***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 Despite the frequent use of the Positive and Negative Syndrome Scale ( PANSS ) for rating the symptoms of schizophrenia , the clinical meaning of its total score and of the cut-offs that are used to define treatment response ( e.g. at least 20 % or 50 % reduction of the baseline score ) are as yet unclear . We therefore compared the PANSS with simultaneous ratings of Clinical Global Impressions ( CGI ) . METHOD PANSS and CGI ratings at baseline ( n = 4091 ) , and after one , two , four and six weeks of treatment taken from a pooled data base of seven pivotal , multi-center antipsychotic drug trials on olanzapine or amisulpride in patients with exacerbations of schizophrenia were compared using equipercentile linking . RESULTS Being considered " mildly ill " according to the CGI approximately corresponded to a PANSS total score of 58 , " moderately ill " to a PANSS of 75 , " markedly ill " to a PANSS of 95 and severely ill to a PANSS of 116 . To be " minimally improved " according to the CGI score was associated with a mean percentage PANSS reduction of 19 % , 23 % , 26 % and 28 % at weeks 1 , 2 , 4 and 6 , respectively . The corresponding figures for a CGI rating " much improved " were 40 % , 45 % , 51 % and 53 % . CONCLUSIONS The results provide a better framework for underst and ing the clinical meaning of the PANSS total score in drug trials of schizophrenia patients with acute exacerbations . Such studies may ideally use at least a 50 % reduction from baseline cut-off to define response rather than lower thresholds . In treatment resistant population s , however , even a small improvement can be important , so that a 25 % cut-off might be appropriate 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 authors estimated components of variance and intraclass correlation coefficients ( ICCs ) to aid in the design of complex surveys and community intervention studies by analyzing data from the Health Survey for Engl and 1994 . This cross-sectional survey of English adults included data on a range of lifestyle risk factors and health outcomes . For the survey , households were sample d in 720 postal code sectors nested within 177 district health authorities and 14 regional health authorities . Study subjects were adults aged 16 years or more .  ICCs and components of variance were estimated from a nested r and om-effects analysis of variance . Results are presented at the district health authority , postal code sector , and household levels . Between-cluster variation was evident at each level of clustering . In these data , ICCs were inversely related to cluster size , but design effects could be substantial when the cluster size was large . Most ICCs were below 0.01 at the district health authority level , and they were mostly below 0.05 at the postal code sector level . At the household level , many ICCs were in the range of 0.0 - 0.3 . These data may provide useful information for the design of epidemiologic studies in which the units sample d or allocated range in size from households to large administrative areas OBJECTIVE This 6-week trial assessed the efficacy , tolerability , and safety of the investigational psychopharmacologic agent asenapine versus placebo and risperidone in patients with acute schizophrenia ( DSM-IV criteria ) . METHOD In a study conducted from August 2001 to May 2002 , patients were r and omly assigned to receive sublingual asenapine 5 mg b.i.d . , placebo b.i.d . , or oral risperidone 3 mg b.i.d . The primary outcome measure was improvement from baseline in Positive and Negative Syndrome Scale ( PANSS ) total score . Secondary outcomes included changes in Clinical Global Impressions-Severity of Illness ( CGI-S ) score and scores on PANSS positive , negative , and general psychopathology subscales . RESULTS The intent-to-treat population comprised 174 patients who received > or= 1 dose of study drug and > or= 1 postbaseline assessment . At study end or last observation , mean improvements on PANSS total , negative subscale , and general psychopathology subscale scores were all significantly greater with asenapine than with placebo ( p < .005 , p = .01 , and p < .005 , respectively ) . Compared with placebo , improvements on CGI-S and PANSS positive subscale scores were significantly greater with both asenapine ( p < .01 and p = .01 ) and risperidone ( p < .005 and p < .05 ) . Overall incidence rates of adverse events were comparable for asenapine and placebo , whereas risperidone was associated with substantial weight gain and prolactin elevation . CONCLUSION Asenapine was effective and well tolerated in patients with acute schizophrenia and may provide a new option for control of negative symptoms OBJECTIVE Long-term efficacy of asenapine in preventing  schizophrenia  relapse was assessed in a 26-week double-blind , placebo-controlled trial that followed 26 weeks of open-label treatment . METHOD Stable schizophrenia patients ( DSM-IV-TR criteria ) who were cross-titrated from previous medication to sublingual asenapine and remained stable during 26 weeks of open-label treatment were eligible for 26 weeks of double-blind treatment , with r and omization to continued asenapine or switch to placebo .  Time to relapse/impending relapse ( primary endpoint , as usually determined by specific scores on the Positive and Negative Syndrome Scale and the Clinical Global Impressions-Severity of Illness Scale ) and discontinuation for any reason ( key secondary endpoint ) were assessed by survival analyses for asenapine versus placebo . The study was conducted from May 2005 through June 2008 . RESULTS Of 700 enrolled patients treated with open-label asenapine , 386 entered ( asenapine , n = 194 ; placebo , n = 192 ) and 207 completed ( n = 135 ; n = 72 ) the double-blind phase . Times to relapse/impending relapse and discontinuation for any reason were significantly longer with asenapine than with placebo ( both P < .0001 ) . Incidence of relapse/impending relapse was lower with asenapine than placebo ( 12.1 % vs 47.4 % , P < .0001 ) . The modal dosage of asenapine was 10 mg twice daily in both phases . During the double-blind phase , the incidence of adverse events ( AEs ) considered serious with asenapine and placebo was 3.1 % and 9.9 % , respectively ; incidence of extrapyramidal symptom-related AEs was 3.1 % and 4.7 % , respectively . The most frequently reported AEs with asenapine versus placebo were anxiety ( 8.2 % ; 10.9 % ) , increased weight ( 6.7 % ; 3.6 % ) , and insomnia ( 6.2 % ; 13.5 % ) . The incidence of clinical ly significant weight gain ( ≥ 7 % increase from double-blind baseline ) was 3.7 % with asenapine and 0.5 % with placebo . CONCLUSIONS Long-term treatment with asenapine was more effective than placebo in preventing relapse of schizophrenia and appeared to be safe and well tolerated . TRIAL REGISTRATION clinical trials.gov Identifier NCT00150176 BACKGROUND In two double-blind trials conducted in North America , 513 patients with chronic schizophrenia received risperidone , haloperidol , or placebo . In the present study , combined data from the two trials were analyzed . METHOD Patients were r and omly assigned to receive placebo , fixed doses of risperidone ( 2 , 6 , 10 , and 16 mg/day ) or 20 mg/day of haloperidol for 8 weeks . Factor analysis of scores on the Positive and Negative Syndrome Scale ( PANSS ) produced five dimensions ( negative symptoms , positive symptoms , disorganized thought , uncontrolled hostility/excitement , and anxiety/depression ) , similar to the five dimensions of previous factor-analytic studies of PANSS data . RESULTS Mean changes ( symptom reductions ) in PANSS factor scores from baseline to treatment Weeks 6 and 8 were significantly greater in patients receiving 6 - 16 mg/day of risperidone than in patients receiving placebo or haloperidol . The advantages of risperidone were greatest for negative symptoms , uncontrolled hostility/excitement , and anxiety/depression . Even at the lowest dose , 2 mg/day , risperidone was significantly ( p < or = .05 ) superior to haloperidol in reducing negative symptoms . The differences in outcomes between risperidone and haloperidol on PANSS scores were not related to extrapyramidal symptoms . CONCLUSION Risperidone produced significantly ( p < or = .05 ) greater improvements than haloperidol on all five dimensions . The large between-group differences on negative symptoms , hostility/excitement , and anxiety/depression suggest that risperidone and other serotonin/dopamine antagonists have qualitatively different effects from those of conventional antipsychotic agents A modification of an earlier rating scale for extrapyramidal system disturbance is described , and evidence for the validity and reliability of the scale is presented . The usefulness of the scale in studies of neuroleptic drugs is discussed . By its application it is possible to quantify extrapyramidal side effects and to separate them into four principal factors BACKGROUND A recent review suggested an association between using unpublished scales in clinical trials and finding significant results . AIMS To determine whether such an association existed in schizophrenia trials . METHOD Three hundred trials were r and omly selected from the Cochrane Schizophrenia Group 's Register . All comparisons between treatment groups and control groups using rating scales  were identified . The publication status of each scale was determined and cl aims of a significant treatment effect were recorded . RESULTS Trials were more likely to report that a treatment was superior to control when an unpublished scale was used to make the comparison ( relative risk 1.37 ( 95 % CI 1.12 - 1.68 ) ) . This effect increased when a ' gold-st and ard ' definition of treatment superiority was applied ( RR 1.94 ( 95 % CI 1.35 - 2.79 ) ) . In non-pharmacological trials , one-third of ' gold-st and ard ' cl aims of treatment superiority would not have been made if published scales had been used . CONCLUSIONS Unpublished scales are a source of bias in schizophrenia trials 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 
    Output:
    
AUTHORS ' CONCLUSIONS There is some , albeit preliminary , evidence that asenapine provides an improvement in positive , negative , and depressive symptoms , whilst minimising the risk of adverse effects .
However due to the low- quality and limited quantity of evidence , it remains difficult to recommend the use of asenapine for people with schizophrenia .