human
***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 This study evaluated the efficacy and safety of risperidone monotherapy in the treatment of acute bipolar mania . METHOD Patients with DSM-IV bipolar I disorder experiencing an acute manic episode ( baseline Young Mania Rating Scale score > /== " BORDER="0">20 ) were r and omly assigned to 3 weeks of treatment with risperidone ( flexible dose : 1 - 6 mg/day ) or placebo . The primary efficacy measure was the mean baseline-to-endpoint change in total score on the Young Mania Rating Scale . Secondary efficacy measures included the Clinical Global Impression ( CGI ) severity rating and scores on the Montgomery-Asberg Depression Rating Scale , Positive and Negative Syndrome Scale , and Global Assessment Scale ( GAS ) . Safety assessment s consisted of monitoring adverse events , vital signs , electrocardiogram and laboratory results , and scores on the Extrapyramidal Symptom Rating Scale . RESULTS Subjects ( N=259 ) received treatment with either risperidone ( N=134 ) or placebo ( N=125 ) . The mean modal dose of risperidone was 4.1 mg/day . Improvement in mean Young Mania Rating Scale total score ( adjusted for covariates ) was significantly greater in the risperidone than in the placebo group at endpoint ( mean change=-10.6 [ SD=9.5 ] versus -4.8 [ SD=9.5 ] , respectively ) , with significant between-group differences seen as early as 3 days after start of treatment ( change with risperidone : mean=-6.8 [ SD=5.8 ] ; change with placebo : mean=-4.0 [ SD=5.8 ] ) and continuing throughout all time points . Improvements in CGI severity ratings and scores on the Montgomery-Asberg Depression Rating Scale , Positive and Negative Syndrome Scale , and GAS were also significantly greater among patients receiving risperidone than those given placebo . The most common adverse event reported among risperidone patients was somnolence . While Extrapyramidal Symptom Rating Scale scores were significantly greater in patients receiving risperidone , mean total and subscale scores were low . CONCLUSIONS Risperidone monotherapy was significantly more efficacious than placebo in the treatment of acute mania and demonstrated a rapid onset of action . Risperidone was well tolerated by patients in this study Recent empirical evidence supports the importance of adequate r and omization in controlled trials . Trials with inadequate allocation concealment have been associated with larger treatment effects compared with trials in which authors reported adequate allocation concealment . While that provides empirical evidence of bias being interjected into trials , trial investigators rarely document the sensitive details of subverting the intended purpose of r and omization . This article relates anonymous accounts run the gamut from simple to intricate operations , from transillumination of envelopes to search ing for code in the office files of the principal investigator . They indicate that deciphering is something more frequent than a rate occurrence . These accounts prompt some method ological recommendations to help prevent deciphering . R and omized controlled trials appear to annoy human nature -- if properly conducted , indeed they should 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 Abstract : Quetiapine ( QTP ) combined with lithium ( Li ) or divalproex ( DVP ) for the treatment of mania was evaluated in 2 double-blind , placebo-controlled studies . Patients were r and omized to 3 or 6 weeks of treatment with QTP plus Li/DVP or placebo ( PBO ) plus Li/DVP . Quetiapine was dosed up to 800 mg/d ; Li was dosed to achieve serum concentrations of 0.7 - 1.0 mEq/L and DVP to 50 - 100 μg/mL. A total of 402 patients were r and omized : 197 to QTP + Li/DVP and 205 to PBO + Li/DVP . The mean quetiapine dose in responders was 492 ( ±204 ) mg/d . Improvement in the Young Mania Rating Scale ( YMRS ) at day 21 in the QTP + Li/DVP group ( −15.29 ) was statistically superior to the PBO + Li/DVP group ( −12.19 ) ( P < 0.05 ) . A statistically significant difference in favor of quetiapine was observed within the first week ( P < 0.05 ) . Significantly more QTP + Li/DVP patients achieved a response ( ≥50 % decrease in the YMRS ) at day 21 ( QTP + Li/DVP , 55.7 % ; PBO + Li/DVP , 41.6%;P < 0.01 ) . Improvements in Clinical Global Impression-Bipolar Severity of Illness scores by day 21 were also significantly greater in QTP + Li/DVP-treated patients ( −1.59 ) versus PBO + Li/DVP ( −1.19 ) ( P < 0.01 ) . Common adverse events ( ≥5 % and twice that in the PBO + Li/DVP group ) in the QTP + Li/DVP group were somnolence , dry mouth , and asthenia . Quetiapine combined with Li/DVP was not associated with extrapyramidal symptoms ( including akathisia ) or emergent depression . More QTP + Li/DVP-treated patients completed the trial , and there was no difference in discontinuation rates due to adverse events between the two groups . Quetiapine , in combination with lithium or divalproex , is well tolerated and has superior efficacy to lithium or divalproex alone in the treatment of bipolar mania BACKGROUND Despite several treatmentoptions , adherenceto therapy is poor in patients with bipolar disorder . AIMS A double-blind , controlled comparison of aripiprazole and haloperidol in patients with bipolar I disorder experiencing acute manic or mixed episodes . METHOD Patients ( n=347 ) were r and omised to receive aripiprazole or haloperidol  in this 12-week , multicentre study . The primary outcome measure was the number of patients in response ( greater , similar 50 % improvement from baseline in Young Mania Rating Scale score ) and receiving therapy at week 12 . RESULTS At week 12 , significantly more patients taking aripiprazole ( 49.7 % ) were in response and receiving therapy compared with those taking haloperidol ( 28.4 % ; P < 0.001 ) . Continuation rates differed markedly between treatments ( week 12 : aripiprazole , 50.9 % ; haloperidol , 29.1 % ) . Extrapyramidal adverse events were more frequent with haloperidol than aripiprazole ( 62.7 % v. 24.0 % ) . CONCLUSIONS Aripiprazole showed superior levels of response and tolerability to haloperidol in the treatment of an acute manic episode for up to 12 weeks OBJECTIVE Evaluate the efficacy and tolerability of quetiapine ( QTP ) combined with lithium ( Li ) or divalproex ( DVP ) in the treatment of acute mania . METHODS Patients were r and omized to 21 days of double-blind treatment with QTP plus Li/DVP , or placebo ( PBO ) plus Li/DVP . QTP was rapidly dosed up to a maximum of 800 mg/day ; Li was dosed to 0.7 - 1.0 mEq/L ; or DVP to 50 - 100 microg/mL. RESULTS Fifty-six of 91 ( 61.5 % ) individuals in the  QTP + Li/DVP group compared with 49 of 100 ( 49 % ) taking PBO + Li/DVP  completed the study . A significantly greater mean reduction in total Young Mania Rating Scale ( YMRS ) score was observed at end-point in patients receiving QTP + Li/DVP compared with those in the PBO + Li/DVP group ( -13.76 versus -9.93 ; p = 0.021 ) . The response rate ( > or = 50 % YMRS improvement ) was significantly higher in the QTP + Li/DVP group than in PBO + Li/DVP-treated patients ( 54.3 % versus 32.6 % ; p = 0.005 ) , as was the proportion of patients achieving clinical remission ( YMRS < 12 ) ( 45.7 % versus 25.8 % ; p = 0.007 ) . Patients receiving QTP + Li/DVP also had a significantly greater improvement in Clinical Global Impressions-Bipolar ( CGI-BP ) Severity of Illness scores ( -1.38 versus -0.78 ; p = 0.001 ) . The mean last-week dose of QTP was 584 mg/day in patients meeting response criteria . Common adverse events ( at least 10 % and twice the rate of Li/DVP ) in the QTP + Li/DVP group included somnolence , dry mouth , asthenia , and postural hypotension . CONCLUSIONS Quetiapine combined with either Li or DVP has superior efficacy compared with Li or DVP monotherapy for treating patients with bipolar mania . Combination therapy was well-tolerated and most adverse events were mild , withdrawal because of adverse events being only 5 % compared with 6 % on Li or DVP monotherapy BACKGROUND Traditional and largely qualitative review s of evidence are now giving way to much more structured systematic overviews that use a quantitative method to calculate the overall effect of treatment . The latter approach is dependent on the quality of primary studies , which may introduce bias if they are of poor method ologic quality . OBJECTIVE To test the hypothesis that the inclusion of poor- quality trials in meta-analyses would bias the conclusions and produce incorrect estimates of treatment effect . METHODS An overview of r and omized trials of antiestrogen therapy in subfertile men with oligospermia was performed to test the hypothesis . Data sources included online search ing of MEDLINE and Science Citation Index data bases between 1966 and 1994 , scanning the bibliography of known primary studies and review articles , and contacting experts in the field . After independent , blind assessment , nine of 149 originally identified studies met the inclusion criteria and were selected . We assessed study quality independently . Outcome data from each study were pooled and statistically summarized . RESULTS There was a marginal improvement in pregnancy rate with antiestrogen treatment ( odds ratio , 1.6 ; 95 % confidence interval , 0.9 to 2.6 ) . Sensitivity analyses on the basis of method ologic quality demonstrated that poor- quality studies produced a positive effect with treatment , whereas no benefit was observed with high- quality studies . CONCLUSION The results of a meta- analysis are influenced by the quality of the primary studies included . Method ologically , poor studies tend to exaggerate the overall estimate of treatment effect and may lead to incorrect inferences & NA ; The objective was to investigate the relationship between pain relief scores produced by placebo and by active interventions in r and omised controlled trials ( RCTs ) . Individual patient categorical pain relief scores from 5 placebo‐controlled single‐dose parallel‐group RCTs in acute postoperative pain were used to calculate the percentage of the maximum possible pain relief score ( % maxTOTPAR ) for the different treatments . One hundred and thirty of the 525 patients in the 5 trials had a placebo .  Individual patients ' scores with placebo varied from 0 to 100 % of the maximum possible pain relief . The proportion who obtained more than 50 % of the maximum possible pain relief with placebo varied from 7 % to 37 % across the trials ; with the active drugs the variation was from 5 to 63 % . Mean placebo scores were related to the mean score for the active treatments in each study ; the higher the mean active score , the higher the mean placebo score . This relationship disappeared when median values were used . Medical folklore has it that the amount of relief obtained 
    Output:
    
agent
In maintenance trials atypical antipsychotics had significantly fewer relapses to depression or mania than placebo or active comparator .
Conclusion Atypical antipsychotics are effective in treating both phases of bipolar disorder compared with placebo , and as effective as established drug therapies .
Atypical antipsychotics produce fewer extrapyramidal symptoms , but weight gain is more common ( with olanzapine ) .
There is insufficient data confidently to distinguish between different atypical antipsychotics
***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 This study evaluated the efficacy and safety of risperidone monotherapy in the treatment of acute bipolar mania . METHOD Patients with DSM-IV bipolar I disorder experiencing an acute manic episode ( baseline Young Mania Rating Scale score > /== " BORDER="0">20 ) were r and omly assigned to 3 weeks of treatment with risperidone ( flexible dose : 1 - 6 mg/day ) or placebo . The primary efficacy measure was the mean baseline-to-endpoint change in total score on the Young Mania Rating Scale . Secondary efficacy measures included the Clinical Global Impression ( CGI ) severity rating and scores on the Montgomery-Asberg Depression Rating Scale , Positive and Negative Syndrome Scale , and Global Assessment Scale ( GAS ) . Safety assessment s consisted of monitoring adverse events , vital signs , electrocardiogram and laboratory results , and scores on the Extrapyramidal Symptom Rating Scale . RESULTS Subjects ( N=259 ) received treatment with either risperidone ( N=134 ) or placebo ( N=125 ) . The mean modal dose of risperidone was 4.1 mg/day . Improvement in mean Young Mania Rating Scale total score ( adjusted for covariates ) was significantly greater in the risperidone than in the placebo group at endpoint ( mean change=-10.6 [ SD=9.5 ] versus -4.8 [ SD=9.5 ] , respectively ) , with significant between-group differences seen as early as 3 days after start of treatment ( change with risperidone : mean=-6.8 [ SD=5.8 ] ; change with placebo : mean=-4.0 [ SD=5.8 ] ) and continuing throughout all time points . Improvements in CGI severity ratings and scores on the Montgomery-Asberg Depression Rating Scale , Positive and Negative Syndrome Scale , and GAS were also significantly greater among patients receiving risperidone than those given placebo . The most common adverse event reported among risperidone patients was somnolence . While Extrapyramidal Symptom Rating Scale scores were significantly greater in patients receiving risperidone , mean total and subscale scores were low . CONCLUSIONS Risperidone monotherapy was significantly more efficacious than placebo in the treatment of acute mania and demonstrated a rapid onset of action . Risperidone was well tolerated by patients in this study Recent empirical evidence supports the importance of adequate r and omization in controlled trials . Trials with inadequate allocation concealment have been associated with larger treatment effects compared with trials in which authors reported adequate allocation concealment . While that provides empirical evidence of bias being interjected into trials , trial investigators rarely document the sensitive details of subverting the intended purpose of r and omization . This article relates anonymous accounts run the gamut from simple to intricate operations , from transillumination of envelopes to search ing for code in the office files of the principal investigator . They indicate that deciphering is something more frequent than a rate occurrence . These accounts prompt some method ological recommendations to help prevent deciphering . R and omized controlled trials appear to annoy human nature -- if properly conducted , indeed they should 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 Abstract : Quetiapine ( QTP ) combined with lithium ( Li ) or divalproex ( DVP ) for the treatment of mania was evaluated in 2 double-blind , placebo-controlled studies . Patients were r and omized to 3 or 6 weeks of treatment with QTP plus Li/DVP or placebo ( PBO ) plus Li/DVP . Quetiapine was dosed up to 800 mg/d ; Li was dosed to achieve serum concentrations of 0.7 - 1.0 mEq/L and DVP to 50 - 100 μg/mL. A total of 402 patients were r and omized : 197 to QTP + Li/DVP and 205 to PBO + Li/DVP . The mean quetiapine dose in responders was 492 ( ±204 ) mg/d . Improvement in the Young Mania Rating Scale ( YMRS ) at day 21 in the QTP + Li/DVP group ( −15.29 ) was statistically superior to the PBO + Li/DVP group ( −12.19 ) ( P < 0.05 ) . A statistically significant difference in favor of quetiapine was observed within the first week ( P < 0.05 ) . Significantly more QTP + Li/DVP patients achieved a response ( ≥50 % decrease in the YMRS ) at day 21 ( QTP + Li/DVP , 55.7 % ; PBO + Li/DVP , 41.6%;P < 0.01 ) . Improvements in Clinical Global Impression-Bipolar Severity of Illness scores by day 21 were also significantly greater in QTP + Li/DVP-treated patients ( −1.59 ) versus PBO + Li/DVP ( −1.19 ) ( P < 0.01 ) . Common adverse events ( ≥5 % and twice that in the PBO + Li/DVP group ) in the QTP + Li/DVP group were somnolence , dry mouth , and asthenia . Quetiapine combined with Li/DVP was not associated with extrapyramidal symptoms ( including akathisia ) or emergent depression . More QTP + Li/DVP-treated patients completed the trial , and there was no difference in discontinuation rates due to adverse events between the two groups . Quetiapine , in combination with lithium or divalproex , is well tolerated and has superior efficacy to lithium or divalproex alone in the treatment of bipolar mania BACKGROUND Despite several treatmentoptions , adherenceto therapy is poor in patients with bipolar disorder . AIMS A double-blind , controlled comparison of aripiprazole and haloperidol in patients with bipolar I disorder experiencing acute manic or mixed episodes . METHOD Patients ( n=347 ) were r and omised to receive aripiprazole or haloperidol  in this 12-week , multicentre study . The primary outcome measure was the number of patients in response ( greater , similar 50 % improvement from baseline in Young Mania Rating Scale score ) and receiving therapy at week 12 . RESULTS At week 12 , significantly more patients taking aripiprazole ( 49.7 % ) were in response and receiving therapy compared with those taking haloperidol ( 28.4 % ; P < 0.001 ) . Continuation rates differed markedly between treatments ( week 12 : aripiprazole , 50.9 % ; haloperidol , 29.1 % ) . Extrapyramidal adverse events were more frequent with haloperidol than aripiprazole ( 62.7 % v. 24.0 % ) . CONCLUSIONS Aripiprazole showed superior levels of response and tolerability to haloperidol in the treatment of an acute manic episode for up to 12 weeks OBJECTIVE Evaluate the efficacy and tolerability of quetiapine ( QTP ) combined with lithium ( Li ) or divalproex ( DVP ) in the treatment of acute mania . METHODS Patients were r and omized to 21 days of double-blind treatment with QTP plus Li/DVP , or placebo ( PBO ) plus Li/DVP . QTP was rapidly dosed up to a maximum of 800 mg/day ; Li was dosed to 0.7 - 1.0 mEq/L ; or DVP to 50 - 100 microg/mL. RESULTS Fifty-six of 91 ( 61.5 % ) individuals in the  QTP + Li/DVP group compared with 49 of 100 ( 49 % ) taking PBO + Li/DVP  completed the study . A significantly greater mean reduction in total Young Mania Rating Scale ( YMRS ) score was observed at end-point in patients receiving QTP + Li/DVP compared with those in the PBO + Li/DVP group ( -13.76 versus -9.93 ; p = 0.021 ) . The response rate ( > or = 50 % YMRS improvement ) was significantly higher in the QTP + Li/DVP group than in PBO + Li/DVP-treated patients ( 54.3 % versus 32.6 % ; p = 0.005 ) , as was the proportion of patients achieving clinical remission ( YMRS < 12 ) ( 45.7 % versus 25.8 % ; p = 0.007 ) . Patients receiving QTP + Li/DVP also had a significantly greater improvement in Clinical Global Impressions-Bipolar ( CGI-BP ) Severity of Illness scores ( -1.38 versus -0.78 ; p = 0.001 ) . The mean last-week dose of QTP was 584 mg/day in patients meeting response criteria . Common adverse events ( at least 10 % and twice the rate of Li/DVP ) in the QTP + Li/DVP group included somnolence , dry mouth , asthenia , and postural hypotension . CONCLUSIONS Quetiapine combined with either Li or DVP has superior efficacy compared with Li or DVP monotherapy for treating patients with bipolar mania . Combination therapy was well-tolerated and most adverse events were mild , withdrawal because of adverse events being only 5 % compared with 6 % on Li or DVP monotherapy BACKGROUND Traditional and largely qualitative review s of evidence are now giving way to much more structured systematic overviews that use a quantitative method to calculate the overall effect of treatment . The latter approach is dependent on the quality of primary studies , which may introduce bias if they are of poor method ologic quality . OBJECTIVE To test the hypothesis that the inclusion of poor- quality trials in meta-analyses would bias the conclusions and produce incorrect estimates of treatment effect . METHODS An overview of r and omized trials of antiestrogen therapy in subfertile men with oligospermia was performed to test the hypothesis . Data sources included online search ing of MEDLINE and Science Citation Index data bases between 1966 and 1994 , scanning the bibliography of known primary studies and review articles , and contacting experts in the field . After independent , blind assessment , nine of 149 originally identified studies met the inclusion criteria and were selected . We assessed study quality independently . Outcome data from each study were pooled and statistically summarized . RESULTS There was a marginal improvement in pregnancy rate with antiestrogen treatment ( odds ratio , 1.6 ; 95 % confidence interval , 0.9 to 2.6 ) . Sensitivity analyses on the basis of method ologic quality demonstrated that poor- quality studies produced a positive effect with treatment , whereas no benefit was observed with high- quality studies . CONCLUSION The results of a meta- analysis are influenced by the quality of the primary studies included . Method ologically , poor studies tend to exaggerate the overall estimate of treatment effect and may lead to incorrect inferences & NA ; The objective was to investigate the relationship between pain relief scores produced by placebo and by active interventions in r and omised controlled trials ( RCTs ) . Individual patient categorical pain relief scores from 5 placebo‐controlled single‐dose parallel‐group RCTs in acute postoperative pain were used to calculate the percentage of the maximum possible pain relief score ( % maxTOTPAR ) for the different treatments . One hundred and thirty of the 525 patients in the 5 trials had a placebo .  Individual patients ' scores with placebo varied from 0 to 100 % of the maximum possible pain relief . The proportion who obtained more than 50 % of the maximum possible pain relief with placebo varied from 7 % to 37 % across the trials ; with the active drugs the variation was from 5 to 63 % . Mean placebo scores were related to the mean score for the active treatments in each study ; the higher the mean active score , the higher the mean placebo score . This relationship disappeared when median values were used . Medical folklore has it that the amount of relief obtained 
    Output:
    