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 test the hypotheses that in children with attention-deficit/hyperactivity disorder ( ADHD ) ( 1 ) symptoms of ADHD , oppositional defiant disorder , and overall functioning are significantly improved by methylpheni date combined with intensive multimodal psychosocial treatment compared with methylpheni date alone and with methylpheni date plus attention control and ( 2 ) more children receiving combined treatment can be taken off methylpheni date . METHOD One hundred three children with ADHD ( ages 7 - 9 ) , free of conduct and learning disorders , who responded to short-term methylpheni date were r and omized for 2 years to ( 1 ) methylpheni date alone ; ( 2 ) methylpheni date plus psychosocial treatment that included parent training and counseling , social skills training , psychotherapy , and academic assistance , or ( 3 ) methylpheni date plus attention psychosocial control treatment . Assessment s included parent , teacher , and psychiatrist ratings , and observations in academic and gym classes . RESULTS Combination treatment did not lead to superior functioning and did not facilitate methylpheni date discontinuation . Significant improvement occurred across all treatments and continued over 2 years . CONCLUSIONS In stimulant-responsive children with ADHD , there is no support for adding ambitious long-term psychosocial intervention to improve ADHD and oppositional defiant disorder symptoms . Significant benefits from methylpheni date were stable over 2 years OBJECTIVE Atomoxetine is an investigational , nonstimulant pharmacotherapy being studied as potential treatment for attention-deficit/hyperactivity disorder ( ADHD ) . It is thought to act via blockade of the presynaptic norepinephrine transporter in the brain . We assessed the efficacy of 3 doses of atomoxetine compared with placebo in children and adolescents with ADHD . METHODS A total of 297 children and adolescents who were 8 to 18 years of age and had ADHD as defined by the Diagnostic and Statistical Manual of Mental Disorders , 4th edition , were r and omized to placebo or atomoxetine dosed on a weight-adjusted basis at 0.5 mg/kg/day , 1.2 mg/kg/day , or 1.8 mg/kg/day for an 8-week period . ADHD symptoms , affective symptoms , and social and family functioning were assessed using parent and investigator rating scales . RESULTS Approximately 71 % of children enrolled were male , approximately 67 % met criteria for mixed subtype ( both inattentive and hyperactive/impulsive symptoms ) , and the only common psychiatric comorbidity was oppositional defiant disorder ( approximately 38 % of the sample ) . At baseline , symptom severity was rated as moderate to severe for most children . At endpoint , atomoxetine 1.2 mg/kg/day and 1.8 mg/kg/day were consistently associated with superior outcomes in ADHD symptoms compared with placebo and were not different from each other . The dose of 0.5 mg/kg/day was associated with intermediate efficacy between placebo and the 2 higher doses , suggesting a grade d dose-response . Social and family functioning also were improved in the atomoxetine groups compared with placebo with statistically significant improvements in measures of children 's ability to meet psychosocial role expectations and parental impact . Discontinuations as a result of adverse events were < 5 % for all groups . CONCLUSION Among children and adolescents aged 8 to 18 , atomoxetine was superior to placebo in reducing ADHD symptoms and in improving social and family functioning symptoms . Atomoxetine was associated with a grade d dose-response , and 1.2 mg/kg/day seems to be as effective as 1.8 mg/kg/day and is likely to be the appropriate initial target dose for most patients . Treatment with atomoxetine was safe and well tolerated BACKGROUND Previous studies have demonstrated the short-term efficacy of pharmacotherapy and behavior therapy for attention-deficit/hyperactivity disorder ( ADHD ) , but no longer-term ( i.e. , > 4 months ) investigations have compared these 2 treatments or their combination . METHODS A group of 579 children with ADHD Combined Type , aged 7 to 9.9 years , were assigned to 14 months of medication management ( titration followed by monthly visits ) ; intensive behavioral treatment ( parent , school , and child components , with therapist involvement gradually reduced over time ) ; the two combined ; or st and ard community care ( treatments by community providers ) . Outcomes were assessed in multiple domains before and during treatment and at treatment end point ( with the combined treatment and medication management groups continuing medication at all assessment points ) . Data were analyzed through intent-to-treat r and om-effects regression procedures . RESULTS All 4 groups showed sizable reductions in symptoms over time , with significant differences among them in degrees of change . For most ADHD symptoms , children in the combined treatment and medication management groups showed significantly greater improvement than those given intensive behavioral treatment and community care . Combined and medication management treatments did not differ significantly on any direct comparisons , but in several instances ( oppositional/aggressive symptoms , internalizing symptoms , teacher-rated social skills , parent-child relations , and reading achievement )  combined treatment proved superior to intensive behavioral treatment and /or community care while medication management did not . Study medication strategies were superior to community care treatments , despite the fact that two thirds of community-treated subjects received medication during the study period . CONCLUSIONS For ADHD symptoms , our carefully crafted medication management was superior to behavioral treatment and to routine community care that included medication . Our combined treatment did not yield significantly greater benefits than medication management for core ADHD symptoms , but may have provided modest advantages for non-ADHD symptom and positive functioning outcomes OBJECTIVES Mathematical modeling is used widely in economic evaluations of pharmaceuticals and other health-care technologies . Users of models in government and the private sector need to be able to evaluate the quality of models according to scientific criteria of good practice . This report describes the consensus of a task force convened to provide modelers with guidelines for conducting and reporting modeling studies . METHODS The task force was appointed with the advice and consent of the Board of Directors of ISPOR . Members were experienced developers or users of models , worked in academia and industry , and came from several countries in North America and Europe . The task force met on three occasions , conducted frequent correspondence and exchanges of drafts by electronic mail , and solicited comments on three drafts from a core group of external review ers and more broadly from the membership of ISPOR . RESULTS Criteria for assessing the quality of models fell into three areas : model structure , data used as inputs to models , and model validation . Several major themes cut across these areas . Models and their results should be represented as aids to decision making , not as statements of scientific fact ; therefore , it is inappropriate to dem and that models be vali date d prospect ively before use . However , model assumptions regarding causal structure and parameter estimates should be continually assessed against data , and models should be revised accordingly . Structural assumptions and parameter estimates should be reported clearly and explicitly , and opportunities for users to appreciate the conditional relationship between inputs and outputs should be provided through sensitivity analyses . CONCLUSIONS Model-based evaluations are a valuable re source for health-care decision makers . It is the responsibility of model developers to conduct modeling studies according to the best practicable st and ards of quality and to communicate results with adequate disclosure of assumptions and with the caveat that conclusions are conditional upon the assumptions and data on which the model is built OBJECTIVE Clinical trials in psychiatry frequently fail to maximize clinical utility for practicing clinicians , or , stated differently , available evidence is not perceived by clinicians ( and other decision makers ) as sufficiently relevant to clinical practice , thereby diluting its impact . To attain maximum clinical relevance and acceptability , research ers must conduct clinical trials design ed to meet the needs of clinicians and others who are making decisions about patients ' care . The authors present the case for psychiatry 's adoption of the practical clinical trials model , which is widely used in research in other areas of medicine . METHOD The authors outline the characteristics and scope of practical clinical trials , give examples of practical clinical trials , and discuss the challenges of using the practical clinical trials model in psychiatry , including issues of funding . RESULTS Practical clinical trials , which are intended to provide generalizable answers to important clinical questions without bias , are characterized by eight key features : a straightforward clinical ly relevant question , a representative sample of patients and practice setting s , sufficient power to identify modest clinical ly relevant effects , r and omization to protect against bias , clinical uncertainty regarding the outcome of treatment at the patient level , assessment and treatment protocol s that enact best clinical practice s , simple and clinical ly relevant outcomes , and limited subject and investigator burden . CONCLUSIONS To implement the practical clinical trials model in psychiatry will require stable funding for network construction and maintenance plus method ological innovation in governance and trial selection , assessment , treatment , data management , site management , and data analytic procedures BACKGROUND The thrice daily dosing regimen of immediate release methylpheni date ( IR-MPH ) for Attention Deficit/Hyperactivity Disorder ( ADHD ) requires in-school dosing , leading to issues surrounding dispensing and storage of controlled substances by school personnel and concerns over children?s privacy and the embarrassment associated with taking medication in public at school . OROS-methylpheni date ( OROS-MPH ) is a once-daily controlled-release formulation of methylpheni date ( MPH ) developed to overcome some of the limitations associated with IR-MPH and first-generation sustained-release formulations . R and omized , controlled trials ( RCTs ) that focus on treatment efficacy provide the best evidence for demonstrating whether an intervention works , but under ideal conditions one can not discount the importance of efficacy study results . However , the most useful information to clinicians comes from an effectiveness study design . OBJECTIVES To evaluate the effectiveness and tolerability of OROS-MPH versus usual care with IR-MPH in children aged 6 to 12 years with ADHD . METHODS This 8 week , multicentre , open-label study r and omized 147 subjects to either once-daily OROS-MPH or usual care with IR-MPH .  Subjects were titrated to a clinical ly effective dose of either study medication over 4 weeks and maintained on that dose for an additional 4 weeks . The SNAP-IV parent-rating scale was used to assess effectiveness . RESULTS OROS-MPH showed statistically significant superiority to IR-MPH in remission rate based on the 18 ADHD symptoms ( p=0.0002 , X2=13.8 , df=1 ) and severity of ADHD and ODD symptoms ( p=0.004 , F=8.4 , df=1,127 ) , as well as on the following secondary assessment s : IOWA Conners , Conners Parent Rating Scale ( short version ) , Parent Stress Index , ( short version ) ; Visual Analogue Scale for social play ; Clinical Global Impression-Severity , Clinical Global Impression-Improvement and Parent Satisfaction with treatment .  OROS-MPH and IR-MPH were both well tolerated with a similar side effect profile . CONCLUSIONS Once-daily OROS-MPH is significantly more effective than usual care with IR-MPH based on multiple outcome measures including remission rate This community-based study was design ed to evaluate treatment outcomes with OROS ® methylpheni date ( MPH ) and atomoxetine in children with attentiondeficit/hyperactivity disorder ( ADHD ) , as assessed by physicians and parents in a setting that resembles clinical practice . In a multicenter , prospect i ve , open-label study , children 6 to 12 years of age with ADHD were r and omized ( 2:1 , respectively ) to 3 weeks of treatment with once-daily OROS MPH or atomoxetine . Investigatorrated measures of symptoms included the ADHD Rating Scale ( ADHD-RS ) and the Clinical Global Impression-Improvement of Illness scale ( CGI-I ) . Assessment s were made at baseline and during a telephone interview in week 1 , a clinic visit in week 2 , and a final clinic visit in week 3 . In total , 1323 patients received OROS MPH ( n=850 ) or atomoxetine ( n=473 ) . Significant reductions from baseline in investigator-evaluated ADHD-RS scores were observed among patients receiving OROS MPH and those receiving atomoxetine . At the end of the study , mean decreases from baseline ADHD-RS scores were 20.24 for OROS MPH and 16 for atomoxetine ( P < .001 ) . Between-treatment differences appeared to increase over time ( 2.77 , 3.44 , and 4.24 at weeks 1 , 2 , and 3 , respectively ; P < .001 ) . Treatment response ( ie , 25 % reduction from baseline ADHD-RS scores ) was significantly greater at each evaluation for patients taking OROS MPH than for those taking atomoxetine ( P < .001 ) . Similar percentages of patients taking OROS MPH ( 4.8 % ) and atomoxetine ( 5.5 % ) withdrew because of adverse events . Although community-based studies often lack the control of r and omized , placebo-controlled trials , these results nevertheless suggest greater ADHD symptom improvement  with OROS MPH compared with atomoxetine This report introduces a method for obtaining behavioral time-response information for a short-acting psychotropic drug ( methylpheni date [ Ritalin ] ) that is widely used to treat behaviorally hyperactive children . We used a laboratory learning task to document that between one and two hours after the administration of a single dose of methylpheni date , the drug exerts its maximum effect on performance in a learning task in the laboratory . This effect on cognitive performance dissipates within the same day . This rapid and transient effect of methylpheni date makes it possible to class 
    Output:
    
agent
Results The technology assessment was unable to differentiate between the various drugs in terms of efficacy , and its economic model was ultimately driven by cost differences .
While the assessment concluded that the economic model " clearly identified an optimal treatment strategy " with first-line dexamphetamine , the NICE appraisal committee subsequently found it impossible to distinguish between the different strategies on grounds of cost-effectiveness .
***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 test the hypotheses that in children with attention-deficit/hyperactivity disorder ( ADHD ) ( 1 ) symptoms of ADHD , oppositional defiant disorder , and overall functioning are significantly improved by methylpheni date combined with intensive multimodal psychosocial treatment compared with methylpheni date alone and with methylpheni date plus attention control and ( 2 ) more children receiving combined treatment can be taken off methylpheni date . METHOD One hundred three children with ADHD ( ages 7 - 9 ) , free of conduct and learning disorders , who responded to short-term methylpheni date were r and omized for 2 years to ( 1 ) methylpheni date alone ; ( 2 ) methylpheni date plus psychosocial treatment that included parent training and counseling , social skills training , psychotherapy , and academic assistance , or ( 3 ) methylpheni date plus attention psychosocial control treatment . Assessment s included parent , teacher , and psychiatrist ratings , and observations in academic and gym classes . RESULTS Combination treatment did not lead to superior functioning and did not facilitate methylpheni date discontinuation . Significant improvement occurred across all treatments and continued over 2 years . CONCLUSIONS In stimulant-responsive children with ADHD , there is no support for adding ambitious long-term psychosocial intervention to improve ADHD and oppositional defiant disorder symptoms . Significant benefits from methylpheni date were stable over 2 years OBJECTIVE Atomoxetine is an investigational , nonstimulant pharmacotherapy being studied as potential treatment for attention-deficit/hyperactivity disorder ( ADHD ) . It is thought to act via blockade of the presynaptic norepinephrine transporter in the brain . We assessed the efficacy of 3 doses of atomoxetine compared with placebo in children and adolescents with ADHD . METHODS A total of 297 children and adolescents who were 8 to 18 years of age and had ADHD as defined by the Diagnostic and Statistical Manual of Mental Disorders , 4th edition , were r and omized to placebo or atomoxetine dosed on a weight-adjusted basis at 0.5 mg/kg/day , 1.2 mg/kg/day , or 1.8 mg/kg/day for an 8-week period . ADHD symptoms , affective symptoms , and social and family functioning were assessed using parent and investigator rating scales . RESULTS Approximately 71 % of children enrolled were male , approximately 67 % met criteria for mixed subtype ( both inattentive and hyperactive/impulsive symptoms ) , and the only common psychiatric comorbidity was oppositional defiant disorder ( approximately 38 % of the sample ) . At baseline , symptom severity was rated as moderate to severe for most children . At endpoint , atomoxetine 1.2 mg/kg/day and 1.8 mg/kg/day were consistently associated with superior outcomes in ADHD symptoms compared with placebo and were not different from each other . The dose of 0.5 mg/kg/day was associated with intermediate efficacy between placebo and the 2 higher doses , suggesting a grade d dose-response . Social and family functioning also were improved in the atomoxetine groups compared with placebo with statistically significant improvements in measures of children 's ability to meet psychosocial role expectations and parental impact . Discontinuations as a result of adverse events were < 5 % for all groups . CONCLUSION Among children and adolescents aged 8 to 18 , atomoxetine was superior to placebo in reducing ADHD symptoms and in improving social and family functioning symptoms . Atomoxetine was associated with a grade d dose-response , and 1.2 mg/kg/day seems to be as effective as 1.8 mg/kg/day and is likely to be the appropriate initial target dose for most patients . Treatment with atomoxetine was safe and well tolerated BACKGROUND Previous studies have demonstrated the short-term efficacy of pharmacotherapy and behavior therapy for attention-deficit/hyperactivity disorder ( ADHD ) , but no longer-term ( i.e. , > 4 months ) investigations have compared these 2 treatments or their combination . METHODS A group of 579 children with ADHD Combined Type , aged 7 to 9.9 years , were assigned to 14 months of medication management ( titration followed by monthly visits ) ; intensive behavioral treatment ( parent , school , and child components , with therapist involvement gradually reduced over time ) ; the two combined ; or st and ard community care ( treatments by community providers ) . Outcomes were assessed in multiple domains before and during treatment and at treatment end point ( with the combined treatment and medication management groups continuing medication at all assessment points ) . Data were analyzed through intent-to-treat r and om-effects regression procedures . RESULTS All 4 groups showed sizable reductions in symptoms over time , with significant differences among them in degrees of change . For most ADHD symptoms , children in the combined treatment and medication management groups showed significantly greater improvement than those given intensive behavioral treatment and community care . Combined and medication management treatments did not differ significantly on any direct comparisons , but in several instances ( oppositional/aggressive symptoms , internalizing symptoms , teacher-rated social skills , parent-child relations , and reading achievement )  combined treatment proved superior to intensive behavioral treatment and /or community care while medication management did not . Study medication strategies were superior to community care treatments , despite the fact that two thirds of community-treated subjects received medication during the study period . CONCLUSIONS For ADHD symptoms , our carefully crafted medication management was superior to behavioral treatment and to routine community care that included medication . Our combined treatment did not yield significantly greater benefits than medication management for core ADHD symptoms , but may have provided modest advantages for non-ADHD symptom and positive functioning outcomes OBJECTIVES Mathematical modeling is used widely in economic evaluations of pharmaceuticals and other health-care technologies . Users of models in government and the private sector need to be able to evaluate the quality of models according to scientific criteria of good practice . This report describes the consensus of a task force convened to provide modelers with guidelines for conducting and reporting modeling studies . METHODS The task force was appointed with the advice and consent of the Board of Directors of ISPOR . Members were experienced developers or users of models , worked in academia and industry , and came from several countries in North America and Europe . The task force met on three occasions , conducted frequent correspondence and exchanges of drafts by electronic mail , and solicited comments on three drafts from a core group of external review ers and more broadly from the membership of ISPOR . RESULTS Criteria for assessing the quality of models fell into three areas : model structure , data used as inputs to models , and model validation . Several major themes cut across these areas . Models and their results should be represented as aids to decision making , not as statements of scientific fact ; therefore , it is inappropriate to dem and that models be vali date d prospect ively before use . However , model assumptions regarding causal structure and parameter estimates should be continually assessed against data , and models should be revised accordingly . Structural assumptions and parameter estimates should be reported clearly and explicitly , and opportunities for users to appreciate the conditional relationship between inputs and outputs should be provided through sensitivity analyses . CONCLUSIONS Model-based evaluations are a valuable re source for health-care decision makers . It is the responsibility of model developers to conduct modeling studies according to the best practicable st and ards of quality and to communicate results with adequate disclosure of assumptions and with the caveat that conclusions are conditional upon the assumptions and data on which the model is built OBJECTIVE Clinical trials in psychiatry frequently fail to maximize clinical utility for practicing clinicians , or , stated differently , available evidence is not perceived by clinicians ( and other decision makers ) as sufficiently relevant to clinical practice , thereby diluting its impact . To attain maximum clinical relevance and acceptability , research ers must conduct clinical trials design ed to meet the needs of clinicians and others who are making decisions about patients ' care . The authors present the case for psychiatry 's adoption of the practical clinical trials model , which is widely used in research in other areas of medicine . METHOD The authors outline the characteristics and scope of practical clinical trials , give examples of practical clinical trials , and discuss the challenges of using the practical clinical trials model in psychiatry , including issues of funding . RESULTS Practical clinical trials , which are intended to provide generalizable answers to important clinical questions without bias , are characterized by eight key features : a straightforward clinical ly relevant question , a representative sample of patients and practice setting s , sufficient power to identify modest clinical ly relevant effects , r and omization to protect against bias , clinical uncertainty regarding the outcome of treatment at the patient level , assessment and treatment protocol s that enact best clinical practice s , simple and clinical ly relevant outcomes , and limited subject and investigator burden . CONCLUSIONS To implement the practical clinical trials model in psychiatry will require stable funding for network construction and maintenance plus method ological innovation in governance and trial selection , assessment , treatment , data management , site management , and data analytic procedures BACKGROUND The thrice daily dosing regimen of immediate release methylpheni date ( IR-MPH ) for Attention Deficit/Hyperactivity Disorder ( ADHD ) requires in-school dosing , leading to issues surrounding dispensing and storage of controlled substances by school personnel and concerns over children?s privacy and the embarrassment associated with taking medication in public at school . OROS-methylpheni date ( OROS-MPH ) is a once-daily controlled-release formulation of methylpheni date ( MPH ) developed to overcome some of the limitations associated with IR-MPH and first-generation sustained-release formulations . R and omized , controlled trials ( RCTs ) that focus on treatment efficacy provide the best evidence for demonstrating whether an intervention works , but under ideal conditions one can not discount the importance of efficacy study results . However , the most useful information to clinicians comes from an effectiveness study design . OBJECTIVES To evaluate the effectiveness and tolerability of OROS-MPH versus usual care with IR-MPH in children aged 6 to 12 years with ADHD . METHODS This 8 week , multicentre , open-label study r and omized 147 subjects to either once-daily OROS-MPH or usual care with IR-MPH .  Subjects were titrated to a clinical ly effective dose of either study medication over 4 weeks and maintained on that dose for an additional 4 weeks . The SNAP-IV parent-rating scale was used to assess effectiveness . RESULTS OROS-MPH showed statistically significant superiority to IR-MPH in remission rate based on the 18 ADHD symptoms ( p=0.0002 , X2=13.8 , df=1 ) and severity of ADHD and ODD symptoms ( p=0.004 , F=8.4 , df=1,127 ) , as well as on the following secondary assessment s : IOWA Conners , Conners Parent Rating Scale ( short version ) , Parent Stress Index , ( short version ) ; Visual Analogue Scale for social play ; Clinical Global Impression-Severity , Clinical Global Impression-Improvement and Parent Satisfaction with treatment .  OROS-MPH and IR-MPH were both well tolerated with a similar side effect profile . CONCLUSIONS Once-daily OROS-MPH is significantly more effective than usual care with IR-MPH based on multiple outcome measures including remission rate This community-based study was design ed to evaluate treatment outcomes with OROS ® methylpheni date ( MPH ) and atomoxetine in children with attentiondeficit/hyperactivity disorder ( ADHD ) , as assessed by physicians and parents in a setting that resembles clinical practice . In a multicenter , prospect i ve , open-label study , children 6 to 12 years of age with ADHD were r and omized ( 2:1 , respectively ) to 3 weeks of treatment with once-daily OROS MPH or atomoxetine . Investigatorrated measures of symptoms included the ADHD Rating Scale ( ADHD-RS ) and the Clinical Global Impression-Improvement of Illness scale ( CGI-I ) . Assessment s were made at baseline and during a telephone interview in week 1 , a clinic visit in week 2 , and a final clinic visit in week 3 . In total , 1323 patients received OROS MPH ( n=850 ) or atomoxetine ( n=473 ) . Significant reductions from baseline in investigator-evaluated ADHD-RS scores were observed among patients receiving OROS MPH and those receiving atomoxetine . At the end of the study , mean decreases from baseline ADHD-RS scores were 20.24 for OROS MPH and 16 for atomoxetine ( P < .001 ) . Between-treatment differences appeared to increase over time ( 2.77 , 3.44 , and 4.24 at weeks 1 , 2 , and 3 , respectively ; P < .001 ) . Treatment response ( ie , 25 % reduction from baseline ADHD-RS scores ) was significantly greater at each evaluation for patients taking OROS MPH than for those taking atomoxetine ( P < .001 ) . Similar percentages of patients taking OROS MPH ( 4.8 % ) and atomoxetine ( 5.5 % ) withdrew because of adverse events . Although community-based studies often lack the control of r and omized , placebo-controlled trials , these results nevertheless suggest greater ADHD symptom improvement  with OROS MPH compared with atomoxetine This report introduces a method for obtaining behavioral time-response information for a short-acting psychotropic drug ( methylpheni date [ Ritalin ] ) that is widely used to treat behaviorally hyperactive children . We used a laboratory learning task to document that between one and two hours after the administration of a single dose of methylpheni date , the drug exerts its maximum effect on performance in a learning task in the laboratory . This effect on cognitive performance dissipates within the same day . This rapid and transient effect of methylpheni date makes it possible to class 
    Output:
    