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 The authors examined the efficacy of intramuscular flunitrazepam compared with intramuscular haloperidol for the immediate control of agitated or aggressive behavior in acutely psychotic patients . METHOD Twenty-eight actively psychotic in patients , aged 20 - 60 years , who were under treatment with neuroleptic agents were selected for the study . Each was r and omly assigned on a double-blind basis to receive either 5 mg i.m . of haloperidol ( N=13 ) or 1 mg i.m . of flunitrazepam ( N=15 ) during an aggressive event . Verbal and physical aggression was measured over time with the Overt Aggression Scale . Patients were also rated with the Brief Psychiatric Rating Scale and the Clinical Global Impression scale . RESULTS Both flunitrazepam and haloperidol exhibited acute antiaggressive activity . This beneficial effect , as assessed by the Overt Aggression Scale , was obtained within 30 minutes . CONCLUSIONS Intramuscular flunitrazepam may serve as a convenient , rapid , safe , and effective adjunct to neuroleptics in reducing aggressive behavior in emergency psychiatric setting OBJECTIVES To determine if midazolam is superior to lorazepam or haloperidol in the management of  violent and severely agitated patients in the emergency department . Superiority would be determined if midazolam result ed in a significantly shorter time to sedation and shorter time to arousal . METHODS This was a r and omized , prospect i ve , double-blind study of a convenience sample of patients from an urban , county teaching emergency department . Participants included 111 violent and severely agitated patients . Patients were r and omized to receive intramuscular midazolam ( 5 mg ) , lorazepam ( 2 mg ) , or haloperidol ( 5 mg ) . RESULTS The mean ( + /-SD ) age was 40.7 ( + /-13 ) years . The mean ( + /-SD ) time to sedation was 18.3 ( + /-14 ) minutes for patients receiving midazolam , 28.3 ( + /-25 ) minutes for haloperidol , and 32.2 ( + /-20 ) minutes for lorazepam . Midazolam had a significantly shorter time to sedation than lorazepam and haloperidol ( p < 0.05 ) . The mean difference between midazolam and lorazepam was 13.0 minutes ( 95 % confidence interval [ 95 % CI ] = 5.1 to 22.8 minutes ) and that between midazolam and haloperidol was 9.9 minutes ( 95 % CI = 0.5 to 19.3 minutes ) . Time to arousal was 81.9 minutes for patients receiving midazolam , 126.5 minutes for haloperidol , and 217.2 minutes for lorazepam .  Time to arousal for midazolam was significantly shorter than for both haloperidol and lorazepam ( p < 0.05 ) . The mean difference in time to awakening between midazolam and lorazepam was 135.3 minutes ( 95 % CI = 89 to 182 minutes ) and that between midazolam and haloperidol was 44.6 minutes ( 95 % CI = 9 to 80 minutes ) . There was no significant difference over time by repeated- measures analysis of variance between groups in regard to changes in systolic and diastolic blood pressure ( p = 0.8965 , p = 0.9581 ) , heart rate ( p = 0.5517 ) , respiratory rate ( p = 0.8191 ) , and oxygen saturation ( p = 0.8991 ) . CONCLUSIONS Midazolam has a significantly shorter time to onset of sedation and a more rapid time to arousal than lorazepam or haloperidol . The efficacies of all three drugs appear to be similar The mechanisms underlying the clinical properties of atypical antipsychotics have been postulated to be mediated , in part , by interactions with the 5-HT2A receptor . Recently , it has been recognized that clinical ly effective antipsychotic drugs are 5-HT2A receptor inverse agonists rather than neutral antagonists . In the present study , which is part of the clinical development of the novel , selective 5-HT2A receptor inverse agonist ACP-103 , we applied positron emission tomography ( PET ) with the radiolig and [11C]N-methylspiperone ( [11C]NMSP ) to study the relationship between oral dose , plasma level , and uptake of ACP-103 in living human brain . The safety of drug administration was also assessed . Four healthy volunteers were examined by PET at baseline , and after the oral administration of various single doses of ACP-103 . Two subjects each received 1 , 5 , and 20 mg doses , and two subjects each received 2 , 10 , and 100 mg doses , respectively . ACP-103 was well tolerated . Detectable receptor binding was observed at very low ACP-103 serum levels . Cortical [11C]NMSP binding was found to be dose-dependent and fitted well to the law of mass action . A reduction in binding was detectable after an oral dose of ACP-103 as low as 1 mg , and reached near maximal displacement following the 10 - 20 mg dose . In conclusion , administration of ACP-103 to healthy volunteers was found to be safe and well tolerated , and single oral doses as low as 10 mg were found to fully saturate 5-HT2A receptors in human brain as determined by PET OBJECTIVE While neuroleptics remain the mainstay of drug intervention in the emergency management of psychosis , a variety of agents have received study as alternatives or adjuncts to these drugs in an attempt to improve the safety and efficacy of acute treatment . The purpose s of this study were to investigate the efficacy and safety of alprazolam as a neuroleptic adjunct for schizophrenic patients in psychotic relapse and to clarify the effects of combination treatment on specific aspects of the psychotic process . METHOD Twenty-eight acutely psychotic patients with schizophrenia who were admitted to an emergency psychiatric service were r and omly assigned to treatment with either haloperidol and alprazolam or haloperidol with placebo under double-blind conditions . Drug administration lasted 72 hours . RESULTS Both groups improved significantly . The combination-treated group required significantly less medication and had 56 % fewer dystonic reactions . The addition of alprazolam was most effective for symptoms of excitement and uncooperativeness , particularly in the initial hours of treatment . CONCLUSIONS The combination of alprazolam and haloperidol seems to be the most effective for agitated patients , particularly in the first 48 hours of treatment . It may also result in fewer dystonic reactions 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 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 Rapid tranquilization is a routinely practice d method of calming agitated psychotic patients by use of neuroleptics , benzodiazepines , or both in combination . Although several studies have examined the efficacy of the three approaches , none have compared these treatments in a prospect i ve , r and omized , double-blind , multicenter trial . Ninety-eight psychotic , agitated , and aggressive patients ( 73 men and 25 women ) were prospect ively enrolled during an 18-month period in emergency departments in five university or general hospitals . Patients were r and omly assigned to receive intramuscular injections of lorazepam ( 2 mg ) , haloperidol ( 5 mg ) , or both in combination . Patients in each treatment group received 1 to 6 injections of the same study drug within 12 hours , based on clinical need . They were evaluated hourly after the first injection until at least 12 hours after the last . Efficacy was assessed on the Agitated Behavior Scale ( ABS ) , a modified Brief Psychiatric Rating Scale ( MBPRS ) , Clinical Global impressions ( CGI ) scale , and an Alertness Scale . Effective symptom reduction was achieved in each treatment group with significant ( P < .01 ) mean decreases from baseline at every hourly ABS evaluation . Significant ( P < .05 ) mean differences on the ABS ( hour 1 ) and MBPRS ( hours 2 and 3 ) suggest that tranquilization was most rapid in patients receiving the combination treatment . Study event incidence ( side effects ) did not differ significantly between treatment groups , although patients receiving haloperidol alone tended to have more extrapyramidal system symptoms . The superior results produced by the combination treatment support the use of lorazepam plus haloperidol as the treatment of choice for acute psychotic agitation 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 Agents currently used for acutely agitated patients such as sodium amytal and haloperidol are disadvantageous because of their adverse effects on the respiratory and extrapyramidal systems . Because of this , a rapid , safe , well-absorbed agent such as midazolam would be useful . This study compares the effectiveness of midazolam , sodium amytal , and haloperidol in agitated schizophrenic patients . Five male patients between 28 and 59 years were r and omly assigned to each group . They were administered intramuscularly either 10 mg of haloperidol , 250 mg of sodium amytal , or 5 mg of midazolam . Over a 2-hour period , patients were rated for motor agitation , hostility , auditory hallucinations , and flight of ideas . Both midazolam and sodium amytal were significantly more effective than haloperidol in controlling motor agitation . There were no treatment differences on any other symptom rated . These results indicate that further studies on the use of midazolam to achieve rapid tranquilization would be useful OBJECTIVE To compare the effectiveness of intramuscular olanzapine , ziprasidone , haloperidol plus promethazine , haloperidol plus midazolam and haloperidol alone as the first medication(s ) used to treat patients with agitation and aggressive behavior . METHOD One hundred fifty patients with agitation caused by psychotic or bipolar disorder were r and omly assigned under double-blind conditions to receive olanzapine , zi 
    Output:
    
agent
When haloperidol and midazolam were compared with olanzapine , there was some evidence the combination was superior in terms of improvement , sedation and behaviour .
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 .
***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 The authors examined the efficacy of intramuscular flunitrazepam compared with intramuscular haloperidol for the immediate control of agitated or aggressive behavior in acutely psychotic patients . METHOD Twenty-eight actively psychotic in patients , aged 20 - 60 years , who were under treatment with neuroleptic agents were selected for the study . Each was r and omly assigned on a double-blind basis to receive either 5 mg i.m . of haloperidol ( N=13 ) or 1 mg i.m . of flunitrazepam ( N=15 ) during an aggressive event . Verbal and physical aggression was measured over time with the Overt Aggression Scale . Patients were also rated with the Brief Psychiatric Rating Scale and the Clinical Global Impression scale . RESULTS Both flunitrazepam and haloperidol exhibited acute antiaggressive activity . This beneficial effect , as assessed by the Overt Aggression Scale , was obtained within 30 minutes . CONCLUSIONS Intramuscular flunitrazepam may serve as a convenient , rapid , safe , and effective adjunct to neuroleptics in reducing aggressive behavior in emergency psychiatric setting OBJECTIVES To determine if midazolam is superior to lorazepam or haloperidol in the management of  violent and severely agitated patients in the emergency department . Superiority would be determined if midazolam result ed in a significantly shorter time to sedation and shorter time to arousal . METHODS This was a r and omized , prospect i ve , double-blind study of a convenience sample of patients from an urban , county teaching emergency department . Participants included 111 violent and severely agitated patients . Patients were r and omized to receive intramuscular midazolam ( 5 mg ) , lorazepam ( 2 mg ) , or haloperidol ( 5 mg ) . RESULTS The mean ( + /-SD ) age was 40.7 ( + /-13 ) years . The mean ( + /-SD ) time to sedation was 18.3 ( + /-14 ) minutes for patients receiving midazolam , 28.3 ( + /-25 ) minutes for haloperidol , and 32.2 ( + /-20 ) minutes for lorazepam . Midazolam had a significantly shorter time to sedation than lorazepam and haloperidol ( p < 0.05 ) . The mean difference between midazolam and lorazepam was 13.0 minutes ( 95 % confidence interval [ 95 % CI ] = 5.1 to 22.8 minutes ) and that between midazolam and haloperidol was 9.9 minutes ( 95 % CI = 0.5 to 19.3 minutes ) . Time to arousal was 81.9 minutes for patients receiving midazolam , 126.5 minutes for haloperidol , and 217.2 minutes for lorazepam .  Time to arousal for midazolam was significantly shorter than for both haloperidol and lorazepam ( p < 0.05 ) . The mean difference in time to awakening between midazolam and lorazepam was 135.3 minutes ( 95 % CI = 89 to 182 minutes ) and that between midazolam and haloperidol was 44.6 minutes ( 95 % CI = 9 to 80 minutes ) . There was no significant difference over time by repeated- measures analysis of variance between groups in regard to changes in systolic and diastolic blood pressure ( p = 0.8965 , p = 0.9581 ) , heart rate ( p = 0.5517 ) , respiratory rate ( p = 0.8191 ) , and oxygen saturation ( p = 0.8991 ) . CONCLUSIONS Midazolam has a significantly shorter time to onset of sedation and a more rapid time to arousal than lorazepam or haloperidol . The efficacies of all three drugs appear to be similar The mechanisms underlying the clinical properties of atypical antipsychotics have been postulated to be mediated , in part , by interactions with the 5-HT2A receptor . Recently , it has been recognized that clinical ly effective antipsychotic drugs are 5-HT2A receptor inverse agonists rather than neutral antagonists . In the present study , which is part of the clinical development of the novel , selective 5-HT2A receptor inverse agonist ACP-103 , we applied positron emission tomography ( PET ) with the radiolig and [11C]N-methylspiperone ( [11C]NMSP ) to study the relationship between oral dose , plasma level , and uptake of ACP-103 in living human brain . The safety of drug administration was also assessed . Four healthy volunteers were examined by PET at baseline , and after the oral administration of various single doses of ACP-103 . Two subjects each received 1 , 5 , and 20 mg doses , and two subjects each received 2 , 10 , and 100 mg doses , respectively . ACP-103 was well tolerated . Detectable receptor binding was observed at very low ACP-103 serum levels . Cortical [11C]NMSP binding was found to be dose-dependent and fitted well to the law of mass action . A reduction in binding was detectable after an oral dose of ACP-103 as low as 1 mg , and reached near maximal displacement following the 10 - 20 mg dose . In conclusion , administration of ACP-103 to healthy volunteers was found to be safe and well tolerated , and single oral doses as low as 10 mg were found to fully saturate 5-HT2A receptors in human brain as determined by PET OBJECTIVE While neuroleptics remain the mainstay of drug intervention in the emergency management of psychosis , a variety of agents have received study as alternatives or adjuncts to these drugs in an attempt to improve the safety and efficacy of acute treatment . The purpose s of this study were to investigate the efficacy and safety of alprazolam as a neuroleptic adjunct for schizophrenic patients in psychotic relapse and to clarify the effects of combination treatment on specific aspects of the psychotic process . METHOD Twenty-eight acutely psychotic patients with schizophrenia who were admitted to an emergency psychiatric service were r and omly assigned to treatment with either haloperidol and alprazolam or haloperidol with placebo under double-blind conditions . Drug administration lasted 72 hours . RESULTS Both groups improved significantly . The combination-treated group required significantly less medication and had 56 % fewer dystonic reactions . The addition of alprazolam was most effective for symptoms of excitement and uncooperativeness , particularly in the initial hours of treatment . CONCLUSIONS The combination of alprazolam and haloperidol seems to be the most effective for agitated patients , particularly in the first 48 hours of treatment . It may also result in fewer dystonic reactions 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 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 Rapid tranquilization is a routinely practice d method of calming agitated psychotic patients by use of neuroleptics , benzodiazepines , or both in combination . Although several studies have examined the efficacy of the three approaches , none have compared these treatments in a prospect i ve , r and omized , double-blind , multicenter trial . Ninety-eight psychotic , agitated , and aggressive patients ( 73 men and 25 women ) were prospect ively enrolled during an 18-month period in emergency departments in five university or general hospitals . Patients were r and omly assigned to receive intramuscular injections of lorazepam ( 2 mg ) , haloperidol ( 5 mg ) , or both in combination . Patients in each treatment group received 1 to 6 injections of the same study drug within 12 hours , based on clinical need . They were evaluated hourly after the first injection until at least 12 hours after the last . Efficacy was assessed on the Agitated Behavior Scale ( ABS ) , a modified Brief Psychiatric Rating Scale ( MBPRS ) , Clinical Global impressions ( CGI ) scale , and an Alertness Scale . Effective symptom reduction was achieved in each treatment group with significant ( P < .01 ) mean decreases from baseline at every hourly ABS evaluation . Significant ( P < .05 ) mean differences on the ABS ( hour 1 ) and MBPRS ( hours 2 and 3 ) suggest that tranquilization was most rapid in patients receiving the combination treatment . Study event incidence ( side effects ) did not differ significantly between treatment groups , although patients receiving haloperidol alone tended to have more extrapyramidal system symptoms . The superior results produced by the combination treatment support the use of lorazepam plus haloperidol as the treatment of choice for acute psychotic agitation 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 Agents currently used for acutely agitated patients such as sodium amytal and haloperidol are disadvantageous because of their adverse effects on the respiratory and extrapyramidal systems . Because of this , a rapid , safe , well-absorbed agent such as midazolam would be useful . This study compares the effectiveness of midazolam , sodium amytal , and haloperidol in agitated schizophrenic patients . Five male patients between 28 and 59 years were r and omly assigned to each group . They were administered intramuscularly either 10 mg of haloperidol , 250 mg of sodium amytal , or 5 mg of midazolam . Over a 2-hour period , patients were rated for motor agitation , hostility , auditory hallucinations , and flight of ideas . Both midazolam and sodium amytal were significantly more effective than haloperidol in controlling motor agitation . There were no treatment differences on any other symptom rated . These results indicate that further studies on the use of midazolam to achieve rapid tranquilization would be useful OBJECTIVE To compare the effectiveness of intramuscular olanzapine , ziprasidone , haloperidol plus promethazine , haloperidol plus midazolam and haloperidol alone as the first medication(s ) used to treat patients with agitation and aggressive behavior . METHOD One hundred fifty patients with agitation caused by psychotic or bipolar disorder were r and omly assigned under double-blind conditions to receive olanzapine , zi 
    Output:
    