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: Positive psychotic symptoms , such as threat/"control-override " delusions or comm and hallucinations , have been related to aggression in patients with schizophrenia . However , retrospective data collection has hampered evaluation of the direct influence of psychopathology on aggressive behavior . In this study , we monitored aggressive behavior and psychopathology prospect ively and in close temporal proximity in 157 treatment-resistant in patients diagnosed with chronic schizophrenia or schizoaffective disorder participating in a 14-week double-blind clinical trial . Aggressive behavior was rated with the overt aggression scale ( OAS ) . Psychopathology was assessed using the positive and negative syndrome scale ( PANSS ) . At baseline , subjects who would be aggressive during the study had higher scores on only two PANSS items : hostility and poor impulse control . During the study PANSS positive subscale scores were significantly higher in aggressive subjects . Total PANSS scores were higher within 3 days of an aggressive incident , as were positive and general psychopathology subscale scores . However , in a smaller sub sample for whom PANSS ratings were available within 3 days before aggressive incidents , only scores on the PANSS positive subscale were significantly higher . These findings in chronic , treatment resistant in patients support the view that positive symptoms may lead to aggression 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 OBJECTIVE Newer antipsychotic drugs have shown promise in ameliorating neurocognitive deficits in patients with schizophrenia , but few studies have compared newer antipsychotic drugs with both clozapine and conventional agents , particularly in patients who have had suboptimal response to prior treatments . METHOD The authors examined the effects of clozapine , olanzapine , risperidone , and haloperidol on 16 measures of neurocognitive functioning in a double-blind , 14-week trial involving 101 patients . A global score was computed along with scores in four neurocognitive domains : memory , attention , motor function , and general executive and perceptual organization . RESULTS Global neurocognitive function improved with olanzapine and risperidone treatment , and these improvements were superior to those seen with haloperidol . Patients treated with olanzapine exhibited improvement in the general and attention domains but not more than that observed with other treatments . Patients treated with risperidone exhibited improvement in memory that was superior to that of both clozapine and haloperidol . Clozapine yielded improvement in motor function but not more than in other groups . Average effect sizes for change were in the small to medium range . More than half of the patients treated with olanzapine and risperidone experienced " clinical ly significant " improvement ( changes in score of at least one-half st and ard deviation relative to baseline ) . These findings did not appear to be mediated by changes in symptoms , side effects , or blood levels of medications . CONCLUSIONS Patients with a history of suboptimal response to conventional treatments may show cognitive benefits from newer antipsychotic drugs , and there may be differences between atypical antipsychotic drugs in their patterns of cognitive effects 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 BACKGROUND Acute psychotic illness , especially when associated with agitated or violent behaviour , can require urgent pharmacological tranquillisation or sedation . In several countries , clinicians often use benzodiazepines ( either alone or in combination with antipsychotics ) for this outcome . OBJECTIVES To estimate the effects of benzodiazepines , alone or in combination with antipsychotics , when compared with placebo or antipsychotics , alone or in combination with antihistamines , to control disturbed behaviour and reduce psychotic symptoms . SEARCH METHODS We search ed the Cochrane Schizophrenia Group 's register ( January 2012 ) , inspected reference lists of included and excluded studies and contacted authors of relevant studies . SELECTION CRITERIA We included all r and omised clinical trials ( RCTs ) comparing benzodiazepines alone or in combination with any antipsychotics , versus antipsychotics alone or in combination with any other antipsychotics , benzodiazepines or antihistamines , for people with acute psychotic illnesses . DATA COLLECTION AND ANALYSIS We reliably selected studies , quality assessed them and extracted data . For binary outcomes , we calculated st and ard estimates of relative risk ( RR ) and their 95 % confidence intervals ( CI ) using a fixed-effect model . For continuous outcomes , we calculated the mean difference ( MD ) between groups . If heterogeneity was identified , this was explored using a r and om-effects model . MAIN RESULTS We included 21 trials with a total of n = 1968 participants . There was no significant difference for most outcomes in the one trial that compared benzodiazepines with placebo , although there was a higher risk of no improvement in people receiving placebo in the medium term ( one to 48 hours ) ( n = 102 , 1 RCT , RR 0.62 , 95 % CI 0.40 to 0.97 , very low quality evidence ) . There was no difference in the number of participants who had not improved in the medium term when benzodiazepines were compared with antipsychotics ( n = 308 , 5 RCTs , RR 1.10 , 95 % CI 0.85 to 1.42 , low quality evidence ) ; however , people receiving benzodiazepines were less likely to experience extrapyramidal effects ( EPS ) in the medium term ( n = 536 , 8 RCTs , RR 0.15 , 95 % CI 0.06 to 0.39 , moderate quality of evidence ) . Data comparing combined benzodiazepines and antipsychotics versus benzodiazepines alone did not yield any significant results . When comparing combined benzodiazepines/antipsychotics ( all studies compared haloperidol ) with the same antipsychotics alone ( haloperidol ) , there was no difference between groups in improvement in the medium term ( n = 155 , 3 RCTs , RR 1.27 , 95 % CI 0.94 to 1.70 , very low quality evidence ) but sedation was more likely in people who received the combination therapy ( n = 172 , 3 RCTs , RR 1.75 , 95 % CI 1.14 to 2.67 , very low quality evidence ) . However , more participants receiving combined benzodiazepines and haloperidol had not improved by medium term when compared to participants receiving olanzapine ( n = 60,1 RCT , RR 25.00 , 95 % CI 1.55 to 403.99 , very low quality evidence ) or ziprasidone ( n = 60 , 1 RCT , RR 4.00 , 95 % CI 1.25 to 12.75very low quality evidence ) . When haloperidol and midazolam were compared with olanzapine , there was some evidence the combination was superior in terms of improvement , sedation and behaviour . AUTHORS ' CONCLUSIONS The evidence from trials for the use of benzodiazepines alone is not good . There were relatively little good data and most trials are too small to highlight differences in either positive or negative effects . Adding a benzodiazepine to other drugs does not seem to confer clear advantage and has potential for adding unnecessary adverse effects . Sole use of older antipsychotics unaccompanied by anticholinergic drugs seems difficult to justify . Much more high quality research is needed in this area BACKGROUND Difficulties with affect regulation and impulse control have a strong influence on violence . The objective of this study was to determine whether baseline depression and impulsivity predict aggression and whether they predict differential response to antiaggressive treatment . This is important , as we lack knowledge as to the selection of antipsychotics for the treatment of aggression . METHODS Physically aggressive in patients with schizophrenia who received an evaluation of depression and impulsivity at baseline were r and omly assigned in a double-blind , parallel group , 12-week trial to clozapine , olanzapine , or haloperidol . Trait impulsivity was measured by the Barratt Impulsiveness Scale ; depression by the Positive and Negative Syndrome Scale Depression factor . The number and severity of aggressive events , as measured by the Modified Overt Aggression Scale ( MOAS ) , were the outcome measures . RESULTS Baseline depression and impulsivity predicted higher levels of aggression , as measured by the MOAS total score , over the 12-week treatment period across all 3 medication groups . In addition , there was a strong interaction effect between baseline depression/impulsivity and medication grouping in predicting MOAS score . In particular , when higher depression and impulsivity were present at baseline , patients on haloperidol presented with more aggression than patients on the other 3 medications . CONCLUSIONS Depression and impulsivity are important predictors of aggression and of differential response to antiaggressive treatment . This is most likely due to the medications ' dissimilar neurotransmitter profiles . By identifying patients who will respond better to a given medication , we will be able to develop individualized strategies for the treatment of violent behavior BACKGROUND There has been considerable support for the observation that atypical antipsychotics have a broader range of therapeutic effects than traditional antipsychotics . We are exploring whether this exp and ed clinical efficacy can also be seen in patients with treatment-resistant schizophrenia . METHOD The subjects were 157 treatment-resistant in patients diagnosed with DSM-IV schizophrenia or schizoaffective disorder . They were r and omly assigned to treatment with clozapine , olanzapine , risperidone , or haloperidol in a 14-week double-blind trial and rated with a st and ard measure of clinical antipsychotic efficacy ( Positive and Negative Syndrome Scale [ PANSS ] ) . Factor analysis at baseline and endpoint together with changes in 5 PANSS-derived factors were examined . Data were gathered from June 1996 to December 1999 . RESULTS The underlying PANSS factor structure , as indicated by the factor loadings , was essentially identical at baseline and endpoint . At baseline , the excitement factor was followed by the positive , negative , cognitive , and depression/anxiety factors , explaining 49.4 % of the total variance . At endpoint , the positive factor was followed by the negative , excitement , cognitive , and depression/anxiety factors , explaining 55.5 % of the total variance . The endpoint data indicated statistically significant ( p < .05 ) improvements over time on the positive factor for all 3 atypicals , but not for haloperidol . The negative factor showed significant improvement for clozapine and olanzapine , with significant worsening for haloperidol . Clozapine , olanzapine , and risperidone were superior to haloperidol on the negative factor , while clozapine was also superior to risperidone . The cognitive factor showed significant improvement for all atypicals , as did the depression/anx 
    Output:
    
agent
MAIN RESULTS We have no good- quality evidence of the absolute effectiveness of haloperidol for people with long-term aggression .
When haloperidol was compared with olanzapine or clozapine , skewed data ( n=83 ) at high risk of bias suggested some advantage in terms of scale scores of unclear clinical meaning for olanzapine/clozapine for ' total aggression ' .
Although there were some data for the outcomes listed above , there were no data on most of the binary outcomes and none on service outcomes ( use of hospital/police ) , satisfaction with treatment , acceptance of treatment , quality of life or economics .
***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: Positive psychotic symptoms , such as threat/"control-override " delusions or comm and hallucinations , have been related to aggression in patients with schizophrenia . However , retrospective data collection has hampered evaluation of the direct influence of psychopathology on aggressive behavior . In this study , we monitored aggressive behavior and psychopathology prospect ively and in close temporal proximity in 157 treatment-resistant in patients diagnosed with chronic schizophrenia or schizoaffective disorder participating in a 14-week double-blind clinical trial . Aggressive behavior was rated with the overt aggression scale ( OAS ) . Psychopathology was assessed using the positive and negative syndrome scale ( PANSS ) . At baseline , subjects who would be aggressive during the study had higher scores on only two PANSS items : hostility and poor impulse control . During the study PANSS positive subscale scores were significantly higher in aggressive subjects . Total PANSS scores were higher within 3 days of an aggressive incident , as were positive and general psychopathology subscale scores . However , in a smaller sub sample for whom PANSS ratings were available within 3 days before aggressive incidents , only scores on the PANSS positive subscale were significantly higher . These findings in chronic , treatment resistant in patients support the view that positive symptoms may lead to aggression 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 OBJECTIVE Newer antipsychotic drugs have shown promise in ameliorating neurocognitive deficits in patients with schizophrenia , but few studies have compared newer antipsychotic drugs with both clozapine and conventional agents , particularly in patients who have had suboptimal response to prior treatments . METHOD The authors examined the effects of clozapine , olanzapine , risperidone , and haloperidol on 16 measures of neurocognitive functioning in a double-blind , 14-week trial involving 101 patients . A global score was computed along with scores in four neurocognitive domains : memory , attention , motor function , and general executive and perceptual organization . RESULTS Global neurocognitive function improved with olanzapine and risperidone treatment , and these improvements were superior to those seen with haloperidol . Patients treated with olanzapine exhibited improvement in the general and attention domains but not more than that observed with other treatments . Patients treated with risperidone exhibited improvement in memory that was superior to that of both clozapine and haloperidol . Clozapine yielded improvement in motor function but not more than in other groups . Average effect sizes for change were in the small to medium range . More than half of the patients treated with olanzapine and risperidone experienced " clinical ly significant " improvement ( changes in score of at least one-half st and ard deviation relative to baseline ) . These findings did not appear to be mediated by changes in symptoms , side effects , or blood levels of medications . CONCLUSIONS Patients with a history of suboptimal response to conventional treatments may show cognitive benefits from newer antipsychotic drugs , and there may be differences between atypical antipsychotic drugs in their patterns of cognitive effects 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 BACKGROUND Acute psychotic illness , especially when associated with agitated or violent behaviour , can require urgent pharmacological tranquillisation or sedation . In several countries , clinicians often use benzodiazepines ( either alone or in combination with antipsychotics ) for this outcome . OBJECTIVES To estimate the effects of benzodiazepines , alone or in combination with antipsychotics , when compared with placebo or antipsychotics , alone or in combination with antihistamines , to control disturbed behaviour and reduce psychotic symptoms . SEARCH METHODS We search ed the Cochrane Schizophrenia Group 's register ( January 2012 ) , inspected reference lists of included and excluded studies and contacted authors of relevant studies . SELECTION CRITERIA We included all r and omised clinical trials ( RCTs ) comparing benzodiazepines alone or in combination with any antipsychotics , versus antipsychotics alone or in combination with any other antipsychotics , benzodiazepines or antihistamines , for people with acute psychotic illnesses . DATA COLLECTION AND ANALYSIS We reliably selected studies , quality assessed them and extracted data . For binary outcomes , we calculated st and ard estimates of relative risk ( RR ) and their 95 % confidence intervals ( CI ) using a fixed-effect model . For continuous outcomes , we calculated the mean difference ( MD ) between groups . If heterogeneity was identified , this was explored using a r and om-effects model . MAIN RESULTS We included 21 trials with a total of n = 1968 participants . There was no significant difference for most outcomes in the one trial that compared benzodiazepines with placebo , although there was a higher risk of no improvement in people receiving placebo in the medium term ( one to 48 hours ) ( n = 102 , 1 RCT , RR 0.62 , 95 % CI 0.40 to 0.97 , very low quality evidence ) . There was no difference in the number of participants who had not improved in the medium term when benzodiazepines were compared with antipsychotics ( n = 308 , 5 RCTs , RR 1.10 , 95 % CI 0.85 to 1.42 , low quality evidence ) ; however , people receiving benzodiazepines were less likely to experience extrapyramidal effects ( EPS ) in the medium term ( n = 536 , 8 RCTs , RR 0.15 , 95 % CI 0.06 to 0.39 , moderate quality of evidence ) . Data comparing combined benzodiazepines and antipsychotics versus benzodiazepines alone did not yield any significant results . When comparing combined benzodiazepines/antipsychotics ( all studies compared haloperidol ) with the same antipsychotics alone ( haloperidol ) , there was no difference between groups in improvement in the medium term ( n = 155 , 3 RCTs , RR 1.27 , 95 % CI 0.94 to 1.70 , very low quality evidence ) but sedation was more likely in people who received the combination therapy ( n = 172 , 3 RCTs , RR 1.75 , 95 % CI 1.14 to 2.67 , very low quality evidence ) . However , more participants receiving combined benzodiazepines and haloperidol had not improved by medium term when compared to participants receiving olanzapine ( n = 60,1 RCT , RR 25.00 , 95 % CI 1.55 to 403.99 , very low quality evidence ) or ziprasidone ( n = 60 , 1 RCT , RR 4.00 , 95 % CI 1.25 to 12.75very low quality evidence ) . When haloperidol and midazolam were compared with olanzapine , there was some evidence the combination was superior in terms of improvement , sedation and behaviour . AUTHORS ' CONCLUSIONS The evidence from trials for the use of benzodiazepines alone is not good . There were relatively little good data and most trials are too small to highlight differences in either positive or negative effects . Adding a benzodiazepine to other drugs does not seem to confer clear advantage and has potential for adding unnecessary adverse effects . Sole use of older antipsychotics unaccompanied by anticholinergic drugs seems difficult to justify . Much more high quality research is needed in this area BACKGROUND Difficulties with affect regulation and impulse control have a strong influence on violence . The objective of this study was to determine whether baseline depression and impulsivity predict aggression and whether they predict differential response to antiaggressive treatment . This is important , as we lack knowledge as to the selection of antipsychotics for the treatment of aggression . METHODS Physically aggressive in patients with schizophrenia who received an evaluation of depression and impulsivity at baseline were r and omly assigned in a double-blind , parallel group , 12-week trial to clozapine , olanzapine , or haloperidol . Trait impulsivity was measured by the Barratt Impulsiveness Scale ; depression by the Positive and Negative Syndrome Scale Depression factor . The number and severity of aggressive events , as measured by the Modified Overt Aggression Scale ( MOAS ) , were the outcome measures . RESULTS Baseline depression and impulsivity predicted higher levels of aggression , as measured by the MOAS total score , over the 12-week treatment period across all 3 medication groups . In addition , there was a strong interaction effect between baseline depression/impulsivity and medication grouping in predicting MOAS score . In particular , when higher depression and impulsivity were present at baseline , patients on haloperidol presented with more aggression than patients on the other 3 medications . CONCLUSIONS Depression and impulsivity are important predictors of aggression and of differential response to antiaggressive treatment . This is most likely due to the medications ' dissimilar neurotransmitter profiles . By identifying patients who will respond better to a given medication , we will be able to develop individualized strategies for the treatment of violent behavior BACKGROUND There has been considerable support for the observation that atypical antipsychotics have a broader range of therapeutic effects than traditional antipsychotics . We are exploring whether this exp and ed clinical efficacy can also be seen in patients with treatment-resistant schizophrenia . METHOD The subjects were 157 treatment-resistant in patients diagnosed with DSM-IV schizophrenia or schizoaffective disorder . They were r and omly assigned to treatment with clozapine , olanzapine , risperidone , or haloperidol in a 14-week double-blind trial and rated with a st and ard measure of clinical antipsychotic efficacy ( Positive and Negative Syndrome Scale [ PANSS ] ) . Factor analysis at baseline and endpoint together with changes in 5 PANSS-derived factors were examined . Data were gathered from June 1996 to December 1999 . RESULTS The underlying PANSS factor structure , as indicated by the factor loadings , was essentially identical at baseline and endpoint . At baseline , the excitement factor was followed by the positive , negative , cognitive , and depression/anxiety factors , explaining 49.4 % of the total variance . At endpoint , the positive factor was followed by the negative , excitement , cognitive , and depression/anxiety factors , explaining 55.5 % of the total variance . The endpoint data indicated statistically significant ( p < .05 ) improvements over time on the positive factor for all 3 atypicals , but not for haloperidol . The negative factor showed significant improvement for clozapine and olanzapine , with significant worsening for haloperidol . Clozapine , olanzapine , and risperidone were superior to haloperidol on the negative factor , while clozapine was also superior to risperidone . The cognitive factor showed significant improvement for all atypicals , as did the depression/anx 
    Output:
    