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Growth hormone therapy needs to be tailored based on individual responsiveness in children with idiopathic short stature
THE JOURNAL OF PEDIATRICS
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between normal and abnormal heart and respiratory rates in children. Rosalind L. Smyth, FMedSci University of Liverpool and Alder Hey Children’s Hospital Liverpool, United Kingdom
Growth hormone therapy needs to be tailored based on individual responsiveness in children with idiopathic short stature Deodati A, Cianfarani S. Impact of growth hormone therapy on adult height of children with idiopathic short stature: systematic review. BMJ 2011;342:c7157. Question Among children with idiopathic short stature, does growth hormone use impact adult height, compared with controls? Design Systematic review. Data Sources Cochrane Central Register of Controlled Trials, Medline, and the bibliographic references from retrieved articles of randomized and non-randomized controlled trials from 1985 to April 2010. Study Selection and Assessment Inclusion criteria were initial short stature (defined as height >2 SD score below the mean), peak growth hormone responses >10 mg/L, prepubertal stage, no previous growth hormone therapy, and no comorbid conditions that would impair growth. Adult height was considered achieved when growth rate was <1.5 cm/year or bone age was 15 years in females and 16 years in males. The authors assigned a quality rating (based on Endocrine Society standards) for each included study. Outcomes Height in adulthood and overall gain in height from baseline measurement in childhood. Main Results Three randomized controlled trials (115 children) met the inclusion criteria. The adult height of the growth hormone treated children exceeded that of the controls by 0.65 SDS (about 4 cm). The mean height gain in treated children was 1.2 SDS compared with 0.34 SDS in untreated children. A slight difference of about 1.2 cm in adult height was observed between the two growth hormone dose regimens. In the seven non-randomized controlled trials, the adult height of the growth hormone treated group exceeded that of the controls by 0.45 SDS (about 3 cm). Conclusions Growth hormone (GH) 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 GH is licensed. The individual response to therapy is highly variable, and additional studies are needed to identify the responders. Commentary Does GH affect the adult height of children with idiopathic short stature? Yes, according to this systematic review by Deodati and Cianfarani. The review found that the overall height gain was 1.2 SDS versus 0.34 SDS, 516
Vol. 159, No. 3 with a large inter-individual variation in growth response, ranging from 0 to 3 SDSs (approx. 18 cm), partly GH dose dependent. This large variation in individual responses indicates that the mean height gain for the group cannot predict the growth response in a single individual. To identify the responders, it is possible to use the models that predict the child’s growth response. The GH-dependent growth of a child depends on the balance between GH-secretion and responsiveness. Tailoring the GH dose according to individual responsiveness reduces the inter-individual variation in both growth and non-growth effects. In addition, the GH dose should be tailored according the intra-individual variation due to the growth period (infancy, childhood, puberty, adulthood), known to normalize growth; this will hopefully minimize the long-term risks of cardiovascular, metabolic, malignant, cognitive, and psychosocial disease. Kerstin Albertsson-Wikland, MD, PhD University of Gothenburg Gothenburg, Sweden
Rapid antigen testing for respiratory virus syncytial can be used in neonates with provisos Yen AB, Demmler-Harrison GJ. Rapid antigen testing to detect respiratory syncytial virus performs well in neonates. Pediatr Infect Disease J 2011;30:234-7. Question In neonates with suspected respiratory syncytial virus (RSV) infection, how accurate is the RSV rapid antigen test? Design Retrospective analysis (1997-2008) of rapid RSV antigen testing in neonates (#30 days) using a laboratory database of the Diagnostic Virology Laboratory. Setting Texas Children’s Hospital, Houston, Texas. Participants 3691 respiratory samples collected consecutively were included. Of these, 784 (21%) were positive for RSV by rapid test and 402 (10.9%) showed growth of RSV in viral culture. Outcomes Sensitivity and specificity were calculated using viral culture as the reference standard. Main Results Overall sensitivity was 90.3% and specificity was 88.2% (likelihood ratio [LR] for a positive rapid test [LR+] = 7.7 and LR for a negative rapid test [LR-] = 0.11). Sensitivity was lower in nonseason samples (76.5% vs. 90.9% [P = .048]), but specificity was higher in nonseason samples (95.6% vs. 87.1% [P # .001]). Lower specificity was seen in samples submitted from neonates evaluated in the emergency department compared with inpatient floors, neonatal intensive care unit, and unspecified venues (85.1% vs. 95.6%, 94.3%, 95.5%, respectively P # .001). Overall, there was no statistical difference in test performance based on specimen type. However, when RSV was in season, nasal washes were more sensitive than tracheal aspirates (LR- = 0.10 vs. 0.43, P = .017).
www.jpeds.com
between normal and abnormal heart and respiratory rates in children. Rosalind L. Smyth, FMedSci University of Liverpool and Alder Hey Children’s Hospital Liverpool, United Kingdom
Growth hormone therapy needs to be tailored based on individual responsiveness in children with idiopathic short stature Deodati A, Cianfarani S. Impact of growth hormone therapy on adult height of children with idiopathic short stature: systematic review. BMJ 2011;342:c7157. Question Among children with idiopathic short stature, does growth hormone use impact adult height, compared with controls? Design Systematic review. Data Sources Cochrane Central Register of Controlled Trials, Medline, and the bibliographic references from retrieved articles of randomized and non-randomized controlled trials from 1985 to April 2010. Study Selection and Assessment Inclusion criteria were initial short stature (defined as height >2 SD score below the mean), peak growth hormone responses >10 mg/L, prepubertal stage, no previous growth hormone therapy, and no comorbid conditions that would impair growth. Adult height was considered achieved when growth rate was <1.5 cm/year or bone age was 15 years in females and 16 years in males. The authors assigned a quality rating (based on Endocrine Society standards) for each included study. Outcomes Height in adulthood and overall gain in height from baseline measurement in childhood. Main Results Three randomized controlled trials (115 children) met the inclusion criteria. The adult height of the growth hormone treated children exceeded that of the controls by 0.65 SDS (about 4 cm). The mean height gain in treated children was 1.2 SDS compared with 0.34 SDS in untreated children. A slight difference of about 1.2 cm in adult height was observed between the two growth hormone dose regimens. In the seven non-randomized controlled trials, the adult height of the growth hormone treated group exceeded that of the controls by 0.45 SDS (about 3 cm). Conclusions Growth hormone (GH) 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 GH is licensed. The individual response to therapy is highly variable, and additional studies are needed to identify the responders. Commentary Does GH affect the adult height of children with idiopathic short stature? Yes, according to this systematic review by Deodati and Cianfarani. The review found that the overall height gain was 1.2 SDS versus 0.34 SDS, 516
Vol. 159, No. 3 with a large inter-individual variation in growth response, ranging from 0 to 3 SDSs (approx. 18 cm), partly GH dose dependent. This large variation in individual responses indicates that the mean height gain for the group cannot predict the growth response in a single individual. To identify the responders, it is possible to use the models that predict the child’s growth response. The GH-dependent growth of a child depends on the balance between GH-secretion and responsiveness. Tailoring the GH dose according to individual responsiveness reduces the inter-individual variation in both growth and non-growth effects. In addition, the GH dose should be tailored according the intra-individual variation due to the growth period (infancy, childhood, puberty, adulthood), known to normalize growth; this will hopefully minimize the long-term risks of cardiovascular, metabolic, malignant, cognitive, and psychosocial disease. Kerstin Albertsson-Wikland, MD, PhD University of Gothenburg Gothenburg, Sweden
Rapid antigen testing for respiratory virus syncytial can be used in neonates with provisos Yen AB, Demmler-Harrison GJ. Rapid antigen testing to detect respiratory syncytial virus performs well in neonates. Pediatr Infect Disease J 2011;30:234-7. Question In neonates with suspected respiratory syncytial virus (RSV) infection, how accurate is the RSV rapid antigen test? Design Retrospective analysis (1997-2008) of rapid RSV antigen testing in neonates (#30 days) using a laboratory database of the Diagnostic Virology Laboratory. Setting Texas Children’s Hospital, Houston, Texas. Participants 3691 respiratory samples collected consecutively were included. Of these, 784 (21%) were positive for RSV by rapid test and 402 (10.9%) showed growth of RSV in viral culture. Outcomes Sensitivity and specificity were calculated using viral culture as the reference standard. Main Results Overall sensitivity was 90.3% and specificity was 88.2% (likelihood ratio [LR] for a positive rapid test [LR+] = 7.7 and LR for a negative rapid test [LR-] = 0.11). Sensitivity was lower in nonseason samples (76.5% vs. 90.9% [P = .048]), but specificity was higher in nonseason samples (95.6% vs. 87.1% [P # .001]). Lower specificity was seen in samples submitted from neonates evaluated in the emergency department compared with inpatient floors, neonatal intensive care unit, and unspecified venues (85.1% vs. 95.6%, 94.3%, 95.5%, respectively P # .001). Overall, there was no statistical difference in test performance based on specimen type. However, when RSV was in season, nasal washes were more sensitive than tracheal aspirates (LR- = 0.10 vs. 0.43, P = .017).