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: GH is often used to treat children with idiopathic short stature despite the lack of definitive , long-term studies of efficacy . We performed a r and omized , double-blind , placebo-controlled trial to determine the effect of GH on adult height in peripubertal children . Subjects ( n = 68 ; 53 males and 15 females ) , 9 - 16 yr old , with marked , idiopathic short stature [ height or predicted height < or = -2.5 sd score ( SDS ) ] received either GH ( 0.074 mg/kg ) or placebo sc three times per week until they were near adult height . At study termination , adult height measurements were available for 33 patients after mean treatment duration of 4.4 yr . Adult height was greater in the GH-treated group ( -1.81 + /- 0.11 SDS , least squares mean + /- sem ) than in the placebo-treated group ( -2.32 + /- 0.17 SDS ) by 0.51 SDS ( 3.7 cm ; P < 0.02 ; 95 % confidence interval , 0.10 - 0.92 SDS ) . A similar GH effect was demonstrated in terms of adult height SDS minus baseline height SDS and adult height SDS minus baseline predicted height SDS . Modified intent-to-treat analysis in 62 patients treated for at least 6 months indicated a similar GH effect on last observed height SDS ( 0.52 SDS ; 3.8 cm ; P < 0.001 ; 95 % confidence interval , 0.22 - 0.82 SDS ) and no important dropout bias . In conclusion , GH treatment increases adult height in peripubertal children with marked idiopathic short stature BACKGROUND Short-term studies have demonstrated acceleration of growth rate following administration of biosynthetic human growth hormone ( r-hGH ) to short normal children . We describe the effect of such treatment on final height . METHODS This was an open study of consecutive referrals to a growth disorder clinic from which 16 short children ( height st and ard deviation score [ SDS ] -2.17 [ range -1.8 to -3.3 ] ; height velocity SDS -0.44 [ 0.33 ] ; peak serum GH response to stimulation 27.9 mU/L [ 9.2 ] were treated with r-hGH , and 7 short children who declined treatment ( height SDS -2.34 [ 0.61 ] ; height velocity SDS -0.36 [ 0.28 ] ; peak serum GH response 28.2 mU/L [ 6.8 ] ) acted as an observation group .  Subcutaneous r-hGH dose ranged between 12.2 and 21.0 U/m2 per week ( 0.02 - 0.04 mg/kg per day ) for the first 2 years of treatment and 20 U/m2 per week thereafter , 3 untreated children were lost to long-term follow-up . FINDINGS r-hGH significantly increased the difference in final height compared with pretreatment predicted height ( + 0.42 SDS [ 0.79 ] , p = 0.03 ) but this change was not significantly greater than that of the observation group ( + 0.16 SDS [ 0.20 ] ) . Treatment had no effect on the timing of puberty . Boys progressed slightly faster through puberty , associated with an acceleration in bone-age maturation . No untoward effects on glucose metabolism were observed . Long-term therapy did not alter body-fat distribution or blood pressure . INTERPRETATION Long-term therapy in this group of children appears safe but the small increment in final height , approximately 2.8 cm in boys and 2.5 cm in girls , does not justify the widespread use of r-hGH for short normal children OBJECTIVES To investigate in an open-label r and omized study , the effect of two doses of growth hormone ( GH ) on final height and height velocity during the first 2 years of treatment of children with idiopathic short stature ( mean baseline height st and ard deviation score [ SDS ] -3.2 ) . STUDY DESIGN Patients were treated with GH at 0.24 mg/kg/week , 0.24 mg/kg/week for the first year and at 0.37 mg/kg/week thereafter ( 0.24 - ->0.37 ) , or 0.37 mg/kg/week . Final height was evaluated in 50 patients at study completion ( mean treatment duration , 6.5 years ) . RESULTS Patients who received 0.37 mg/kg/week ( n = 72 ) experienced a significantly greater increase in height velocity than those who received 0.24 mg/kg/week ( n = 70 ) ( treatment difference = 0.8 cm/year ; P = .003 ) or 0.24 - ->0.37 mg/kg/week ( n = 67 ) ( treatment difference = 0.9 cm/year ; P = .001 ) . For the 50 patients for whom final height measurements were available , mean height SDS increased by 1.55 , 1.52 , and 1.85 SDS , respectively , for the three dose groups . For the primary comparison between the 0.37 mg/kg/week and 0.24 mg/kg/week dose groups , the mean treatment difference ( adjusted for differences in baseline predicted height SDS ) was 0.57 SDS ( 3.6 cm ; P = .025 ) . Mean overall height gains ( final height minus baseline predicted height ) were 7.2 cm and 5.4 cm for the 0.37 mg/kg/week and 0.24 mg/kg/week dose groups , respectively , without dose effects on safety parameters . Final height measurements were within the normal adult height range for 94 % of patients r and omized to 0.37 mg/kg/week who continued to final height . CONCLUSION GH treatment dose-dependently increases height velocity and final height in children with idiopathic short stature CONTEXT The effect of GH therapy in short non-GH-deficient children , especially those with idiopathic short stature ( ISS ) , has not been clearly established owing to the lack of controlled trials continuing until final height ( FH ) . OBJECTIVE The aim of the study was to investigate the effect on growth to FH of two GH doses given to short children , mainly with ISS , compared with untreated controls . DESIGN AND SETTING A r and omized , controlled , long-term multicenter trial was conducted in Sweden . INTERVENTION Two doses of GH ( Genotropin ) were administered , 33 or 67 microg/kg.d ; control subjects were untreated . SUBJECTS A total of 177 subjects with short stature were enrolled . Of these , 151 were included in the intent to treat ( AllITT ) population , and 108 in the per protocol ( AllPP ) population . Analysis of ISS subjects included 126 children in the ITT ( ISSITT ) population and 68 subjects in the PP ( ISSPP ) population . MAIN OUTCOME MEASURES We measured FH sd score ( SDS ) , difference in SDS to midparenteral height ( diff MPHSDS ) , and gain in heightSDS . RESULTS After 5.9+/-1.1 yr on GH therapy , the FHSDS in the AllPP population treated with GH vs. controls was -1.5+/-0.81 ( 33 microg/kg.d , -1.7+/-0.70 ; and 67 microg/kg.d , -1.4+/-0.86 ; P<0.032 ) , vs. -2.4+/-0.85 ( P<0.001 ) ; the diff MPHSDS was -0.2+/-1.0 vs. -1.0+/-0.74 ( P<0.001 ) ; and the gain in heightSDS was 1.3+/-0.78 vs. 0.2+/-0.69 ( P<0.001 ) . GH therapy was safe and had no impact on time to onset of puberty . A dose-response relationship identified after 1 yr remained to FH for all growth outcome variables in all four population s. CONCLUSION GH treatment significantly increased FH in ISS children in a dose-dependent manner , with a mean gain of 1.3 SDS ( 8 cm ) and a broad range of response from no gain to 3 SDS compared to a mean gain of 0.2 SDS in the untreated controls We measured adult heights ( Ht ) of 94 healthy GH-sufficient children ( peak GH > 10 ng/mL , polyclonal RIA ) whose Ht at presentation were more than 2 SD below the mean for chronological age , with normal weight-to-Ht ratios , normal body proportions , and pathologic growth velocity for chronological age . Group 1 ( n 36 , 6 females ) received st and ardized doses ( 0.3 mg/kg x week ) of GH ( mean duration = 41 months ) , while group 2 ( n = 58 , 17 females )  received no treatment . Our conclusion was that the mean final Ht SD score in the GH-treated group ( -1.5 ) was significantly greater than in the untreated group ( -2.1 ) ; P < .001 . Genetic predisposition to short stature was evident in both groups : the midparental Ht SD score was -1.1 in the treated and -1.0 in the untreated group . Midparental Ht was met or exceeded by 42 % of the GH-treated group but only 15 % of the untreated group . Final Ht was not significantly different from predicted Ht , except from GH-treated girls , who exceeded their predicted Ht . Although the mean Ht gains ( 6.8 cm in girls and 3 cm in boys ) were modest and variable , GH treatment provided significantly better Ht outcomes for the majority of children with idiopathic growth failure We report the effect of growth hormone ( GH ) treatment for 4 to 10 years in 15 prepubertal non-GH-deficient short children ( 10 boys , 5 girls , aged 7.4 to 13.2 years ) . In 7 patients , GH was administered at a dosage of 0.5 U/kg per week ( group 1 : 4 boys , 3 girls ) and in 8 patients ( group 2 : 6 boys , 2 girls ) at a dosage of 1.0 U/kg per week . After the first year , mean linear growth velocity had significantly increased in both groups . The increase in growth velocity was sustained during the first 4 years and then declined to pretreatment values in the majority of subjects . Treatment with GH did not induce an earlier onset of puberty , but there was a tendency toward faster skeletal maturation . The mean final height st and ard deviation score ( SDS ) was similar in the two groups and was significantly higher than the height SDS for chronologic age before treatment , but it did not differ from mean pretreatment predicted adult height SDS nor from mean target height SDS in both groups . Final height was significantly correlated with target height in both groups . These preliminary observations indicate that GH treatment does not generally increase final height over target height in short non-GH-deficient children Idiopathic short stature ( ISS ) includes a heterogeneous group of patients with common characteristics to those of familial short stature and constitutional delay . Some authors state that these children can often respond to GH treatment , thus increasing their adult height . The aims of this study were to determine the effect of GH treatment ( 0.5 - 0.7 IU/kg/week ) and the influence of some initial variables on adult height in patients with ISS . It was a non-r and omized , observational study of 30 boys with ISS and a historical control group of 42 patients . The patients were followed until achieving their adult height . The mean height gain of the treated group attributable to GH was 4.5 cm . A stepwise regression model considering predicted adult height and target height as independent variables and final height as dependent variable gave an R2 coefficient of 0.38 . We conclude that GH significantly increases final height in boys with ISS Recombinant human GH therapy to children with idiopathic short stature ( ISS ) increases growth velocity , but its effect on final height ( FH ) is still uncertain . The aim of this study was to investigate the effect of recombinant human GH on FH of patients with ISS who were treated according to two protocol s in comparison to untreated historical controls . In study 1 ( n = 24 ) , all patients were treated with 14 IU ( 4.6 mg)/m(2 ) body surface x wk in the first year ; thereafter the dosage was doubled if the growth response was insufficient . In study 2 ( n = 34 ) , patients were r and omized into three arms : 18 IU ( 6 mg)/m(2 ) x wk ; 27 IU ( 9 mg)/m(2 ) x wk ; and 18 IU/m(2 ) x wk in the first year , followed by 27 IU/m(2 ) x wk thereafter .  Observed or estimated FH was available for 53 patients . Thirty-four untreated controls from the same centers were available for comparison . Mean FH SD score in GH-treated children was -2.1 , vs. -2.4 in controls ( -2.4 ) ( NS ) , but height SD score gain ( 1.3 vs. 0.7 ) and the difference between FH and predicted adult height ( 4.0 vs. 0.8 cm ) were significantly greater . The growth response on an initial dosage of 27 IU/m(2 ) x wk ( 6.9 cm ) was significantly better than on other regimens ( 2.8 cm ) . We conclude that a GH dosage of 27 IU ( 9 mg)/m(2 ) x wk to prepubertal children with ISS leads to a mean FH gain of approximately 7 cm , whereas regimens starting on lower 
    Output:
    
agent
CONCLUSIONS Growth hormone therapy in children with idiopathic short stature seems to be effective in partially reducing the deficit in height as adults , although the magnitude of effectiveness is on average less than that achieved in other conditions for which growth hormone is licensed .
***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: GH is often used to treat children with idiopathic short stature despite the lack of definitive , long-term studies of efficacy . We performed a r and omized , double-blind , placebo-controlled trial to determine the effect of GH on adult height in peripubertal children . Subjects ( n = 68 ; 53 males and 15 females ) , 9 - 16 yr old , with marked , idiopathic short stature [ height or predicted height < or = -2.5 sd score ( SDS ) ] received either GH ( 0.074 mg/kg ) or placebo sc three times per week until they were near adult height . At study termination , adult height measurements were available for 33 patients after mean treatment duration of 4.4 yr . Adult height was greater in the GH-treated group ( -1.81 + /- 0.11 SDS , least squares mean + /- sem ) than in the placebo-treated group ( -2.32 + /- 0.17 SDS ) by 0.51 SDS ( 3.7 cm ; P < 0.02 ; 95 % confidence interval , 0.10 - 0.92 SDS ) . A similar GH effect was demonstrated in terms of adult height SDS minus baseline height SDS and adult height SDS minus baseline predicted height SDS . Modified intent-to-treat analysis in 62 patients treated for at least 6 months indicated a similar GH effect on last observed height SDS ( 0.52 SDS ; 3.8 cm ; P < 0.001 ; 95 % confidence interval , 0.22 - 0.82 SDS ) and no important dropout bias . In conclusion , GH treatment increases adult height in peripubertal children with marked idiopathic short stature BACKGROUND Short-term studies have demonstrated acceleration of growth rate following administration of biosynthetic human growth hormone ( r-hGH ) to short normal children . We describe the effect of such treatment on final height . METHODS This was an open study of consecutive referrals to a growth disorder clinic from which 16 short children ( height st and ard deviation score [ SDS ] -2.17 [ range -1.8 to -3.3 ] ; height velocity SDS -0.44 [ 0.33 ] ; peak serum GH response to stimulation 27.9 mU/L [ 9.2 ] were treated with r-hGH , and 7 short children who declined treatment ( height SDS -2.34 [ 0.61 ] ; height velocity SDS -0.36 [ 0.28 ] ; peak serum GH response 28.2 mU/L [ 6.8 ] ) acted as an observation group .  Subcutaneous r-hGH dose ranged between 12.2 and 21.0 U/m2 per week ( 0.02 - 0.04 mg/kg per day ) for the first 2 years of treatment and 20 U/m2 per week thereafter , 3 untreated children were lost to long-term follow-up . FINDINGS r-hGH significantly increased the difference in final height compared with pretreatment predicted height ( + 0.42 SDS [ 0.79 ] , p = 0.03 ) but this change was not significantly greater than that of the observation group ( + 0.16 SDS [ 0.20 ] ) . Treatment had no effect on the timing of puberty . Boys progressed slightly faster through puberty , associated with an acceleration in bone-age maturation . No untoward effects on glucose metabolism were observed . Long-term therapy did not alter body-fat distribution or blood pressure . INTERPRETATION Long-term therapy in this group of children appears safe but the small increment in final height , approximately 2.8 cm in boys and 2.5 cm in girls , does not justify the widespread use of r-hGH for short normal children OBJECTIVES To investigate in an open-label r and omized study , the effect of two doses of growth hormone ( GH ) on final height and height velocity during the first 2 years of treatment of children with idiopathic short stature ( mean baseline height st and ard deviation score [ SDS ] -3.2 ) . STUDY DESIGN Patients were treated with GH at 0.24 mg/kg/week , 0.24 mg/kg/week for the first year and at 0.37 mg/kg/week thereafter ( 0.24 - ->0.37 ) , or 0.37 mg/kg/week . Final height was evaluated in 50 patients at study completion ( mean treatment duration , 6.5 years ) . RESULTS Patients who received 0.37 mg/kg/week ( n = 72 ) experienced a significantly greater increase in height velocity than those who received 0.24 mg/kg/week ( n = 70 ) ( treatment difference = 0.8 cm/year ; P = .003 ) or 0.24 - ->0.37 mg/kg/week ( n = 67 ) ( treatment difference = 0.9 cm/year ; P = .001 ) . For the 50 patients for whom final height measurements were available , mean height SDS increased by 1.55 , 1.52 , and 1.85 SDS , respectively , for the three dose groups . For the primary comparison between the 0.37 mg/kg/week and 0.24 mg/kg/week dose groups , the mean treatment difference ( adjusted for differences in baseline predicted height SDS ) was 0.57 SDS ( 3.6 cm ; P = .025 ) . Mean overall height gains ( final height minus baseline predicted height ) were 7.2 cm and 5.4 cm for the 0.37 mg/kg/week and 0.24 mg/kg/week dose groups , respectively , without dose effects on safety parameters . Final height measurements were within the normal adult height range for 94 % of patients r and omized to 0.37 mg/kg/week who continued to final height . CONCLUSION GH treatment dose-dependently increases height velocity and final height in children with idiopathic short stature CONTEXT The effect of GH therapy in short non-GH-deficient children , especially those with idiopathic short stature ( ISS ) , has not been clearly established owing to the lack of controlled trials continuing until final height ( FH ) . OBJECTIVE The aim of the study was to investigate the effect on growth to FH of two GH doses given to short children , mainly with ISS , compared with untreated controls . DESIGN AND SETTING A r and omized , controlled , long-term multicenter trial was conducted in Sweden . INTERVENTION Two doses of GH ( Genotropin ) were administered , 33 or 67 microg/kg.d ; control subjects were untreated . SUBJECTS A total of 177 subjects with short stature were enrolled . Of these , 151 were included in the intent to treat ( AllITT ) population , and 108 in the per protocol ( AllPP ) population . Analysis of ISS subjects included 126 children in the ITT ( ISSITT ) population and 68 subjects in the PP ( ISSPP ) population . MAIN OUTCOME MEASURES We measured FH sd score ( SDS ) , difference in SDS to midparenteral height ( diff MPHSDS ) , and gain in heightSDS . RESULTS After 5.9+/-1.1 yr on GH therapy , the FHSDS in the AllPP population treated with GH vs. controls was -1.5+/-0.81 ( 33 microg/kg.d , -1.7+/-0.70 ; and 67 microg/kg.d , -1.4+/-0.86 ; P<0.032 ) , vs. -2.4+/-0.85 ( P<0.001 ) ; the diff MPHSDS was -0.2+/-1.0 vs. -1.0+/-0.74 ( P<0.001 ) ; and the gain in heightSDS was 1.3+/-0.78 vs. 0.2+/-0.69 ( P<0.001 ) . GH therapy was safe and had no impact on time to onset of puberty . A dose-response relationship identified after 1 yr remained to FH for all growth outcome variables in all four population s. CONCLUSION GH treatment significantly increased FH in ISS children in a dose-dependent manner , with a mean gain of 1.3 SDS ( 8 cm ) and a broad range of response from no gain to 3 SDS compared to a mean gain of 0.2 SDS in the untreated controls We measured adult heights ( Ht ) of 94 healthy GH-sufficient children ( peak GH > 10 ng/mL , polyclonal RIA ) whose Ht at presentation were more than 2 SD below the mean for chronological age , with normal weight-to-Ht ratios , normal body proportions , and pathologic growth velocity for chronological age . Group 1 ( n 36 , 6 females ) received st and ardized doses ( 0.3 mg/kg x week ) of GH ( mean duration = 41 months ) , while group 2 ( n = 58 , 17 females )  received no treatment . Our conclusion was that the mean final Ht SD score in the GH-treated group ( -1.5 ) was significantly greater than in the untreated group ( -2.1 ) ; P < .001 . Genetic predisposition to short stature was evident in both groups : the midparental Ht SD score was -1.1 in the treated and -1.0 in the untreated group . Midparental Ht was met or exceeded by 42 % of the GH-treated group but only 15 % of the untreated group . Final Ht was not significantly different from predicted Ht , except from GH-treated girls , who exceeded their predicted Ht . Although the mean Ht gains ( 6.8 cm in girls and 3 cm in boys ) were modest and variable , GH treatment provided significantly better Ht outcomes for the majority of children with idiopathic growth failure We report the effect of growth hormone ( GH ) treatment for 4 to 10 years in 15 prepubertal non-GH-deficient short children ( 10 boys , 5 girls , aged 7.4 to 13.2 years ) . In 7 patients , GH was administered at a dosage of 0.5 U/kg per week ( group 1 : 4 boys , 3 girls ) and in 8 patients ( group 2 : 6 boys , 2 girls ) at a dosage of 1.0 U/kg per week . After the first year , mean linear growth velocity had significantly increased in both groups . The increase in growth velocity was sustained during the first 4 years and then declined to pretreatment values in the majority of subjects . Treatment with GH did not induce an earlier onset of puberty , but there was a tendency toward faster skeletal maturation . The mean final height st and ard deviation score ( SDS ) was similar in the two groups and was significantly higher than the height SDS for chronologic age before treatment , but it did not differ from mean pretreatment predicted adult height SDS nor from mean target height SDS in both groups . Final height was significantly correlated with target height in both groups . These preliminary observations indicate that GH treatment does not generally increase final height over target height in short non-GH-deficient children Idiopathic short stature ( ISS ) includes a heterogeneous group of patients with common characteristics to those of familial short stature and constitutional delay . Some authors state that these children can often respond to GH treatment , thus increasing their adult height . The aims of this study were to determine the effect of GH treatment ( 0.5 - 0.7 IU/kg/week ) and the influence of some initial variables on adult height in patients with ISS . It was a non-r and omized , observational study of 30 boys with ISS and a historical control group of 42 patients . The patients were followed until achieving their adult height . The mean height gain of the treated group attributable to GH was 4.5 cm . A stepwise regression model considering predicted adult height and target height as independent variables and final height as dependent variable gave an R2 coefficient of 0.38 . We conclude that GH significantly increases final height in boys with ISS Recombinant human GH therapy to children with idiopathic short stature ( ISS ) increases growth velocity , but its effect on final height ( FH ) is still uncertain . The aim of this study was to investigate the effect of recombinant human GH on FH of patients with ISS who were treated according to two protocol s in comparison to untreated historical controls . In study 1 ( n = 24 ) , all patients were treated with 14 IU ( 4.6 mg)/m(2 ) body surface x wk in the first year ; thereafter the dosage was doubled if the growth response was insufficient . In study 2 ( n = 34 ) , patients were r and omized into three arms : 18 IU ( 6 mg)/m(2 ) x wk ; 27 IU ( 9 mg)/m(2 ) x wk ; and 18 IU/m(2 ) x wk in the first year , followed by 27 IU/m(2 ) x wk thereafter .  Observed or estimated FH was available for 53 patients . Thirty-four untreated controls from the same centers were available for comparison . Mean FH SD score in GH-treated children was -2.1 , vs. -2.4 in controls ( -2.4 ) ( NS ) , but height SD score gain ( 1.3 vs. 0.7 ) and the difference between FH and predicted adult height ( 4.0 vs. 0.8 cm ) were significantly greater . The growth response on an initial dosage of 27 IU/m(2 ) x wk ( 6.9 cm ) was significantly better than on other regimens ( 2.8 cm ) . We conclude that a GH dosage of 27 IU ( 9 mg)/m(2 ) x wk to prepubertal children with ISS leads to a mean FH gain of approximately 7 cm , whereas regimens starting on lower 
    Output:
    