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: Background The treatment of children with attention deficit hyperactivity disorder ( ADHD ) and Tourette syndrome ( TS ) has been problematic because methylpheni date (MPH)—the most commonly used drug to treat ADHD — has been reported to worsen tics and because clonidine (CLON)—the most commonly prescribed alternative — has unproven efficacy . Methods The authors conducted a multicenter , r and omized , double-blind clinical trial in which 136 children with ADHD and a chronic tic disorder were r and omly administered CLON alone , MPH alone , combined CLON + MPH , or placebo ( 2 × 2 factorial design ) . Each subject participated for 16 weeks ( weeks 1–4 CLON/placebo dose titration , weeks 5–8 added MPH/placebo dose titration , weeks 9–16 maintenance therapy ) . Results Thirty-seven children were administered MPH alone , 34 were administered CLON alone , 33 were administered CLON + MPH , and 32 were administered placebo . For our primary outcome measure of ADHD ( Conners Abbreviated Symptom Question naire – Teacher ) , significant improvement occurred for subjects assigned to CLON ( p < 0.002 ) and those assigned to MPH ( p < 0.003 ) . Compared with placebo , the greatest benefit occurred with combined CLON + MPH ( p < 0.0001 ) . CLON appeared to be most helpful for impulsivity and hyperactivity ; MPH appeared to be most helpful for inattention . The proportion of individual subjects reporting a worsening of tics as an adverse effect was no higher in those treated with MPH ( 20 % ) than those being administered CLON alone ( 26 % ) or placebo ( 22 % ) . Compared with placebo , measured tic severity lessened in all active treatment groups in the following order : CLON + MPH , CLON alone , MPH alone . Sedation was common with CLON treatment ( 28 % reported moderate or severe sedation ) , but otherwise the drugs were tolerated well , including absence of any evident cardiac toxicity . Conclusions Methylpheni date and clonidine ( particularly in combination ) are effective for ADHD in children with comorbid tics . Prior recommendations to avoid methylpheni date in these children because of concerns of worsening tics are unsupported by this trial BACKGROUND Despite the persistence of attention-deficit/hyperactivity disorder ( ADHD ) into adolescence , little is known about the efficacy and tolerability of stimulant medications in this age group . OBJECTIVE To report the results of a multisite controlled study among adolescents with ADHD evaluating the efficacy and tolerability of osmotic-release oral system ( OROS ) methylpheni date . DESIGN Adolescents ( N = 220 ) having a confirmed Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition diagnosis of ADHD underwent dose titration to identify dosages of OROS methylpheni date that improved symptoms to predefined criteria . Subjects successfully completing the dose titration phase ( n = 177 ) ( ie , tolerated and responded to treatment and adhered to the protocol ) were r and omized to receive 2 weeks ' treatment with their individualized dosage of OROS methylpheni date ( 18 , 36 , 54 , or 72 mg once daily ) or placebo .  Treatment effectiveness was measured using investigator , parent , and adolescent assessment s of ADHD . RESULTS A significant reduction from baseline in the investigator-rated ADHD Rating Scale , the primary efficacy measure , was found with OROS methylpheni date treatment compared with placebo . Similar findings were noted with parent- and adolescent-report measures . Based on a Clinical Global Impression improvement subscale score of much or very much improved , 52 % of subjects in the OROS methylpheni date group improved compared with 31 % receiving placebo . Thirty-seven percent of subjects required the maximum dosage of 72 mg/d . The incidence of drug-related adverse events was similar between the 2 study groups . CONCLUSION In adolescents , once-daily OROS methylpheni date significantly reduced ADHD symptoms and was well tolerated using dosages up to 72 mg/d The effects of methylpheni date on the academic performance and classroom behavior of 45 adolescents with attention deficit hyperactivity disorder were studied . During a 6-week , placebo-controlled medication assessment in the context of a summer treatment program , participants received a double-blind , crossover trial of 3 doses of methylpheni date . Dependent measures included note-taking quality , quiz and worksheet scores , written language usage and productivity , teacher ratings , on-task and disruptive behavior , and homework completion . Group data showed positive effects of methylpheni date on academic measures ; however , the greatest benefit came with the lowest dose . Although additional benefit did occur for some participants with higher doses , the largest increment of change usually occurred between the placebo and 10-mg dose . Many adolescents did not experience added benefit with increased dosages , and in some cases they experienced deterioration . Guidelines for assessment of medication effects are discussed OBJECTIVE The effects of stimulant medication treatment were investigated in children with mental retardation ( MR ) and attention-deficit/hyperactivity disorder ( ADHD ) . METHOD Parent and teacher behavioral ratings and reports of side effects were obtained for children ( N = 24 , mean age = 10.9 years , SD = 2.4 ) during a placebo-controlled , double-blind , crossover treatment trial with 0.15 mg/kg , 0.30 mg/kg , and 0.60 mg/kg b.i.d . dosages of methylpheni date . RESULTS The most significant improvements occurred at the 0.60 mg/kg methylpheni date dose for teacher ratings of inattention ( p = .024 ) , hyperactivity ( p < .001 ) , aggression ( p < .001 ) , and asocial behavior ( p = .009 ) . No significant improvements , relative to placebo , occurred at the 0.15 mg/kg dosage . Of interest , nearly all significant medication-related behavioral improvements were detected by teachers . However , parents were sensitive raters of side effects , noting more sleeping problems and loss of appetite at the 0.60 mg/kg dose compared with placebo . CONCLUSIONS These results suggest that symptoms of ADHD can be treated successfully in children with ADHD/MR , and consistent with MTA study results , higher doses were most effective . Furthermore , these improvements were not accompanied by increases in symptoms such as staring , social withdrawal , or anxiety Objective To compare the efficacy and safety of two methylpheni date ( MPH ) formulations — once-daily modified-release MPH ( EqXL , Equasym ™ XL ) and twice-daily immediate-release methylpheni date ( MPH-IR , Ritalin ® )— and placebo in children with Attention Deficit/Hyperactivity Disorder ( ADHD ) . Methods Children aged 6–12 years on a stable dose of MPH were r and omized into a double-blind , three-arm , parallel-group , multi-center study and received 3 weeks of EqXL ( 20 , 40 , or 60 mg qd ) , MPH-IR ( 10 , 20 , or 30 mg bid ) or placebo . Non-inferiority of EqXL to MPH-IR was assessed by the difference in the inattention/overactivity component of the overall teacher ’s IOWA Conners ’ Rating Scale on the last week of treatment ( per protocol population ) . Safety was monitored by adverse events , laboratory parameters , vital signs , physical exam , and a Side Effect Rating Scale . Results The lower 97.5 % confidence interval bound of the difference between MPH groups fell above the non-inferiority margin ( −1.5 points ) not only during the last week of treatment but during all three treatment weeks . Both MPH-treatment groups experienced superior benefit when compared to placebo during all treatment weeks ( P < 0.001 ) . All treatments were well tolerated . Conclusions EqXL given once-daily was non-inferior to MPH-IR given twice-daily . Both treatments were superior to placebo in reducing ADHD symptoms OBJECTIVE To compare clonidine with placebo added to ongoing psychostimulant therapy for the treatment of attention-deficit/hyperactivity disorder with comorbid oppositional defiant disorder or conduct disorder . METHOD Children 6 to 14 years of age recruited through 2000 to 2001 were r and omized to receive clonidine syrup 0.10 to 0.20 mg/day ( n = 38 ) or placebo ( n = 29 ) for 6 weeks . Primary outcome measures were the Conduct and Hyperactive Index subscales of the parent-report Conners Behavior Checklist . Side effects were monitored using physiological measures and the Barkley Side Effect Rating Scale . RESULTS Evaluable patient analysis showed that significantly more clonidine-treated children than controls were responders on the Conduct scale ( 21 of 37 versus 6 of 29 ; chi2(1 ) = 8.75 , p < .01 ) but not the Hyperactive Index ( 13 of 37 versus 5 of 29 ) . Compared with placebo , clonidine was associated with a greater reduction in systolic blood pressure measured st and ing and with transient sedation and dizziness .  Clonidine-treated individuals had a greater reduction in a number of unwanted effects associated with psychostimulant treatment compared with placebo . CONCLUSIONS The findings support the continued use of clonidine in combination with psychostimulant medication to reduce conduct symptoms associated with attention-deficit/hyperactivity disorder . Treatment is well tolerated and unwanted effects are transient INTRODUCTION Aggression is frequently observed in children and adolescents with attention-deficit/hyperactivity disorder ( ADHD ) . The aim of this study was to assess the efficacy with regard to oppositional and aggressive behavior of a new long-acting methylpheni date preparation ( Medikinet retard , MPH-MR ) , with equal portions of the immediate-release and the sustained-release active substance , and especially to look at correlations between either teacher or parent assessment of aggression and ADHD sub-symptomatology . METHODS Eighty five children and adolescents ( 6 - 16 years ) were investigated in a double-blind , r and omized , clinical trial over 5 weeks under a treatment with MPH-MR  using symptom checklists for ADHD , oppositional-defiant and conduct disorder according to the Diagnostic and Statistical Manual of Mental Disorders , 4th edition ( DSM-IV ) . RESULTS A total of 64.9 % of the children showed oppositional defiant disorder/conduct disorder ( ODD/CD ) symptoms . A statistically significant effect was found in the group treated with MPH ( verum-group ) . On the basis of Cohen 's criteria , high effects were found for aggressive symptoms in school ( d = 1.0 ) , but not in the afternoon ( d = 0.4 ) . There were also lower effect sizes for more severe aggressive symptoms . We found characteristic correlations between ODD/CD symptoms and the ADHD subscale hyperactivity/impulsivity compared to the subscale inattention . CONCLUSIONS Long-acting MPH is effective in the treatment of oppositional-defiant and aggressive behavior , especially concerning milder symptoms . The expected correlation between impulsivity and aggressiveness could be confirmed Objective : To describe trends in the prevalence of prescribed attention-deficit hyperactivity disorder ( ADHD ) medication by Canadian preschoolers and school-age children and to compare these with trends in the prevalence of the ADHD diagnosis between 1994 and 2007 . Methods : Subjects participated in the National Longitudinal Survey on Children and Youth , a Canadian prospect i ve survey collecting data biennially . Three cross-sectional sample s of nonreferred children , aged 3 to 9 years and representative of Canadian children for 1994–1995 ( n = 12 595 ) , 2000–2001 ( n = 13 904 ) , and 2006–2007 ( n = 14 655 ) , were selected for the analyses . Information on prescribed medications and ADHD diagnosis was reported by each child 's parents . Prevalence was estimated at each cycle , taking the child 's age and sex into account . Results : The estimated prevalence of prescribed medications and ADHD diagnosis in Canada was generally low ( less than 3 % ) , but higher for boys ( less than 4 % ) and school-age children ( less than 5 % ) .  Preschoolers ' prevalence of both prescribed medications and ADHD diagnosis stayed stable between 1994 and 2007 ( 1 % or less ) , while that of school-age children increased nearly 2-fold . Boys ' prevalence was higher than that of girls , but girls show the steepest increase over time , up to 2.1-fold . The association between prescribed medications and ADHD diagnosis has strengthened during the 2000s : a greater number of medications were used for children with ADHD ( from 43 % in 2000 to 59 % in 2007 ) while off-label use of prescribed medications decreased among school-age children . Conclusions : The upward trend in the prevalence of prescribed ADHD medications and ADHD diagnosis currently observed in contemporary societies is also occurring in Canada , except with preschoolers OBJECTIVE To examine efficacy , tolerability , and safety of guanfacine extended release ( GXR ; ≤4 mg/d ) adjunctive to a long-acting psychostimulant for the treatment of attention-deficit/hyperactivity disorder ( ADHD ) in children 
    Output:
    
agent
There is very-low- quality evidence that clonidine has a small effect on oppositional behaviour and conduct problems in youth with ADHD , with and without ODD or CD .
There is moderate- quality evidence that guanfacine has a small-to-moderate effect on oppositional behaviour in youth with ADHD , with and without ODD .
There is high- quality evidence that atomoxetine has a small effect on oppositional behaviour in youth with ADHD , with and without ODD or CD .
Conclusions : Evidence indicates that psychostimulants , alpha-2 agonists , and atomoxetine can be beneficial for disruptive and aggressive behaviours in addition to core ADHD symptoms ; however , psychostimulants generally provide the most benefit
***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: Background The treatment of children with attention deficit hyperactivity disorder ( ADHD ) and Tourette syndrome ( TS ) has been problematic because methylpheni date (MPH)—the most commonly used drug to treat ADHD — has been reported to worsen tics and because clonidine (CLON)—the most commonly prescribed alternative — has unproven efficacy . Methods The authors conducted a multicenter , r and omized , double-blind clinical trial in which 136 children with ADHD and a chronic tic disorder were r and omly administered CLON alone , MPH alone , combined CLON + MPH , or placebo ( 2 × 2 factorial design ) . Each subject participated for 16 weeks ( weeks 1–4 CLON/placebo dose titration , weeks 5–8 added MPH/placebo dose titration , weeks 9–16 maintenance therapy ) . Results Thirty-seven children were administered MPH alone , 34 were administered CLON alone , 33 were administered CLON + MPH , and 32 were administered placebo . For our primary outcome measure of ADHD ( Conners Abbreviated Symptom Question naire – Teacher ) , significant improvement occurred for subjects assigned to CLON ( p < 0.002 ) and those assigned to MPH ( p < 0.003 ) . Compared with placebo , the greatest benefit occurred with combined CLON + MPH ( p < 0.0001 ) . CLON appeared to be most helpful for impulsivity and hyperactivity ; MPH appeared to be most helpful for inattention . The proportion of individual subjects reporting a worsening of tics as an adverse effect was no higher in those treated with MPH ( 20 % ) than those being administered CLON alone ( 26 % ) or placebo ( 22 % ) . Compared with placebo , measured tic severity lessened in all active treatment groups in the following order : CLON + MPH , CLON alone , MPH alone . Sedation was common with CLON treatment ( 28 % reported moderate or severe sedation ) , but otherwise the drugs were tolerated well , including absence of any evident cardiac toxicity . Conclusions Methylpheni date and clonidine ( particularly in combination ) are effective for ADHD in children with comorbid tics . Prior recommendations to avoid methylpheni date in these children because of concerns of worsening tics are unsupported by this trial BACKGROUND Despite the persistence of attention-deficit/hyperactivity disorder ( ADHD ) into adolescence , little is known about the efficacy and tolerability of stimulant medications in this age group . OBJECTIVE To report the results of a multisite controlled study among adolescents with ADHD evaluating the efficacy and tolerability of osmotic-release oral system ( OROS ) methylpheni date . DESIGN Adolescents ( N = 220 ) having a confirmed Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition diagnosis of ADHD underwent dose titration to identify dosages of OROS methylpheni date that improved symptoms to predefined criteria . Subjects successfully completing the dose titration phase ( n = 177 ) ( ie , tolerated and responded to treatment and adhered to the protocol ) were r and omized to receive 2 weeks ' treatment with their individualized dosage of OROS methylpheni date ( 18 , 36 , 54 , or 72 mg once daily ) or placebo .  Treatment effectiveness was measured using investigator , parent , and adolescent assessment s of ADHD . RESULTS A significant reduction from baseline in the investigator-rated ADHD Rating Scale , the primary efficacy measure , was found with OROS methylpheni date treatment compared with placebo . Similar findings were noted with parent- and adolescent-report measures . Based on a Clinical Global Impression improvement subscale score of much or very much improved , 52 % of subjects in the OROS methylpheni date group improved compared with 31 % receiving placebo . Thirty-seven percent of subjects required the maximum dosage of 72 mg/d . The incidence of drug-related adverse events was similar between the 2 study groups . CONCLUSION In adolescents , once-daily OROS methylpheni date significantly reduced ADHD symptoms and was well tolerated using dosages up to 72 mg/d The effects of methylpheni date on the academic performance and classroom behavior of 45 adolescents with attention deficit hyperactivity disorder were studied . During a 6-week , placebo-controlled medication assessment in the context of a summer treatment program , participants received a double-blind , crossover trial of 3 doses of methylpheni date . Dependent measures included note-taking quality , quiz and worksheet scores , written language usage and productivity , teacher ratings , on-task and disruptive behavior , and homework completion . Group data showed positive effects of methylpheni date on academic measures ; however , the greatest benefit came with the lowest dose . Although additional benefit did occur for some participants with higher doses , the largest increment of change usually occurred between the placebo and 10-mg dose . Many adolescents did not experience added benefit with increased dosages , and in some cases they experienced deterioration . Guidelines for assessment of medication effects are discussed OBJECTIVE The effects of stimulant medication treatment were investigated in children with mental retardation ( MR ) and attention-deficit/hyperactivity disorder ( ADHD ) . METHOD Parent and teacher behavioral ratings and reports of side effects were obtained for children ( N = 24 , mean age = 10.9 years , SD = 2.4 ) during a placebo-controlled , double-blind , crossover treatment trial with 0.15 mg/kg , 0.30 mg/kg , and 0.60 mg/kg b.i.d . dosages of methylpheni date . RESULTS The most significant improvements occurred at the 0.60 mg/kg methylpheni date dose for teacher ratings of inattention ( p = .024 ) , hyperactivity ( p < .001 ) , aggression ( p < .001 ) , and asocial behavior ( p = .009 ) . No significant improvements , relative to placebo , occurred at the 0.15 mg/kg dosage . Of interest , nearly all significant medication-related behavioral improvements were detected by teachers . However , parents were sensitive raters of side effects , noting more sleeping problems and loss of appetite at the 0.60 mg/kg dose compared with placebo . CONCLUSIONS These results suggest that symptoms of ADHD can be treated successfully in children with ADHD/MR , and consistent with MTA study results , higher doses were most effective . Furthermore , these improvements were not accompanied by increases in symptoms such as staring , social withdrawal , or anxiety Objective To compare the efficacy and safety of two methylpheni date ( MPH ) formulations — once-daily modified-release MPH ( EqXL , Equasym ™ XL ) and twice-daily immediate-release methylpheni date ( MPH-IR , Ritalin ® )— and placebo in children with Attention Deficit/Hyperactivity Disorder ( ADHD ) . Methods Children aged 6–12 years on a stable dose of MPH were r and omized into a double-blind , three-arm , parallel-group , multi-center study and received 3 weeks of EqXL ( 20 , 40 , or 60 mg qd ) , MPH-IR ( 10 , 20 , or 30 mg bid ) or placebo . Non-inferiority of EqXL to MPH-IR was assessed by the difference in the inattention/overactivity component of the overall teacher ’s IOWA Conners ’ Rating Scale on the last week of treatment ( per protocol population ) . Safety was monitored by adverse events , laboratory parameters , vital signs , physical exam , and a Side Effect Rating Scale . Results The lower 97.5 % confidence interval bound of the difference between MPH groups fell above the non-inferiority margin ( −1.5 points ) not only during the last week of treatment but during all three treatment weeks . Both MPH-treatment groups experienced superior benefit when compared to placebo during all treatment weeks ( P < 0.001 ) . All treatments were well tolerated . Conclusions EqXL given once-daily was non-inferior to MPH-IR given twice-daily . Both treatments were superior to placebo in reducing ADHD symptoms OBJECTIVE To compare clonidine with placebo added to ongoing psychostimulant therapy for the treatment of attention-deficit/hyperactivity disorder with comorbid oppositional defiant disorder or conduct disorder . METHOD Children 6 to 14 years of age recruited through 2000 to 2001 were r and omized to receive clonidine syrup 0.10 to 0.20 mg/day ( n = 38 ) or placebo ( n = 29 ) for 6 weeks . Primary outcome measures were the Conduct and Hyperactive Index subscales of the parent-report Conners Behavior Checklist . Side effects were monitored using physiological measures and the Barkley Side Effect Rating Scale . RESULTS Evaluable patient analysis showed that significantly more clonidine-treated children than controls were responders on the Conduct scale ( 21 of 37 versus 6 of 29 ; chi2(1 ) = 8.75 , p < .01 ) but not the Hyperactive Index ( 13 of 37 versus 5 of 29 ) . Compared with placebo , clonidine was associated with a greater reduction in systolic blood pressure measured st and ing and with transient sedation and dizziness .  Clonidine-treated individuals had a greater reduction in a number of unwanted effects associated with psychostimulant treatment compared with placebo . CONCLUSIONS The findings support the continued use of clonidine in combination with psychostimulant medication to reduce conduct symptoms associated with attention-deficit/hyperactivity disorder . Treatment is well tolerated and unwanted effects are transient INTRODUCTION Aggression is frequently observed in children and adolescents with attention-deficit/hyperactivity disorder ( ADHD ) . The aim of this study was to assess the efficacy with regard to oppositional and aggressive behavior of a new long-acting methylpheni date preparation ( Medikinet retard , MPH-MR ) , with equal portions of the immediate-release and the sustained-release active substance , and especially to look at correlations between either teacher or parent assessment of aggression and ADHD sub-symptomatology . METHODS Eighty five children and adolescents ( 6 - 16 years ) were investigated in a double-blind , r and omized , clinical trial over 5 weeks under a treatment with MPH-MR  using symptom checklists for ADHD , oppositional-defiant and conduct disorder according to the Diagnostic and Statistical Manual of Mental Disorders , 4th edition ( DSM-IV ) . RESULTS A total of 64.9 % of the children showed oppositional defiant disorder/conduct disorder ( ODD/CD ) symptoms . A statistically significant effect was found in the group treated with MPH ( verum-group ) . On the basis of Cohen 's criteria , high effects were found for aggressive symptoms in school ( d = 1.0 ) , but not in the afternoon ( d = 0.4 ) . There were also lower effect sizes for more severe aggressive symptoms . We found characteristic correlations between ODD/CD symptoms and the ADHD subscale hyperactivity/impulsivity compared to the subscale inattention . CONCLUSIONS Long-acting MPH is effective in the treatment of oppositional-defiant and aggressive behavior , especially concerning milder symptoms . The expected correlation between impulsivity and aggressiveness could be confirmed Objective : To describe trends in the prevalence of prescribed attention-deficit hyperactivity disorder ( ADHD ) medication by Canadian preschoolers and school-age children and to compare these with trends in the prevalence of the ADHD diagnosis between 1994 and 2007 . Methods : Subjects participated in the National Longitudinal Survey on Children and Youth , a Canadian prospect i ve survey collecting data biennially . Three cross-sectional sample s of nonreferred children , aged 3 to 9 years and representative of Canadian children for 1994–1995 ( n = 12 595 ) , 2000–2001 ( n = 13 904 ) , and 2006–2007 ( n = 14 655 ) , were selected for the analyses . Information on prescribed medications and ADHD diagnosis was reported by each child 's parents . Prevalence was estimated at each cycle , taking the child 's age and sex into account . Results : The estimated prevalence of prescribed medications and ADHD diagnosis in Canada was generally low ( less than 3 % ) , but higher for boys ( less than 4 % ) and school-age children ( less than 5 % ) .  Preschoolers ' prevalence of both prescribed medications and ADHD diagnosis stayed stable between 1994 and 2007 ( 1 % or less ) , while that of school-age children increased nearly 2-fold . Boys ' prevalence was higher than that of girls , but girls show the steepest increase over time , up to 2.1-fold . The association between prescribed medications and ADHD diagnosis has strengthened during the 2000s : a greater number of medications were used for children with ADHD ( from 43 % in 2000 to 59 % in 2007 ) while off-label use of prescribed medications decreased among school-age children . Conclusions : The upward trend in the prevalence of prescribed ADHD medications and ADHD diagnosis currently observed in contemporary societies is also occurring in Canada , except with preschoolers OBJECTIVE To examine efficacy , tolerability , and safety of guanfacine extended release ( GXR ; ≤4 mg/d ) adjunctive to a long-acting psychostimulant for the treatment of attention-deficit/hyperactivity disorder ( ADHD ) in children 
    Output:
    