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: In this paper , we review and discuss ten common method ological mistakes found in  retrospective chart review s. The retrospective chart review is a widely applicable research methodology that can be used by healthcare disciplines as a means to direct subsequent prospect i ve investigations . In many cases in this review , we have also provided suggestions or accessible re sources that research ers can apply as a “ best practice s ” guide when planning , conducting , or review ing this investigative method Rationale Fragile X syndrome ( FXS ) is the most common inherited form of developmental disability and most common single gene cause of autism . Persons with FXS frequently exhibit irritable behavior marked by aggression , self-injury , and severe tantrums . Despite frequent clinical use of atypical antipsychotic drugs to target this behavioral cluster , no systematic trials to date have assessed the efficacy and safety of these drugs in persons with FXS . Methods We conducted a prospect i ve open-label 12-week trial of aripiprazole in 12 persons aged 6–25 years ( mean age , 14.3 years ) with FXS who were free of concomitant psychoactive drugs .  Results Aripiprazole use ( mean dose , 9.8 mg/day ) was associated with treatment response ( defined by a Clinical Global Impressions-Improvement scale score of much improved or very much improved and a ≥25 % improvement on the Aberrant Behavior Checklist-Irritability subscale ) in 10 of 12 ( 87 % ) persons . Two individuals ( 13 % ) discontinued aripiprazole prior to study completion due to adverse events . One discontinuation was due to akathisia , mild drooling , and mild tiredness and the other due to moderate tiredness and moderate drooling . No significant changes in vital signs including weight or laboratory measures occurred during treatment with aripiprazole . Conclusions Aripiprazole was generally safe and well tolerated and was associated with significant improvement in irritable behavior . Given these findings , a double-blind , placebo-controlled study of aripiprazole in FXS is warranted INTRODUCTION Retrospective research has become largely undervalued and underutilized in child and adolescent psychiatry with the increasing singular focus on r and omized control trials , despite the wealth of clinical ly relevant data available in historical medical records . In this paper a systematic and scientific approach to chart review research methodology for psychiatry is described . METHOD Informed by available literature , a method ological stepwise approach for retrospective chart review was developed . RESULTS A nine step method aim ed at maximizing benefits and minimizing limitations is discussed . CONCLUSIONS Retrospective chart review is an important methodology with distinct advantages and has the potential to provide psychiatry with valuable research opportunities . This method of study should not be lost in the field of psychiatry OBJECTIVE The aim of this study was to conduct a prospect i ve safety and tolerability study of aripiprazole for the treatment of tics in children and adolescents with Tourette 's disorder ( TD ) . METHOD Eleven subjects ( 10 males ) with TD ( age 9 - 19 years , mean 13.36 , st and ard deviation [ SD ] 3.33 ) who did not respond or were unable to tolerate previous tic medication were treated with aripiprazole in an open-label , flexible-dosing study over 10 weeks . Tic severity was rated using the Yale Global Tic Severity Scale ( YGTSS ) and the Clinical Global Impressions Scale for tics ( CGI-Tics ) at baseline and at follow-up . RESULTS The mean ( + /-SD ) daily dose for aripiprazole was 4.5 + /- 3.0 mg . Mean ( + /-SD ) YGTSS Global Severity scores reduced from 61.82 + /- 13.49 at baseline to 33.73 + /- 15.18 at end point ; mean YGTSS total tic scores reduced from 28.18 + /- 7.74 at baseline to 16.73 + /- 7.54 at end point . Mean ( + /-SD ) CGI-Tic severity scores reduced from 4.45 + /- 0.52 ( moderate-marked ) at baseline to 3.18 + /- 0.60 ( mild ) at end point . On the CGI-Tic improvement scale , 10 ( 91 % ) subjects achieved 1 ( " very much improved " ) or 2 ( " much improved " ) at end point . Most common adverse effects included appetite increase and weight gain in 5 subjects , mild extrapyramidal effects in 7 subjects , and headaches and tiredness/fatigue in 7 subjects ; 1 subject experienced akathisia and muscle cramps . CONCLUSION Aripiprazole appears to be a safe and tolerable treatment in children and adolescents with TD that appears to reduce tics ; it should be further investigated as a treatment option in controlled trials OBJECTIVE : The objective of this study was to evaluate short-term efficacy and safety of aripiprazole in the treatment of irritability in children and adolescents with autistic disorder who were manifesting behaviors such as tantrums , aggression , self-injurious behavior , or a combination of these . METHODS : This 8-week , double-blind , r and omized , placebo-controlled , parallel-group study was conducted of children and adolescents ( aged 6–17 years ) with autistic disorder . Patients were r and omly assigned ( 1:1 ) to flexibly dosed aripiprazole ( target dosage : 5 , 10 , or 15 mg/day ) or placebo . Efficacy outcome measures included the Aberrant Behavior Checklist irritability subscale and the Clinical Global Impression – Improvement score ( CGI-I ) . Safety and tolerability were also assessed . RESULTS : Ninety-eight patients were r and omly assigned to receive placebo ( n = 51 ) or aripiprazole ( n = 47 ) . Mean improvement in Aberrant Behavior Checklist irritability subscale score was significantly greater with aripiprazole than with placebo from week 1 through week 8 . Aripiprazole demonstrated significantly greater global improvements than placebo , as assessed by the mean CGI-I score from week 1 through week 8 ; however , clinical ly significant residual symptoms may still persist for some patients . Discontinuation rates as a result of adverse events ( AEs ) were 10.6 % for aripiprazole and 5.9 % for placebo . Extrapyramidal symptom-related AE rates were 14.9 % for aripiprazole and 8.0 % for placebo . No serious AEs were reported . Mean weight gain was 2.0 kg on aripiprazole and 0.8 kg on placebo at week 8 . CONCLUSIONS : Aripiprazole was efficacious in children and adolescents with irritability associated with autistic disorder and was generally safe and well tolerated Forty-six patients ( 36 male , mean age 11.9 ± 2.6 ) with a variety of diagnoses and with significant aggressive behavior were treated in an open , non-r and omized fashion with Aripiprazole or Ziprasidone . Patients were diagnosed with the Mini International Neuropsychiatric Interview and the Child/Adolescent Symptom Inventory . The primary outcome measure was the Overt Aggression Scale ( OAS ) . After 2 months , 34 patients were still in treatment . The average improvement of the OAS in these 34 patients was 63 % . Clinical Global Impression-Improvement Scale was 2.1 ± 1.2 . Neither at baseline , nor at 2 months , were there any statistically significant differences between the Aripiprazole and Ziprasidone groups . Sedation was the most common side effect OBJECTIVES This study aim ed to investigate the efficacy and tolerability of aripiprazole , an atypical antipsychotic with dual agonist and antagonist actions toward dopaminergic imbalance and partial serotonin-2A receptor antagonism , for treating children and adolescents with tic disorders . METHOD Twenty-four out patients aged 7 to 18 years with DSM-IV-diagnosed tic disorders were treated with aripiprazole using an open-label , flexible dosing schedule for 8 weeks from January 2005 to August 2006 . The Korean versions of the Yale Global Tic Severity Scale ( YGTSS ) , the Clinical Global Impressions-Improvement scale ( CGI-I ) , and the CGI-Severity of Illness scale ( CGI-S ) scores were used to measure the drug efficacy . Side effects were assessed using an adverse effect checklist , the Extrapyramidal Symptom Rating Scale , height and weight measurements , laboratory tests , and electrocardiograms . RESULTS Aripiprazole was prematurely discontinued in 6 ( 25 % ) of the 24 subjects due to intolerable adverse effects . After a mean of 9.8 + /- 4.8 mg/day of aripiprazole for 8 weeks , there was a 52.8 % reduction in the mean YGTSS Total Tic scores ( from 26.7 + /- 5.5 to 12.6 + /- 7.6 , p < .001 ) . Nineteen patients ( 79.2 % ) showed either much improved or very much improved status according to the CGI-I. The CGI-S score was also reduced ( from 5.5 + /- 0.5 to 3.0 + /- 1.4 , p < .001 ) . The initial dose of 5 mg/day aripiprazole for 2 weeks was also found to reduce tic symptoms significantly ( Total Tic scores decreased from 26.7 + /- 5.5 to 17.9 + /- 8.7 , p < .001 ) . Fourteen subjects ( 58.3 % ) experienced unwanted side effects , the most common being hypersomnia ( 37.5 % ) , nausea ( 20.8 % ) , and headache ( 16.6 % ) . CONCLUSION This open-label study suggests that aripiprazole is an efficacious and safe treatment for children and adolescents with tic disorders OBJECTIVE To examine the short-term efficacy and tolerability of aripiprazole for children and adolescents with Tourette 's disorder . METHOD This 10-week multicenter , double-blind , r and omized , placebo-controlled trial was conducted from August 2008 to April 2010 . Children and adolescents ( aged 6 - 18 years ) with a DSM-IV diagnosis of Tourette 's disorder and a Yale Global Tic Severity Scale total tic score of 22 or more were r and omly assigned ( 1:1 ratio ) to placebo or aripiprazole . The primary outcome measure was mean change from baseline in the total tic score on the Yale Global Tic Severity Scale ( last observation carried forward ) . Assessment s of safety and tolerability included spontaneously reported adverse events , extrapyramidal symptoms , serum prolactin level , metabolic variables , and other laboratory evaluations . RESULTS Of 61 subjects , 89 % completed the study . Patients who received aripiprazole demonstrated a significant reduction from baseline to end of study on the mean ( SD ) total tic score of the Yale Global Tic Severity Scale compared to those who received placebo ( -15.0 [ 8.4 ] and -9.6 [ 8.8 ] , respectively , P=.0196 ) . Response rate on the Tourette 's Syndrome Clinical Global Impression-Improvement was 66 % and 45 % in the aripiprazole and placebo groups , respectively . Mean decrease in the Tourette 's Syndrome Clinical Global Impression-Severity of Illness score was significantly different between the groups ( P=.0321 ) . In general , aripiprazole was well tolerated and there were no early discontinuations due to adverse events . The incidence of treatment-emergent adverse events between the groups was not significantly different ( P=.7550 ) . While aripiprazole decreased serum prolactin concentration ( P<.0001 ) , it increased mean body weight , body mass index , and waist circumference significantly ( P=.0055 , P=.0142 , and P=.0270 , respectively ) . CONCLUSIONS In comparison with placebo , aripiprazole was efficacious , generally tolerated and safe in the short-term treatment of children and adolescents with Tourette 's disorder . TRIAL REGISTRATION Clinical Trials.gov identifier : NCT00706589 OBJECTIVE Evaluate the long-term safety and tolerability of aripiprazole in the treatment of irritability in pediatric subjects ( 6 - 17 years ) with autistic disorder . METHOD A 52-week , open-label , flexibly dosed ( 2 - 15 mg/d ) study of the safety and tolerability of aripiprazole in out patients with a DSM-IV-TR diagnosis of autistic disorder who either had completed 1 of 2 antecedent , 8-week r and omized trials or were enrolled de novo ( ie , not treated in the r and omized trials ) .  Safety and tolerability measures included incidences of adverse events , extrapyramidal symptoms , weight , metabolic measures , vital signs , and other clinical assessment s. RESULTS Subjects were enrolled between September 2006 and June 2009 . Three hundred thirty subjects entered the treatment phase : 86 de novo , 174 prior aripiprazole , and 70 prior placebo . A total of 199 ( 60.3 % ) subjects completed 52 weeks of treatment . Adverse events were experienced by 286/330 subjects ( 8 
    Output:
    
agent
The side effects ‘ EPS ’ , ‘ parkinsonism ’ , and ‘ tremor ’ were significantly more common in children and adolescents treated with aripiprazole than in those treated with placebo .
Conclusion Our meta- analysis provides evidence for a non-negligible incidence of acute EPS in children and adolescents treated with aripiprazole .
***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: In this paper , we review and discuss ten common method ological mistakes found in  retrospective chart review s. The retrospective chart review is a widely applicable research methodology that can be used by healthcare disciplines as a means to direct subsequent prospect i ve investigations . In many cases in this review , we have also provided suggestions or accessible re sources that research ers can apply as a “ best practice s ” guide when planning , conducting , or review ing this investigative method Rationale Fragile X syndrome ( FXS ) is the most common inherited form of developmental disability and most common single gene cause of autism . Persons with FXS frequently exhibit irritable behavior marked by aggression , self-injury , and severe tantrums . Despite frequent clinical use of atypical antipsychotic drugs to target this behavioral cluster , no systematic trials to date have assessed the efficacy and safety of these drugs in persons with FXS . Methods We conducted a prospect i ve open-label 12-week trial of aripiprazole in 12 persons aged 6–25 years ( mean age , 14.3 years ) with FXS who were free of concomitant psychoactive drugs .  Results Aripiprazole use ( mean dose , 9.8 mg/day ) was associated with treatment response ( defined by a Clinical Global Impressions-Improvement scale score of much improved or very much improved and a ≥25 % improvement on the Aberrant Behavior Checklist-Irritability subscale ) in 10 of 12 ( 87 % ) persons . Two individuals ( 13 % ) discontinued aripiprazole prior to study completion due to adverse events . One discontinuation was due to akathisia , mild drooling , and mild tiredness and the other due to moderate tiredness and moderate drooling . No significant changes in vital signs including weight or laboratory measures occurred during treatment with aripiprazole . Conclusions Aripiprazole was generally safe and well tolerated and was associated with significant improvement in irritable behavior . Given these findings , a double-blind , placebo-controlled study of aripiprazole in FXS is warranted INTRODUCTION Retrospective research has become largely undervalued and underutilized in child and adolescent psychiatry with the increasing singular focus on r and omized control trials , despite the wealth of clinical ly relevant data available in historical medical records . In this paper a systematic and scientific approach to chart review research methodology for psychiatry is described . METHOD Informed by available literature , a method ological stepwise approach for retrospective chart review was developed . RESULTS A nine step method aim ed at maximizing benefits and minimizing limitations is discussed . CONCLUSIONS Retrospective chart review is an important methodology with distinct advantages and has the potential to provide psychiatry with valuable research opportunities . This method of study should not be lost in the field of psychiatry OBJECTIVE The aim of this study was to conduct a prospect i ve safety and tolerability study of aripiprazole for the treatment of tics in children and adolescents with Tourette 's disorder ( TD ) . METHOD Eleven subjects ( 10 males ) with TD ( age 9 - 19 years , mean 13.36 , st and ard deviation [ SD ] 3.33 ) who did not respond or were unable to tolerate previous tic medication were treated with aripiprazole in an open-label , flexible-dosing study over 10 weeks . Tic severity was rated using the Yale Global Tic Severity Scale ( YGTSS ) and the Clinical Global Impressions Scale for tics ( CGI-Tics ) at baseline and at follow-up . RESULTS The mean ( + /-SD ) daily dose for aripiprazole was 4.5 + /- 3.0 mg . Mean ( + /-SD ) YGTSS Global Severity scores reduced from 61.82 + /- 13.49 at baseline to 33.73 + /- 15.18 at end point ; mean YGTSS total tic scores reduced from 28.18 + /- 7.74 at baseline to 16.73 + /- 7.54 at end point . Mean ( + /-SD ) CGI-Tic severity scores reduced from 4.45 + /- 0.52 ( moderate-marked ) at baseline to 3.18 + /- 0.60 ( mild ) at end point . On the CGI-Tic improvement scale , 10 ( 91 % ) subjects achieved 1 ( " very much improved " ) or 2 ( " much improved " ) at end point . Most common adverse effects included appetite increase and weight gain in 5 subjects , mild extrapyramidal effects in 7 subjects , and headaches and tiredness/fatigue in 7 subjects ; 1 subject experienced akathisia and muscle cramps . CONCLUSION Aripiprazole appears to be a safe and tolerable treatment in children and adolescents with TD that appears to reduce tics ; it should be further investigated as a treatment option in controlled trials OBJECTIVE : The objective of this study was to evaluate short-term efficacy and safety of aripiprazole in the treatment of irritability in children and adolescents with autistic disorder who were manifesting behaviors such as tantrums , aggression , self-injurious behavior , or a combination of these . METHODS : This 8-week , double-blind , r and omized , placebo-controlled , parallel-group study was conducted of children and adolescents ( aged 6–17 years ) with autistic disorder . Patients were r and omly assigned ( 1:1 ) to flexibly dosed aripiprazole ( target dosage : 5 , 10 , or 15 mg/day ) or placebo . Efficacy outcome measures included the Aberrant Behavior Checklist irritability subscale and the Clinical Global Impression – Improvement score ( CGI-I ) . Safety and tolerability were also assessed . RESULTS : Ninety-eight patients were r and omly assigned to receive placebo ( n = 51 ) or aripiprazole ( n = 47 ) . Mean improvement in Aberrant Behavior Checklist irritability subscale score was significantly greater with aripiprazole than with placebo from week 1 through week 8 . Aripiprazole demonstrated significantly greater global improvements than placebo , as assessed by the mean CGI-I score from week 1 through week 8 ; however , clinical ly significant residual symptoms may still persist for some patients . Discontinuation rates as a result of adverse events ( AEs ) were 10.6 % for aripiprazole and 5.9 % for placebo . Extrapyramidal symptom-related AE rates were 14.9 % for aripiprazole and 8.0 % for placebo . No serious AEs were reported . Mean weight gain was 2.0 kg on aripiprazole and 0.8 kg on placebo at week 8 . CONCLUSIONS : Aripiprazole was efficacious in children and adolescents with irritability associated with autistic disorder and was generally safe and well tolerated Forty-six patients ( 36 male , mean age 11.9 ± 2.6 ) with a variety of diagnoses and with significant aggressive behavior were treated in an open , non-r and omized fashion with Aripiprazole or Ziprasidone . Patients were diagnosed with the Mini International Neuropsychiatric Interview and the Child/Adolescent Symptom Inventory . The primary outcome measure was the Overt Aggression Scale ( OAS ) . After 2 months , 34 patients were still in treatment . The average improvement of the OAS in these 34 patients was 63 % . Clinical Global Impression-Improvement Scale was 2.1 ± 1.2 . Neither at baseline , nor at 2 months , were there any statistically significant differences between the Aripiprazole and Ziprasidone groups . Sedation was the most common side effect OBJECTIVES This study aim ed to investigate the efficacy and tolerability of aripiprazole , an atypical antipsychotic with dual agonist and antagonist actions toward dopaminergic imbalance and partial serotonin-2A receptor antagonism , for treating children and adolescents with tic disorders . METHOD Twenty-four out patients aged 7 to 18 years with DSM-IV-diagnosed tic disorders were treated with aripiprazole using an open-label , flexible dosing schedule for 8 weeks from January 2005 to August 2006 . The Korean versions of the Yale Global Tic Severity Scale ( YGTSS ) , the Clinical Global Impressions-Improvement scale ( CGI-I ) , and the CGI-Severity of Illness scale ( CGI-S ) scores were used to measure the drug efficacy . Side effects were assessed using an adverse effect checklist , the Extrapyramidal Symptom Rating Scale , height and weight measurements , laboratory tests , and electrocardiograms . RESULTS Aripiprazole was prematurely discontinued in 6 ( 25 % ) of the 24 subjects due to intolerable adverse effects . After a mean of 9.8 + /- 4.8 mg/day of aripiprazole for 8 weeks , there was a 52.8 % reduction in the mean YGTSS Total Tic scores ( from 26.7 + /- 5.5 to 12.6 + /- 7.6 , p < .001 ) . Nineteen patients ( 79.2 % ) showed either much improved or very much improved status according to the CGI-I. The CGI-S score was also reduced ( from 5.5 + /- 0.5 to 3.0 + /- 1.4 , p < .001 ) . The initial dose of 5 mg/day aripiprazole for 2 weeks was also found to reduce tic symptoms significantly ( Total Tic scores decreased from 26.7 + /- 5.5 to 17.9 + /- 8.7 , p < .001 ) . Fourteen subjects ( 58.3 % ) experienced unwanted side effects , the most common being hypersomnia ( 37.5 % ) , nausea ( 20.8 % ) , and headache ( 16.6 % ) . CONCLUSION This open-label study suggests that aripiprazole is an efficacious and safe treatment for children and adolescents with tic disorders OBJECTIVE To examine the short-term efficacy and tolerability of aripiprazole for children and adolescents with Tourette 's disorder . METHOD This 10-week multicenter , double-blind , r and omized , placebo-controlled trial was conducted from August 2008 to April 2010 . Children and adolescents ( aged 6 - 18 years ) with a DSM-IV diagnosis of Tourette 's disorder and a Yale Global Tic Severity Scale total tic score of 22 or more were r and omly assigned ( 1:1 ratio ) to placebo or aripiprazole . The primary outcome measure was mean change from baseline in the total tic score on the Yale Global Tic Severity Scale ( last observation carried forward ) . Assessment s of safety and tolerability included spontaneously reported adverse events , extrapyramidal symptoms , serum prolactin level , metabolic variables , and other laboratory evaluations . RESULTS Of 61 subjects , 89 % completed the study . Patients who received aripiprazole demonstrated a significant reduction from baseline to end of study on the mean ( SD ) total tic score of the Yale Global Tic Severity Scale compared to those who received placebo ( -15.0 [ 8.4 ] and -9.6 [ 8.8 ] , respectively , P=.0196 ) . Response rate on the Tourette 's Syndrome Clinical Global Impression-Improvement was 66 % and 45 % in the aripiprazole and placebo groups , respectively . Mean decrease in the Tourette 's Syndrome Clinical Global Impression-Severity of Illness score was significantly different between the groups ( P=.0321 ) . In general , aripiprazole was well tolerated and there were no early discontinuations due to adverse events . The incidence of treatment-emergent adverse events between the groups was not significantly different ( P=.7550 ) . While aripiprazole decreased serum prolactin concentration ( P<.0001 ) , it increased mean body weight , body mass index , and waist circumference significantly ( P=.0055 , P=.0142 , and P=.0270 , respectively ) . CONCLUSIONS In comparison with placebo , aripiprazole was efficacious , generally tolerated and safe in the short-term treatment of children and adolescents with Tourette 's disorder . TRIAL REGISTRATION Clinical Trials.gov identifier : NCT00706589 OBJECTIVE Evaluate the long-term safety and tolerability of aripiprazole in the treatment of irritability in pediatric subjects ( 6 - 17 years ) with autistic disorder . METHOD A 52-week , open-label , flexibly dosed ( 2 - 15 mg/d ) study of the safety and tolerability of aripiprazole in out patients with a DSM-IV-TR diagnosis of autistic disorder who either had completed 1 of 2 antecedent , 8-week r and omized trials or were enrolled de novo ( ie , not treated in the r and omized trials ) .  Safety and tolerability measures included incidences of adverse events , extrapyramidal symptoms , weight , metabolic measures , vital signs , and other clinical assessment s. RESULTS Subjects were enrolled between September 2006 and June 2009 . Three hundred thirty subjects entered the treatment phase : 86 de novo , 174 prior aripiprazole , and 70 prior placebo . A total of 199 ( 60.3 % ) subjects completed 52 weeks of treatment . Adverse events were experienced by 286/330 subjects ( 8 
    Output:
    