour followed by activation with blue light or pulsed dye laser or topical 5-FU . Efficacy was evaluated by grading AK lesions and photoaging signs . Tolerability was assessed by scoring crusting/erosions , erythema and stinging/burning . Treatment with PDT using ALA plus blue light was as effective as topical 5-FU in clearing AK . PDT using ALA plus laser light was the least effective treatment . All treatments made improvements in the signs of photoaging . Both PDT treatments were better tolerated than 5-FU . In conclusion , broad area PDT treatment with ALA plus activation with blue light appears to be as effective as 5-FU in the treatment of AK . ALA plus laser light is somewhat less effective than the above therapies . Efficacy could likely be improved with further study of laser parameters and incubation times Background . Organ transplant recipients on long-term immunosuppressive therapy are at increased risk of non-melanoma skin lesions . Repeated field photodynamic therapy using topical methyl aminolevulinate ( MAL ) may have potential as a preventive treatment . Methods . This open r and omized , intrapatient , comparative , multicenter study included 81 transplant recipients with 889 lesions ( 90 % actinic keratoses ( AK ) ] . In each patient , the study treatment was initially administered to one 50 cm2 area on the face , scalp , neck , trunk , or extremities ( n=476 lesions ) twice ( 1 week apart ) , with additional single treatments at 3 , 9 , and 15 months . On each occasion , the area was debrided gently and MAL cream ( 160 mg/g ) applied for 3 hr , before illumination with noncoherent red light ( 630 nm , 37 J/cm2 ) . The control , 50 cm2 area ( n=413 lesions ) received lesion-specific treatment ( 83 % cryotherapy ) at baseline and 3 , 9 , and 15 months . Additionally , all visible lesions were given lesion-specific treatment 21 and 27 months in both treatment and control areas . Results . At 3 months , MAL photodynamic therapy significantly reduced the occurrence of new lesions ( 65 vs. 103 lesions in the control area ; P=0.01 ) , mainly AK ( 46 % reduction ; 43 vs. 80 ; P=0.006 ) . This effect was not significant at 27 months ( 253 vs. 312 ; P=0.06 ) . Hypopigmentation , as assessed by the investigator , was less evident in the treatment than control areas ( 16 % vs. 51 % of patients ; P<0.001 ) at 27 months . Conclusion . Our results suggest that repeated field photodynamic therapy using topical MAL may prevent new AK in transplant recipients although further studies are needed Background Photodynamic therapy ( PDT ) is increasingly used for treatment of actinic keratoses ( AKs ) but is a cumbersome procedure . A thin self‐adhesive patch ( PD P 506 A ) containing 5‐aminolaevulinic acid ( 5‐ALA ) was developed to facilitate PDT BACKGROUND Photodynamic therapy has been proved to be effective in skin rejuvenation . OBJECTIVE To evaluate clinical efficacy and side effects of photodynamic therapy using topical 5-methyl aminolevulinate and red light for photorejuvenation . METHODS A r and omized , prospect i ve , split-face comparison study of 10 white , adult patients with moderate photodamage , Fitzpatrick skin types 2 or 3 , and no occurrence of actinic keratosis was performed . Three treatments using topical methyl aminolevulinate cream , applied for 1 hour on one half of the face and 3 hours on the other half before illumination with red light . A blinded investigator prior to treatment and 2 months after the third treatment evaluated each side of the subject 's faces . RESULTS A moderate improvement in fine lines , tactile roughness , and skin tightness was observed in most of the patients , mostly on the 3-hour time side . There were no changes in mottled pigmentation or telangiectasias . Side effects were observed in all subjects ( erythema , edema , scaling ) mainly in the 3-hour incubation time side . LIMITATIONS The small number of patients and the lack of placebo group . CONCLUSION Methyl aminolevulinic-photodynamic therapy with red light can improve fine lines , tactile roughness and skin tightness in patients with moderate photoaging and no occurrence of actinic keratosis BACKGROUND Actinic keratoses ( AKs ) are the most common premalignant tumors . Without treatment , a significant number of patients with AK will experience squamous cell carcinoma . Photodynamic therapy ( PDT ) using the new highly selective photosensitizer methyl 5-aminolevulinate is a promising new treatment modality for AK . OBJECTIVE We investigated the complete response rates , cosmetic outcome , and patient satisfaction after photodynamic therapy ( PDT ) using methyl 5-aminolevulinate ( Metvix ) versus cryotherapy in the treatment of AKs . METHODS Patients were r and omized to receive either cryotherapy with liquid nitrogen spray or PDT using methyl 5-aminolevulinate cream 160 mg/g , 3 hours application time , and red light ( 75 J/cm(2 ) ) . RESULTS Efficacy results from 193 patients with 699 lesions ( 92 % face/scalp and 93 % thin/moderately thick ) were analyzed . Overall complete response rates after 3 months were 69 % for PDT and 75 % for cryotherapy . Both treatments gave higher response rates in thin lesions ( PDT 75 % , cryotherapy 80 % ) . PDT gave better cosmetic results and higher patient satisfaction than cryotherapy . CONCLUSION PDT using methyl 5-aminolevulinate is an attractive treatment option for patients with AK , with a response rate similar to that of cryotherapy , but with superior cosmetic results and high patient satisfaction BACKGROUND Actinic keratoses are the most common actinic lesions on Caucasian skin . Cryosurgery with liquid nitrogen is commonly used to treat actinic keratoses , but there have been few studies examining the true rate of cure in everyday dermatologic practice . AIM To determine prospect ively the true efficacy of cryosurgery as a treatment for actinic keratoses in everyday dermatologic practice . METHODS A prospect i ve , multicentered study ( a subsidiary study of a photodynamic therapy trial ) was performed . Patients with untreated actinic keratoses greater than 5 mm in diameter on the face and scalp were recruited . Eligible lesions received a single freeze-thaw cycle with liquid nitrogen given via a spray device and were review ed 3 months thereafter . Each center used their preferred freeze time . The only treatment criterion was complete freezing of actinic keratoses and a 1-mm rim of normal skin . Treated lesions were assessed as complete response or noncomplete response . The influence of the duration of freeze , cosmetic outcomes , and adverse events were examined . RESULTS Ninety adult patients from the community with 421 eligible actinic keratoses were recruited . The overall individual complete response rate was 67.2%[SEM = + /-3.5 % ; 95 % confidence interval ( CI ) = 60.4 - 74.1 % ] . Complete response was 39 % for freeze times of less than 5 s , 69 % for freeze times greater than 5 s , and 83 % for freeze times greater than 20 s. Cosmetic outcomes were good to excellent in 94 % of complete response lesions . The main adverse events were pain , stinging , and burning during treatment , and hypopigmentation after healing . CONCLUSIONS Cryosurgery is an effective treatment for actinic keratoses . The true complete response rate is significantly lower than that previously reported . The freeze duration influences successful treatment . Adverse events are mild and well tolerated BACKGROUND Actinic keratoses ( AKs ) are considered as in situ squamous cell carcinoma . Early and effective treatment is important . Objective To compare the efficacy , cosmetic outcome and patient preference of 5-aminolevulinic acid photodynamic therapy ( ALA-PDT ) with that of 5 % imiquimod ( IMIQ ) cream in patients with AKs on the dorsa of h and s and forearms . METHODS Subjects received two ALA-PDT treatment sessions and one or two courses of imiquimod ( three times per week for 4 weeks each ) . Treatments were r and omly allocated to alternate upper extremities . Assessment s included lesion response one and six months after treatment , cosmetic outcome evaluated by the investigators and patients ' preference 6 months after treatment . Efficacy end point included the individual AK lesion clearance rate . RESULTS Thirty patients with 256 lesions were included in the study . At the first follow-up , treatment with ALA-PDT result ed in significantly larger rate of cured lesions relative to 5 % IMIQ cream ( 70.16 % vs. 18.26 % ) . At the second follow-up both treatments showed a high rate of cured lesions ( 65.32 % for PDT vs. 55.65 % for IMIQ cream ) . Response rates obtained in grade I lesions were higher for both treatments ( 71.64 % for PDT vs. 72.13 % for IMIQ ) , while treatment with PDT result ed in a significant larger rate of cured grade II lesions ( 57.89 % for PDT vs. 37.03 for IMIQ ) . Difference in cosmetic outcome was not statistically significant . Results for subject preference favoured ALA-PDT . CONCLUSIONS Our study shows that ALA-PDT and 5 % IMIQ cream are both attractive treatment options for upper extremities AKs with comparable efficacy and cosmetic outcomes OBJECTIVE To examine clinical and molecular changes after topical fluorouracil treatment of photodamaged human facial skin for actinic keratoses . DESIGN Nonr and omized , open-label 2-week treatment with fluorouracil cream , 5 %
Output:
| AND RELEVANCE Photodynamic therapy has a 14%better chance of complete lesion clearance at 3 months after treatment than cryotherapy for thin AKs on the face and scalp |
MS213789 | ***TASK*** the task is to summarize an input biomedical literature in six sentences
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Input: OBJECTIVE To identify predictors of skin-related quality of life ( QOL ) after treatment of nonmelanoma skin cancer ( NMSC ) . DESIGN Prospect i ve cohort study of consecutive patients with NMSC diagnosed in 1999 and 2000 . SETTING University-affiliated private practice and a Veterans Affairs clinic . PATIENTS A total of 633 patients who responded to a question naire before treatment . MAIN OUTCOME MEASURE Skin-related QOL , measured with the 16-item version of Skindex-16 , a vali date d measure . Skindex-16 scores vary from 0 ( best QOL ) to 100 ( worst QOL ) and are reported in 3 domains : symptoms , emotional effects , and effects on functioning . RESULTS Controlling for treatment group , the strongest independent predictor of skin-related QOL after treatment of NMSC was pretreatment skin-related QOL . Other patient characteristics that predicted better QOL included less comorbidity and better mental health status . No tumor or care characteristic ( including location of tumor , size of tumor , site of therapy , or training level of treating clinician [ attending physician , resident , or nurse practitioner ] ) was found to predict better skin-related QOL after treatment of NMSC . CONCLUSIONS Patients with better pretreatment skin-related QOL , less comorbidity , and better mental health status had better skin-related QOL after treatment of NMSC . These findings may be useful for pretreatment assessment and counseling BACKGROUND Patient satisfaction is an important aspect of patient‐centered care but has not been systematic ally studied after treatment of nonmelanoma skin cancer ( NMSC ) , the most prevalent cancer . OBJECTIVE To compare patient satisfaction after treatment for NMSC and to determine factors associated with better satisfaction . METHODS We prospect ively measured patient , tumor , and care characteristics in 834 consecutive patients at two centers before and after destruction , excision , and Mohs surgery . We evaluated factors associated with short‐term and long‐term satisfaction . RESULTS In all treatment groups , patients were more satisfied with the interpersonal manners of the staff , communication , and financial aspects of their care than with the technical quality , time with the clinician , and accessibility of their care ( p<.05 ) . Short‐term satisfaction did not differ across treatment groups . In multivariable regression models adjusting for patient , tumor , and care characteristics , higher long‐term satisfaction was independently associated with younger age , better pretreatment mental health and skin‐related quality of life , and treatment with Mohs surgery ( p<.05 ) . CONCLUSIONS Long‐term patient satisfaction after treatment of NMSC is related to pretreatment patient characteristics ( mental health , skin‐related quality of life ) and treatment type ( Mohs ) but not tumor characteristics . These results can guide informed decision‐making for treatment of NMSC . The authors have indicated no significant interest with commercial supporters BACKGROUND Quality of life ( QOL ) has been identified as an important outcome in cancer research , yet the most common malignancy among humans , nonmelanoma skin cancer ( NMSC ) , has been poorly studied in this regard . OBJECTIVE To determine whether change occurred in the QOL of NMSC patients after surgery using a general , vali date d dermatology QOL instrument : the Dermatology Life Quality Index ( DLQI ) . METHODS A prospect i ve study was conducted on 121 consecutive patients referred to a dermatologic Mohs surgery clinic with NMSC of the head and neck . QOL assessment was performed using the DLQI before ( n=121 ) and after surgical treatment at 4 months ( n=101 ) . RESULTS QOL scores demonstrated little h and icap at initial diagnosis . The total DLQI scores showed little change over time , but an item analysis revealed that 2 of the 10 items demonstrated statistically significant change over time , with QOL improving after treatment — decreased painfulness/itchiness/soreness and less necessity to use concealing clothing . CONCLUSIONS General dermatology QOL instruments demonstrated minimal h and icap at initial diagnosis and little change after treatment of NMSC . Although the associations were modest , improvement in some aspects of well-being after treatment of NMSC was demonstrated . A more disease-specific instrument may be necessary to study this disease process further Background An accurate , sensitive , but brief quality -of-life outcomes measure is needed for studies of dermatologic care . Objective To construct a single-page version of Skindex ( a dermatologic quality -of-life instrument ) that would have two new features compared with the current 29-item version : ( 1 ) fewer items to which a majority of patients choose the same response , and ( 2 ) measurement ofbother rather than frequency of patient experiences . Methods R and om sample s of patients waiting for dermatology appointments in clinics of Veterans Affairs hospitals and in private dermatology practice s completed question naires ; 692 patients responded to the parent instrument and 541 additional patients responded to the brief version . Reproducibility , internal consistency reliability , validity , and responsiveness of the brief version of Skindex were determined . Results For 16 items of the current 29-item version ( 55 % ) , more than 50 % of patients responded “ Never . ” After an explicit process of item analysis and elimination , a single-page 16-item version was composed that asks patients about bother from their experiences ; responses are reported as three scales , Symptoms , Emotions , and Functioning . For 6 items of the 16-item version ( 38 % ) , more than 50 % of patients responded “ Never . ” Scale scores were reproducible after 72 hours ( r = 0.88 - 0.90 ) and were internally reliable ( Cronbach ’s α = 0.86 - 0.93 ) . The instrument demonstrated both content and construct validity : Most patients ’ responses to an open-ended question about their skin disease was addressed by the items ; patients with inflammatory dermatoses had higher scores than those with isolated lesions ; and in an exploratory principal axes factor analysis with an oblique rotation , 74 % of the common variance was explained by three factors that correlated with thea priori scales . Mean scale scores stayed the same or changed in the expected direction in patients who reported that their skin was the same or had improved . Conclusion This brief single-page version of Skindex accurately and sensitively measures how much patients are bothered by their skin conditions . SommaireAntécédentsLa mesure des résultats relatifs à la qualité de vie lors d’études sur les soins dermatologiques doit être précise , sensible mais concise . ObjectifÉlaborer une version en une seule page du Skindex ( instrument de mesure de la qualité de vie sur le plan dermatologique ) qui comporterait deux nouvelles caractéristiques par rapport à la version actuelle de 29 questions : ( 1 ) moins de questions pour lesquelles la majorité des patients choisissent la même réponse , et ( 2 ) la mesure des ennuis causés par la maladie plutôt que celle de la fréquence des épisodes . MéthodesDes échantillonnages r and omisés de patients en attente de rendezvous à la clinique de dermatologie des hôpitaux des Anciens Combattants et en cabinets privés ont rempli les question naires ; 692 patients ont répondu à l’instrument de mesure principal et 541 à la version simplifiée . La reproductibilité , la cohérence interne , la fiabilité , la validité et la réactivité de la version simplifée du Skindex ont été évaluées . RésultatsPlus de 50 % des patients ont répondu « jamais » à 16 des 29 questions de la version actuelle ( 55 % ) . Après un travail en profondeur d’analyse et d’élimination des questions , on a rédigé une version d’une page comportant 16 questions sur les ennuis causés par la maladie , les réponses étant rapportées selon trois échelles : symptômes , émotions et fonctionnement . Plus de 50 % des patients ont répondu « jamais » à 6 des 16 questions ( 38 % ) . Les résultats de l’échelle étaient reproductibles après 72 heures ( r = 0 , 88 - 0,90 ) et fiables sur le plan interne ( Cronbach ’s α = 0,86 - 0,93 ) . L’instrument de mesure a permis de démontrer la validité du contenu et de la conception : la plupart des réponses des patients à une question ouverte sur leur affection cutanée étaient abordées dans la question ; les patients atteints de dermatoses inflammatoires avaient des résultats plus élevés que ceux présentant des lésions isolées ; et dans une analyse factorielle exploratoire des principaux axes , la variance commune s’expliquait à 74 % par trois facteurs qui étaient en corrélation avec les échelles établies a priori . Les résultats moyens sont demeurés les mêmes ou ont changé dans le sens attendu chez les patients qui avaient rapporté que l’état de leur peau était le même ou qu’il s’était amélioré . Conclusion Cette version simplifiée d’une page du Skindex mesure de façon précise et sensible l ’ importance des ennuis que causent les affections cutanées aux patients OBJECTIVE To establish the clinical responsiveness of the Skin Cancer Index ( SCI ) , a new disease-specific quality of life ( QOL ) instrument , and to assess demographic and clinical factors which impact QOL in patients with nonmelanoma skin cancer ( NMSC ) . STUDY DESIGN Prospect i ve study of 183 patients with NMSC of the face and neck referred to a tertiary care Mohs surgery clinic . METHODS The SCI is a 15 item , vali date d , disease-specific QOL instrument with 3 distinct subscales , Emotion , Social , and Appearance . Higher scores reflect better QOL . The SCI and the Dermatology Life Quality Index ( DLQI ) , a general dermatology instrument , was administered at initial consultation and 4 months after surgical treatment . Multivariate analysis was conducted to assess demographic and clinical factors predictive of QOL for both instruments . RESULTS The SCI total score and all three subscale scores increased with treatment , demonstrating strong evidence of responsiveness over time ( P < .001 ) in contrast with the DLQI ( P = .46 ) . Predictors of poorer QOL for the SCI included female sex and cancers located on the lip . Patients who demonstrated greatest improvement in QOL with treatment included those who were younger ( < 50 yr ) and had lower reported household income . Also , first time NMSC patients and those patients who underwent less extensive reconstructions demonstrated greater improvements in QOL . CONCLUSION The SCI is a sensitive and responsive QOL instrument for patients with NMSC . Distinct demographic and clinical variables that impact QOL have been demonstrated using this multidimensional , disease-specific instrument CONTEXT Nonmelanoma skin cancer ( NMSC ) is the most common cancer among humans , yet risk perceptions and preventive health behaviors in those who survive this cancer are relatively unknown . OBJECTIVES To assess the impact of the disease and its treatment on sun-protective behaviors , general preventive health behaviors , and risk perception in NMSC patients , and to determine factors associated with behavioral change . DESIGN AND SETTING A prospect i ve study was conducted of 211 consecutive NMSC patients presenting to a dermatologic surgery clinic at a tertiary care university medical center from February 2005 to March 2006 . These patients were all adults , were fluent in English , and had NMSC of the head and neck . Of the 211 eligible patients , complete data was obtained for 183 ( 87 % ) . The most common reasons for dropout were voluntary withdrawal and incompletely answered surveys . INTERVENTION AND OUTCOME MEASURES Surveys that assessed disease-specific quality of life ( QoL ) , preventive health behaviors , sun-protective behaviors , and risk perception were administered before and after surgical treatment of NMSC . RESULTS Sun-protective behaviors improved postsurgery even after controlling for seasons ( P<0.001 ) . Predictor factors associated with increased sun-protective behavior included poor skin tanning ability , summer season , no employment , less comorbid conditions , and previous NMSC treatment . Baseline QoL was not predictive of behavioral change . As for risk perception , respondents thought they were more likely than someone similar to themselves to develop future NMSCs but thought they had similar risks of developing melanoma or other non-skin cancers ( P<0.001 ) . NMSC patients demonstrated disease-specific behavior modifications by selectively improving their sun habits but showed no significant improvement in other preventive health behaviors . This finding is consistent with patients ' specific perception of increased risk for future NMSCs , but surprisingly , not for melanoma . Increased patient education of associated cancer risks with NMSC is warranted . CONCLUSIONS NMSC patients demonstrated disease-specific behavior modifications by selectively improving their sun habits but showed no significant improvement in other preventive health behaviors . This finding is consistent with patients ' specific perception of increased risk for future NMSCs , but surprisingly , not for melanoma . Increased patient education of associated cancer risks with NMSC is warranted BACKGROUND Keratinocyte carcinomas ( KCs ) are the most common malignancies of the skin . As lesions have a low mortality rate , underst and ing quality -of-life ( QoL ) factors is necessary in their management . OBJECTIVE To assess QoL and associated patient characteristics in those with a history of keratinocyte carcinomas . METHODS We conducted a cross-sectional study of veterans with a history of KCs enrolled in a r and omized controlled trial for chemoprevention of keratinocyte carcinomas . Study dermatologists counted actinic keratoses ( AKs ) and assessed for skin photodamage . QoL was assessed using Skindex-29 and KC-specific questions . Demographics were self-reported . RESULTS Participants ( n = 931 ) enrolled at 5 clinical sites had worse QoL on all subscales (
Output:
| The Skin Cancer Index demonstrates the most evidence of its usefulness in patients with BCC/SCC .
The Patient Outcomes of Surgery-Head/Neck may be beneficial to assess perceptions in appearance before and after surgical intervention |
MS213790 | ***TASK*** the task is to summarize an input biomedical literature in six sentences
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Input: Background — Evidence on economically efficient strategies to lower blood pressure ( BP ) from low- and middle-income countries remains scarce . The Control of Blood Pressure and Risk Attenuation ( COBRA ) trial r and omized 1341 hypertensive subjects in 12 r and omly selected communities in Karachi , Pakistan , to 3 intervention programs : ( 1 ) combined home health education ( HHE ) plus trained general practitioner ( GP ) ; ( 2 ) HHE only ; and ( 3 ) trained GP only . The comparator was no intervention ( or usual care ) . The reduction in BP was most pronounced in the combined group . The present study examined the cost-effectiveness of these strategies . Methods and Results — Total costs were assessed at baseline and 2 years to estimate incremental cost-effectiveness ratios based on ( 1 ) intervention cost ; ( 2 ) cost of physician consultation , medications , diagnostics , changes in lifestyle , and productivity loss ; and ( 3 ) change in systolic BP . Precision of the incremental cost-effectiveness ratio estimates was assessed by 1000 bootstrapping replications . Bayesian probabilistic sensitivity analysis was also performed . The annual costs per participant associated with the combined HHE plus trained GP , HHE alone , and trained GP alone were $ 3.99 , $ 3.34 , and $ 0.65 , respectively . HHE plus trained GP was the most cost-effective intervention , with an incremental cost-effectiveness ratio of $ 23 ( 95 confidence interval , 6–99 ) per mm Hg reduction in systolic BP compared with usual care , and remained so in 97.7 of 1000 bootstrapped replications . Conclusions — The combined intervention of HHE plus trained GP is potentially affordable and more cost-effective for BP control than usual care or either strategy alone in some communities in Pakistan , and possibly other countries in Indochina with similar healthcare infrastructure . Clinical Trial Registration — http://www . clinical trials.gov . Unique identifier : NCT00327574 Background Intermittent preventive treatment of malaria in children ( IPTc ) involves the administration of a course of anti-malarial drugs at specified time intervals to children at risk of malaria regardless of whether or not they are known to be infected . IPTc provides a high level of protection against uncomplicated and severe malaria , with monthly sulphadoxine-pyrimethamine plus amodiaquine ( SP&AQ ) and sulphadoxine-pyrimethamine plus piperaquine being the most efficacious regimens . A key challenge is the identification of a cost-effective delivery strategy . Methods A community r and omized trial was undertaken in Jasikan district , Ghana to assess IPTc effectiveness and costs using SP&AQ delivered in three different ways . Twelve villages were r and omly selected to receive IPTc from village health workers ( VHWs ) or facility-based nurses working at health centres ' outpatient departments ( OPD ) or EPI outreach clinics . Children aged 3 to 59 months-old received one IPT course ( three doses ) in May , June , September and October . Effectiveness was measured in terms of children covered and adherent to a course and delivery costs were calculated in financial and economic terms using an ingredient approach from the provider perspective . Results The economic cost per child receiving at least the first dose of all 4 courses was US$ 4.58 when IPTc was delivered by VHWs , US$ 4.93 by OPD nurses and US$ 5.65 by EPI nurses . The unit economic cost of receiving all 3 doses of all 4 courses was US$ 7.56 and US$ 8.51 when IPTc was delivered by VHWs or facility-based nurses respectively . The main cost driver for the VHW delivery was supervision , reflecting re sources used for travelling to more remote communities rather than more intense supervision , and for OPD and EPI delivery , it was the opportunity cost of the time spent by nurses in dispensing IPTc . Conclusions VHWs achieve higher IPTc coverage and adherence at lower costs than facility-based nurses in Jasikan district , Ghana . Trial Registration Clinical Trials.gov NCT00119132 Background We assessed overall annual and unit cost of delivering package of services and specific services at sub-centre level by CHWs and cost effectiveness of Government of India ’s policy of introducing a second auxiliary nurse midwife ( ANM ) at the sub-centre compared to scenario of single ANM sub-centre . Methods We undertook an economic costing of health services delivered by CHWs , from a health system perspective . Bottom-up costing method was used to collect data on re sources spent in 50 r and omly selected sub-centres selected from 4 districts . Mean unit cost along with its 95 % confidence intervals were estimated using bootstrap method . Multiple linear regression model was used to st and ardize cost and assess its determinants . Results Annually it costs INR 1.03 million ( USD 19,381 ) , or INR 187 ( USD 3.5 ) per capita per year , to provide a package of preventive , curative and promotive services through community health workers . Unit costs for antenatal care , postnatal care , DOTS treatment and immunization were INR 525 ( USD 10 ) per full ANC care , INR 767 ( USD 14 ) per PNC case registered , INR 974 ( USD 18 ) per DOTS treatment completed and INR 97 ( USD 1.8 ) per child immunized in routine immunization respectively . A 10 % increase in human re source costs results in 6 % rise in per capita cost . Similarly , 10 % increment in the ANC case registered per provider through-put results in a decline in unit cost ranging from 2 % in the event of current capacity utilization to 3 % reduction in case of full capacity utilization . Incremental cost of introducing 2nd ANM at sub-centre level per unit percent increase ANC coverage was INR 23,058 ( USD 432 ) . Conclusion Our estimates would be useful in undertaking full economic evaluations or equity analysis of CHW programs . Government of India ’s policy of hiring 2nd ANM at sub-centre level is very cost effective from Indian health system perspective BACKGROUND AND METHODS In the setting of a cluster r and omized study to assess impact of the Integrated Management of Neonatal and Childhood Illnesses ( IMNCI ) program in the district of Faridabad in India , we r and omly selected auxiliary nurse midwives ( ANM ) , anganwadi workers ( AWW ) and accredited social health activists ( ASHA ) from intervention and control areas to collect cost data using an economic perspective . Bootstrap method was used to estimate 95 % confidence interval . RESULTS The annual per-child cost of providing health services through an ANM , AWW and ASHA is INR 348 ( USD 7.7 ) , INR 588 ( USD 13.1 ) and INR 87 ( USD 1.9 ) , respectively . The annual per-child incremental cost of delivering IMNCI is INR 124.8 ( USD 2.77 ) , INR 26 ( USD 0.6 ) and INR 31 ( USD 0.7 ) at the ANM , AWW and ASHA level , respectively . CONCLUSION Implementation of IMNCI imposes additional costs to the health system . A comprehensive economic evaluation of the IMNCI is imperative to estimate the net cost implication s in India We did a cost-effectiveness analysis alongside a cluster-r and omised controlled trial of a participatory intervention with women 's groups to improve birth outcomes in rural Nepal . The average provider cost of the women 's group intervention was US0.75 dollars per person per year ( 0.90 dollars with health-service strengthening ) in a population of 86,704 . The incremental cost per life-year saved ( LYS ) was 211 dollars ( 251 dollars ) , and expansion could rationalise on start-up costs and technical assistance , reducing the cost per LYS to 138 dollars ( 179 dollars ) . Sensitivity analysis showed a variation from 83 dollars to 263 dollars per LYS for most variables . This intervention could provide a cost-effective way of reducing neonatal deaths OBJECTIVE To carry out an economic evaluation of a task-shifting intervention for the treatment of depressive and anxiety disorders in primary -care setting s in Goa , India . METHODS Cost-utility and cost-effectiveness analyses based on generalized linear models were performed within a trial set in 24 public and private primary -care facilities . Subjects were r and omly assigned to an intervention or a control arm . Eligible subjects in the intervention arm were given psycho-education , case management , interpersonal psychotherapy and /or antidepressants by lay health workers . Subjects in the control arm were treated by physicians . The use of health-care re sources , the disability of each subject and degree of psychiatric morbidity , as measured by the Revised Clinical Interview Schedule , were determined at 2 , 6 and 12 months . FINDINGS Complete data , from all three follow-ups , were collected from 1243 ( 75.4 % ) and 938 ( 81.7 % ) of the subjects enrolled in the study facilities from the public and private sectors , respectively . Within the public facilities , subjects in the intervention arm showed greater improvement in all the health outcomes investigated than those in the control arm . Time costs were also significantly lower in the intervention arm than in the control arm , whereas health system costs in the two arms were similar . Within the private facilities , however , the effectiveness and costs recorded in the two arms were similar . CONCLUSION Within public primary -care facilities in Goa , the use of lay health workers in the care of subjects with common mental disorders was not only cost-effective but also cost-saving Background Intermittent preventive treatment for malaria in children ( IPTc ) involves the administration of a full course of an anti-malarial treatment to children under 5 years old at specified time points regardless of whether or not they are known to be infected , in areas where malaria transmission is seasonal . It is important to determine the costs associated with IPTc delivery via community based volunteers and also the potential savings to health care providers and caretakers due to malaria episodes averted as a consequence of IPTc . Methods Two thous and four hundred and fifty-one children aged 3–59 months were r and omly allocated to four groups to receive : three days of artesunate plus amodiaquine ( AS+AQ ) monthly , three days of AS+AQ bimonthly , one dose of sulphadoxine-pyrimethamine ( SP ) bi-monthly or placebo . This paper focuses on incremental cost effectiveness ratios ( ICERs ) of the three IPTc drug regimens as delivered by community based volunteers ( CBV ) in Hohoe , Ghana compared to current practice , i.e. case management in the absence of IPTc . Financial and economic costs from the publicly funded health system perspective are presented . Treatment costs borne by patients and their caretakers are also estimated to present societal costs . The costs and effects of IPTc during the intervention period were considered with and without a one year follow up . Probabilistic sensitivity analysis was undertaken to account for uncertainty . Results Economic costs per child receiving at least the first dose of each course of IPTc show SP bimonthly , at US$ 8.19 , is the cheapest to deliver , followed by AS+AQ bimonthly at US$ 10.67 and then by AS+AQ monthly at US$ 14.79 . Training , drug delivery and supervision accounted for approximately 20–30 % each of total unit costs . During the intervention period AS & AQ monthly was the most cost effective IPTc drug regimen at US$ 67.77 ( 61.71–74.75 , CI 95 % ) per malaria case averted based on intervention costs only , US$ 64.93 ( 58.92–71.92 , CI 95 % ) per malaria case averted once the provider cost savings are included and US$ 61.00 ( 54.98 , 67.99 , CI 95 % ) when direct household cost savings are also taken into account . SP bimonthly was US$ 105.35 ( 75.01–157.31 , CI 95 % ) and AS & AQ bimonthly US$ 211.80 ( 127.05–399.14 , CI 95 % ) per malaria case averted based on intervention costs only . The incidence of malaria in the post intervention period was higher in children who were < 1 year old when they received AS+AQ monthly compared to the placebo group leading to higher cost effectiveness ratios when one year follow up is included . The cost per child enrolled fell considerably when modelled to district level as compared to those encountered under trial conditions . Conclusions We demonstrate how cost-effective IPTc is using three different drug regimens and the possibilities for reducing costs further if the intervention was to be scaled up to the district level . The need for effective training , drug delivery channels and supervision to support a strong network of community based volunteers is emphasised Background The Lufwanyama Neonatal Survival Project ( “ LUNESP ” ) was a cluster r and omized , controlled trial that showed that training traditional birth attendants ( TBAs ) to perform interventions targeting birth asphyxia , hypothermia , and neonatal sepsis reduced all-cause neonatal mortality by 45 % . This companion analysis was undertaken to analyze intervention costs and cost-effectiveness , and factors that might improve cost-effectiveness . Methods and Findings We calculated LUNESP 's financial and economic costs and the economic cost of implementation for a forecasted ten-year program ( 2011–2020 ) . In each case , we calculated the incremental cost per death avoided and disability-adjusted life years ( DALYs ) averted in real 2011 US dollars . The forecasted 10-year program
Output:
| Results Existing evidence suggests that , compared with st and ard care , using CHWs in health programmes can be a cost-effective intervention in LMICs , particularly for tuberculosis , but also – although evidence is weaker – in other areas such as reproductive , maternal , newborn and child health ( RMNCH ) and malaria .
Conclusion Notwithst and ing important caveats about the heterogeneity of the studies and their method ological limitations , findings reinforce the hypothesis that CHWs may represent , in some setting s , a cost-effective approach for the delivery of essential health services .
The less conclusive evidence about the cost-effectiveness of CHWs in other areas may reflect that these areas have been evaluated less ( and less rigorously ) than others , rather than an actual difference in cost-effectiveness in the various service delivery areas or interventions . |
MS213791 | ***TASK*** the task is to summarize an input biomedical literature in six sentences
***INPUT*** the input is a biomedical literature
***OUTPUT*** the output is the summary of an input biomedical literature in six sentences
***DOCUMENTATION***
***EXAMPLES***
Input: BACKGROUND in a secondary analysis of a r and omised controlled trial , we investigated whether 6 months of music-based multitask training had beneficial effects on cognitive functioning and mood in older adults . METHODS 134 community-dwellers aged ≥65 years at increased risk for falling were r and omly assigned to either an intervention group ( n = 66 ) who attended once weekly 1-h supervised group classes of multitask exercises , executed to the rhythm of piano music , or a control group with delayed intervention ( n = 68 ) who maintained usual lifestyle habits , for 6 months . A short neuropsychological test battery was administered by an intervention-blinded neuropsychologist at baseline and Month 6 , including the mini-mental state examination ( MMSE ) , the clock-drawing test , the frontal assessment battery ( FAB ) and the hospital anxiety ( HADS-A ) and depression scale . RESULTS intention-to-treat analysis showed an improvement in the sensitivity to interference subtest of the FAB ( adjusted between-group mean difference ( AMD ) , 0.12 ; 95 % CI , 0.00 to 0.25 ; P = 0.047 ) and a reduction in anxiety level ( HADS-A ; AMD , -0.88 ; 95 % CI , -1.73 to -0.05 ; P = 0.039 ) in intervention participants , as compared with the controls . Within-group analysis revealed an increase in MMSE score ( P = 0.004 ) and a reduction in the number of participants with impaired global cognitive performance ( i.e. , MMSE score ≤23 ; P = 0.003 ) with intervention . CONCLUSION six months of once weekly music-based multitask training was associated with improved cognitive function and decreased anxiety in community-dwelling older adults , compared with non-exercising controls . Studies design ed to further delineate whether training-induced changes in cognitive function could contribute to dual-task gait improvements and falls reduction , remain to be conducted Physical exercise has been shown to increase brain volume and improve cognition in r and omized trials of non-demented elderly . Although greater social engagement was found to reduce dementia risk in observational studies , r and omized trials of social interventions have not been reported . A representative sample of 120 elderly from Shanghai , China was r and omized to four groups ( Tai Chi , Walking , Social Interaction , No Intervention ) for 40 weeks . Two MRIs were obtained , one before the intervention period , the other after . A neuropsychological battery was administered at baseline , 20 weeks , and 40 weeks . Comparison of changes in brain volumes in intervention groups with the No Intervention group were assessed by t-tests . Time-intervention group interactions for neuropsychological measures were evaluated with repeated- measures mixed models . Compared to the No Intervention group , significant increases in brain volume were seen in the Tai Chi and Social Intervention groups ( p < 0.05 ) . Improvements also were observed in several neuropsychological measures in the Tai Chi group , including the Mattis Dementia Rating Scale score ( p = 0.004 ) , the Trailmaking Test A ( p = 0.002 ) and B ( p = 0.0002 ) , the Auditory Verbal Learning Test ( p = 0.009 ) , and verbal fluency for animals ( p = 0.01 ) . The Social Interaction group showed improvement on some , but fewer neuropsychological indices . No differences were observed between the Walking and No Intervention groups . The findings differ from previous clinical trials in showing increases in brain volume and improvements in cognition with a largely non-aerobic exercise ( Tai Chi ) . In addition , intellectual stimulation through social interaction was associated with increases in brain volume as well as with some cognitive improvements Strength training has been reported as a potentially useful exercise to improve psychological aspects in the elderly , but its effects remain controversial . This study investigated the effectiveness of strength training conducted twice a week for 12 weeks for improving health-related quality of life ( HRQOL ) and executive cognitive function . The study was a single-blind r and omized controlled trial with assessment s before and after intervention . HRQOL and executive function were assessed using the SF-36 Health Status Survey and a computerized neuro-cognitive assessment using task-switch reaction time trials , respectively . Subjects comprised 119 participants > or = 65 years old , r and omized to either strength training ( n=65 ) or health education classes ( controls , n=54 ) . The strength training program was design ed to strengthen the large muscle groups most important for functional activities and to improve balance . The effects of the intervention on the eight dimensions of the SF-36 in the control and training groups were analyzed . Only the mental health scale of the SF-36 was significantly improved for the training group compared with controls after 12 weeks . Task-switch reaction time and correct response rate remained unchanged . Short-term strength training might have modest positive effects on HRQOL , although this training period may not be sufficient to affect executive function in relatively healthy older people Overwhelming evidence shows the quality of reporting of r and omised controlled trials ( RCTs ) is not optimal . Without transparent reporting , readers can not judge the reliability and validity of trial findings nor extract information for systematic review s. Recent method ological analyses indicate that inadequate reporting and design are associated with biased estimates of treatment effects . Such systematic error is seriously damaging to RCTs , which are considered the gold st and ard for evaluating interventions because of their ability to minimise or avoid bias . A group of scientists and editors developed the CONSORT ( Consoli date d St and ards of Reporting Trials ) statement to improve the quality of reporting of RCTs . It was first published in 1996 and up date d in 2001 . The statement consists of a checklist and flow diagram that authors can use for reporting an RCT . Many leading medical journals and major international editorial groups have endorsed the CONSORT statement . The statement facilitates critical appraisal and interpretation of RCTs . During the 2001 CONSORT revision , it became clear that explanation and elaboration of the principles underlying the CONSORT statement would help investigators and others to write or appraise trial reports . A CONSORT explanation and elaboration article was published in 2001 alongside the 2001 version of the CONSORT statement . After an expert meeting in January 2007 , the CONSORT statement has been further revised and is published as the CONSORT 2010 Statement . This up date improves the wording and clarity of the previous checklist and incorporates recommendations related to topics that have only recently received recognition , such as selective outcome reporting bias . This explanatory and elaboration document-intended to enhance the use , underst and ing , and dissemination of the CONSORT statement-has also been extensively revised . It presents the meaning and rationale for each new and up date d checklist item providing examples of good reporting and , where possible , references to relevant empirical studies . Several examples of flow diagrams are included . The CONSORT 2010 Statement , this revised explanatory and elaboration document , and the associated website ( www.consort-statement.org ) should be helpful re sources to improve reporting of r and omised trials The aims of this study were to examine the effects of aerobic exercise on measures of executive performance and their relationships with changes in cardiorespiratory fitness , cardiac vagal control ( heart rate variability ) and psychological variables . Thirty-six sedentary seniors aged 60 - 75 years were r and omly assigned to a swimming and aquaerobics program or a stretching program two times a week for 21 weeks . Executive functions ( inhibition , updating of working memory and cognitive flexibility ) and cardiorespiratory fitness ( estimated VO2max ) were assessed at the start , after 10 weeks of program and at the end of the program . Resting HRV and measures of psychological outcomes ( depression , self-efficacy , decisional balance ) were obtained at the start and at the end of the program . Participants of both groups significantly improved their VO2max level , their psychological state and their performance for the 2-back task . Only the participants in the aquaerobics group significantly improved their vagally-mediated HRV and their performance for the Stroop test and the verbal running-span test at the end of the program . Only improvements in cardiac vagal control and in inhibition were shown to be functionally related . These results are discussed in line with the model of neurovisceral integration Executive function declines with age , but engaging in aerobic exercise may attenuate decline . One mechanism by which aerobic exercise may preserve executive function is through the up-regulation of brain-derived neurotropic factor ( BDNF ) , which also declines with age . The present study examined BDNF as a mediator of the effects of a 1-year walking intervention on executive function in 90 older adults ( mean age = 66.82 ) . Participants were r and omized to a stretching and toning control group or a moderate intensity walking intervention group . BDNF serum levels and performance on a task-switching paradigm were collected at baseline and follow-up . We found that age moderated the effect of intervention group on changes in BDNF levels , with those in the highest age quartile showing the greatest increase in BDNF after 1-year of moderate intensity walking exercise ( p = 0.036 ) . The mediation analyses revealed that BDNF mediated the effect of the intervention on task-switch accuracy , but did so as a function of age , such that exercise-induced changes in BDNF mediated the effect of exercise on task-switch performance only for individuals over the age of 71 . These results demonstrate that both age and BDNF serum levels are important factors to consider when investigating the mechanisms by which exercise interventions influence cognitive outcomes , particularly in elderly population BACKGROUND Cognitive decline among seniors is a pressing health care issue . Specific exercise training may combat cognitive decline . We compared the effect of once-weekly and twice-weekly resistance training with that of twice-weekly balance and tone exercise training on the performance of executive cognitive functions in senior women . METHODS In this single-blinded r and omized trial , 155 community-dwelling women aged 65 to 75 years living in Vancouver were r and omly allocated to once-weekly ( n = 54 ) or twice-weekly ( n = 52 ) resistance training or twice-weekly balance and tone training ( control group ) ( n = 49 ) . The primary outcome measure was performance on the Stroop test , an executive cognitive test of selective attention and conflict resolution . Secondary outcomes of executive cognitive functions included set shifting as measured by the Trail Making Tests ( parts A and B ) and working memory as assessed by verbal digit span forward and backward tests . Gait speed , muscular function , and whole-brain volume were also secondary outcome measures . RESULTS Both resistance training groups significantly improved their performance on the Stroop test compared with those in the balance and tone group ( P < or = .03 ) . Task performance improved by 12.6 % and 10.9 % in the once-weekly and twice-weekly resistance training groups , respectively ; it deteriorated by 0.5 % in the balance and tone group . Enhanced selective attention and conflict resolution was significantly associated with increased gait speed . Both resistance training groups demonstrated reductions in whole-brain volume compared with the balance and tone group at the end of the study ( P < or = .03 ) . CONCLUSION Twelve months of once-weekly or twice-weekly resistance training benefited the executive cognitive function of selective attention and conflict resolution among senior women . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00426881 Background Mild cognitive impairment ( MCI ) represents a critical window to intervene against dementia . Exercise training is a promising intervention strategy , but the efficiency ( i.e. , relationship of costs and consequences ) of such types of training remains unknown . Thus , we estimated the incremental cost-effectiveness of resistance training or aerobic training compared with balance and tone exercises in terms of changes in executive cognitive function among senior women with probable MCI . Methods Economic evaluation conducted concurrently with a six-month three arm r and omized controlled trial including eighty-six community dwelling women aged 70 to 80 years living in Vancouver , Canada . Participants received twice-weekly resistance training ( n = 28 ) , twice weekly aerobic training ( n = 30 ) or twice-weekly balance and tone ( control group ) classes ( n = 28 ) for 6 months . The primary outcome measure of the Exercise for Cognition and Everyday Living ( EXCEL ) study assessed executive cognitive function , a test of selective attention and conflict resolution ( i.e. , Stroop Test ) . We collected healthcare re source utilization costs over six months . Results Based on the bootstrapped estimates from our base case analysis , we found that both the aerobic training and resistance training interventions were less costly than twice weekly balance and tone classes . Compared with the balance and tone group , the resistance-training group had significantly improved performance on the Stroop Test ( p = 0.04 ) . Conclusions Resistance training and aerobic training result in health care cost saving and are more effective than balance and tone classes after only 6 months of intervention . Resistance training is a promising strategy to alter the trajectory of cognitive decline in seniors with MCI . Trial Registration Clinical Trials.gov NCT00958867 OBJECTIVES To evaluate the efficacy of a municipality-led walking program under the Japanese public Long-Term Care Insurance Act to prevent mental decline . DESIGN R and omized controlled trial . SETTING The city of Takasaki . PARTICIPANTS One hundred fifty community members aged 72.0 ± 4.0 were r and omly divided into intervention ( n = 75 ) and control ( n = 75 ) groups . INTERVENTION A walking program was conducted once a week for 90 minutes for 3 months . The program encouraged participants to walk on a regular basis and to increase their steps per day gradually . The intervention was conducted in small groups of approximately six , so combined benefits of exercise and social interaction were expected . MEASUREMENTS Cognitive function was evaluated focusing on nine tests in five
Output:
| This suggests that women 's executive processes may benefit more from exercise than men .
Regardless of sex , compared to control , all three exercise training approaches enhanced visuospatial function , but only multimodal training enhanced episodic memory .
Overall , aerobic training led to greater benefits than resistance training in global cognitive function and executive functions , while multimodal combined training led to greater benefits than aerobic training for global cognitive function , episodic memory , and word fluency . |
MS213792 | ***TASK*** the task is to summarize an input biomedical literature in six sentences
***INPUT*** the input is a biomedical literature
***OUTPUT*** the output is the summary of an input biomedical literature in six sentences
***DOCUMENTATION***
***EXAMPLES***
Input: Background and Purpose — A new gait training strategy for patients with stroke seeks to increase walking speed through treadmill training . This study compares the effects of structured speed-dependent treadmill training ( STT ) ( with the use of an interval paradigm to increase the treadmill speed stepwise according to principles of sport physiology ) with limited progressive treadmill training ( LTT ) and conventional gait training ( CGT ) on clinical outcome measures for patients with hemiparesis . Methods — Sixty ambulatory poststroke patients were each r and omly selected to receive 1 of the 3 different gait therapies : 20 subjects were treated with STT , 20 subjects were trained to walk on a treadmill with a 20 % increase of belt speed over the treatment period ( LTT ) , and 20 subjects were treated with CGT . Treatment outcomes were assessed on the basis of overground walking speed , cadence , stride length , and Functional Ambulation Category scores . Results — After a 4-week training period , the STT group scored significantly higher than the LTT and CGT groups for overground walking speed ( STT versus LTT , P < 0.001 ; STT versus CGT , P < 0.001 ) , cadence ( STT versus LTT , P = 0.007 ; STT versus CGT , P < 0.001 ) , stride length ( STT versus LTT , P < 0.001 ; STT versus CGT , P < 0.001 ) , and Functional Ambulation Category scores ( STT versus LTT , P = 0.007 ; STT versus CGT , P < 0.001 ) . Conclusions — Structured STT in poststroke patients result ed in better walking abilities than LTT or CGT . This gait training strategy provides a dynamic and integrative approach for the treatment of gait dysfunction after stroke OBJECTIVE To compare the effects of speed-dependent treadmill training on gait and balance performance in patients with sub-acute stroke . DESIGN Single-blinded r and omized controlled trial . SUBJECTS A total of 26 patients with sub-acute stroke were r and omly assigned to experimental ( n = 13 ) and control ( n = 13 ) groups . METHODS Subjects in the experimental group underwent short interval walking trials with stepwise increases in treadmill speed ( speed-dependent treadmill training ) , following the principles of sprint training . Control subjects received gait training on the treadmill at a steady speed . Gait speed , stride length , cadence , and Berg 's Balance Score were recorded and analysed before and after the 10 training sessions . RESULTS Results of 2-way repeated measures analysis of variance showed significant group × time interactions for gait speed and stride length ( p < 0.05 ) . Within each subject group there were improvements in all gait parameters and Berg ’s Balance Score after the training programme . In addition , the experimental group showed significantly larger increases in gait speed ( mean 0.15 m/s , 95 % confidence interval 0.04–0.26 ) and stride length ( mean 0.16 m , 95 % confidence interval 0.02–0.30 ) than the control subjects . CONCLUSION Speed-dependent treadmill training in patients with sub-acute stroke result ed in larger gains in gait speed and stride length compared with steady speed . The positive findings provide evidence for clinical practice of speed-dependent treadmill training in enhancing gait function after stroke Background — Exercise training reduces the symptoms of chronic heart failure . Which exercise intensity yields maximal beneficial adaptations is controversial . Furthermore , the incidence of chronic heart failure increases with advanced age ; it has been reported that 88 % and 49 % of patients with a first diagnosis of chronic heart failure are > 65 and > 80 years old , respectively . Despite this , most previous studies have excluded patients with an age > 70 years . Our objective was to compare training programs with moderate versus high exercise intensity with regard to variables associated with cardiovascular function and prognosis in patients with postinfa rct ion heart failure . Methods and Results — Twenty-seven patients with stable postinfa rct ion heart failure who were undergoing optimal medical treatment , including & bgr;-blockers and angiotensin-converting enzyme inhibitors ( aged 75.5±11.1 years ; left ventricular [ LV ] ejection fraction 29 % ; & OV0312;o2peak 13 mL · kg−1 · min−1 ) were r and omized to either moderate continuous training ( 70 % of highest measured heart rate , ie , peak heart rate ) or aerobic interval training ( 95 % of peak heart rate ) 3 times per week for 12 weeks or to a control group that received st and ard advice regarding physical activity . & OV0312;o2peak increased more with aerobic interval training than moderate continuous training ( 46 % versus 14 % , P<0.001 ) and was associated with reverse LV remodeling . LV end-diastolic and end-systolic volumes declined with aerobic interval training only , by 18 % and 25 % , respectively ; LV ejection fraction increased 35 % , and pro-brain natriuretic peptide decreased 40 % . Improvement in brachial artery flow-mediated dilation ( endothelial function ) was greater with aerobic interval training , and mitochondrial function in lateral vastus muscle increased with aerobic interval training only . The MacNew global score for quality of life in cardiovascular disease increased in both exercise groups . No changes occurred in the control group . Conclusions — Exercise intensity was an important factor for reversing LV remodeling and improving aerobic capacity , endothelial function , and quality of life in patients with postinfa rct ion heart failure . These findings may have important implication s for exercise training in rehabilitation programs and future studies Low-volume sprint interval training ( SIT ) , or repeated sessions of brief , intense intermittent exercise , elicits metabolic adaptations that resemble traditional high-volume endurance training ( ET ) . The effects of these different forms of exercise training on vascular structure and function remain largely unexplored . To test the hypothesis that SIT and ET would similarly improve peripheral artery distensibility and endothelial function and central artery distensibility , we recruited 20 healthy untrained subjects ( age : 23.3 + /- 2.8 yr ) and had them perform 6 wk of SIT or ET ( n = 5 men and 5 women per group ) . The SIT group completed four to six 30-s " all-out " Wingate tests separated by 4.5 min of recovery 3 days/wk . The ET group completed 40 - 60 min of cycling at 65 % of their peak oxygen uptake ( Vo2peak ) 5 days/wk . Popliteal endothelial function , both relative and normalized to shear stimulus , was improved after training in both groups ( main effect for time , P < 0.05 ) . Carotid artery distensibility was not statistically altered by training ( P = 0.29 ) in either group ; however , popliteal artery distensibility was improved in both groups to the same degree ( main effect , P < 0.05 ) . We conclude that SIT is a time-efficient strategy to elicit improvements in peripheral vascular structure and function that are comparable to ET . However , alterations in central artery distensibility may require a longer training stimuli and /or greater initial vascular stiffness than observed in this group of healthy subjects In this large multicenter trial , we aim ed to assess the effect of aerobic exercise training in stable coronary artery disease ( CAD ) patients on cellular markers of endothelial integrity and to examine their relation with improvement of endothelial function . Two-hundred CAD patients ( left ventricular ejection fraction > 40 % , 90 % male , mean age 58.4 ± 9.1 yr ) were r and omized on a 1:1 base to a supervised 12-wk rehabilitation program of either aerobic interval training or aerobic continuous training on a bicycle . At baseline and after 12 wk , numbers of circulating CD34(+)/KDR(+)/CD45dim endothelial progenitor cells ( EPCs ) , CD31(+)/CD3(+)/CXCR4(+ ) angiogenic T cells , and CD31(+)/CD42b(- ) endothelial microparticles ( EMPs ) were analyzed by flow cytometry . Endothelial function was assessed by flow-mediated dilation ( FMD ) of the brachial artery . After 12 wk of aerobic interval training or aerobic continuous training , numbers of circulating EPCs , angiogenic T cells , and EMPs were comparable with baseline levels . Whereas improvement in peak oxygen consumption was correlated to improvement in FMD ( Pearson r = 0.17 , P = 0.035 ) , a direct correlation of baseline or posttraining EPCs , angiogenic T cells , and EMP levels with FMD was absent . Baseline EMPs related inversely to the magnitude of the increases in peak oxygen consumption ( Spearman rho = -0.245 , P = 0.027 ) and FMD ( Spearman rho = -0.374 , P = 0.001 ) following exercise training . In conclusion , endothelial function improvement in response to exercise training in patients with CAD did not relate to altered levels of EPCs and angiogenic T cells and /or a diminished shedding of EMPs into the circulation . EMP flow cytometry may be predictive of the increase in aerobic capacity and endothelial function Background —In stable coronary artery disease ( CAD ) , exercise training has well-documented positive effects on arterial endothelial function . NO derived from endothelial NO synthase ( eNOS ) is regarded as a protective factor against atherosclerosis . The aim of the present study was to investigate the effects of exercise training on the endothelial function in relation to the expression of eNOS and Akt-dependent eNOS phosphorylation in the left internal mammary artery ( LIMA ) of patients with stable CAD . Methods and Results —In 17 training patients ( T ) and 18 control patients ( C ) , endothelium-dependent vasodilation and average peak flow velocity ( APV ) in response to acetylcholine were measured invasively at study beginning and after 4 weeks in the LIMA . In LIMA tissue sample d during bypass surgery , eNOS expression and content of pospho-eNOS-Ser1177 , Akt , and phospho-Akt were determined by Western blot and quantitative reverse transcriptase – polymerase chain reaction . After exercise training , LIMA APV in response to acetylcholine was increased by 56±8 % ( from + 48±8 % at beginning to + 104±11 % after 4 weeks , P < 0.001 ) . Patients in T had a 2-fold higher eNOS protein expression ( T 1.0±0.7 versus C 0.5±0.3 arbitrary units , P < 0.05 ) and 4-fold higher eNOS Ser1177-phosphorylation levels in LIMA-endothelium ( 1.2±0.9 versus 0.3±0.2 arbitrary units , P < 0.01 ) . A linear correlation was confirmed between Akt phosphorylation and phospho-eNOS levels ( R = 0.80 , P < 0.05 ) and between phospho-eNOS and & Dgr ; APV ( R = 0.59 , P < 0.05 ) . Conclusions —Exercise training in stable CAD leads to an improved agonist-mediated endothelium-dependent vasodilatory capacity . The change in acetylcholine-induced vasodilatation was closely related to a shear stress – induced/Akt-dependent phosphorylation of eNOS on Ser1177 Background Despite the cardiovascular etiology of stroke , exercise and risk factor modification programs akin to cardiac rehabilitation ( CR ) are not available . This study aim ed to establish the feasibility of adapting a CR model for individuals with mild to moderate stroke disability . A secondary objective was to determine the program 's effects on aerobic and walking capacity , and stroke risk factors . Methods A repeated measures design was used with a 3-month baseline period and 6-month adapted CR intervention ( n = 43 , mean ± SD age 65 ± 12 years , 30 ± 28 months post stroke ) . Feasibility was determined by the number of participants who completed the study , occurrence of adverse events and frequency , duration and intensity of exercise performed . To determine effectiveness of the program , outcomes measured included aerobic capacity ( VO2peak , ventilatory threshold ) , 6-Minute Walk Test ( 6MWT ) distance , and risk factors . Descriptive statistics characterized the classes attended and number and intensity of exercise sessions . Paired t-tests , one-factor repeated measures analyses of variance contrasts and chi-square analyses were used to compare changes over time . Results Two participants withdrew during the baseline period . Of the remaining 41 participants who commenced the program , 38 ( 93 % ) completed all aspects . No serious adverse effects occurred . Post-intervention , VO2peak improved relative to the stable baseline period ( P = 0.046 ) and the increase in ventilatory threshold approached significance ( P = 0.062 ) . Conclusions CR is feasible after stroke and may be adapted to accommo date for those with a range of post-stroke disability . It is effective in increasing aerobic capacity . CR may be an untapped opportunity for stroke survivors to access programs of exercise and risk factor modification to lower future event risk . Trial registration Clinical Trials.gov registration number : Objective : To evaluate risk factor reduction and health-related quality of life following a 10-week cardiac rehabilitation programme in non-acute ischaemic stroke subjects . Design : Single-blinded r and omized control trial . Setting : Outpatient rehabilitation . Subjects : Forty-
Output:
| Conclusion : High-intensity training is promising as a time-efficient exercise strategy in cardiovascular rehabilitation , but data on endothelial effects in cerebrovascular rehabilitation are warranted . |
MS213793 | ***TASK*** the task is to summarize an input biomedical literature in six sentences
***INPUT*** the input is a biomedical literature
***OUTPUT*** the output is the summary of an input biomedical literature in six sentences
***DOCUMENTATION***
***EXAMPLES***
Input: BACKGROUND The mesolimbic dopaminergic reward system seems to play a crucial role in reinforcing effects of nicotine . Recently , acute high-frequency repetitive transcranial magnetic stimulation ( rTMS ) of frontal brain regions has been shown to efficiently modulate the mesostriatal and mesolimbic dopaminergic system in both animals and humans . For this reason , we investigated whether high-frequency rTMS would be able to influence nicotine-related behavior by study ing rTMS effects on craving and cigarette smoking . METHOD Fourteen treatment-seeking smokers were included in a double-blind crossover trial , conducted in 2002 , comparing single days of active versus sham stimulation . Outcome measures were rTMS effects on number of cigarettes smoked during an ad libitum smoking period and effects on craving after a period of acute abstinence . RESULTS High-frequency ( 20-Hz ) rTMS of left dorsolateral prefrontal cortex reduced cigarette smoking significantly ( p < .01 ) in an active stimulation compared with sham stimulation . Levels of craving did not change significantly . CONCLUSION High-frequency rTMS may be useful for treatment in smoking cessation OBJECTIVE Because neuroimaging studies have shown that cue-provoked smoking craving is associated with changes in the activity of the bilateral dorsolateral prefrontal cortex ( DLPFC ) , we aim ed to investigate whether a powerful technique of noninvasive brain stimulation , transcranial direct current stimulation ( tDCS ) , reduces cue-provoked smoking craving as indexed by a visual analog scale . METHOD We performed a r and omized , sham-controlled crossover study in which 24 subjects received sham and active tDCS ( anodal tDCS of the left and right DLPFC ) in a r and omized order . Craving was induced by cigarette manipulation and exposure to a smoking video . The study ran from January 2006 to October 2006 . RESULTS Smoking craving was significantly increased after exposure to smoking-craving cues ( p < .0001 ) . Stimulation of both left and right DLPFC with active , but not sham , tDCS reduced craving significantly when comparing craving at baseline and after stimulation , without ( p = .007 ) and with ( p = .005 ) smoking-craving cues . There were no significant mood changes in any of the conditions of stimulation . Adverse events were mild and distributed equally across all treatment conditions . CONCLUSIONS Our findings extend the results of a previous study on the use of brain stimulation to reduce craving , showing that cortical stimulation with tDCS is beneficial for reducing cue-provoked craving , and thus support the further exploration of this technique for smoking cessation Background Prefrontal repetitive transcranial magnetic stimulation ( rTMS ) has been used to induce side-specific mood changes in volunteers and patients . To clarify inconsistencies between reports that used different stimulation frequencies , we conducted a controlled study with a low ( 1 Hz ) frequency , comparing left with right-sided stimulation Methods Nineteen healthy volunteers received r and omised left or right prefrontal rTMS at a frequency of 1 Hz and 100 % of motor threshold in two sessions two weeks apart . Results There were significant improvements with TMS for performance in the digit symbol substitution and verbal fluency tests , but no change of mood on a number of measures . There was also a reduction of pulse rate after TMS . The only side-specific TMS-effect was on mean arterial pressure , which decreased pressure after left , but not after right prefrontal TMS . Conclusions Apart from the unexpected and so far unreplicated effect on mean arterial pressure , there were no side-specific effects on mood in volunteers . It is unlikely that a simple laterality model of mood together with the assumed activating effect of higher and ' quenching ' effect of lower stimulation frequency can account for the effects of TMS on mood BACKGROUND Functional neuroimaging studies have shown that specific brain areas are associated with alcohol craving including the dorsolateral prefrontal cortex ( DLPFC ) . We tested whether modulation of DLPFC using transcranial direct current stimulation ( tDCS ) could alter alcohol craving in patients with alcohol dependence while being exposed to alcohol cues . METHODS We performed a r and omized sham-controlled study in which 13 subjects received sham and active bilateral tDCS delivered to DLPFC ( anodal left/cathodal right and anodal right/cathodal left ) . For sham stimulation , the electrodes were placed at the same positions as in active stimulation ; however , the stimulator was turned off after 30s of stimulation . Subjects were presented videos depicting alcohol consumption to increase alcohol craving . RESULTS Our results showed that both anodal left/cathodal right and anodal right/cathodal left significantly decreased alcohol craving compared to sham stimulation ( p<0.0001 ) . In addition , we found that following treatment , craving could not be further increased by alcohol cues . CONCLUSIONS Our findings showed that tDCS treatment to DLPFC can reduce alcohol craving . These findings extend the results of previous studies using noninvasive brain stimulation to reduce craving in humans . Given the relatively rapid suppressive effect of tDCS and the highly fluctuating nature of alcohol craving , this technique may prove to be a valuable treatment strategy within the clinical setting We aim ed to assess whether modulation of the dorsolateral prefrontal cortex ( DLFPC ) with noninvasive brain stimulation , namely transcranial direct current stimulation ( tDCS ) , modifies food craving in healthy subjects . We performed a r and omized sham-controlled cross-over study in which 23 subjects received sham and active tDCS ( anode left/cathode right and anode right/cathode left ) of the DLPFC . Subjects were exposed to food and also watched a movie of food associated with strong craving . Desire for food consumption was evaluated by visual analogue scales ( VAS ) and food consumption before and after treatment . In addition we measured visual attention to food using an eye tracking system . Craving for viewed foods as indexed by VAS was reduced by anode right/cathode left tDCS . After sham stimulation , exposure to real food or food-related movie increased craving ; whereas after anode left/cathode right tDCS , the food-related stimuli did not increase craving levels , as revealed by the VAS scale . Moreover , compared with sham stimulation , subjects fixated food-related pictures less frequently after anode right/cathode left tDCS and consumed less food after both active stimulation conditions . These changes were not related to mood changes after any type of tDCS treatment . The effects of tDCS on food craving might be related to a modulation of neural circuits associated with reward and decision-making This study examined whether a single session of repetitive transcranial magnetic stimulation ( rTMS ) of the left prefrontal cortex ( PFC ) would inhibit food cravings in healthy women who endorsed frequent food cravings . Ten participants viewed images of food and completed ratings for food cravings before and after receiving either real or sham rTMS over the left PFC ( 10 Hz , 100 % resting motor threshold , 10 s-on , 20 s-off for 15 min ; 3000 pulses ) . Sham-TMS was matched with real TMS with respect to perceived painfulness of the stimulation . Each participant received both real and sham rTMS in r and om order and were blind to the condition in a within-subject cross-over design . With an improved sham control condition , prefrontal rTMS inhibited food cravings no better than sham rTMS . The mild pain from the real and sham rTMS may distract or inhibit food craving , and the decreased craving may not be caused by the effect of rTMS itself . Further studies are needed to eluci date whether rTMS has any true effects on food craving and whether painful stimuli inhibit food or other cravings . A sham condition which matches the painfulness is important to underst and the true effects of TMS on behaviors and diseases CONTEXT Depressive symptoms predict adverse cardiovascular outcomes in patients with coronary heart disease , but the mechanisms responsible for this association are unknown . OBJECTIVE To determine why depressive symptoms are associated with an increased risk of cardiovascular events . DESIGN AND PARTICIPANTS The Heart and Soul Study is a prospect i ve cohort study of 1017 out patients with stable coronary heart disease followed up for a mean ( SD ) of 4.8 ( 1.4 ) years . SETTING Participants were recruited between September 11 , 2000 , and December 20 , 2002 , from 12 outpatient clinics in the San Francisco Bay Area and were followed up to January 12 , 2008 . MAIN OUTCOME MEASURES Baseline depressive symptoms were assessed using the Patient Health Question naire ( PHQ ) . We used proportional hazards models to evaluate the extent to which the association of depressive symptoms with subsequent cardiovascular events ( heart failure , myocardial infa rct ion , stroke , transient ischemic attack , or death ) was explained by baseline disease severity and potential biological or behavioral mediators . RESULTS A total of 341 cardiovascular events occurred during 4876 person-years of follow-up . The age-adjusted annual rate of cardiovascular events was 10.0 % among the 199 participants with depressive symptoms ( PHQ score > or = 10 ) and 6.7 % among the 818 participants without depressive symptoms ( hazard ratio [ HR ] , 1.50 ; 95 % confidence interval , [ CI ] , 1.16 - 1.95 ; P = .002 ) . After adjustment for comorbid conditions and disease severity , depressive symptoms were associated with a 31 % higher rate of cardiovascular events ( HR , 1.31 ; 95 % CI , 1.00 - 1.71 ; P = .04 ) . Additional adjustment for potential biological mediators attenuated this association ( HR , 1.24 ; 95 % CI , 0.94 - 1.63 ; P = .12 ) . After further adjustment for potential behavioral mediators , including physical inactivity , there was no significant association ( HR , 1.05 ; 95 % CI , 0.79 - 1.40 ; P = .75 ) . CONCLUSION In this sample of out patients with coronary heart disease , the association between depressive symptoms and adverse cardiovascular events was largely explained by behavioral factors , particularly physical inactivity Previous studies in healthy volunteers reported a possible impact of high frequency repetitive transcranial magnetic stimulation ( HF-rTMS ) on stress hormones , like cortisol . In this sham-controlled , “ single blind ” , crossover study , we examined whether HF-rTMS had an effect on the hypothalamic-pituitary-adrenal ( HPA ) axis , by analysing salivary cortisol levels . Two studies were conducted . First , HF-rTMS on the left dorsolateral prefrontal cortex ( DLPFC ) was performed in 28 young healthy female volunteers . Second , in a comparable , but different group of 26 healthy females , HF-rTMS was performed on the right DLPFC . Salivary cortisol levels were assessed before , immediately after and 30 min after real and sham HF-rTMS . We found no support for the hypothesis that one single session of HF-rTMS on the left or the right DLPFC has an immediate or delayed impact on the HPA – axis , as measured by salivary cortisol . Although we controlled for several method ological problems in HF-rTMS research , the hypothesis that one single session of HF-rTMS on the left or on the right DLPFC can influence the HPA-axis in healthy volunteers was not supported Abstract Objectives . Neuroimaging studies have found that alcohol dependent patients display dopaminergic dysfunction in the ventral striatum , which is associated with alcohol craving . Repetitive transcranial magnetic stimulation ( rTMS ) was introduced as a promising new treatment option for depression , and among other neurobiological mechanisms , it is able to stimulate the striatal dopaminergic system . The aim of our study was to investigate the effect of high frequency rTMS of the left dorsolateral prefrontal cortex compared to sham stimulation on craving and mood in alcohol dependent women . Furthermore , the impact on an attentional blink ( AB ) paradigm to pictures with neutral , emotional and alcohol-related contents was proofed . Methods . Nineteen female detoxified patients were r and omized either to a high frequency rTMS ( 20 Hz ) over the left DLPFC ( n = 10 ) or a sham stimulations ( n = 9 ) at 10 days . Alcohol craving was determined with the Obsessive Compulsive Drinking Scale , depressive symptoms were registered by means of Hamilton Depression Rating Scale and Beck ’ Depression Inventory . For the AB paradigm an age-matched control group was investigated . Results . There were no significantly differences between both groups regarding alcohol craving or mood . In the AB paradigm , real stimulated patients detected alcohol related T2 targets incorrectly in comparison to the sham stimulated and control subjects . Summary . Although there were no differences in clinical parameters such as craving or mood after real high frequency rTMS compared to sham stimulation , we found an interesting difference between the real and the sham stimulated group and controls in the AB paradigm indicating an increase of the AB effect to alcohol-related pictures after real stimulation . Further studies are needed to replicate these findings and correlate them to clinical and neurophysiological data BACKGROUND Prior research in substance dependence has suggested potential anti-craving effects of repetitive transcranial magnetic stimulation ( rTMS ) when applied to the dorsolater
Output:
| Our main findings were that NIBS techniques might be effective strategies for down-regulating HPA activity and regulating food , alcohol , and cigarette consumption . |
MS213794 | ***TASK*** the task is to summarize an input biomedical literature in six sentences
***INPUT*** the input is a biomedical literature
***OUTPUT*** the output is the summary of an input biomedical literature in six sentences
***DOCUMENTATION***
***EXAMPLES***
Input: OBJECTIVES Femoroacetabular impingement is proposed to cause early osteoarthritis ( OA ) in the non-dysplastic hip . We previously reported on the prevalence of femoral deformities in a young asymptomatic male population . The aim of this study was to determine the prevalence of both femoral and acetabular types of impingement in young females . METHODS We conducted a population -based cross-sectional study of asymptomatic young females . All participants completed a set of question naires and underwent clinical examination of the hip . A r and om sample was subsequently invited to obtain magnetic resonance images ( MRI ) of the hip . All MRIs were read for cam-type deformities , increased acetabular depths , labral lesions , and impingement pits . Prevalence estimates of cam-type deformities and increased acetabular depths were estimated , and relationships between deformities and signs of joint damage were examined using logistic regression models . RESULTS The study included 283 subjects , and 80 asymptomatic females with a mean age of 19.3 years attended MRI . Fifteen showed some evidence of cam-type deformities , but none were scored to be definite . The overall prevalence was therefore 0 % [ 95 % confidence interval ( 95 % CI ) 0 - 5 % ] . The prevalence of increased acetabular depth was 10 % ( 95 % CI 5 - 19 ) . No association was found between increased acetabular depth and decreased internal rotation of the hip . Increased acetabular depth was not associated with signs of labral damage . CONCLUSIONS Definite cam-type deformities in women are rare compared to men , whereas the prevalence of increased acetabular depth is higher , suggesting that femoroacetabular impingement has different gender-related biomechanical mechanisms BACKGROUND The conduct of r and omized , controlled trials of nonpharmacologic treatments presents specific challenges that are not adequately addressed in trial reports . OBJECTIVE To develop an extension of the CONSORT ( Consoli date d St and ards of Reporting Trials ) Statement for trials of nonpharmacologic treatments . DESIGN A consensus meeting was organized to develop an extension of the CONSORT Statement that addresses r and omized trials of nonpharmacologic treatments . To prepare for the meeting , a survey was conducted to identify the specific issues for discussion . SETTING Consensus meeting in Paris , France . PARTICIPANTS A total of 33 experts attended the meeting . The experts were method ologists ( n = 17 ) ; surgeons ( n = 6 ) ; editors ( n = 5 ) ; and clinicians involved in rehabilitation ( n = 1 ) , psychotherapy ( n = 2 ) , education ( n = 1 ) , and implantable devices ( n = 1 ) . MEASUREMENTS Experts indicated which of the 22 items on the CONSORT checklist should be modified or which additional items should be added specifically for nonpharmacologic treatments . During a 3-day consensus meeting , all items were discussed and additional method ological issues related to nonpharmacologic research were identified . RESULTS The consensus was that 11 items on the CONSORT checklist needed some modifications for nonpharmacologic trials : item 1 ( title and abstract ) , item 3 ( participants ) , item 4 ( interventions ) , item 7 ( sample size ) , item 8 ( r and omization ) , item 11 ( blinding ) , item 12 ( statistical methods ) , item 13 ( participant flow ) , item 15 ( baseline data ) , item 20 ( discussion : interpretation ) , and item 21 ( generalizability ) . In addition , the meeting participants added 1 item related to implementation of the intervention . LIMITATION Evidence was not always available to support the inclusion of each checklist item . CONCLUSION The methods and processes used to develop this extension could be used for other reporting guidelines . The use of this extension to the CONSORT Statement should improve the quality of reporting r and omized , controlled trials assessing nonpharmacologic treatments Background Surgical placebos are controversial . This in-depth study explored the design , acceptability , and feasibility issues relevant to design ing a surgical placebo-controlled trial for the evaluation of the clinical and cost effectiveness of arthroscopic lavage for the management of people with osteoarthritis of the knee in the UK . Methods Two surgeon focus groups at a UK national meeting for orthopaedic surgeons and one regional surgeon focus group ( 41 surgeons ) ; plenary discussion at a UK national meeting for orthopaedic anaesthetists ( 130 anaesthetists ) ; three focus groups with anaesthetists ( one national , two regional ; 58 anaesthetists ) ; two focus groups with members of the patient organisation Arthritis Care ( 7 participants ) ; telephone interviews with people on consultant waiting lists from two UK regional centres ( 15 participants ) ; interviews with Chairs of UK ethics committees ( 6 individuals ) ; postal surveys of members of the British Association of Surgeons of the Knee ( 382 surgeons ) and members of the British Society of Orthopaedic Anaesthetists ( 398 anaesthetists ) ; two centre pilot ( 49 patients assessed ) . Results There was widespread acceptance that evaluation of arthroscopic lavage had to be conducted with a placebo control if scientific rigour was not to be compromised . The choice of placebo surgical procedure ( three small incisions ) proved easier than the method of anaesthesia ( general anaesthesia ) . General anaesthesia , while an excellent mimic , was more intrusive and raised concerns among some stakeholders and caused extensive discussion with local decision-makers when seeking formal approval for the pilot . Patients were willing to participate in a pilot with a placebo arm ; although some patients when allocated to surgery became apprehensive about the possibility of receiving placebo , and withdrew . Placebo surgery was undertaken successfully . Conclusions Our study illustrated the opposing and often strongly held opinions about surgical placebos , the ethical issues underpinning this controversy , and the challenges that exist even when ethics committee approval has been granted . It showed that a placebo-controlled trial could be conducted in principle , albeit with difficulty . It also highlighted that not only does a placebo-controlled trial in surgery have to be ethically and scientifically acceptable but that it also must be a feasible course of action . The place of placebo-controlled surgical trials more generally is likely to be limited and require specific circumstances to be met . Suggested criteria are presented . Trial registration numberThe trial was assigned IS RCT N02328576 through http://controlled-trials.com/ in June 2006 . The first patient was r and omised to the pilot in July 2007 The benefit of arthroscopy of the hip in the treatment of femoroacetabular impingement ( FAI ) in terms of quality of life ( QoL ) has not been reported . We prospect ively collected data on 612 patients ( 257 women ( 42 % ) and 355 men ( 58 % ) ) with a mean age at the time of surgery of 36.7 years ( 14 to 75 ) who underwent arthroscopy of the hip for FAI under the care of a single surgeon . The minimum follow-up was one year ( mean 3.2 years ( 1 to 7 ) ) . The responses to the modified Harris hip score were translated using the Rosser Index Matrix in order to provide a QoL score . The mean QoL score increased from 0.946 ( -1.486 to 0.995 ) to 0.974 ( 0.7 to 1 ) at one year after surgery ( p < 0.001 ) . The mean QoL score in men was significantly higher than in women , both before and one year after surgery ( both p < 0.001 ) . However , the mean change in the QoL score was not statistically different between men and women ( 0.02 ( -0.21 to 0.27 ) and 0.04 ( -0.16 to 0.87 ) , respectively ; p = 0.12 ) . Linear regression analysis revealed that the significant predictors of a change in QoL score were pre-operative QoL score ( p < 0.001 ) and gender ( p = 0.04 ) . The lower the pre-operative score , the higher the gain in QoL post-operatively ( ρ = -0.66 ; p < 0.001 ) . One year after surgery the QoL scores in the 612 patients had improved in 469 ( 76.6 % ) , remained unchanged in 88 ( 14.4 % ) and had deteriorated in 55 ( 9.0 % ) Objectives The number of surgical procedures performed each year to treat femoroacetabular impingement ( FAI ) continues to rise . Although there is evidence that surgery can improve symptoms in the short-term , there is no evidence that it slows the development of osteoarthritis ( OA ) . We performed a feasibility study to determine whether patient and surgeon opinion was permissive for a R and omised Controlled Trial ( RCT ) comparing operative with non-operative treatment for FAI . Methods Surgeon opinion was obtained using vali date d question naires at a Specialist Hip Meeting ( n = 61 , 30 of whom stated that they routinely performed FAI surgery ) and patient opinion was obtained from clinical patients with a new diagnosis of FAI ( n = 31 ) . Results Clinical equipoise was demonstrated when surgeons were given clinical scenarios and asked whether they would manage a patient operatively or non-operatively . A total of 23 surgeons ( 77 % ) who routinely perform FAI surgery were willing to recruit patients into a RCT , and 28 patients ( 90 % ) were willing to participate . 75 % of responding surgeons believed it was appropriate to r and omise patients to non-operative treatment for ≥ 12 months . Conversely , only eight patients ( 26 % ) felt this was acceptable , although 29 ( 94 % ) were willing to continue non-operative treatment for six months . More patients were concerned about their risk of developing OA than their current symptoms , although most patients felt that the two were of equal importance . Conclusions We conclude that a RCT comparing operative and non-operative management of FAI is feasible and should be considered a research priority . An important finding for orthopaedic surgical trials is that patients without life-threatening pathology appear willing to trial a treatment for six months without improvement in their symptoms OBJECTIVES To ascertain the acceptability of a r and omised controlled trial comparing arthroscopic lavage with a placebo-surgical procedure for the management of osteoarthritis of the knee ; and to assess the practical feasibility of mounting such a multicentre placebo-controlled trial . DESIGN Mixed methods study including : focus groups with surgeons and anaesthetists ; focus groups and interviews with potential participants ; interviews with chairpersons of UK Multicentre Research Ethics Committees ( MRECs ) ; surveys of surgeons and anaesthetists ; and a two-centre , three-arm pilot . SETTING UK secondary care . PARTICIPANTS Members of the British Association of Surgeons of the Knee and members of the British Society of Orthopaedic Anaesthetists took part in the focus groups and surveys . Surgeons and anaesthetists from two regional centres in the UK also contributed to focus groups , as did patients from consultant lists in two UK regional centres , and members of Arthritis Care . Chairpersons of six UK MRECs were interviewed . Participants were eligible for the pilot if they were adults ( 18 years or older ) with radiological evidence of osteoarthritis of the knee who might be considered for arthroscopic lavage , and were fit for general anaesthetic ( defined by the American Society of Anaesthesiologists grade s 1 and 2 ) , and able to give informed consent . INTERVENTIONS Participants in the pilot study were r and omised to arthrosocopic lavage ( with or without debridement at the clinical discretion of the surgeon ) ; placebo surgery ; or non-operative management with specialist re assessment . MAIN OUTCOME MEASURES The acceptability and feasibility of mounting a placebo-controlled trial for the evaluation of knee arthroscopic lavage . RESULTS There was broad acceptance across all stakeholder groups of the need to find out more about the effectiveness of arthroscopic lavage . Despite this there was variation in opinion within all the groups about how research ers should approach this and whether or not it would be acceptable to investigate using placebo surgery . Within the health professional groups , there tended to be a split between those who were strongly opposed to the inclusion of a placebo surgery arm and those who were more in favour . For prospect i ve trial participants who had osteoarthritis of the knee , the acceptability of the trial was discussed from a more individual perspective - reflecting on their personal reasons for or against participating . The majority of this group said they would consider taking part . The pilot study showed that , in principle , a placebo-controlled trial could be conducted . It showed that patients were willing to participate in a trial which would involve a placebo-surgical arm and that it was possible to undertake placebo surgery successfully and to blind patients to their allocation - although once patients knew their allocation , some patients allocated to surgery became more concerned about the possibility of undergoing placebo surgery , and withdrew . The experience of the pilot , however , showed that , despite full MREC approval , the study required major discussion and negotiation before local clinical approvals could be obtained . The fact that ethics approval had been granted did not mean that clinicians would automatically accept that the process was ethical . CONCLUSIONS The study showed that , in principle , a placebo-controlled trial of arthroscopic lavage could be conducted in the UK , albeit with difficulty . Against the background of falling use of arthroscopic lavage the decision was , therefore , taken not to proceed to full-scale trial for this procedure . The study showed that for some health professionals the use of
Output:
| AUTHORS ' CONCLUSIONS There is no high quality evidence examining the effectiveness of surgery for femoroacetabular impingement . |
MS213795 | ***TASK*** the task is to summarize an input biomedical literature in six sentences
***INPUT*** the input is a biomedical literature
***OUTPUT*** the output is the summary of an input biomedical literature in six sentences
***DOCUMENTATION***
***EXAMPLES***
Input: In the nutritional management of digestive disorders , it is important to know the relative secretory and metabolic responses to enteral and parenteral feeding . Twenty-seven healthy volunteers were studied while receiving either oral drinks or duodenal infusions of a complex formula diet , duodenal or intravenous infusions of elemental ( protein as free amino acids , low fat ) formulae , or saline . Pancreaticobiliary secretory responses were measured by nasoduodenal polyethylene glycol perfusion and aspiration , while monitoring blood hormone and nutrient levels . Diets were matched for protein ( 1.5 g x kg(-1 ) x d(-1 ) ) and energy ( 40 kcal x kg(-1 ) x d(-1 ) ) . Compared with placebo , all oroenteral diets stimulated amylase , lipase , trypsin , and bile acid secretion and increased plasma concentrations of gastrin and cholecystokinin , whereas intravenous feeding did not . The complex formula produced a similar response whether given as drinks or duodenal infusions . Changing the duodenal formula to elemental reduced enzyme secretion by 50 % , independently of CCK . Higher increases in plasma insulin , glucose , and amino acids were noted with intravenous feeding . Delivering food directly to the intestine by a feeding tube does not reduce pancreaticobiliary secretion . Enteral " elemental " formulae diminish , but only intravenous feeding avoids pancreatic stimulation . Intravenous administration impairs metabolic clearance Studies in humans have shown that pancreatic enzyme secretion is reduced during acute pancreatitis . It is not known , however , whether the reduction is due to impaired synthesis or disruption of the secretory pathway . The rate of secretion and turnover of trypsin was measured in 12 patients with acute pancreatitis of variable etiology and severity ( median Ranson 's score 2.5 , range 0 - 5 , 4 with severe necrotizing disease ) and eight healthy volunteers by 4-h primed/continuous intravenous infusions of 1-(13)C-labeled l-leucine , and collection of pancreatic secretions by duodenal perfusion and sampling . Trypsin secretion was reduced from 476 + /- 73 to 153 + /- 60 U/h ( means + /- SE , P = 0.005 ) in acute pancreatitis , with the greatest reductions being observed in patients with necrotizing disease ( 32 + /- 7 U/h , P = 0.003 ) . The time for newly labeled trypsin to first appear in digestive juice was not , however , delayed in pancreatitis patients ( 87.2 + /- 11.1 vs. 94.7 + /- 4.9 min ) ; on the contrary , there was an early appearance of newly labeled trypsin at 30 min in patients with severe necrotizing pancreatitis ( P < 0.05 ) . Calculated zymogen pool turnover was unchanged , but pool size was decreased ( P = 0.01 ) . Despite low rates of luminal secretion , trypsin continues to be synthesized in patients with acute pancreatitis . Our findings could be explained by post-Golgi leakage of enzymes from acinar cells or by loss of synthetic function in some cells with preservation in others BACKGROUND : After 50 yr in which nasoenteric feeding was considered contraindicated in acute pancreatitis ( AP ) , several clinical studies have shown that early nasojejunal ( NJ ) feeding can be achieved in most patients . A pilot study of early nasogastric ( NG ) feeding in patients with objective ly grade d severe AP proved that this approach was also feasible . A r and omized study comparing NG versus NJ feeding has been performed . METHODS : A total of 50 consecutive patients with objective ly grade d severe AP were r and omized to receive either NG or NJ feeding via a fine bore feeding tube . The end points were markers of the acute phase response APACHE II scores and C-reactive protein ( CRP ) measurements , and pain patterns by visual analogue score ( VAS ) and analgesic requirements . Complications were monitored and comparisons made of both total hospital and intensive-care stays . RESULTS : A total of 27 patients were r and omized to NG feeding and 23 to NJ . One of those in the NJ group had a false diagnosis , thereby reducing the number to 22 . Demographics were similar between the groups and no significant differences were found between the groups in APACHE II score , CRP measurement , VAS , or analgesic requirement . Clinical differences between the two groups were not significant . Overall mortality was 24.5 % with five deaths in the NG group and seven in the NJ group . CONCLUSIONS : The simpler , cheaper , and more easily used NG feeding is as good as NJ feeding in patients with objective ly grade d severe AP . This appears to be a useful and practical therapeutic approach to enteral feeding in the early management of patients with severe AP Objective : To compare the efficacy and safety of early , nasogastric enteral nutrition ( EN ) with total parenteral nutrition ( TPN ) in patients with predicted severe acute pancreatitis ( SAP ) . Summary Background Data : In SAP , the magnitude of the inflammatory response as well as increased intestinal permeability correlates with outcome . Enteral feeding has been suggested superior to parenteral feeding due to a proposed beneficial effect on the gut barrier . Methods : Fifty patients who met the inclusion criteria were r and omized to TPN or EN groups . The nutritional regimen was started within 24 hours from admission and EN was provided through a nasogastric tube . The observation period was 10 days . Intestinal permeability was measured by excretion of polyethylene glycol ( PEG ) and concentrations of antiendotoxin core antibodies ( Endocab ) . Interleukins (IL)-6 IL-8 , and C-reactive protein ( CRP ) were used as markers of the systemic inflammatory response . Morbidity and feasibility of the nutritional route were evaluated by the frequency of complications , gastrointestinal symptoms , and abdominal pain . Results : PEG , Endocab , CRP , IL-6 , APACHE II score , severity according to the Atlanta classification ( 22 patients ) , and gastrointestinal symptoms or abdominal pain did not significantly differ between the groups . The incidence of hyperglycemia was significantly higher in TPN patients ( 21 of 26 vs. 7 of 23 ; P < 0.001 ) . Total complications ( 25 vs. 52 ; P = 0.04 ) and pulmonary complications ( 10 vs. 21 ; P = 0.04 ) were significantly more frequent in EN patients , although complications were diagnosed dominantly within the first 3 days . Conclusion : In predicted SAP , nasogastric early EN was feasible and result ed in better control of blood glucose levels , although the overall early complication rate was higher in the EN group . No beneficial effects on intestinal permeability or the inflammatory response were seen by EN treatment Background : Infectious complications are the main cause of late death in patients with acute pancreatitis . Routine prophylactic antibiotic use following a severe attack has been proposed but remains controversial . On the other h and , nutritional support has recently yielded promising clinical results . The aim of study was to compare enteral vs. parenteral feeding for prevention of infectious complications in patients with predicted severe acute pancreatitis . Methods : We screened 466 consecutive patients with acute pancreatitis . A total of 70 patients with objective ly grade d severe acute pancreatitis were r and omly allocated to receive either total enteral nutrition ( TEN ) or total parenteral nutrition ( TPN ) , within 72 h of onset of symptoms . Baseline characteristics were well matched in the two groups . Results : The incidence of pancreatic infectious complications ( infected pancreatic necrosis , pancreatic abscess ) was significantly lower in the enterally fed group ( 7 vs. 16 , p = 0.02 ) . In the TEN group , 7 patients developed multiple organ failure whereas 17 parenterally fed patients developed multiple organ failure ( p = 0.02 ) . Overall mortality was 20 % with two deaths in the TEN group and twelve in the TPN group ( p < 0.01 ) . Conclusion : Early TEN could be used as prophylactic therapy for infected pancreatic necrosis since it significantly decreased the incidence of pancreatic infectious complications as well as the frequency of multiple organ failure and mortality In recent years , a number of articles have been published on the treatment of acute pancreatitis in experimental models and most of them were published about animals with mild disease . However , it is difficult to translate these results into clinical practice . For example , infliximab , a monoclonal TNF antibody , was experimentally tested in rats and it was able to significantly reduce the pathologic score and serum amylase activity , and also alleviate alveolar edema and acute respiratory distress syndrome ; no studies are available in clinical human acute pancreatitis . Another substance , such as interleukin 10 , was efficacious in decreasing the severity and mortality of lethal pancreatitis in rats , but seems to have no effect on human severe acute pancreatitis . Thus , the main problem in acute pancreatitis , especially in the severe form of the disease , is the difficulty of planning clinical studies capable of giving hard statistically significant answers regarding the benefits of the various proposed therapeutic agents previously tested in experimental setting s. According to the pathophysiology of acute pancreatitis , we may re-evaluate the efficacy of the drugs already available , such as gabexate mesilate , lexipafant and somatostatin which should be probably administered in a different manner . Of course , also in this case , we need large studies to test this hypothesis . Another great problem is prevention of the infection of pancreatic necrosis . A r and omized study has been published to test the hypothesis that probiotics and specific fibres used as supplements in early enteral nutrition may be effective in reducing pancreatic sepsis and the number of surgical interventions . A study named PROPATRIA ( Probiotic Prophylaxis in Patients with Predicted Severe Acute Pancreatitis ) has been planned to give a more robust confirmation to the previous study . Furthermore , the open question of the prevention of the fungal infection of necrosis is still being debated . Finally , the prevention of pain relapse after oral feeding in patients with mild or severe acute pancreatitis should be explored . Even if some studies exist on this issue , the question of optimal treatment is still unanswered . As in other diseases , obtaining results when treating patients with acute pancreatitis is difficult and will take continuous small steps Aims : The aim of this prospect i ve study was to assess pancreatic exocrine function in patients recovering from a first attack of acute pancreatitis , and to evaluate its relationship to severity of attack , extent of pancreatic necrosis and severity of pancreatic endocrine insufficiency . Methods : Between December 2000 and November 2001 , 23 patients were prospect ively evaluated . Pancreatic exocrine function was measured by the faecal elastase-1 test and insufficiency was classified as moderately impaired or severely impaired . Pancreatic necrosis was determined by contrast-enhanced CT scan , and its extent was categorised according to Balthazar ’s classification . The severity of pancreatic endocrine insufficiency was categorised according to insulin dependence . Attacks were classified as mild ( n = 16 ) or severe ( n = 7 ) according to the Atlanta criteria . Results : Pancreatic exocrine insufficiency was significantly more frequent in patients recovering from severe attacks than mild ( n = 6 , 86 % vs. n = 2 , 13 % ; p = 0.002 ) , and in those who developed pancreatic necrosis or pseudocyst than those who did not ( 6 of 7 patients vs. 2 of 16 patients , and 5 of 5 patients vs. 3 of 18 patients respectively ; p = 0.002 ) . The development of exocrine insufficiency correlated strongly with the extent of pancreatic necrosis ( r = –0.754 , p < 0.001 ) , and the severity of pancreatic endocrine insufficiency ( n = 4 , r = –0.453 , p = 0.03 ) . Conclusion : Pancreatic exocrine insufficiency is a common occurrence in patients recovering from severe acute pancreatitis , and its severity correlates with the extent of pancreatic necrosis and the severity of concomitant pancreatic endocrine insufficiency Summary Background . Severe acute pancreatitis may be protracted and some form of nutritional support is frequently required to maintain the patient ’s nutritional status . Recent work has suggested that enteral feeding via a jejunal route of delivery may reduce the magnitude of the inflammatory response . Insertion of nasojejunal ( NJ ) tubes in the patient with severe acute pancreatitis involves both delay and inconvenience . We undertook a prospect i ve , feasibility study to assess the safety and practicability of nasogastric ( NG ) feeding in patients with severe acute pancreatitis . Patients and Methods . Twenty-six patients with objective evidence of severe acute pancreatitis received nasogastric feeding within 48 h of admission to our unit . Results . Etiology was identified as cholelithiasis ( 18 patients ) , ethanol ( 5 ) , and miscellaneous ( 3 ) . The median Glasgow score was 4 ( range 2–7 ) , APACHE II score 10 ( 4–28 ) , and C-reactive protein concentration 286 mg/L (
Output:
| Nasogastric feeding appears safe and well tolerated in patients with predicted severe acute pancreatitis . |
MS213796 | ***TASK*** the task is to summarize an input biomedical literature in six sentences
***INPUT*** the input is a biomedical literature
***OUTPUT*** the output is the summary of an input biomedical literature in six sentences
***DOCUMENTATION***
***EXAMPLES***
Input: Forty-eight community living women 66–87 years old volunteered to participate in a 12-month prospect i ve , r and omized , controlled , trial . The aim was to determine if a combined weight-bearing training program twice a week would be beneficial to bone mineral density and neuromuscular function . The participants were pairwise age-matched and r and omly assigned to either an exercise group ( n=24 ) or a control group ( n=24 ) . Twenty-one subjects in the intervention group and 19 in the control group completed the study . The exercise program lasted for 50 min and consisted of a combination of strengthening , aerobic , balance and coordination exercises . The mean percentage of scheduled sessions attended for the exercise group was 67 % . At the completion of the study , the intervention group showed significant increments in bone mineral density of the Ward ’s triangle ( 8.4 % , P<0.01 ) as well as improvement in maximum walking speed ( 11.4 % , P<0.001 ) and isometric grip strength ( 9.9 % , P<0.05 ) , as compared to the control group . The conclusion was that a combined weight-bearing training program might reduce fracture risk factors by improving bone density as well as muscle strength and walking ability . This program could be suitable for older community living women in general , and might , therefore , have important implication s for fracture prevention Reports on the efficacy of physical activity intervention trials usually only include discussion of the primary outcomes . However , assessing factors such as participant retention , adherence and compliance can assist in the accurate interpretation of the overall impact of a program in terms of reach and appeal . A quasi-r and omised trial was carried out to assess and compare retention and adherence rates , and compliance with , a twice weekly resistance training program provided either individually at home or in a group format . Retirement villages ( n=6 ) were assigned to either ' Have A Try ' ( HAT , home-based ) or ' Come Have A Try ' ( CHAT , group-based ) ; both programs included nine strength and two balance exercises . The program involved a 20-week Intervention Phase a 24-week Maintenance Phase and a 20-week On-going Maintenance Phase . One hundred and nineteen participants ( mean age 80+/-6 years ) were recruited ( HAT=38 , CHAT=81 ) . There was no difference in retention rates at the end of the Intervention Phase , but significantly more HAT than CHAT participants had dropped out of the study ( p<0.01 ) after the Maintenance Phase and the On-going Maintenance Phase . During the Intervention Phase , over half the HAT and CHAT participants completed > or = 75 % of the prescribed activity sessions , but adherence was significantly greater in CHAT than HAT during the Maintenance Phase ( p<0.01 ) . Participants in CHAT were significantly more compliant than HAT participants ( p<0.05 ) . Both home- and group-based formats were successful over the short-term , but , in retirement villages , the group program had better adherence and compliance in the longer-term OBJECTIVES We assessed the impact of existing best- practice physical activity programs for older adults on physical activity participation and health-related outcomes . METHODS We used a multisite , r and omized trial with 544 older adults ( mean age 66 years ) and measures at baseline , 5 , and 10 months to test the impact of a multiple-component physical activity program compared with results for a control group that did not participate in such a program . RESULTS For adults who participated in a multiple-component physical activity program , we found statistically significant benefits at 5 and 10 months with regard to self-efficacy for exercise adherence over time ( P < .001 ) , adherence in the face of barriers ( P = .01 ) , increased upper- and lower-body strength ( P = .02 , P = .01 ) , and exercise participation ( P = .01 ) . CONCLUSIONS Best- practice community-based physical activity programs can measurably improve aspects of functioning that are risk factors for disability among older adults . US public policy should encourage these inexpensive health promotion programs Objectives The effectiveness of community level interventions depends to a great extent on adherence . Currently , information on factors related to adherence in older adults from developing countries is scarce . Our aim was to identify factors associated to adherence to a physical activity intervention in older adults from a post-transitional middle income country . Design , setting and participants Using a combination of quantitative and qualitative methods we studied 996 older Chilean subjects ( 65–67.9 years at baseline ) with low to medium socioeconomic status from 10 health centers r and omized to receive a physical activity intervention as part of the CENEX cluster trial ( IS RCT N48153354 ) . Measurements Using a multilevel regression model , the relationship between adherence ( defined a priori as attendance at a minimum of 24 physical activity classes spread over at least 12 months ) and individual , intervention-related and context ual factors was evaluated . We also conducted 40 semi-structured interviews with older adults ( n=36 ) and instructors ( n=4 ) . Transcripts of the interviews were analyzed using content analysis to identify barriers and facilitators to adherence . Results Adherence to physical activity intervention was 42.6 % ( CI 95 % 39.5 to 45.6 ) . Depression , diabetes mellitus , percentage of impoverished households and rate of arrests for violent crimes in the neighborhood predicted less adherence ( p<0.05 ) while being retired , participation in physical activity prior to the intervention , and green areas per habitant were positively associated with adherence ( p<0.05 ) . The qualitative interviews identified three primary barriers to adherence : current health problems , lack of time due to commitments for caring for family members , and being employed , and two primary facilitators to adherence : the health benefits attributed to the intervention and the opportunity the classes provided for social interaction with others . Conclusion In order to enhance effectiveness of community exercise interventions , strategies to improve participation should be targeted to older adults from deprived areas and those with psychological and medical conditions BACKGROUND Although inactivity is an important contributor to impaired functioning and disability with age , little is known concerning how improvements in physical functioning and well-being in older adults vary with the type of physical activity undertaken . METHODS One hundred three adults age 65 years and older , recruited via population -based methods , were r and omized to 12 months of community-based , moderate-intensity endurance and strengthening exercises ( Fit & Firm ) or stretching and flexibility exercises ( Stretch & Flex ) . A combination of class- and home-based exercise formats was used . Measured and self-rated physical performance along with perceived functioning and well-being were assessed pre- and postintervention . RESULTS Fit & Firm subjects showed greater 12-month improvements in both measured and self-rated endurance and strength compared to Stretch & Flex subjects . Stretch & Flex subjects reported greater improvements in bodily pain , and Stretch & Flex men evidence d greater improvements in flexibility relative to Fit & Firm subjects . Although overall exercise adherence was high in both exercise conditions ( approximately 80 % ) , subjects in both conditions showed better adherence to the home- versus class-based portions of their exercise prescriptions . CONCLUSIONS Community-based programs focusing on moderate-intensity endurance and strengthening exercises or flexibility exercises can be delivered through a combination of formats that result in improvement in important functional and well-being outcomes . This represents one of the first studies to report significant improvements in an important quality of life outcome -bodily pain-with a regular regimen of stretching and flexibility exercises in a community-based sample of older adults After a r and omized controlled trial showing that improvement on some aspects of cognitive function was related to adherence to an exercise program , determinants of adherence and maintenance were further studied . Older adults with mild cognitive impairment were contacted 6 mo after the end of exercise programs for a telephone interview addressing patterns of adherence and determinants of maintenance . Mean adherence during the trial was 53 % . About one third of participants had lapses during the trial but completed , one third had no lapses , and one third dropped out or never started . Practical barriers ( time , location ) were related to not starting and functional limitations to dropout . After the trial 25 % of participants continued the programs , 14 % reported intention to continue , and 61 % quit . Maintenance was determined by fewer health complaints , higher satisfaction with the programs , and better adherence during the programs . Although maintenance was low , this study identified several reasons and barriers to adherence and maintenance that could be addressed PURPOSE We present final outcomes from the multiple-component Fit and Strong ! intervention for older adults with lower extremity osteoarthritis . DESIGN AND METHODS A r and omized controlled trial compared the effects of this exercise and behavior-change program followed by home-based reinforcement ( n=115 ) with a wait list control ( n=100 ) at 2 , 6 , and 12 months . Fit and Strong ! combined flexibility , aerobic walking , and resistance training with education and group problem solving to enhance self-efficacy for exercise and maintenance of physical activity . All participants developed individualized plans for long-term maintenance . RESULTS Relative to controls , treatment participants experienced statistically significant improvements in self-efficacy for exercise ( p=.001 ) , minutes of exercise per week ( p=.000 ) , and lower extremity stiffness ( p=.018 ) at 2 months . These benefits were maintained at 6 months and were accompanied by increased self-efficacy for adherence to exercise over time ( p=.001 ) , reduced pain ( p=.040 ) , and a marginally significant increase in self-efficacy for arthritis pain management ( p=.052 ) . Despite a substantially smaller sample size at 12 months , significant treatment-group effects were maintained on self-efficacy for exercise ( p=.006 ) and minutes of exercise per week ( p=.001 ) , accompanied by marginally significant reductions in lower extremity stiffness ( p=.056 ) and pain ( p=.066 ) . No adverse health effects were seen . Effect sizes for self-efficacy for exercise and for maintenance of physical activity were 0.798 and 0.713 , and 0.905 and 0.669 , respectively , in the treatment group at 6 and 12 months . IMPLICATION S This consistent pattern of benefits indicates that this low-cost intervention is efficacious for older adults with lower extremity osteoarthritis Background and Purpose : Physical activity has many benefits for older adults , but adherence is often low . The purpose s of this study were to ( 1 ) identify motivators and barriers for participation in EnhanceFitness ( EF ) , a group-based exercise program ; and ( 2 ) quantitatively examine the association between motivators , barriers and individual characteristics , and ongoing participation in the program . Methods : This was a prospect i ve , cross-sectional study . We mailed a pilot , investigator-developed survey to assess motivators and barriers to exercising to 340 adults who started a new EF class , regardless of their attendance rate . We precoded surveys on the basis of class attendance , with former participants defined as having no attendance a month or more before a 4-month fitness check . Results : Of the 241 respondents ( 71 % response rate ) , 61 ( 25 % ) were precoded as former participants and 180 ( 75 % ) as current participants . The mean age of respondents was 71 years and they were predominately female ( 89 % ) . More than half of respondents were whites ( 58 % ) , and almost half were married ( 46 % ) . Former participants reported lower total motivation scores than current participants ( P < .01 ) and had a significantly higher mean total barrier score ( P < .001 ) . The effects of 5 barriers ( “ Class was too hard , ” “ Class was too easy , ” “ I do n't like to exercise , ” “ Personal illness , ” and “ Exercise caused pain ” ) and 2 motivators ( “ I want to exercise ” and “ I plan exercise as part of my day ” ) were significantly different between current and former participants . Discrete event history models show that dropout was related positively to ethnicity ( whites were more likely to drop out ) and health-related barriers . Discussion : In newly formed EF classes , participants who drop out report more program , psychosocial , and health barriers , and fewer program and psychosocial motivators . Total barrier score and health barriers significantly predict a participant 's dropping out , and white ethnicity is associated with a higher likelihood of dropping out . Conclusions : Employing strategies that address health barriers to participation could improve attendance rates for group-based exercise programs Increasing evidence suggests that physical activity can prevent some aspects of mental illness in older people such as depression , dementia and Alzheimer ’s disease . Additionally , limited research has shown that engagement in structured exercise can improve aspects of psychological well-being such as mood and self-perceptions in older adults . However , the relationship between incidental daily activity such as walking or time spent sedentary , with psychological well-being has not been investigated . The Better Ageing Project provided an opportunity to assess well-being and quality of life using st and ardised question naires with 176 adults aged 70 and over . Accelerometry was used to objective ly assess daily energy expended in physical activity at different levels of intensity . In addition , an assessment of the impact of the 12-month Better Ageing structured group exercise programme was assessed through question naires and interviews . Total daily physical activity energy expenditure ( joules/day ) and amount of time spent in activity of at least moderate intensity were weakly related ( r = 0.20–0.28 ) to quality of life , subjective well-being and physical self-perceptions . Time spent sedentary ( min/day ) was weakly and negatively related to several mental health indicators . The quantitative data showed only minor psychological benefits of the exercise intervention . In contrast , interviews with 27 research participants and 4 exercise leaders suggested that important improvements
Output:
| Evidence surrounding these programmes is limited both in terms of long-term adherence measures and the views of participants .
However , based on limited findings there is some indication that community based group exercise programmes have long-term adherence rates of almost 70 % .
Incorporating the views of older people into programme design s may provide guidance for innovative interventions leading to sustained adherence |
MS213797 | ***TASK*** the task is to summarize an input biomedical literature in six sentences
***INPUT*** the input is a biomedical literature
***OUTPUT*** the output is the summary of an input biomedical literature in six sentences
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Input: OBJECTIVES The objectives of this study were to describe our laparoscopic nerve-sparing radical hysterectomy ( LNSRH ) technique and to assess the feasibility and safety of the procedure , as well as its impact on voiding function . We introduce a fascia space dissection technique in order to preserve the pelvic splanchnic nerve , the hypogastric nerve and the bladder branch of the inferior hypogastric plexus under magnification ( ×10.5 ) during laparoscopic radical hysterectomy ( LRH ) with pelvic lymphadenectomy . METHODS From October 2006 to November 2009 , 163 consecutive patients with cervical cancer underwent laparoscopic radical hysterectomy ( LRH ) and pelvic lymphadenectomy , with 82 women undergoing LNSRH with fascia space dissection technique ( LNSRH group ) and 81 undergoing LRH ( LRH group ) . Data from 163 patients were prospect ively collected and compared . Post-operative assessment of bladder function included the following : the time to recover the ability to void spontaneously and to achieve a post-void residual urine ( PVR ) volume of less than 50 ml , with urination function grade d. RESULTS The laparoscopic nerve-sparing radical hysterectomy procedure was completed successfully and was conducted safely in all of the patients . There were no conversions to open surgery in the two groups . The median operative duration in the LNSRH and the LRH groups were 163.52±34.47 min and 132.13±31.42 min , respectively . Blood loss was 142.12±62.38 ml and 187.69±68.63 ml , respectively . The time taken to obtain a post-void residual urine volume of less than 50 ml after removal of the urethral catheter was 7.42±2.35 d ( 5 - 18 d ) in LNSRH group and was 16.75±7.73 d ( 5 - 35 d ) in LRH group ( P<0.05 ) . The bladder void function recovery to Grade s 0-I was 76 ( 92.7 % ) for the LNSRH group and 59 ( 72.8 % ) for the LRH group . A mean follow-up of 22.3 ( 5 - 42 ) months was adhered to , and no patient had a recurrence or metastasis . CONCLUSIONS The technique described in this preliminary study appears to be safe , feasible , and easy in our population , with satisfactory recovery of voiding function STUDY OBJECTIVE To compare laparoscopic modified radical hysterectomy ( LMRH ) with traditional modified radical hysterectomy ( MRH ) in women with early invasive cervical cancer . DESIGN Prospect i ve , nonr and omized study ( Canadian Task Force classification II-1 ) . SETTING Chi Mei Foundation Medical Center , Tainan , Taiwan . PATIENTS Ten women with cervical cancer stage Ia2 to Ib1 ( < /=2 cm ) . Intervention . LMRH ( class II radical hysterectomy ) and pelvic lymphadenectomy . MEASUREMENTS AND MAIN RESULTS The pathologist examined all specimens . The width of parametrium ( mean + /- SD ) was 1.75 + /- 0.68 cm on the right and 1.70 + /- 0.54 cm on the left . The length of the vaginal cuff was 1.37 + /- 0.86 cm . Operating time for LMRH ( 159 + /- 26.4 min ) was similar to that for MRH ( 165.7 + /- 30.5 min ) . Postoperative hospitalization for LMRH ( 4.1 + /- 1.5 days ) and estimated blood loss ( 250 + /- 147.2 ml ) were significantly less than for MRH ( 8.3 + /- 4.4 days and 611.5 + /- 256.8 ml , respectively ) . No intraoperative complications occurred , and no patient experienced postoperative voiding dysfunction or constipation . CONCLUSIONS Based on preliminary results , LMRH is feasible for treatment of early invasive cervical cancer , and may become preferred for surgical staging of the disease Background R and omised Controlled Trials ( RCTs ) are the preferred study design when comparing therapeutical interventions in medicine . To improve clarity , consistency and transparency of reporting RCTs , the Consoli date d St and ards of Reporting Trials ( CONSORT ) statement was developed . Objectives ( 1 ) To assess the quality of reports and abstract s of RCTs in otorhinolaryngologic literature by using CONSORT checklists , ( 2 ) to compare the quality of reports and abstract s of otorhinolaryngologic RCTs between the top 5 general medical journals and top 5 otorhinolaryngologic journals , and ( 3 ) to formulate recommendations for authors and editors of otorhinolaryngologic ( ‘ ENT ’ ) journals . Methods Based on 2012 ISI Web of Knowledge impact factors , the top 5 general medical and ENT journals were selected . On 25 June 2014 , using a highly sensitive Cochrane RCT filter and ENT filter , possibly relevant articles since January 1st , 2010 were retrieved and relevant RCTs were selected . We assessed how many CONSORT items were reported adequately in reports and abstract s and compared the two journal types . Results Otorhinolaryngologic RCTs ( n = 15 ) published in general medical journals reported a mean of 92.1 % ( 95 % confidence interval : 89.5%–94.7 % ) of CONSORT items adequately , whereas RCTs ( n = 18 ) published in ENT journals reported a mean of 71.8 % ( 66.7%–76.8 % ) adequately ( p < 0.001 ) . For abstract s , means of 70.0 % ( 63.7%–76.3 % ) and 32.3 % ( 26.6–38.0 % ) were found respectively ( p < 0.001 ) . Large differences for specific items exist between the two journal types . Conclusion The quality of reporting of RCTs in otorhinolaryngologic journals is suboptimal . RCTs published in general medical journals have a higher quality of reporting than RCTs published in ENT journals . We recommend authors to report their trial according to the CONSORT Statement and advise editors to endorse the CONSORT Statement and implement the CONSORT Statement in the editorial process to ensure more adequate reporting of RCTs and their abstract OBJECTIVE To investigate bladder and intestinal function recovery and quality of sexual life after laparoscopic nerve-sparing radical hysterectomy ( LNRH ) for treatment of early invasive cervical carcinoma . METHODS Subjects included patients who underwent radical hysterectomy by laparotomy who were r and omly assigned to 2 groups : 30 patients who underwent LNRH and 35 classical laparoscopic radical hysterectomy ( LRH ) . We assessed the patients general clinical information , surgical characteristics , pathological findings , and adjuvant therapies . A urodynamic study was used to assess bladder function . Intestinal function recovery and quality of sexual life were evaluated by question naire . RESULTS No significant differences were found in age , surgery characteristics , pathological findings , adjuvant therapies , and main adverse effects between the 2 groups . The mean duration of the postoperative catheterization ( DPC ) in group LNRH was shorter than that in group LRH ( P < 0.001 ) . The maximum flow rate , maximum cystometric capacity , maximum detrusor pressure and urinary complications in group LNRH were better than those in group LRH . The quality of sexual life evaluated according to the female sexual function index ( FSFI ) was better in group LNRH than in those who underwent LRH . The intestinal function of patients in group LNRH also recovered better compared with patients in group LRH Background Nerve‐sparing radical hysterectomy ( NSRH ) was developed in an attempt to minimize complications after radical hysterectomy . Since 2008 , a modified NSRH‐nerve plane‐sparing radical hysterectomy ( NPSRH ) has been developed at the Cancer Hospital , Chinese Academy of Medical Sciences . The aim of this study was to investigate the role of NPSRH in improving postoperative pelvic visceral dysfunctions . Methods Eighty‐three patients with International Federation of Gynecology and Obstetrics ( FIGO ) stage IB1‐IIA2 cervical cancer received NPSRH ( the study group ) from January 2008 to October 2012 . One hundred and sixty‐six patients who underwent conventional radical hysterectomy ( CRH ) were r and omly selected as the control group . Age , pathological type and stage were matched between the two groups . The safety of surgery was assessed by duration of operation and blood transfusion rate . Postoperative short‐term bladder function was analyzed by duration of catheterization . Long‐term bladder , anorectal and sexual function were evaluated with question naires . Results Seventy‐eight patients ( 94.0 % ) in the NPSRH group and one hundred and sixty patients ( 96.4 % ) in the CRH group completed the study . Median follow‐up time was 31.9 months and 31.0 months respectively ( P=0.708 ) . There was no significant difference between the two groups in terms of age , body mass index , FIGO stage , pathologic type , preoperative and postoperative therapy ( P > 0.05 ) . The blood transfusion rate shared no difference between two groups ( P=0.364 ) . The operation time in the NPSRH group was significantly longer than CRH group ( P < 0.01 ) . But the duration of catheterization and hospitalization in the NPSRH group was significantly reduced compared with CRH group ( P < 0.01 ) . In addition , the incidence of long‐term urinary frequency , urinary incontinence , urinary retention , straining to void , constipation and diarrhea was significantly lower in the NPSRH group ( P < 0.05 ) . However , there was no significant difference regarding sexual function ( P > 0.05 ) . Conclusions The current evidence indicated that NPSRH improved long‐term bladder function compared to CRH . Moreover , it may improve long‐term anorectal function as well The objective of this study is to describe a technique for preserving the autonomic nerve systematic ally , including the hypogastric nerves , pelvic splanchnic nerves , and pelvic plexus and its vesical branches , based on anatomic considerations for the autonomic nerves innervating the urinary bladder , in radical hysterectomies and to assess postsurgical bladder function . A nerve-sparing radical hysterectomy was carried out on 27 consecutive patients with uterine cervical cancer treated between 2000 and 2002 . The FIGO stages of the disease consisted of 10 stage Ib1 , 6 stage Ib2 , 3 stage IIa , and 8 stage IIb . The nerve-sparing procedure was successfully completed in 22 of the 27 patients ( 81.5 % ) in the study . At 1 year after the operation , bladder symptoms were significantly improved in the nerve-sparing group compared to the non – nerve-sparing group . Urinary incontinence and abnormal ( diminished ) bladder sensation were observed in three of the five patients ( two patients had both symptoms ) , for whom the nerve-sparing procedure could not be performed , but none of the 22 patients for whom the nerve-sparing procedure was performed had incontinence , and only two patients had abnormal ( increased ) bladder sensation ( P = 0.0034 for incontinence and P = 0.030 for abnormal bladder sensation ) . The patients ' survival was not adversely affected by the nerve-sparing procedure . Although it is still preliminary , the surgical technique described in this report is thought to be effective for preserving bladder function , and thus , the quality of life could be improved for patients with cervical cancer who are treated with a radical hysterectomy . For further evaluation of the efficacy of nerve-sparing radical hysterectomy , a prospect i ve r and omized trial needs to be performed OBJECTIVE To describe the anatomy of pelvic autonomic nerves as it applies to nerve-sparing radical hysterectomy , and the technique , feasibility , and results of robotic nerve-sparing radical hysterectomy . METHODS Prospect i ve evaluation of 6 patients undergoing robotic nerve-sparing radical hysterectomy ( type C1 ) for cervical cancer Stage IB ( 1B1 in 3 and 1B2 in 3 patients ) . Pelvic lymphadenectomy was performed in 3 patients and pelvic and aortic in the remaining 3 patients . RESULTS The operation was completed in all patients . The mean age of the patients was 51.0 ( range 33 - 73 ) and mean BMI 27.8 ( range 23.2 - 35.1 ) . The mean operating time was 238.6 min ( range 207 - 256 ) , mean blood loss 135 ml ( range 100 - 150 ) , mean number of lymph nodes was 23.6 ( range 19 - 29 ) , mean hospital stay was 2 days ( range 1 - 4 ) . There were no intraoperative complications . Postoperative complications occurred in 1 patient with an ileus who required an extended hospital stay . One
Output:
| Nerve sparing radical hysterectomy is associated with reduced lower urinary tract dysfunction . |
MS213798 | ***TASK*** the task is to summarize an input biomedical literature in six sentences
***INPUT*** the input is a biomedical literature
***OUTPUT*** the output is the summary of an input biomedical literature in six sentences
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Input: Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more
Output:
| In addition , it developed students ’ learning enthusiasm , students ’ self- study ability , thinking ability , and enhanced students ’ communication skills .
The results indicated that such novel pedagogy is compatible with the present situation of Chinese pharmacy education .
And it could be considered as an effective method to enhance both the theoretical test scores and various abilities of Chinese pharmacy students |
MS213799 | ***TASK*** the task is to summarize an input biomedical literature in six sentences
***INPUT*** the input is a biomedical literature
***OUTPUT*** the output is the summary of an input biomedical literature in six sentences
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Input: BACKGROUND Female-initiated HIV-prevention options , such as microbicides , are urgently needed . We assessed Carraguard , a carrageenan-based compound developed by the Population Council , for its efficacy and long-term safety in prevention of HIV infection in women . METHODS We undertook a r and omised , placebo-controlled , double-blind trial in three South African sites in sexually-active , HIV-negative women , aged 16 years and older . 6202 participants , who were r and omly assigned by a block r and omisation scheme to Carraguard ( n=3103 ) or placebo ( methylcellulose [ n=3099 ] ) , were instructed to use one applicator of gel plus a condom during each vaginal sex act . Participants were followed up for up to 2 years . Visits every 3 months included testing for HIV presence and pregnancy , pelvic examinations , risk reduction counselling , and treatment for curable sexually transmitted infections and symptomatic vaginal infections . The primary outcome was time to HIV seroconversion . Analysis was in the efficacy population ( a subset of the intention-to-treat population , excluding participants for whom efficacy could not be assessed ) . This study is registered with Clinical Trials.gov , number NCT00213083 . FINDINGS For the primary outcome ( time to HIV seroconversion ) we analysed 3011 women in the Carraguard group and 2994 in the placebo group . HIV incidence was 3.3 per 100 woman-years ( 95 % CI 2.8 - 3.9 ) in the Carraguard group ( 134 events ) and 3.8 per 100 woman-years ( 95 % CI 3.2 - 4.4 ) in the placebo group ( 151 events ) , with no significant difference in the distribution of time to seroconversion ( p=0.30 ) . The covariate-adjusted hazard ratio was 0.87 ( 95 % CI 0.69 - 1.09 ) . Rates of self-reported gel use ( 96.2 % Carraguard , 95.9 % placebo ) and condom use ( 64.1 % in both groups ) at last sex acts were similar in both groups . On the basis of applicator testing , however , gel was estimated to have been used in only 42.1 % of sex acts , on average ( 41.1 % Carraguard , 43.1 % placebo ) . 1420 ( 23 % ) women in the intention-to-treat population had adverse events ( 713 Carraguard , 707 placebo ) , and 95 ( 2 % ) women had adverse events that were related to gel use ( 48 Carraguard , 47 placebo ) . Serious adverse events occurred in 72 ( 2 % ) women in the Carraguard group and 78 ( 3 % ) in the placebo group , only one of which was considered possibly related to gel use ( placebo group ) . INTERPRETATION This study did not show Carraguard 's efficacy in prevention of vaginal transmission of HIV . No safety concerns were recorded Purpose The Manical and cohort was established to provide robust scientific data on HIV prevalence and incidence , patterns of sexual risk behaviour and the demographic impact of HIV in a sub-Saharan African population subject to a generalised HIV epidemic . The aims were later broadened to include provision of data on the coverage and effectiveness of national HIV control programmes including antiretroviral therapy ( ART ) . Participants General population open cohort located in 12 sites in Manical and , east Zimbabwe , representing 4 major socioeconomic strata ( small towns , agricultural estates , roadside settlements and subsistence farming areas ) . 9,109 of 11,453 ( 79.5 % ) eligible adults ( men 17 - 54 years ; women 15–44 years ) were recruited in a phased household census between July 1998 and January 2000 . Five rounds of follow-up of the prospect i ve household census and the open cohort were conducted at 2-year or 3-year intervals between July 2001 and November 2013 . Follow-up rates among surviving residents ranged between 77.0 % ( over 3 years ) and 96.4 % ( 2 years ) . Findings to date HIV prevalence was 25.1 % at baseline and had a substantial demographic impact with 10-fold higher mortality in HIV-infected adults than in uninfected adults and a reduction in the growth rate in the worst affected areas ( towns ) from 2.9 % to 1.0%pa . HIV infection rates have been highest in young adults with earlier commencement of sexual activity and in those with older sexual partners and larger numbers of lifetime partners . HIV prevalence has since fallen to 15.8 % and HIV incidence has also declined from 2.1 % ( 1998 - 2003 ) to 0.63 % ( 2009 - 2013 ) largely due to reduced sexual risk behaviour . HIV-associated mortality fell substantially after 2009 with increased availability of ART . Future plans We plan to extend the cohort to measure the effects on the epidemic of current and future HIV prevention and treatment programmes . Proposals for access to these data and for collaboration are welcome BACKGROUND Universal antiretroviral therapy ( ART ) , as per the 2015 WHO recommendations , might reduce population HIV incidence . We investigated the effect of universal test and treat on HIV acquisition at population level in a high prevalence rural region of South Africa . METHODS We did a phase 4 , open-label , cluster r and omised trial of 22 communities in rural KwaZulu-Natal , South Africa . We included individuals residing in the communities who were aged 16 years or older . The clusters were composed of aggregated local areas ( neighbourhoods ) that had been identified in a previous study in the Hlabisa subdistrict . The study statisticians r and omly assigned clusters ( 1:1 ) with MapInfo Pro ( version 11.0 ) to either the control or intervention communities , stratified on the basis of antenatal HIV prevalence . We offered residents repeated rapid HIV testing during home-based visits every 6 months for about 4 years in four clusters , 3 years in six clusters , and 2 years in 12 clusters ( 58 cluster-years ) and referred HIV-positive participants to trial clinics for ART ( fixed-dose combination of tenofovir , emtricitabine , and efavirenz ) regardless of CD4 cell count ( intervention ) or according to national guidelines ( initially ≤350 cells per μL and < 500 cells per μL from January , 2015 ; control ) . Participants and investigators were not masked to treatment allocation . We used dried blood spots once every 6 months provided by participants who were HIV negative at baseline to estimate the primary outcome of HIV incidence with cluster-adjusted Poisson generalised estimated equations in the intention-to-treat population after 58 cluster-years of follow-up . This study is registered with Clinical Trials.gov , number NCT01509508 , and the South African National Clinical Trials Register , number DOH-27 - 0512 - 3974 . FINDINGS Between March 9 , 2012 , and June 30 , 2016 , we contacted 26 518 ( 93 % ) of 28 419 eligible individuals . Of 17 808 ( 67 % ) individuals with a first negative dried blood spot test , 14 223 ( 80 % ) had subsequent dried blood spot tests , of whom 503 seroconverted after follow-up of 22 891 person-years . Estimated HIV incidence was 2·11 per 100 person-years ( 95 % CI 1·84 - 2·39 ) in the intervention group and 2·27 per 100 person-years ( 2·00 - 2·54 ) in the control group ( adjusted hazard ratio 1·01 , 95 % CI 0·87 - 1·17 ; p=0·89 ) . We documented one case of suicidal attempt in a woman following HIV seroconversion . 128 patients on ART had 189 life-threatening or grade 4 clinical events : 69 ( 4 % ) of 1652 in the control group and 59 ( 4 % ) of 1367 in the intervention group ( p=0·83 ) . INTERPRETATION The absence of a lowering of HIV incidence in universal test and treat clusters most likely result ed from poor linkage to care . Policy change to HIV universal test and treat without innovation to improve health access is unlikely to reduce HIV incidence . FUNDING ANRS , GiZ , and 3ie BACKGROUND Preexposure prophylaxis with antiretroviral drugs has been effective in the prevention of human immunodeficiency virus ( HIV ) infection in some trials but not in others . METHODS In this r and omized , double-blind , placebo-controlled trial , we assigned 2120 HIV-negative women in Kenya , South Africa , and Tanzania to receive either a combination of tenofovir disoproxil fumarate and emtricitabine ( TDF-FTC ) or placebo once daily . The primary objective was to assess the effectiveness of TDF-FTC in preventing HIV acquisition and to evaluate safety . RESULTS HIV infections occurred in 33 women in the TDF-FTC group ( incidence rate , 4.7 per 100 person-years ) and in 35 in the placebo group ( incidence rate , 5.0 per 100 person-years ) , for an estimated hazard ratio in the TDF-FTC group of 0.94 ( 95 % confidence interval , 0.59 to 1.52 ; P=0.81 ) . The proportions of women with nausea , vomiting , or elevated alanine aminotransferase levels were significantly higher in the TDF-FTC group ( P=0.04 , P<0.001 , and P=0.03 , respectively ) . Rates of drug discontinuation because of hepatic or renal abnormalities were higher in the TDF-FTC group ( 4.7 % ) than in the placebo group ( 3.0 % , P=0.051 ) . Less than 40 % of the HIV-uninfected women in the TDF-FTC group had evidence of recent pill use at visits that were matched to the HIV-infection window for women with seroconversion . The study was stopped early , on April 18 , 2011 , because of lack of efficacy . CONCLUSIONS Prophylaxis with TDF-FTC did not significantly reduce the rate of HIV infection and was associated with increased rates of side effects , as compared with placebo . Despite substantial counseling efforts , drug adherence appeared to be low . ( Supported by the U.S. Agency for International Development and others ; FEM-PrEP Clinical Trials.gov number , NCT00625404 . ) Introduction Prevention of acute HIV infections in pregnancy is required to achieve elimination of pediatric HIV . Identification and support for HIV negative pregnant women and their partners , particularly serodiscordant couples , are critical . A mixed method study done in Southern Mozambique estimated HIV incidence during pregnancy , associated risk factors and factors influencing partner 's HIV testing . Methods Between April 2008 and November 2011 , a prospect i ve cohort of 1230 HIV negative pregnant women was followed during pregnancy . A structured question naire , HIV testing , and collection of dried blood spots were done at 2–3 scheduled visits . HIV incidence rates were calculated by repeat HIV testing and risk factors assessed by Poisson regression . A qualitative study including 37 individual interviews with men , women , and nurses and 11 focus group discussion s ( n = 94 ) with men , women and gr and mothers explored motivators and barriers to uptake of male HIV testing . Results HIV incidence rate was estimated at 4.28/100 women-years ( 95%CI : 2.33–7.16 ) . Significant risk factors for HIV acquisition were early sexual debut ( RR 3.79 , 95%CI : 1.04–13.78 , p = 0.04 ) and living in Maputo Province ( RR 4.35 , 95%CI : 0.97–19.45 , p = 0.05 ) . Nineteen percent of women reported that their partner had tested for HIV ( 93 % knew the result with 8/213 indicating an HIV positive partner ) , 56 % said their partner had not tested and 19 % did not know their partner test status . Of the 14 seroconversions , only one reported being in a serodiscordant relationship . Fear of discrimination or stigma was reported as a key barrier to male HIV testing , while knowing the importance of getting tested and receiving care was the main motivator . Conclusions HIV incidence during pregnancy is high in Southern Mozambique , but knowledge of partners ' HIV status remains low . Knowledge of both partners ' HIV status is critical for maximal effectiveness of prevention and treatment services to reach elimination of pediatric HIV/AIDS Background The study aim ed to assess the feasibility of conducting large scale HIV prevention clinical trials in Mozambique by measuring HIV prevalence and incidence among women of reproductive age . This paper describes the baseline socio-demographic characteristics of the Mozambique Microbicides Development Programme ( MDP
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| Incidence often peaked earlier ( during teenage years ) among high-risk groups compared with general population s. Since 2005 , HIV incidence among adolescent girls and young women declined in Rakai ( Ug and a ) and Manical and ( Zimbabwe ) , and also declined among female sex workers in Kenya , but not in the highest-risk communities in South Africa and Ug and a. INTERPRETATION Few sources of direct estimates of HIV incidence exist in high-burden countries and trend analyses with disaggregated data for age and sex are rare but indicate recent declines among adolescent girls and young women .
In some of the highest-risk setting s , however , little evidence exists to suggest ART availability and other efforts slowed transmission by 2016 .
Despite wide geographical diversity in absolute levels of incidence in adolescent girls and young women , risk relative to males persisted in all setting s , with the greatest sex differentials in the youngest age groups . |
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