***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: Abstract Objective : The objective of this study was to psychometrically evaluate a tool to measure adult caregivers ’ level of satisfaction with the delivery device used to administer injections of recombinant human growth hormone ( rhGH ) to a child – the Satisfaction Measure of the Injection of Growth Hormone Therapy ( SMIGHTy * SMIGHTy is a trademark of Genentech , Inc. , South San Francisco , CA , USA . ) question naire . Research design and methods : One hundred caregivers who administer rhGH to a child using an injection device completed the SMIGHTy question naire at baseline and 7–14 days later , and also completed other measures of treatment adherence and treatment satisfaction at baseline . Main outcome measures : SMIGHTy reliability ( inter-item and test – retest ) and external validity ( association with other study measures ) were assessed . Results : Analyses revealed good inter-item agreement and test – retest reliability for the SMIGHTy question naire . External validity , measured by associations with adherence and other measures of treatment satisfaction , was high . Study limitations : This study assessed only adult caregivers ; the instrument was not vali date d for use by young or adult patients . Conclusions : The SMIGHTy instrument is more comprehensive than existing instruments for assessing the growth hormone treatment experience . It is multidimensional , assesses both positive and negative aspects of the treatment experience ( Device Satisfaction , Negative Events , Benefits ) , and has separate measures of overall satisfaction and preference The causes of growth retardation of children with thalassaemia major are multifactorial . We studied the GH response to provocation by clonidine and glucagon , measured the circulating concentrations of insulin , IGF-I , IGF-binding protein-3 ( IGFBP-3 ) and ferritin , and evaluated IGF-I generation after a single dose of GH ( 0.1 mg/kg per dose ) in 15 prepubertal patients with thalassaemia , 15 age-matched children with constitutional short stature ( CSS ) ( height st and ard deviation score less than -2 , with normal GH response to provocation ) and 11 children with isolated GH deficiency ( GHD ) . Children with thalassaemia had significantly lower peak GH response to provocation by clonidine and glucagon ( 6.2 + /- 2.3 and 6.8 + /- 2.1 microg/l respectively ) than the CSS group ( 18.6 + /- 2.7 and 16.7 + /- 3.7 microg/l respectively ) . They had significantly decreased circulating concentrations of IGF-I and IGFBP-3 ( 47.5 + /- 19 ng/ml and 1.2 + /- 0.27 mg/l respectively ) compared with those with CSS ( 153 + /- 42 ng/ml and 2.06 + /- 0.37 mg/l respectively ) , but the IGF-I and IGFBP-3 concentrations were not different from those with GHD ( 56 + /- 25 ng/ml and 1.1 + /- 0.32 mg/l respectively ) . These data demonstrate that the GH-IGF-I-IGFBP-3 axis in thalassaemic children is defective . Serum ferritin concentration correlated significantly with GH peak response to provocation ( r = -0.36 , P < 0.05 ) and circulating IGF-I ( r = -0.47 , P < 0.01 ) and IGFBP-3 ( r = -0.42 , P < 0.01 ) concentrations . In the IGF-I generation test , after GH injection , the thalassaemic children had significantly lower IGF-I and IGFBP-3 levels 86.7 + /- 11.2 ng/ml and 2.05 + /- 0.51 mg/l respectively ) than those in the CSS group ( 226 + /- 45.4 ng/ml and 2.8 + /- 0.43 mg/l respectively ) . The IGF-I response was significantly higher in children with GHD ( 158 + /- 50 ng/ml ) than in thalassaemic children . Six short ( height st and ard deviation score less than -2 ) thalassaemic children who had defective GH response to provocation ( < 10 microg/l ) , all the children with GHD and eight short normal children ( CSS ) were treated for 1 year with human GH ( 18 units/m2 per week divided into daily s.c . doses ) . After 1 year of GH therapy there was a marked acceleration of growth velocity in both thalassaemic children ( from 3.8 + /- 0.6 cm/year to 7.2 + /- 0.8 cm/year ) and controls . However , the linear acceleration of growth velocity on GH therapy was significantly slower in thalassaemic children ( 3.3 + /- 0.3 cm/year increment ) compared with those with CSS ( 5.3 + /- 0.4 cm/year increment ) and GHD ( 6.9 + /- 1.2 cm/year increment ) ( P < 0.05 ) . Their circulating IGF-I concentration ( 105 + /- 36 ng/ml ) was significantly lower than those for CSS ( 246 + /- 58 ng/ml ) and GHD ( 189 + /- 52 ng/ml ) after 1 year of GH therapy . These data prove that some children with beta-thalassaemia major have a defective GH-IGF-I-IGFBP-3 axis and suggest the presence of partial resistance to GH Background : Quality of life ( QoL ) as it is related with growth hormone deficiency ( GHD ) is a matter of controversy . Methods : We analyzed QoL in 95 children aged 8–18 years with isolated GHD ( 72 % male ) treated with growth hormone ( GH ) .  These children were compared to 190 age- and gender-matched healthy children with similar height [ height < 10th percentile ; control group 1 ( CG1 ) ] and age- and gender-matched 285 healthy children of normal stature ( control group 2 : CG2 ) .  QoL was measured by the KINDL ® question naire referring to six domains ( physical well-being , emotional well-being , self-esteem , family , friends , and school ) . Results : QoL was significantly reduced in CG1 ( effect-size 0.21 ) compared to CG2 , while QoL was not significantly altered in children with GHD . In multiple linear regression analyses adjusted to age , gender , BMI , migration background , and socioeconomic status , decreasing height-SDS was associated with poorer QoL ( especially emotional well-being ) , and treatment with GH was related significantly to better self-esteem . Increase of height-SDS in children treated with GH was associated positively with QoL and all its subscales except family and school . Conclusions : These findings suggest psychological consequences of short stature in children and an improvement of QoL in children treated with GH with the focus on self-esteem and emotional well-being To assess whether delaying puberty may improve final height in GH-deficient children with a poor height prediction at early puberty , we studied 24 girls with isolated GH deficiency until they reached their final height , in a controlled trial . Patients were taking recombinant human GH ( r-hGH ) substitutive therapy from 2.1 + /- 0.5 yr ( 0.1 IU/kg.day sc ) before entering the study , without showing any improvement in height prediction ( 149.6 + /- 2.9 vs.150.3 + /- 2.2 cm ) on entering puberty . Fourteen girls agreed to add a GnRH agonist ( GnRHa ) to r-hGH , whereas the remaining 10 decided against it and served as controls . At the start of the study , girls treated with or without GnRHa had similar auxological characteristics ( bone age , 10.9 + /- 0.6 vs. 10.7 + /- 1.3 yr ; height SD score for chronological age , -1.87 + /- 0.3 vs. -1.82 + /- 0.2 ) , including pubertal development . The GnRHa ( long-acting D-Trp-6-GnRH ) was given at 60 microg/kg i m every 28 days for 1.9 + /- 0.9 yr , then patients continued the r-hGH at the same dosage ( 3.1 + /- 0.7 yr ) . At the end of the study , bone age was 16.2 + /- 0.3 yr in GnRHa-treated girls and 16.6 + /- 0.9 yr in controls . Bone maturation was significantly slower during GnRHa ( 1.4 + /- 0.2 yr ) , and height SD score for bone age improved ( -0.31 + /- 0.3 ) in comparison with controls ( 2.6 + /- 0.4 yr and -1.35 + /- 0.3 SD score ; P < 0.001 and P < 0.0001 , respectively ) . As a result , girls given the combined therapy reached a final height higher than that of controls ( height SD score , -0.39 + /- 0.5 vs. -1.45 + /- 0.2 ; P < 0.0001 ) and also higher than their midparental height ( -1.1 + /- 0.5 ; P < 0.0005 ) . Controls reached their midparental height . In conclusion , our results demonstrate that slowing pubertal development with the administration of GnRHa for a limited time may improve final height in GH-deficient girls selected because of a poor height prediction at early puberty We measured the  final height ( FH ) of 25 short polytransfused thalassemia major ( Th ) patients ( 18 males ) with a reduced GH reserve treated for 3.3±1.2 yr with recombinant GH ( rhGH ) , 0.2 mg/kg/week sc . At baseline , all patients were clinical ly prepubertal ;  their chronological ( CA ) and bone ages ( BA ) were 13.6±2.0 and 11.4±1.6 yr , respectively . In 9 out of 18 males and 5 out of 7 females , the onset of puberty occurred spontaneously during the treatment . At the end of the rhGH administration , the height of the enrolled children was not significantly increased when calculated for CA ( HxCA ) , while it was significantly decreased ( p=0.004 ) when calculated for BA ( HxBA ) ; the BA increase ( 3.29±1.65 yr ) was significantly higher ( p<0.001 ) than the height age increase ( 2.16±0.98 yr ) . The FHxCA showed a significant increase ( p=0.001 ) compared to both baseline and the end of therapy , while the FHxBA was significantly decreased ( p<0.001 ) compared with the corresponding value at baseline . At the end of therapy , both HxCA and HxBA result ed positively related to the BA at baseline ( r=0.50 and 0.42 , p=0.012 and 0.034 , respectively ) . FH was positively correlated with CA ( r=0.63 , p=0.001 ) , BA ( r=0.68 , p<0.001 ) and HxBA ( r=0.59 , p=0.002 ) evaluated at baseline , and with both HxCA and HxBA ( r=0.82 and 0.74 , respectively , p<0.001 ) , evaluated at the end of treatment . A negative correlation was found between FH and the length of treatment ( r=−0.56 , p=0.004 ) . Our data seem to exclude that prolonged rhGH therapy  could improve FH in Th patients ; on the contrary , a negative effect may be hypothesized Patients with beta-thalassemia major ( beta-thalassemia ) frequently have bone disorders of multifactorial etiology . We attempted to analyze the relationship between the bone mineral density ( [ BMD ] measured by dual-photon absorptiometry ) and auxanologic parameters , degree of siderosis , function of the growth hormone (GH)/insulin-like growth factor-I (IGF-I)/IGF-binding protein-3 ( IGFBP3 ) axis , calcium-phosphate balance , parathyroid hormone ( PTH ) , and cytokines ( interleukin-1beta [ IL-1 ] and tumor necrosis factor-alpha [ TNF-alpha ] ) in 30 prepubertal children with beta-thalassemia major and 15 age-matched children with constitutional short stature ( CSS ) , who have normal glucose tolerance and thyroid function . Children with beta-thalassemia had a significantly decreased BMD and mean BMD% for age and sex ( 0.75+/-0.24 g/cm2 and 71%+/-10 % , respectively ) versus children with CSS ( 1.06+/-0.3 g/cm2 and 92%+/-7 % , respectively ) . Thalassemic patients had significantly lower circulating concentrations of IGF-I and IGFBP3 ( 49+/-21 ng/mL and 1.2+/-0.25 mg/L , respectively ) compared with control children ( 153+/-42 ng/mL and 2.1+/-0.37 mg/L , respectively ) . The GH response to provocation by clonidine and glucagon was defective ( peak GH < 7 microg/L ) in 12 of the 30 thalassemic children . Serum concentrations of IL-1beta and TNF-alpha did not differ among the two study groups . Hypocalcemia 
    Output:
    
A small single trial contributed evidence of moderate quality that the use of growth hormone for a year may improve height velocity of children with thalassaemia although height SD score in the treatment group was similar to the control group .