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: A comparison was made of the growth responses of prepubertal naive GH-deficient children who were r and omly assigned to receive 0.3 mg/kg.week  recombinant human GH administered either daily ( QD ) or three times weekly ( TIW ) over 4 yr . The effects of the two regimens on annual growth velocity , change in height SD score , bone maturation , and age at onset of puberty are presented as the mean + /- SD . During each of the 4 yr , the annual growth velocity was significantly greater in the QD vs. TIW group . At 48 months , the mean total gain in height was 9.7 cm greater in the QD group ( 38.4 + /- 5.5 ) than that in the TIW group 28.7 + /- 3.2 ; P = 0.0002 ) . The mean height SD score at the end of each year was significantly greater in the QD group . After 4 yr , the total gain in height SD score was 3.2 + /- 1.2 in the QD group compared to 1.5 + /- 0.5 in the TIW group ( P = 0.0003 ) . The height SD score at 4 yr was 0.2 in the QD group ( pretreatment , -2.9 ) compared to -1.4 in the TIW group ( pretreatment , -2.9 ) . After 4 yr of rhGH treatment , the increment in bone age was similar in the QD ( 4.9 + /- 1.0 yr ) and TIW ( 4.8 + /- 1.1 yr ) groups . The change in height age minus the change in bone age was more favorable in the QD ( 1.2 + /- 0.8 yr ) than in the TIW ( 0.0 + /- 0.9 yr ) group ( P = 0.003 ) . The mean age at onset of puberty in boys was the same in the QD ( 13.2 yr ) and TIW ( 13.0 yr ) groups ( P = 0.71 ) , and the mean bone age at the start of puberty was also similar ( 11.5 in QD and 11.3 in TIW groups ; P = 0.66 ) . The advantages of QD rhGH treatment in prepubertal GH-deficient children after 4 yr were additional gains of 1.7 height SD score and 9.7 cm in height over those treated with the TIW regimen ( P = 0.0002 ) OBJECTIVE . The goal was to determine how often common laboratory tests yield normal results at the time of diagnosis for children with inflammatory bowel disease . METHODS . Data were obtained from a registry of children with newly diagnosed inflammatory bowel disease who were enrolled prospect ively in 18 US/Canadian centers . Laboratory values investigated included hemoglobin level , platelet count , albumin level , and erythrocyte sedimentation rate . Disease severity was categorized by physician global assessment . RESULTS . A total of 526 children ( mean age : 11.6 years ; 58 % male ; 392 with Crohn disease and 134 with ulcerative colitis ) were studied . All 4 values were normal for 21 % of patients with mild Crohn disease and 54 % with mild ulcerative colitis . In contrast , only 3.8 % of children with moderate/severe Crohn disease and 4.3 % with moderate/severe ulcerative colitis had normal results for all 4 tests . The erythrocyte sedimentation rate was least likely to be normal ; overall , 26 % of patients with inflammatory bowel disease had a normal erythrocyte sedimentation rate , including 18 % with moderate/severe disease . Hemoglobin levels were normal for 32 % , platelet counts for 50 % , and albumin levels for 60 % . There was no clear association between Crohn disease location and either severity or number of normal laboratory values . In contrast , there were direct correlations between ulcerative colitis disease severity and both the extent of bowel inflammation and the number of abnormal laboratory tests . CONCLUSION . The presence of normal screening laboratory studies should not dissuade clinicians from considering a diagnosis of inflammatory bowel disease 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 OBJECTIVE Our objective was to assess final height ( FH ) and adverse effects of combined GH and GnRH agonist ( GnRHa ) treatment in short adolescents born small for gestational age or with normal birth size ( idiopathic short stature ) . DESIGN AND PATIENTS Thirty-two adolescents with Tanner stage 2 - 3 , age and bone age ( BA ) less than 12 yr for girls or less than 13 yr for boys , height sd score ( SDS ) less than -2.0 SDS or between -1.0 and -2.0 SDS plus a predicted adult height ( PAH0 ) less than -2.0 SDS were r and omly allocated to receive  GH plus GnRHa  ( n=17 ) or no treatment ( n=15 ) for 3 yr . FH was assessed at the age of 18 yr or older in girls or 19 yr or older in boys . RESULTS FH was not different between treatment and control groups . Treated children had a larger height gain ( FH-PAH0 ) than controls : 4.4 ( 4.9 ) and -0.5 ( 6.4 ) cm , respectively ( P<0.05 ) . FH was higher than PAH0 in 76 and 60 % of treated and control subjects , respectively . During follow-up , 50 % of the predicted height gain at treatment withdrawal was lost , result ing in a mean gain of 4.9 cm ( range , -4.0 to 12.3 cm ) compared with controls . Treatment did not affect body mass index or hip bone mineral density . Mean lumbar spine bone mineral density and bone mineral apparent density tended to be lower in treated boys , albeit statistically not significant . CONCLUSION Given the expensive and intensive treatment regimen , its modest height gain results , and the possible adverse effect on peak bone mineralization in males , GH plus GnRHa can not be considered routine treatment for children with idiopathic short stature or persistent short stature after being born small for gestational age 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 , - 
    Output:
    
agent
For height outcome , articles were limited to studies reporting adult height and to systematic review s. FINDINGS Recombinant human growth hormone therapy of children with idiopathic short stature increases height in some children .
The cost-benefit ratio is controversial .
AND RELEVANCE Growth hormone treatment may be considered in some children with idiopathic short stature
***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: A comparison was made of the growth responses of prepubertal naive GH-deficient children who were r and omly assigned to receive 0.3 mg/kg.week  recombinant human GH administered either daily ( QD ) or three times weekly ( TIW ) over 4 yr . The effects of the two regimens on annual growth velocity , change in height SD score , bone maturation , and age at onset of puberty are presented as the mean + /- SD . During each of the 4 yr , the annual growth velocity was significantly greater in the QD vs. TIW group . At 48 months , the mean total gain in height was 9.7 cm greater in the QD group ( 38.4 + /- 5.5 ) than that in the TIW group 28.7 + /- 3.2 ; P = 0.0002 ) . The mean height SD score at the end of each year was significantly greater in the QD group . After 4 yr , the total gain in height SD score was 3.2 + /- 1.2 in the QD group compared to 1.5 + /- 0.5 in the TIW group ( P = 0.0003 ) . The height SD score at 4 yr was 0.2 in the QD group ( pretreatment , -2.9 ) compared to -1.4 in the TIW group ( pretreatment , -2.9 ) . After 4 yr of rhGH treatment , the increment in bone age was similar in the QD ( 4.9 + /- 1.0 yr ) and TIW ( 4.8 + /- 1.1 yr ) groups . The change in height age minus the change in bone age was more favorable in the QD ( 1.2 + /- 0.8 yr ) than in the TIW ( 0.0 + /- 0.9 yr ) group ( P = 0.003 ) . The mean age at onset of puberty in boys was the same in the QD ( 13.2 yr ) and TIW ( 13.0 yr ) groups ( P = 0.71 ) , and the mean bone age at the start of puberty was also similar ( 11.5 in QD and 11.3 in TIW groups ; P = 0.66 ) . The advantages of QD rhGH treatment in prepubertal GH-deficient children after 4 yr were additional gains of 1.7 height SD score and 9.7 cm in height over those treated with the TIW regimen ( P = 0.0002 ) OBJECTIVE . The goal was to determine how often common laboratory tests yield normal results at the time of diagnosis for children with inflammatory bowel disease . METHODS . Data were obtained from a registry of children with newly diagnosed inflammatory bowel disease who were enrolled prospect ively in 18 US/Canadian centers . Laboratory values investigated included hemoglobin level , platelet count , albumin level , and erythrocyte sedimentation rate . Disease severity was categorized by physician global assessment . RESULTS . A total of 526 children ( mean age : 11.6 years ; 58 % male ; 392 with Crohn disease and 134 with ulcerative colitis ) were studied . All 4 values were normal for 21 % of patients with mild Crohn disease and 54 % with mild ulcerative colitis . In contrast , only 3.8 % of children with moderate/severe Crohn disease and 4.3 % with moderate/severe ulcerative colitis had normal results for all 4 tests . The erythrocyte sedimentation rate was least likely to be normal ; overall , 26 % of patients with inflammatory bowel disease had a normal erythrocyte sedimentation rate , including 18 % with moderate/severe disease . Hemoglobin levels were normal for 32 % , platelet counts for 50 % , and albumin levels for 60 % . There was no clear association between Crohn disease location and either severity or number of normal laboratory values . In contrast , there were direct correlations between ulcerative colitis disease severity and both the extent of bowel inflammation and the number of abnormal laboratory tests . CONCLUSION . The presence of normal screening laboratory studies should not dissuade clinicians from considering a diagnosis of inflammatory bowel disease 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 OBJECTIVE Our objective was to assess final height ( FH ) and adverse effects of combined GH and GnRH agonist ( GnRHa ) treatment in short adolescents born small for gestational age or with normal birth size ( idiopathic short stature ) . DESIGN AND PATIENTS Thirty-two adolescents with Tanner stage 2 - 3 , age and bone age ( BA ) less than 12 yr for girls or less than 13 yr for boys , height sd score ( SDS ) less than -2.0 SDS or between -1.0 and -2.0 SDS plus a predicted adult height ( PAH0 ) less than -2.0 SDS were r and omly allocated to receive  GH plus GnRHa  ( n=17 ) or no treatment ( n=15 ) for 3 yr . FH was assessed at the age of 18 yr or older in girls or 19 yr or older in boys . RESULTS FH was not different between treatment and control groups . Treated children had a larger height gain ( FH-PAH0 ) than controls : 4.4 ( 4.9 ) and -0.5 ( 6.4 ) cm , respectively ( P<0.05 ) . FH was higher than PAH0 in 76 and 60 % of treated and control subjects , respectively . During follow-up , 50 % of the predicted height gain at treatment withdrawal was lost , result ing in a mean gain of 4.9 cm ( range , -4.0 to 12.3 cm ) compared with controls . Treatment did not affect body mass index or hip bone mineral density . Mean lumbar spine bone mineral density and bone mineral apparent density tended to be lower in treated boys , albeit statistically not significant . CONCLUSION Given the expensive and intensive treatment regimen , its modest height gain results , and the possible adverse effect on peak bone mineralization in males , GH plus GnRHa can not be considered routine treatment for children with idiopathic short stature or persistent short stature after being born small for gestational age 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 , - 
    Output:
    