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: We have investigated the action of pimozide in  tardive dyskinesia induced by prolonged administration of phenothiazines .  Improvement was recorded in a double blind study of 18 patients treated with maximum tolerated dosage ( mean 18.8 mg/day ) for 6 weeks . There was no deterioration in the therapeutic action of pimozide over this time . Parkinsonism and sedation were the main adverse effects . They were corrected by reduction of the dose of pimozide , but often recurred so that further adjustments of dosage were necessary . Our findings support the view that tardive dyskinesia is produced by a disturbance in the balance of central transmitters such that dopaminergic transmission is increased 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 Background Agitated or violent patients constitute 10 % of all emergency psychiatric treatment . Management guidelines , the preferred treatment of clinicians and clinical practice all differ . Systematic review s show that all relevant studies are small and none are likely to have adequate power to show true differences between treatments . Worldwide , current treatment is not based on evidence from r and omised trials . In Brazil , the combination haloperidol-promethazine is frequently used , but no studies involving this mix exist . Methods TREC-Rio ( Tranquilização Rápida-Ensaio Clínico [ Translation : Rapid Tranquillisation- Clinical Trial ] ) will compare midazolam with haloperidol-promethazine mix for treatment of agitated patients in emergency psychiatric rooms of Rio de Janeiro , Brazil . TREC-Rio is a r and omised , controlled , pragmatic and open study . Primary measure of outcome is tranquillisation at 20 minutes but effects on other measures of morbidity will also be assessed . TREC-Rio will involve the collaboration of as many health care professionals based in four psychiatric emergency rooms of Rio as possible . Because the design of this trial does not substantially complicate clinical management , and in several aspects simplifies it , the study can be large , and treatments used in everyday practice can be evaluated OBJECTIVE To determine the incidence and causes of agitation states in patients presenting at the Rouen University Hospital emergency room and to analyze the management scheme . PATIENTS AND METHOD A prospect i ve study was conducted over a 9 month period in 100 consecutive patients presenting a state of agitation assessed using the Overt Aggression Scale . A pre-planned management protocol was applied . RESULTS The incidence of states of agitation was 0.56 % . There were 43 women and 57 men , mean age 33 years . Most of the agitated patients were admitted between 6 p.m. and 4 a.m. ( 69 % ) . Over the 9 month period , 2 patients were admitted twice for agitation and 2 absconded . Low glucose level was the cause of agitation in 4 cases . Alcohol and /or drug use concerned 73 % of the agitated patients and was the most frequently observed triggering factor ( 17 % ) . Only 6 % of the patients had a regular employment . Physical restraining measures and sedation were required in 86 % and 84 % of the cases respectively . Among 67 patients given loxapine for sedation , 2 developed acute dyskinesia and 9 low blood pressure . One out of 4 patients were referred to a psychiatric unit . CONCLUSION Patients in a state of agitation are young , often female , and in a difficult socio-economic situation . Hypoglycemia is the main differential diagnosis . A triggering factor can often be identified . A state of agitation is not a repetitive condition but occurs as a short-lived episode in the patientís history . Such patients need rapid care to avoid further aggravation and disruption of the emergency room activity , and to prevent the patient from fleeing . Loxapine provides effective sedation but requires regular monitoring of blood pressure and can provoke acute dyskinesia in young subjects 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 The medical management of aggressive and violent behaviour is a critical situation for which there is little evidence . In order to prepare for a r and omised trial , due to start in the psychiatric emergency rooms of Rio de Janeiro in 2001 , a survey of current practice was necessary . Methods A seven day survey of pharmacological management of aggressive people with psychosis in the emergency rooms of all four public psychiatric hospitals in Rio de Janeiro , Brazil . Results In one hospital data were not available . Of the 764 people with psychosis attending these ERs , 74 were given IM medication for rapid tranquillisation ( 9.7 % , 2.1/week/100,000 ) . A haloperidol-promethazine mix ( with or without other drugs ) was used for the majority of patients ( 83 % ) . Conclusion The haloperidol-promethazine mix , given intramuscularly for rapid tranquilization , is prevalent in Rio , where it is considered both safe and efficient . However , scientific evaluation of all pharmacological approaches to rapid tranquilization of psychotic people is inadequate or incomplete and a r and omized trial of IM haloperidol-promethazine is overdue SINCE THE discovery of rapid eye movements ( REMs ) associated with a desynchronized electroencephalogram ( EEG ) during behavioral sleep 1 and the correlation of this sleep stage with dreaming , 2 considerable investigation of REM sleep has been instituted to assess its significance in normal man and in various psychiatric illnesses . The similarity between mentation during dreaming in normal people and thought patterns in schizophrenia has led to many investigations of REM sleep in this disease . These studies have not consistently demonstrated marked differences in REM sleep between schizophrenics and normal subjects . 3 Similarly , REM sleep does not appear to be markedly altered in mental illness characterized primarily by depression . 3 Several recent studies have suggested , however , that Stage 4 or delta sleep may be decreased in schizophrenia 4 and depressive psychosis . 5,6 Various drugs used in the treatment of mental illness have BACKGROUND An intramuscular ( IM ) formulation of olanzapine has been developed because there are no rapid-acting IM atypical antipsychotic drugs currently available in the United States for treating acute agitation in patients with schizophrenia . METHODS Recently hospitalized acutely agitated patients with schizophrenia ( N = 270 ) were r and omized to receive 1 to 3 IM injections of olanzapine ( 2.5 , 5.0 , 7.5 , or 10.0 mg ) , haloperidol ( 7.5 mg ) , or placebo within 24 hours . A dose-response relationship for IM olanzapine in the reduction of agitation was assessed by measuring the reduction in Positive and Negative Syndrome Scale Excited Component ( PANSS-EC ) scores 2 hours after the first injection . Safety was assessed by recording adverse events and with extrapyramidal symptom scales and electrocardiograms at 24 hours after the first injection . RESULTS Olanzapine exhibited a dose-response relationship for reduction in agitation ( F(1,179)= 14.4 ; P<.001 ) . Mean PANSS-EC reductions 2 hours after the first injection of olanzapine ( 2.5 mg = -5.5 ; 5.0 mg = -8.1 ; 7.5 mg = -8.7 ; 10.0 mg = -9.4 ) were superior to those with placebo ( -2.9 ; P = .01 vs olanzapine at 2.5 mg ; P<.001 for each other olanzapine dose ) but not with haloperidol ( -7.5 ) . A dose of 5.0 , 7.5 , or 10.0 mg of olanzapine caused a greater reduction in agitation than placebo 30 minutes after the first injection . There were no differences between treatment groups for hypotension , the most frequently reported adverse event , or for clinical ly relevant changes in the QTc interval . There was a greater incidence of treatment-emergent parkinsonism during treatment with IM haloperidol ( 16.7 % ) than with 2.5 ( P = .03 ) , 5.0 ( P = .03 ) , or 7.5 mg ( P = .01 ) of IM olanzapine ( 0 % ) or with placebo ( 0 % ) ( P = .01 ) . CONCLUSIONS Intramuscular olanzapine at a dose of 2.5 to 10.0 mg per injection exhibits a dose-response relationship in the rapid treatment of acute agitation in patients with schizophrenia and demonstrates a favorable safety profile BACKGROUND The aim of this study was to examine differences in the improvement of clinical psychopathology and in fine motor functions at 2 doses of risperidone in first-episode , acutely psychotic patients . METHOD In a double-blind , fixed-dose study , 49 acutely psychotic , neuroleptic-naive patients who were admitted for the first time and who met DSM-IV criteria for schizophrenia , schizophreniform disorder , or schizoaffective disorder were r and omly assigned to 2 or 4 mg/day of risperidone .  Treatment efficacy was measured using the Brief Psychiatric Rating Scale , the Scale for the Assessment of Negative Symptoms , The Clinical Global Impressions scale , and the Social and Occupational Functioning Assessment Scale . Fine motor functions were assessed using a computerized device ( the Vienna Test System ) and were compared with those of a control group of 20 healthy subjects who were matched for age , gender , and educational level . RESULTS Treatment with doses of 2 and 4 mg of risperidone daily significantly reduced positive ( p < .0001 ) and negative ( p < .01 ) symptoms at 8 weeks . Although there were no significant differences in motor movements as measured using the Barnes Akathisia Scale and the Simpson-Angus Scale , computerized fine motor assessment showed significantly less motor dysfunction in the 2-mg/day group at 8 weeks . No significant correlations to plasma concentration of active moiety were found for data on psychopathology and fine motor functions . CONCLUSION The 2 doses of risperidone did not differ in terms of clinical improvement , but the 2-mg/day dose produced fewer fine motor dysfunctions . These results suggest that a dose as low as 2 mg/day of risperidone may be effective for patients with first-episode psychosis Two studies tested the reliability and validity of the  Overt Agitation Severity Scale ( OASS )  , a new instrument developed to define and objective ly rate the severity of  agitated behavior . The authors postulate that agitation should be conceptualized as vocal and motor behaviors on a continuum of expressions that extends from anxiety to aggression . Content validity through expert agreement was achieved in the development of test construction over a 2-year period . Results of two pilot studies ( n = 25 and n = 14 subjects ) established the reliability and validity of the OASS  to measure agitation severity . The OASS differs from other agitation scales in 
    Output:
    
agent
This review suggests that both benzodiazepines work , but that midazolam has a faster onset and thereby reduces the risk of exposure to violence .
Most evidence , however , exists for the haloperidol plus promethazine mix , with currently more than 400 people r and omised to the combination .
The onset of action is swift and faster than lorazepam .
The combination also seems safe with no clear longer term consequences .
***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 have investigated the action of pimozide in  tardive dyskinesia induced by prolonged administration of phenothiazines .  Improvement was recorded in a double blind study of 18 patients treated with maximum tolerated dosage ( mean 18.8 mg/day ) for 6 weeks . There was no deterioration in the therapeutic action of pimozide over this time . Parkinsonism and sedation were the main adverse effects . They were corrected by reduction of the dose of pimozide , but often recurred so that further adjustments of dosage were necessary . Our findings support the view that tardive dyskinesia is produced by a disturbance in the balance of central transmitters such that dopaminergic transmission is increased 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 Background Agitated or violent patients constitute 10 % of all emergency psychiatric treatment . Management guidelines , the preferred treatment of clinicians and clinical practice all differ . Systematic review s show that all relevant studies are small and none are likely to have adequate power to show true differences between treatments . Worldwide , current treatment is not based on evidence from r and omised trials . In Brazil , the combination haloperidol-promethazine is frequently used , but no studies involving this mix exist . Methods TREC-Rio ( Tranquilização Rápida-Ensaio Clínico [ Translation : Rapid Tranquillisation- Clinical Trial ] ) will compare midazolam with haloperidol-promethazine mix for treatment of agitated patients in emergency psychiatric rooms of Rio de Janeiro , Brazil . TREC-Rio is a r and omised , controlled , pragmatic and open study . Primary measure of outcome is tranquillisation at 20 minutes but effects on other measures of morbidity will also be assessed . TREC-Rio will involve the collaboration of as many health care professionals based in four psychiatric emergency rooms of Rio as possible . Because the design of this trial does not substantially complicate clinical management , and in several aspects simplifies it , the study can be large , and treatments used in everyday practice can be evaluated OBJECTIVE To determine the incidence and causes of agitation states in patients presenting at the Rouen University Hospital emergency room and to analyze the management scheme . PATIENTS AND METHOD A prospect i ve study was conducted over a 9 month period in 100 consecutive patients presenting a state of agitation assessed using the Overt Aggression Scale . A pre-planned management protocol was applied . RESULTS The incidence of states of agitation was 0.56 % . There were 43 women and 57 men , mean age 33 years . Most of the agitated patients were admitted between 6 p.m. and 4 a.m. ( 69 % ) . Over the 9 month period , 2 patients were admitted twice for agitation and 2 absconded . Low glucose level was the cause of agitation in 4 cases . Alcohol and /or drug use concerned 73 % of the agitated patients and was the most frequently observed triggering factor ( 17 % ) . Only 6 % of the patients had a regular employment . Physical restraining measures and sedation were required in 86 % and 84 % of the cases respectively . Among 67 patients given loxapine for sedation , 2 developed acute dyskinesia and 9 low blood pressure . One out of 4 patients were referred to a psychiatric unit . CONCLUSION Patients in a state of agitation are young , often female , and in a difficult socio-economic situation . Hypoglycemia is the main differential diagnosis . A triggering factor can often be identified . A state of agitation is not a repetitive condition but occurs as a short-lived episode in the patientís history . Such patients need rapid care to avoid further aggravation and disruption of the emergency room activity , and to prevent the patient from fleeing . Loxapine provides effective sedation but requires regular monitoring of blood pressure and can provoke acute dyskinesia in young subjects 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 The medical management of aggressive and violent behaviour is a critical situation for which there is little evidence . In order to prepare for a r and omised trial , due to start in the psychiatric emergency rooms of Rio de Janeiro in 2001 , a survey of current practice was necessary . Methods A seven day survey of pharmacological management of aggressive people with psychosis in the emergency rooms of all four public psychiatric hospitals in Rio de Janeiro , Brazil . Results In one hospital data were not available . Of the 764 people with psychosis attending these ERs , 74 were given IM medication for rapid tranquillisation ( 9.7 % , 2.1/week/100,000 ) . A haloperidol-promethazine mix ( with or without other drugs ) was used for the majority of patients ( 83 % ) . Conclusion The haloperidol-promethazine mix , given intramuscularly for rapid tranquilization , is prevalent in Rio , where it is considered both safe and efficient . However , scientific evaluation of all pharmacological approaches to rapid tranquilization of psychotic people is inadequate or incomplete and a r and omized trial of IM haloperidol-promethazine is overdue SINCE THE discovery of rapid eye movements ( REMs ) associated with a desynchronized electroencephalogram ( EEG ) during behavioral sleep 1 and the correlation of this sleep stage with dreaming , 2 considerable investigation of REM sleep has been instituted to assess its significance in normal man and in various psychiatric illnesses . The similarity between mentation during dreaming in normal people and thought patterns in schizophrenia has led to many investigations of REM sleep in this disease . These studies have not consistently demonstrated marked differences in REM sleep between schizophrenics and normal subjects . 3 Similarly , REM sleep does not appear to be markedly altered in mental illness characterized primarily by depression . 3 Several recent studies have suggested , however , that Stage 4 or delta sleep may be decreased in schizophrenia 4 and depressive psychosis . 5,6 Various drugs used in the treatment of mental illness have BACKGROUND An intramuscular ( IM ) formulation of olanzapine has been developed because there are no rapid-acting IM atypical antipsychotic drugs currently available in the United States for treating acute agitation in patients with schizophrenia . METHODS Recently hospitalized acutely agitated patients with schizophrenia ( N = 270 ) were r and omized to receive 1 to 3 IM injections of olanzapine ( 2.5 , 5.0 , 7.5 , or 10.0 mg ) , haloperidol ( 7.5 mg ) , or placebo within 24 hours . A dose-response relationship for IM olanzapine in the reduction of agitation was assessed by measuring the reduction in Positive and Negative Syndrome Scale Excited Component ( PANSS-EC ) scores 2 hours after the first injection . Safety was assessed by recording adverse events and with extrapyramidal symptom scales and electrocardiograms at 24 hours after the first injection . RESULTS Olanzapine exhibited a dose-response relationship for reduction in agitation ( F(1,179)= 14.4 ; P<.001 ) . Mean PANSS-EC reductions 2 hours after the first injection of olanzapine ( 2.5 mg = -5.5 ; 5.0 mg = -8.1 ; 7.5 mg = -8.7 ; 10.0 mg = -9.4 ) were superior to those with placebo ( -2.9 ; P = .01 vs olanzapine at 2.5 mg ; P<.001 for each other olanzapine dose ) but not with haloperidol ( -7.5 ) . A dose of 5.0 , 7.5 , or 10.0 mg of olanzapine caused a greater reduction in agitation than placebo 30 minutes after the first injection . There were no differences between treatment groups for hypotension , the most frequently reported adverse event , or for clinical ly relevant changes in the QTc interval . There was a greater incidence of treatment-emergent parkinsonism during treatment with IM haloperidol ( 16.7 % ) than with 2.5 ( P = .03 ) , 5.0 ( P = .03 ) , or 7.5 mg ( P = .01 ) of IM olanzapine ( 0 % ) or with placebo ( 0 % ) ( P = .01 ) . CONCLUSIONS Intramuscular olanzapine at a dose of 2.5 to 10.0 mg per injection exhibits a dose-response relationship in the rapid treatment of acute agitation in patients with schizophrenia and demonstrates a favorable safety profile BACKGROUND The aim of this study was to examine differences in the improvement of clinical psychopathology and in fine motor functions at 2 doses of risperidone in first-episode , acutely psychotic patients . METHOD In a double-blind , fixed-dose study , 49 acutely psychotic , neuroleptic-naive patients who were admitted for the first time and who met DSM-IV criteria for schizophrenia , schizophreniform disorder , or schizoaffective disorder were r and omly assigned to 2 or 4 mg/day of risperidone .  Treatment efficacy was measured using the Brief Psychiatric Rating Scale , the Scale for the Assessment of Negative Symptoms , The Clinical Global Impressions scale , and the Social and Occupational Functioning Assessment Scale . Fine motor functions were assessed using a computerized device ( the Vienna Test System ) and were compared with those of a control group of 20 healthy subjects who were matched for age , gender , and educational level . RESULTS Treatment with doses of 2 and 4 mg of risperidone daily significantly reduced positive ( p < .0001 ) and negative ( p < .01 ) symptoms at 8 weeks . Although there were no significant differences in motor movements as measured using the Barnes Akathisia Scale and the Simpson-Angus Scale , computerized fine motor assessment showed significantly less motor dysfunction in the 2-mg/day group at 8 weeks . No significant correlations to plasma concentration of active moiety were found for data on psychopathology and fine motor functions . CONCLUSION The 2 doses of risperidone did not differ in terms of clinical improvement , but the 2-mg/day dose produced fewer fine motor dysfunctions . These results suggest that a dose as low as 2 mg/day of risperidone may be effective for patients with first-episode psychosis Two studies tested the reliability and validity of the  Overt Agitation Severity Scale ( OASS )  , a new instrument developed to define and objective ly rate the severity of  agitated behavior . The authors postulate that agitation should be conceptualized as vocal and motor behaviors on a continuum of expressions that extends from anxiety to aggression . Content validity through expert agreement was achieved in the development of test construction over a 2-year period . Results of two pilot studies ( n = 25 and n = 14 subjects ) established the reliability and validity of the OASS  to measure agitation severity . The OASS differs from other agitation scales in 
    Output:
    