Growth hormone receptor polymorphism and growth hormone therapy response in children: a Bayesian meta-analysis.

Recombinant human growth hormone (rhGH) therapy is used in the long-term treatment of children with growth disorders, but there is considerable treatment response variability. The exon 3-deleted growth hormone receptor polymorphism (GHR(d3)) may account for some of this variability. The authors performed a systematic review (to April 2011), including investigator-only data, to quantify the effects of the GHR(fl-d3) and GHR(d3-d3) genotypes on rhGH therapy response and used a recently established Bayesian inheritance model-free approach to meta-analyze the data. The primary outcome was the 1-year change-in-height standard-deviation score for the 2 genotypes. Eighteen data sets from 12 studies (1,527 children) were included. After several prior assumptions were tested, the most appropriate inheritance model was codominant (posterior probability = 0.93). Compared with noncarriers, carriers had median differences in 1-year change-in-height standard-deviation score of 0.09 (95% credible interval (CrI): 0.01, 0.17) for GHR(fl-d3) and of 0.14 (95% CrI: 0.02, 0.26) for GHR(d3-d3). However, the between-study standard deviation of 0.18 (95% CrI: 0.10, 0.33) was considerable. The authors tested by meta-regression for potential modifiers and found no substantial influence. They conclude that 1) the GHR(d3) polymorphism inheritance is codominant, contrasting with previous reports; 2) GHR(d3) genotypes account for modest increases in rhGH effects in children; and 3) considerable unexplained variability in responsiveness remains.

The effect of different patterns of growth hormone administration on the IGF axis and somatic and skeletal growth of the dwarf rat.

Normal childhood growth is determined by ultradian and infradian variations in GH secretion, yet GH treatment of children with short stature is restricted to daily fixed doses. We have used GH-deficient dwarf rats to determine whether variable GH dose regimens promote growth more effectively than fixed doses. Animals were treated with saline or 4.2 mg of recombinant bovine GH given as 1) 700 microg/wk in 100 microg/day doses, 2) alternating weekly doses of 966 (138 microg/day) or 434 microg (62 microg/day), or 3) 700 microg/wk in randomized daily doses (5-250 microg/day). Body weight and length were measured weekly. Femur and tibia lengths and internal organ, fat pad, and muscle weights were recorded at the end of the study (6 wk); blood was collected for IGF axis measurements. GH promoted femur [F(3,60) = 14.67, P < 0.05], tibia [F(3,60) = 14.90, P < 0.05], muscle [F(3,60) = 10.37, P < 0.05], and organ growth [liver: F(3,60) = 9.30, P < 0.05; kidney: F(3,60) = 2.82, P < 0.05] and an increase in serum IGF-I [F(3,60) = 9.18, P < 0.05] and IGFBP-3 [F(3,60) = 6.70, P < 0.05] levels. IGF-I levels correlated with final weight (r = 0.45, P < 0.05) and length (r = 0.284, P < 0.05) in the whole cohort, but within each group, growth parameters correlated with serum IGF-I only in animals treated with random GH doses. The variable regimens promoted femur length (P < 0.05) and muscle (P < 0.05) and kidney (P < 0.05) weight more effectively than treatment with the fixed regimen. This study demonstrates that aspects of growth are improved following introduction of infradian variation to GH treatment in a GH-deficient model. The data suggest that varying the pattern of GH doses administered to children may enhance growth performance without increasing the overall GH dose.

The patient-reported impact of scars measure: development and validation.

BACKGROUND: Skin scars have a unique impact on patients' lives. Quantification with disease-specific patient-reported outcome measures is essential for assessing disease severity. This study aimed to develop and validate the first scar-specific patient-reported outcome measure. METHODS: Instrument content was derived from qualitative interviews with scar patients. Quotes were identified from transcripts for use as instrument items. This draft measure was field tested in cognitive debriefing interviews. The final instrument was determined using Rasch analysis in a large-scale validation survey. RESULTS: Five hundred sixty-seven potential items were extracted from interviews (n = 34 patients; 24 women; mean age, 35.7 years). Patients primarily reported physical symptoms and impacts on quality of life. Consequently, a symptom scale (16 items) and quality-of-life scale (36 items) were created. Cognitive debriefing (n = 16 patients; 10 women; mean age, 32.8 years) indicated the draft measure was relevant, clear, and practical. Two quality-of-life items, considered too extreme by patients, were deleted. Ten quality-of-life and three symptom items were removed as a result of the validation survey (n = 103 patients; 69 women; mean age, 35.5 years). Final Rasch analysis confirmed two unidimensional scales (p > 0.05) with good internal consistency (0.85 for the symptom scale and 0.93 for the quality-of-life scale). Reproducibility was adequate for the symptom scale (0.83) and good for the quality-of-life scale (0.89). CONCLUSIONS: The Patient-Reported Impact of Scars Measure is the first scientifically rigorous, scar-specific, patient-reported outcome measure. It has two unidimensional scales with good psychometric and scaling properties. It is well accepted by patients and easy to use, and should prove valuable for assessing scar disease severity in clinical trials and in general and specialty clinics.