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 To address the lack of a simple and st and ardized instrument to assess overall panic disorder severity , the authors developed a scale for the measurement of panic disorder severity . METHOD Ten independent evaluators used the seven-item Panic Disorder Severity Scale to assess 186 patients with principal DSM-III-R diagnoses of panic disorder ( with no or mild agoraphobia ) who were participating in the Multicenter Collaborative Treatment Study of Panic Disorder . In addition , 89 of these patients were reevaluated with the same scale after short-term treatment . A subset of 24 patients underwent two independent assessment s to establish interrater reliability . Internal consistency , convergent and discriminant validity , and sensitivity to change were also determined . RESULTS The Panic Disorder Severity Scale was associated with excellent interrater reliability , moderate internal consistency , and favorable levels of validity and sensitivity to change . Individual items showed good convergent and discriminant validity . Analysis suggested a two-factor model fit the data best . CONCLUSIONS The Panic Disorder Severity Scale is a simple , efficient way for clinicians to rate severity in patients with established diagnoses of panic disorder . However , further research with more diverse groups of panic disorder patients and with a broader range of convergent and discriminant validity measures is needed Background Because a large proportion of patients with panic attacks receiving approved pharmacotherapy do not respond or respond poorly to medication , it is important to identify additional therapeutic strategies for the management of panic symptoms . This article describes a r and omized , rater-blind study comparing low-dose risperidone to st and ard-of-care paroxetine for the treatment of panic attacks . Methods Fifty six subjects with a history of panic attacks were r and omized to receive either risperidone or paroxetine .  The subjects were then followed for eight weeks . Outcome measures included the Panic Disorder Severity Scale ( PDSS ) , the Hamilton Anxiety Scale ( Ham-A ) , the Hamilton Depression Rating Scale ( Ham-D ) , the Sheehan Panic Anxiety Scale-Patient ( SPAS-P ) , and the Clinical Global Impression scale ( CGI ) . Results All subjects demonstrated a reduction in both the frequency and severity of panic attacks regardless of treatment received . Statistically significant improvements in rating scale scores for both groups were identified for the PDSS , the Ham-A , the Ham-D , and the CGI . There was no difference between treatment groups in the improvement in scores on the measures PDSS , Ham-A , Ham-D , and CGI . Post hoc tests suggest that subjects receiving risperidone may have a quicker clinical response than subjects receiving paroxetine . Conclusion We can identify no difference in the efficacy of paroxetine and low-dose risperidone in the treatment of panic attacks . Low-dose risperidone appears to be tolerated equally well as paroxetine . Low-dose risperidone may be an effective treatment for anxiety disorders in which panic attacks are a significant component . Trial Registration Clinical Trials.gov Identifier : The objective of this study was to evaluate the efficacy and tolerability of extended release quetiapine fumarate ( quetiapine XR ) as maintenance monotherapy for patients with generalized anxiety disorder ( GAD ) .  Time-to-event ( anxiety symptom recurrence ; maximum 52 weeks ) multicenter , r and omized-withdrawal , parallel-group , double-blind , placebo-controlled study of quetiapine XR ( 50–300 mg/day ) following open-label run-in ( 4–8 weeks ) and open-label stabilization ( ≥12 weeks ) . Primary variable : time from r and omization to anxiety event . Secondary variables included : Hamilton Anxiety Rating Scale ( HAM-A ) total , HAM-A psychic/somatic anxiety factors , Clinical Global Impression-Severity of Illness ( CGI-S ) , and Quality of Life , Enjoyment and Satisfaction Question naire ( Q-LES-Q ) scores ; adverse events ( AE ) reporting . Four hundred and thirty-two patients , stabilized on quetiapine XR , were r and omized to continue quetiapine XR ( N=216 ) or switch to placebo ( N=216 ) . Risk of anxiety symptom recurrence was significantly reduced by 81 % for quetiapine XR versus placebo : hazard ratio=0.19 ( 95 % confidence interval 0.12–0.31 ; P<0.001 ) . Fewer patients receiving quetiapine XR ( N=22 , 10.2 % ) than placebo ( N=84 , 38.9 % ) experienced anxiety symptom recurrence . Significant differences were observed between quetiapine XR and placebo in : HAM-A total , psychic/somatic , CGI-S ( all P<0.001 ) and Q-LES-Q ( P<0.05 ) scores . AEs ( > 10 % ) during open-label treatment were dry mouth , sedation , somnolence , dizziness , fatigue , and constipation . During r and omized treatment , the most common AEs for quetiapine XR were headache and nasopharyngitis  . Quetiapine XR monotherapy reduced the risk of anxiety symptom recurrence in patients with GAD stabilized on quetiapine XR , with tolerability results consistent with the known profile of quetiapine The efficacy and tolerability of extended-release quetiapine fumarate ( quetiapine XR ) once-daily monotherapy in generalized anxiety disorder ( GAD ) was assessed . This multicentre , double-blind , r and omized , placebo- and active-controlled , phase III trial consisted of a 1- to 4-wk enrolment/wash-out period and a 10-wk ( 8-wk active treatment , 2-wk post-treatment drug-discontinuation ) study period ; 873 patients were r and omized to 50 mg or 150 mg quetiapine XR , 20 mg paroxetine , or placebo . Primary endpoint was change from r and omization at week 8 in Hamilton Rating Scale for Anxiety ( HAMA ) total score . At week 8 , all active agents produced significant improvements in HAMA total and psychic subscale scores vs. placebo ; HAMA somatic subscale scores were significantly reduced only by 150 mg quetiapine XR . Significant separation from placebo ( -2.90 ) in HAMA total score was observed at day 4 for 50 mg quetiapine XR ( -4.43 , p<0.001 ) and 150 mg quetiapine XR ( -3.86 , p<0.05 ) , but not for paroxetine ( -2.69 ) . Remission ( HAMA total score 7 ) rates at week 8 were significantly higher for 150 mg quetiapine XR ( 42.6 % , p<0.01 ) and paroxetine ( 38.8 % , p<0.05 ) vs. placebo ( 27.2 % ) . The most common adverse events ( AEs ) were dry mouth , somnolence , fatigue , dizziness , and headache , for quetiapine  XR , and nausea , headache , dizziness for paroxetine . A lower proportion of patients reported sexual dysfunction with quetiapine XR [ 0.9 % ( 50 mg ) , 1.8 % ( 150 mg ) ] than with placebo ( 2.3 % ) or paroxetine ( 7.4 % ) . The incidence of AEs potentially related to extrapyramidal symptoms was : quetiapine XR : 50 mg , 6.8 % , 150 mg , 5.0 % ; placebo , 1.8 % ; and paroxetine , 8.4 % . Once-daily quetiapine XR is an effective and generally well-tolerated treatment for patients with GAD , with symptom improvement seen as early as day 4 BACKGROUND Depression and anxiety are common disorders and have substantially overlapping symptom complexes . Not surprisingly , treatment approaches are similar for both conditions with the selective serotonin reuptake inhibitors ( SSRIs ) as the initial therapy of choice . However , after first line treatments have been deployed , residual symptoms are often problematic . Augmentation strategies to address these difficulties are an area of active investigation . This study assessed aripiprazole as adjunctive therapy to SSRIs for patients with persistent anxiety symptoms complicating a depression or anxiety disorder . METHODS Ten patients who had been receiving SSRIs for at least 6 weeks , but still had clinical ly significant anxiety symptoms , were enrolled in an open label , flexibly-dosed study of adjunctive aripiprazole . Clinical status was assessed with the Hamilton Anxiety Rating Scale ( HAM-A ) , Montgomery Asberg Rating Scale ( MADRS ) , and Sheehan Disability Scale ( SDS ) . RESULTS Eighty percent of the subjects had a greater than 50 % reduction of symptoms on these outcome measures by week 2 of therapy , and continued with further decrements in symptoms throughout the course of the study . CONCLUSIONS The results of this trial provide preliminary evidence that aripiprazole may be an effective adjunctive treatment in individuals on SSRIs with residual symptoms of anxiety or depression . More rigorous double-blind studies are warranted to confirm and eluci date the potential role of aripiprazole in these conditions 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 The purpose of our study was to evaluate the efficacy and tolerability of low-dose olanzapine augmentation in selective serotonin reuptake inhibitor (SSRI)-resistant panic disorder ( PD ) with or without agoraphobia . In this 12-week , open-label study , 31 adult out patients with treatment-resistant PD who had previously failed to respond to SSRI treatment were treated with fixed dose of olanzapine ( 5 mg/d ) in addition to SSRI .  Efficacy was assessed using the Panic Attack and Anticipatory Anxiety Scale ( PAAAS ) , the Agoraphobic Cognitions Question naire ( ACQ ) , the Hamilton Rating Scale for Anxiety ( HAM-A ) , the Hamilton Rating Scale for Depression ( HAM-D ) , the Global Assessment of Functioning Scale ( GAF ) , and the Clinical Global Impression of Improvement ( CGI-I ) . Twenty-six patients completed the trial period with a dropout rate of 16.1 % . At week 12 , 21 patients were responders ( 81.8 % ) , and an overall improvement on all rating scales was observed in all patients both with or without agoraphobia . Fifteen patients ( 57.7 % ) achieved remission . Olanzapine was well tolerated and the most frequent adverse effects were mild-to-moderate weight gain and drowsiness . No extrapyramidal symptoms were reported . Olanzapine appears to be effective as augmentation strategy in the treatment of SSRI-resistant PD , but study limitations must be considered and placebo-controlled studies are needed Rationale More data are needed to guide “ next step ” strategies for patients with generalized anxiety disorder ( GAD ) remaining symptomatic despite initial pharmacotherapy . Objective This study prospect ively examined the relative efficacy of quetiapine versus placebo augmentation for individuals with GAD remaining symptomatic with initial paroxetine CR pharmacotherapy . Material s and methods Adult out patients with GAD were recruited from 2004 to 2007 at two academic centers . Phase 1 consisted of 10 weeks of open-label paroxetine CR flexibly dosed to a maximum of 62.5 mg/day . Those remaining symptomatic ( Hamilton Anxiety Scale [ HAM-A ] ≥ 7 ) at week 10 were r and omized to quetiapine or placebo augmentation flexibly dosed from 25 to 400 mg/day . Results For participants receiving paroxetine CR ( n = 50 ) , there was a significant reduction in HAM-A scores ( baseline mean ± SD = 22.4 ± 4.2 to endpoint mean ± SD = 11.2 ± 6.9 ; paired t = 12.1 , df = 49 , t < 0.0001 ) with 40 % ( n = 20 ) achieving remission . Counter to our hypothesis , we did not find significant benefit for quetiapine augmentation of continued paroxetine CR ( HAM-A reduction mean ± SD = 2.6 ± 5.8 points quetiapine , 0.3 ± 5.5 points placebo ; t = 0.98 , df = 20 , p = n.s . ) in the r and omized sample ( n =  
    Output:
    
agent
Monotherapy with quetiapine seems to be efficacious in reducing symptoms of generalised anxiety disorder and this effect may be similar to that of antidepressants .
***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 To address the lack of a simple and st and ardized instrument to assess overall panic disorder severity , the authors developed a scale for the measurement of panic disorder severity . METHOD Ten independent evaluators used the seven-item Panic Disorder Severity Scale to assess 186 patients with principal DSM-III-R diagnoses of panic disorder ( with no or mild agoraphobia ) who were participating in the Multicenter Collaborative Treatment Study of Panic Disorder . In addition , 89 of these patients were reevaluated with the same scale after short-term treatment . A subset of 24 patients underwent two independent assessment s to establish interrater reliability . Internal consistency , convergent and discriminant validity , and sensitivity to change were also determined . RESULTS The Panic Disorder Severity Scale was associated with excellent interrater reliability , moderate internal consistency , and favorable levels of validity and sensitivity to change . Individual items showed good convergent and discriminant validity . Analysis suggested a two-factor model fit the data best . CONCLUSIONS The Panic Disorder Severity Scale is a simple , efficient way for clinicians to rate severity in patients with established diagnoses of panic disorder . However , further research with more diverse groups of panic disorder patients and with a broader range of convergent and discriminant validity measures is needed Background Because a large proportion of patients with panic attacks receiving approved pharmacotherapy do not respond or respond poorly to medication , it is important to identify additional therapeutic strategies for the management of panic symptoms . This article describes a r and omized , rater-blind study comparing low-dose risperidone to st and ard-of-care paroxetine for the treatment of panic attacks . Methods Fifty six subjects with a history of panic attacks were r and omized to receive either risperidone or paroxetine .  The subjects were then followed for eight weeks . Outcome measures included the Panic Disorder Severity Scale ( PDSS ) , the Hamilton Anxiety Scale ( Ham-A ) , the Hamilton Depression Rating Scale ( Ham-D ) , the Sheehan Panic Anxiety Scale-Patient ( SPAS-P ) , and the Clinical Global Impression scale ( CGI ) . Results All subjects demonstrated a reduction in both the frequency and severity of panic attacks regardless of treatment received . Statistically significant improvements in rating scale scores for both groups were identified for the PDSS , the Ham-A , the Ham-D , and the CGI . There was no difference between treatment groups in the improvement in scores on the measures PDSS , Ham-A , Ham-D , and CGI . Post hoc tests suggest that subjects receiving risperidone may have a quicker clinical response than subjects receiving paroxetine . Conclusion We can identify no difference in the efficacy of paroxetine and low-dose risperidone in the treatment of panic attacks . Low-dose risperidone appears to be tolerated equally well as paroxetine . Low-dose risperidone may be an effective treatment for anxiety disorders in which panic attacks are a significant component . Trial Registration Clinical Trials.gov Identifier : The objective of this study was to evaluate the efficacy and tolerability of extended release quetiapine fumarate ( quetiapine XR ) as maintenance monotherapy for patients with generalized anxiety disorder ( GAD ) .  Time-to-event ( anxiety symptom recurrence ; maximum 52 weeks ) multicenter , r and omized-withdrawal , parallel-group , double-blind , placebo-controlled study of quetiapine XR ( 50–300 mg/day ) following open-label run-in ( 4–8 weeks ) and open-label stabilization ( ≥12 weeks ) . Primary variable : time from r and omization to anxiety event . Secondary variables included : Hamilton Anxiety Rating Scale ( HAM-A ) total , HAM-A psychic/somatic anxiety factors , Clinical Global Impression-Severity of Illness ( CGI-S ) , and Quality of Life , Enjoyment and Satisfaction Question naire ( Q-LES-Q ) scores ; adverse events ( AE ) reporting . Four hundred and thirty-two patients , stabilized on quetiapine XR , were r and omized to continue quetiapine XR ( N=216 ) or switch to placebo ( N=216 ) . Risk of anxiety symptom recurrence was significantly reduced by 81 % for quetiapine XR versus placebo : hazard ratio=0.19 ( 95 % confidence interval 0.12–0.31 ; P<0.001 ) . Fewer patients receiving quetiapine XR ( N=22 , 10.2 % ) than placebo ( N=84 , 38.9 % ) experienced anxiety symptom recurrence . Significant differences were observed between quetiapine XR and placebo in : HAM-A total , psychic/somatic , CGI-S ( all P<0.001 ) and Q-LES-Q ( P<0.05 ) scores . AEs ( > 10 % ) during open-label treatment were dry mouth , sedation , somnolence , dizziness , fatigue , and constipation . During r and omized treatment , the most common AEs for quetiapine XR were headache and nasopharyngitis  . Quetiapine XR monotherapy reduced the risk of anxiety symptom recurrence in patients with GAD stabilized on quetiapine XR , with tolerability results consistent with the known profile of quetiapine The efficacy and tolerability of extended-release quetiapine fumarate ( quetiapine XR ) once-daily monotherapy in generalized anxiety disorder ( GAD ) was assessed . This multicentre , double-blind , r and omized , placebo- and active-controlled , phase III trial consisted of a 1- to 4-wk enrolment/wash-out period and a 10-wk ( 8-wk active treatment , 2-wk post-treatment drug-discontinuation ) study period ; 873 patients were r and omized to 50 mg or 150 mg quetiapine XR , 20 mg paroxetine , or placebo . Primary endpoint was change from r and omization at week 8 in Hamilton Rating Scale for Anxiety ( HAMA ) total score . At week 8 , all active agents produced significant improvements in HAMA total and psychic subscale scores vs. placebo ; HAMA somatic subscale scores were significantly reduced only by 150 mg quetiapine XR . Significant separation from placebo ( -2.90 ) in HAMA total score was observed at day 4 for 50 mg quetiapine XR ( -4.43 , p<0.001 ) and 150 mg quetiapine XR ( -3.86 , p<0.05 ) , but not for paroxetine ( -2.69 ) . Remission ( HAMA total score 7 ) rates at week 8 were significantly higher for 150 mg quetiapine XR ( 42.6 % , p<0.01 ) and paroxetine ( 38.8 % , p<0.05 ) vs. placebo ( 27.2 % ) . The most common adverse events ( AEs ) were dry mouth , somnolence , fatigue , dizziness , and headache , for quetiapine  XR , and nausea , headache , dizziness for paroxetine . A lower proportion of patients reported sexual dysfunction with quetiapine XR [ 0.9 % ( 50 mg ) , 1.8 % ( 150 mg ) ] than with placebo ( 2.3 % ) or paroxetine ( 7.4 % ) . The incidence of AEs potentially related to extrapyramidal symptoms was : quetiapine XR : 50 mg , 6.8 % , 150 mg , 5.0 % ; placebo , 1.8 % ; and paroxetine , 8.4 % . Once-daily quetiapine XR is an effective and generally well-tolerated treatment for patients with GAD , with symptom improvement seen as early as day 4 BACKGROUND Depression and anxiety are common disorders and have substantially overlapping symptom complexes . Not surprisingly , treatment approaches are similar for both conditions with the selective serotonin reuptake inhibitors ( SSRIs ) as the initial therapy of choice . However , after first line treatments have been deployed , residual symptoms are often problematic . Augmentation strategies to address these difficulties are an area of active investigation . This study assessed aripiprazole as adjunctive therapy to SSRIs for patients with persistent anxiety symptoms complicating a depression or anxiety disorder . METHODS Ten patients who had been receiving SSRIs for at least 6 weeks , but still had clinical ly significant anxiety symptoms , were enrolled in an open label , flexibly-dosed study of adjunctive aripiprazole . Clinical status was assessed with the Hamilton Anxiety Rating Scale ( HAM-A ) , Montgomery Asberg Rating Scale ( MADRS ) , and Sheehan Disability Scale ( SDS ) . RESULTS Eighty percent of the subjects had a greater than 50 % reduction of symptoms on these outcome measures by week 2 of therapy , and continued with further decrements in symptoms throughout the course of the study . CONCLUSIONS The results of this trial provide preliminary evidence that aripiprazole may be an effective adjunctive treatment in individuals on SSRIs with residual symptoms of anxiety or depression . More rigorous double-blind studies are warranted to confirm and eluci date the potential role of aripiprazole in these conditions 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 The purpose of our study was to evaluate the efficacy and tolerability of low-dose olanzapine augmentation in selective serotonin reuptake inhibitor (SSRI)-resistant panic disorder ( PD ) with or without agoraphobia . In this 12-week , open-label study , 31 adult out patients with treatment-resistant PD who had previously failed to respond to SSRI treatment were treated with fixed dose of olanzapine ( 5 mg/d ) in addition to SSRI .  Efficacy was assessed using the Panic Attack and Anticipatory Anxiety Scale ( PAAAS ) , the Agoraphobic Cognitions Question naire ( ACQ ) , the Hamilton Rating Scale for Anxiety ( HAM-A ) , the Hamilton Rating Scale for Depression ( HAM-D ) , the Global Assessment of Functioning Scale ( GAF ) , and the Clinical Global Impression of Improvement ( CGI-I ) . Twenty-six patients completed the trial period with a dropout rate of 16.1 % . At week 12 , 21 patients were responders ( 81.8 % ) , and an overall improvement on all rating scales was observed in all patients both with or without agoraphobia . Fifteen patients ( 57.7 % ) achieved remission . Olanzapine was well tolerated and the most frequent adverse effects were mild-to-moderate weight gain and drowsiness . No extrapyramidal symptoms were reported . Olanzapine appears to be effective as augmentation strategy in the treatment of SSRI-resistant PD , but study limitations must be considered and placebo-controlled studies are needed Rationale More data are needed to guide “ next step ” strategies for patients with generalized anxiety disorder ( GAD ) remaining symptomatic despite initial pharmacotherapy . Objective This study prospect ively examined the relative efficacy of quetiapine versus placebo augmentation for individuals with GAD remaining symptomatic with initial paroxetine CR pharmacotherapy . Material s and methods Adult out patients with GAD were recruited from 2004 to 2007 at two academic centers . Phase 1 consisted of 10 weeks of open-label paroxetine CR flexibly dosed to a maximum of 62.5 mg/day . Those remaining symptomatic ( Hamilton Anxiety Scale [ HAM-A ] ≥ 7 ) at week 10 were r and omized to quetiapine or placebo augmentation flexibly dosed from 25 to 400 mg/day . Results For participants receiving paroxetine CR ( n = 50 ) , there was a significant reduction in HAM-A scores ( baseline mean ± SD = 22.4 ± 4.2 to endpoint mean ± SD = 11.2 ± 6.9 ; paired t = 12.1 , df = 49 , t < 0.0001 ) with 40 % ( n = 20 ) achieving remission . Counter to our hypothesis , we did not find significant benefit for quetiapine augmentation of continued paroxetine CR ( HAM-A reduction mean ± SD = 2.6 ± 5.8 points quetiapine , 0.3 ± 5.5 points placebo ; t = 0.98 , df = 20 , p = n.s . ) in the r and omized sample ( n =  
    Output:
    