Short-time least squares spectral analysis of pass-by noise in water from a rigid inflatable boat.

This paper investigates least squares spectral analysis as a tool to analyze non-stationary signals from pass-by noise measurements in water. The spectral analysis involves successive least squares fitting of a finite Fourier series to approximate the observation in a piecewise manner. The least squares spectral analysis is used to search the signals for first- and second-order periodicity as well as the presence of fundamental periodicity. A first-order analysis reveals line components in the signals, whereas a second-order analysis reveals periodic amplitude modulations. Analysis with a higher-order finite Fourier series reveals harmonic structures in the signals. The main contribution of this paper is the model of a magnitude-squared cosine wave which can be used to analyze second-order periodicity. The developed short-time least squares spectral analysis is illustrated on noise radiated from a rigid inflatable boat in shallow water.

Near Adult Height in Girls with Turner Syndrome Treated with Growth Hormone Following Either Induced or Spontaneous Puberty.

OBJECTIVE: To understand whether spontaneous vs induced puberty and the type and route of estrogen influence the height of girls with Turner syndrome on growth hormone (GH). STUDY DESIGN: Search of an international database of children treated with GH revealed 772 girls with Turner syndrome followed from GH initiation to near adult height. Data from girls with sustained spontaneous puberty (n = 145) were compared with those requiring estrogens for induction or maintenance of puberty (n = 627). RESULTS: At GH start, mean age (7.5 vs 7.9 years), weight (-1.7 vs -1.7 SDS), and body mass index (0.2 SDS vs 0.1 SDS) were similar for girls with spontaneous puberty and with induced puberty. Although those girls with spontaneous puberty were shorter than those with induced puberty, when midparental height was taken into consideration, starting heights in both groups averaged -2.8 SDS. Both groups received approximately 0.3 mg/kg/week of GH. Girls with spontaneous puberty initiated puberty and reached near adult height earlier than girls with induced puberty (12.6 ± 1.8 years vs 13.4 ± 1.4 years and 16.0 ± 1.3 years vs 16.9 ± 1.4 years, respectively). Although girls with spontaneous puberty grew more in the first year of GH therapy and between the onset of puberty and near adult height (11.0 cm vs 9.3 cm), height SDS at near adult height and the length of time in puberty before reaching near adult height were comparable. A 45,X karyotype was detected in 22.1% of girls with spontaneous puberty and in 58.4% of girls with induced puberty. Patients receiving transdermal estrogens did not grow better than those on oral estrogens. Adverse event reporting was comparable between groups. CONCLUSIONS: Girls with Turner syndrome with spontaneous puberty tended to grow better in response to GH than girls with induced puberty, but not enough to produce a difference in height SDS at near adult height.

Efficacy of Growth Hormone Treatment in Children with Type 1 Diabetes Mellitus and Growth Hormone Deficiency-An Analysis of KIGS Data.

OBJECTIVE: To analyze first-year treatment growth response and growth hormone (GH) dosage in prepubertal patients with the combination of type 1 diabetes mellitus (T1DM) and growth hormone deficiency (GHD). STUDY DESIGN: A total of 69 patients with T1DM and GHD treated with GH have been enrolled in KIGS (Pfizer International Growth Database). Of these, 24 prepubertal patients had developed T1DM before GHD and were included in this analysis. Of 30 570 patients with GHD without T1DM, 15 024 were prepubertal and served as controls. Values are expressed as mean ± SD. RESULTS: Patients with T1DM and GHD had similar characteristics compared with the GHD-alone group. Neither age (10.2 ± 3.13 vs 8.42 ± 3.46 years, P = .14), height SDS corrected for midparental height SDS at start of treatment (-1.62 ± 1.38 vs -1.61 ± 1.51, P = .80), nor GH dosage (0.24 ± 0.08 mg/kg/wk vs 0.20 ± 0.04 mg/kg/wk, P = .09) were different between those with and without T1DM. First-year catch-up growth was comparable between the 2 patient groups (first treatment year height velocity 7.54 ± 3.11 cm/year compared with 8.35 ± 2.54 cm/year in control patients, P = .38). Height SDS of children with T1DM and GHD improved from -2.62 ± 1.04 to -1.88 ± 1.11 over 1 year of GH treatment. CONCLUSION: Short-term response to GH therapy appeared similar in subjects with T1DM who then developed GHD and in those with GHD alone. Thus, T1DM does not appear to compromise GH response in children with GHD and should not exclude GH treatment in these children. GH treatment was safe in both subgroups of patients.

Using a spontaneous profile rather than stimulation test makes the KIGS idiopathic growth hormone deficiency model more accessible for clinicians.

AIM: Children treated with a growth hormone (GH) for idiopathic growth hormone deficiency (IGHD) may be monitored with the first-year prediction model from the Pfizer International Growth Database (KIGS) using auxology, age, GH dose and the maximum GH concentration from a stimulation test (GHmax stim). We tested the hypothesis that using a 12-hour spontaneous profile (GHmax 12h) would be as accurate. METHODS: We studied 98 prepubertal Swedish children (78 boys) aged 2-12 years enrolled in KIGS. The first-year growth was predicted using the GHmax from the GH profile and a stimulation test, and both of these were compared separately with the observed growth response. RESULTS: The increased height observed in the first year was 0.74 standard deviation scores (SDS), and the studentised residuals for the predicted and observed growth with GHmax stim (-0.16 SDS) and GHmax 12h (-0.22) were similar. Individual predictions calculated with stimulated or spontaneous GHmax showed a significant correlation (r = 0.80). CONCLUSION: We validated the KIGS IGHD prediction model and found that the stimulated GHmax peak can be reliably replaced by the GHmax 12h with similar accuracy. This makes the model more accessible for clinicians, who can then provide realistic expectations for the growth response during the first year of treatment.

Weight gain in Turner Syndrome: association to puberty induction? - longitudinal analysis of KIGS data.

CONTEXT: Girls with Turner Syndrome (TS) treated or not treated with growth hormone (GH) are prone to overweight. Therefore, we hypothesize that puberty induction in TS is associated with weight gain. METHODS: We analyzed weight changes (BMI-SDS) between onset of GH treatment and near adult height (NAH) in 887 girls with TS enrolled in KIGS (Pfizer International Growth Database). Puberty was induced with estrogens in 646 (72·8%) girls with TS. RESULTS: Weight status did not change significantly between GH treatment start and 1 year later (mean difference -0·02 BMI-SDS), but increased significantly (P < 0·001) until NAH (+0·40 BMI-SDS). The BMI-SDS increased +0·21 until start of puberty (P < 0·001). Girls with spontaneous and induced puberty showed similar BMI-SDS changes. Puberty induction at ≥12 years was associated with a significant (P < 0·001) less increase of BMI-SDS (+0·7 BMI-SDS) between baseline and NAH compared to puberty induction at <12 year (+1·0 BMI-SDS). In multiple linear regression analyses changes of BMI-SDS between baseline and NAH were negatively associated with baseline BMI-SDS (P < 0·001), GH doses (P = 0·015), and age at puberty induction (P < 0·001), positively with years on GH treatment (P = 0·004), while duration and dose of estrogens, its route of administration (transdermal/oral), changes of height-SDS, thyroxin and oxandrolone treatment, and karyotype did not correlate significantly to changes of BMI-SDS in this time period. CONCLUSIONS: Puberty does not seem to play a major role in weight gain in girls with TS since the majority of the increases in BMI-SDS occurred before puberty. However, late puberty induction seems to decrease the risk of weight gain.

Long-term growth hormone treatment in short children with CKD does not accelerate decline of renal function: results from the KIGS registry and ESCAPE trial.

BACKGROUND: Recombinant human (rh) growth hormone (GH) raises the glomerular filtration rate (GFR) in healthy individuals. Concern has been raised that long-term rhGH treatment in short children with chronic kidney disease (CKD) may accelerate the progression of CKD via induction of glomerular hyperfiltration. PATIENTS AND METHODS: We compared the decline in GFR in children with CKD enrolled in two large clinical studies with (KIGS registry) and without (ESCAPE trial) concomitant rhGH treatment and followed for up to 10 years. Estimated GFR (eGFR) was determined at yearly intervals. The annual decline in eGFR was analyzed cross-sectionally for up to 10 years and longitudinally for 5 years. RESULTS: In the KIGS registry 367 patients with CKD stages II-IV (mean age 8.0 years; 72% boys; mean eGFR 38.4 ml/min/1.73 m(2)) were treated with 0.33 mg rhGH/kg per week for at least 1 year. In the ESCAPE trial 274 non-rhGH-treated patients with CKD stages II-IV (mean age 11.6 years; 61% boys; mean GFR 47.3 ml/min/1.73 m(2)) were followed for at least 1 year. At the 5-year follow-up, the mean loss of eGFR in the KIGS children receiving continuous rhGH treatment (n = 97) did not differ significantly from that in the controls (n = 113) in the ESCAPE trial (-5.8 vs. -8.6 ml/5 years, respectively; p = 0.17). Absolute height and eGFR at baseline were significant correlates of the annual eGFR loss (model R (2) =0.121). CONCLUSIONS: Long-term rhGH-treatment does not accelerate the decline in GFR in short children with CKD. Height and baseline eGFR are significant predictors of the loss of GFR in CKD patients.

Computation of sound radiation by a driver in a cabinet using a substitute source approach.

Sound radiation by a driver set in a rigid closed cabinet is modeled analytically using the principle of wave superposition. The driver-cabinet assembly is replaced by an array of volumeless substitute sources-monopoles-confined within its surface. The role of substitute sources is to reproduce the sound field exterior to the surface as close to the original field as possible. The frequency dependent positions and strengths of substitute monopoles are optimized by an iterative search procedure aimed at matching the prescribed surface boundary conditions of the original source. The time-consuming optimization of monopole positions is carried out at narrowband center frequencies reducing the computational cost without significant loss of accuracy. The consistency of computed results is verified by checking the power output through the cabinet surface. Modeling is done for anechoic and semi-anechoic conditions. The model has been validated experimentally in a semi-anechoic room with satisfactory results using a mid-range driver set in a closed-box baffle.

Is growth hormone treatment in children associated with weight gain?--longitudinal analysis of KIGS data.

OBJECTIVE: Growth hormone (GH) increases lean body mass and reduces fat mass. However, the long-term changes in weight status during growth hormone treatment, according to age and weight status at onset of treatment, have not previously been reported in large data sets. METHODS: Changes in BMI-SDS between starting GH treatment and attaining near adult height (NAH) were analysed in 2643 children with idiopathic GH deficiency (IGHD), 281 children small for gestational age (SGA), 1661 girls with Turner syndrome (TS), and 142 children with Prader-Willi syndrome (PWS) in the KIGS database. RESULTS: BMI-SDS increased significantly between onset of GH treatment and NAH (IGHD:+0·29, SGA:+0·69, TS:+0·48) except in PWS (-0·02). These increases were greater in children with younger age at onset of GH treatment (significant in all indications) and with lower doses of GH treatment (significant in IGHD & TS) in multiple linear regression analyses also including gender, duration of GH treatment, BMI-SDS and height-SDS at onset of treatment, and birth weight-SDS. Obese children at onset of GH treatment decreased their BMI-SDS, while underweight and normal weight children at onset of GH treatment increased their BMI-SDS independently of GH treatment indication. CONCLUSIONS: Long-term GH treatment was associated with changes in weight status, which were beneficial for underweight and obese children independent of the indication for GH. However, the increase in BMI-SDS in normal weight children treated with GH needs to be investigated in future prospective longitudinal studies to analyse whether this represents an increase of fat mass, lean body mass or both.

Comparison of two prediction models in a clinical setting to predict growth in prepubertal children on recombinant growth hormone.

OBJECTIVE: Prediction models that calculate the growth response in children on recombinant growth hormone (GH) have shown to be helpful tools in deciding who should start treatment, as identifying GH deficiency can be a challenge. The aim of the study is to compare two prediction models; the KIGS (Pfizer International Growth Study) prediction models which are more accessible and the Gothenburg model which has previously been clinically validated. DESIGN: All prepubertal patients who commenced GH treatment at Queen Silvia Children's Hospital in Gothenburg during a 13-year-period were candidates for the study. Children were excluded if suspected syndrome, malignant disease, chronic disease, or poor adherence to treatment were found. The KIGS model and the Gothenburg model were used to make predictions. Data was obtained from medical charts for the period from birth to the end of the first year of treatment. The predicted height outcome was compared against observed. RESULTS: The study included 123 prepubertal children (76 males). The average age at treatment start and standard deviation (SD) was 5.7 (1.8) years. Correlation analyses were performed between predicted growth by both the Gothenburg and KIGS models versus the first year observed growth response showing strong correlations of r = 0.990 and r = 0.991 respectively with studentized residuals of 0.10 (0.81) for the Gothenburg model and 0.03 (0.96) for the KIGS model. CONCLUSION: We found that both the Gothenburg model and the KIGS model are equivalent when applying to our clinical cohort. Both models are very precise, hence it is encouraged to use either based on accessibility for the clinic.

Neuronal temperature perception induces specific defenses that enable C. elegans to cope with the enhanced reactivity of hydrogen peroxide at high temperature.

Hydrogen peroxide is the most common reactive chemical that organisms face on the microbial battlefield. The rate with which hydrogen peroxide damages biomolecules required for life increases with temperature, yet little is known about how organisms cope with this temperature-dependent threat. Here, we show that Caenorhabditis elegans nematodes use temperature information perceived by sensory neurons to cope with the temperature-dependent threat of hydrogen peroxide produced by the pathogenic bacterium Enterococcus faecium. These nematodes preemptively induce the expression of specific hydrogen peroxide defenses in response to perception of high temperature by a pair of sensory neurons. These neurons communicate temperature information to target tissues expressing those defenses via an insulin/IGF1 hormone. This is the first example of a multicellular organism inducing their defenses to a chemical when they sense an inherent enhancer of the reactivity of that chemical.

The Earth's environment is full of reactive chemicals that can cause harm to organisms. One of the most common is hydrogen peroxide, which is produced by several bacteria in concentrations high enough to kill small animals, such as the roundworm Caenorhabditis elegans. Forced to live in close proximity to such perils, C. elegans have evolved defenses to ensure their survival, such as producing enzymes that can break down hydrogen peroxide. However, this battle is compounded by other factors. For instance, rising temperatures can increase the rate at which the hydrogen peroxide produced by bacteria reacts with the molecules and proteins of C. elegans. In 2020, a group of researchers found that roundworms sense these temperature changes through special cells called sensory neurons and use this information to control the generation of enzymes that break down hydrogen peroxide. This suggests that C. elegans may pre-emptively prepare their defenses against hydrogen peroxide in response to higher temperatures so they are better equipped to shield themselves from this harmful chemical. To test this theory, Servello et al. ­ including some of the authors involved in the 2020 study ­ exposed C. elegans to a species of bacteria that produces hydrogen peroxide. This revealed that the roundworms were better at dealing with the threat of hydrogen peroxide when growing in warmer temperatures. Experiments done in C. elegans lacking a class of sensory cells, the AFD neurons, showed that these neurons increased the roundworms' resistance to the chemical when temperatures increase. They do this by repressing the activity of INS-39, a hormone that stops C. elegans from switching on their defense mechanism against peroxides. This is the first example of a multicellular organism preparing its defenses to a chemical after sensing something (such as temperature) that enhances its reactivity. It is possible that other animals may also use this 'enhancer sensing' strategy to anticipate and shield themselves from hydrogen peroxide and potentially other external threats.

Prediction models for short children born small for gestational age (SGA) covering the total growth phase. Analyses based on data from KIGS (Pfizer International Growth Database).

BACKGROUND: Mathematical models can be developed to predict growth in short children treated with growth hormone (GH). These models can serve to optimize and individualize treatment in terms of height outcomes and costs. The aims of this study were to compile existing prediction models for short children born SGA (SGA), to develop new models and to validate the algorithms. METHODS: Existing models to predict height velocity (HV) for the first two and the fourth prepubertal years and during total pubertal growth (TPG) on GH were applied to SGA children from the KIGS (Pfizer International Growth Database)--1st year: N = 2340; 2nd year: N = 1358; 4th year: N = 182; TPG: N = 59. A new prediction model was developed for the 3rd prepubertal year based upon 317 children by means of the all-possible regression approach, using Mallow's C(p) criterion. RESULTS: The comparison between the observed and predicted height velocity showed no significant difference when the existing prediction models were applied to new cohorts. A model for predicting HV during the 3rd year explained 33% of the variability with an error SD of 1.0 cm/year. The predictors were (in order of importance): HV previous year; chronological age; weight SDS; mid-parent height SDS and GH dose. CONCLUSIONS: Models to predict growth to GH from prepubertal years to adult height are available for short children born SGA. The models utilize easily accessible predictors and are accurate. The overall explained variability in SGA is relatively low, due to the heterogeneity of the disorder. The models can be used to provide patients with a realistic expectation of treatment, and may help to identify compliance problems or other underlying causes of treatment failure.

Near-Adult Height After Growth Hormone Treatment in Children Born Prematurely-Data From KIGS.

CONTEXT: Children born prematurely have been treated with growth hormone (GH), and a significant improvement in height during the first years of treatment has been described. OBJECTIVE: To evaluate the influence of prematurity on near-adult height (NAH) after GH treatment. DESIGN: KIGS (Pfizer International Growth Database) was queried for children born preterm treated with GH. SETTING: KIGS database. PATIENTS: A total of 586 children short in stature born preterm with various GH status and with available gestational age (GA), birth weight, and NAH, all treated with GH. INTERVENTION: GH treatment. MAIN OUTCOME MEASURE: NAH. RESULTS: Values were expressed as median. From the 586 children included, 482 born appropriate for GA (AGA; median age 8.26 years) and 104 born small for gestational age (SGA) (median age 8.54 years); 66.6% of preterm AGA had GH peak < 7 µg/L during a provocation test, whereas only 8.6% of preterm SGA. Change in height standard deviation scores (SDS) from GH start to NAH after 8.04 years of GH treatment was 1.82 in preterm AGA. Respective values were 7.08 years and 1.08 SDS for preterm SGA (P < 0.001); 57% of the variability of the growth response to NAH could be explained, and the distance to parental height was the strongest predictor. No significant changes in height SDS were observed from puberty start to NAH. No correlation was found with GA. GH treatment was well tolerated. CONCLUSION: GH treatment resulted in significant improvement in height in children born preterm, particularly during prepubertal years and for those with GH deficiency. The degree of prematurity did not influence the growth response.

A Genome-Wide Pharmacogenetic Study of Growth Hormone Responsiveness.

CONTEXT: Individual patients vary in their response to growth hormone (GH). No large-scale genome-wide studies have looked for genetic predictors of GH responsiveness. OBJECTIVE: To identify genetic variants associated with GH responsiveness. DESIGN: Genome-wide association study (GWAS). SETTING: Cohorts from multiple academic centers and a clinical trial. PATIENTS: A total of 614 individuals from 5 short stature cohorts receiving GH: 297 with idiopathic short stature, 276 with isolated GH deficiency, and 65 born small for gestational age. INTERVENTION: Association of more than 2 million variants was tested. MAIN OUTCOME MEASURES: Primary analysis: individual single nucleotide polymorphism (SNP) association with first-year change in height standard deviation scores. Secondary analyses: SNP associations in clinical subgroups adjusted for clinical variables; association of polygenic score calculated from 697 genome-wide significant height SNPs with GH responsiveness. RESULTS: No common variant associations reached genome-wide significance in the primary analysis. The strongest suggestive signals were found near the B4GALT4 and TBCE genes. After meta-analysis including replication data, signals at several loci reached or retained genome-wide significance in secondary analyses, including variants near ST3GAL6. There was no significant association with variants previously reported to be associated with GH response nor with a polygenic predicted height score. CONCLUSIONS: We performed the largest GWAS of GH responsiveness to date. We identified 2 loci with a suggestive effect on GH responsiveness in our primary analysis and several genome-wide significant associations in secondary analyses that require further replication. Our results are consistent with a polygenic component to GH responsiveness, likely distinct from the genetic regulators of adult height.

Clinical effectiveness of a low-shrinkage resin composite: a five-year evaluation.

PURPOSE: To study the durability of a recently developed low-shrinkage resin composite, suggested to counter the stress formation in direct resin composite restorations. MATERIALS AND METHODS: Each of 50 patients received one or two pair(s) of Class II restorations. The first restoration in the pair was a low-shrinkage resin composite (InTen-S) and the second a hybrid resin composite restoration (Point 4). Both restorations were placed with an etch-and-rinse bonding system and an oblique layering technique. A total of 106 restorations, 33 premolar and 73 molars, were placed. The restorations were evaluated annually. RESULTS: At 5 years, 97 restorations were evaluated. Two participants reported slight postoperative sensitivity symptoms for a few weeks after placement. Twelve non acceptable restorations were observed during the 5 years, five InTen-S (10.4%) and 7 Point 4 (14.3%) (not significant). Secondary caries was the main reason for failure (8) followed by composite fracture (2) and tooth fracture (2). CONCLUSION: The low-shrinkage resin composite showed good durability, but not significantly better than the control resin composite in Class II cavities. Most failures occurred at the last part of the study. Secondary caries was the main reason for failure.

Treatment with Growth Hormone in Noonan Syndrome Observed during 25 Years of KIGS: Near Adult Height and Outcome Prediction.

BACKGROUND/AIMS: There is little information how rhGH treatment affects height in NS. This study aims to analyze data from the NS patients assembled in KIGS over 25 years. PATIENTS/METHODS: Of 613 (389 m/224 f) NS patients documented, 476 (302 m/174 f) were treated for 1 year, 237 (160 m/77 f) of which served to develop a 1st year height velocity (HV) prediction algorithm. One-hundred and forty (74 m/66 f) had reached near adult height (NAH). Factors affecting NAH on rhGH were determined. RESULTS: At the start of rhGH, the NAH groups were (median, m, f) 11.0 and 10.3 years, with a height SDS of -3.2 and -3.8 SDS (Prader), respectively. The total gain after 6.3 and 5.6 years on rhGH (0.27 and 0.30 mg/kg/week) was 1.2 and 1.3 SDS. Age at the start of rhGH (negative), height at the start of rhGH, rhGH dose, number of rhGH injections/wk and birth weight (all positive) explained 36% of the variability of 1st year HV. Height at the start of rhGH, 1st year growth on rhGH, birth weight, and gender explained 74% of the variability of NAH. Causes for rhGH treatment discontinuation and adverse events were also analyzed. CONCLUSION: rhGH treatment increases NAH in NS. Prediction algorithms may optimize treatment in the future.

Diabetes in patients with acromegaly treated with pegvisomant: observations from acrostudy.

PURPOSE: To explore the effects of pegvisomant (PEGV) on glucose metabolism in patients with acromegaly within ACROSTUDY, an international, observational, prospective safety surveillance study. METHODS: Patients were retrospectively divided into two cohorts, with (DM group) or without diabetes mellitus (no-DM). Parameters of glucose metabolism and IGF-I values were analyzed yearly both cross-sectionally for 4 years (yrs) and longitudinally at 1 and 4-5 yrs of PEGV treatment. RESULTS: Among 1762 patients, 510 (28.9%) had DM before PEGV start. At cross-sectional analyses, in the DM group mean blood glucose was 140.0 ± 58.7 mg/dl at baseline, 116.4 ± 44.8 mg/dl at year 1 and 120.0 ± 44.3 mg/dl at yr 4. Mean HbA1c was 6.6 ± 1.2 % at yr 1 vs. 7.0 ± 1.4 % at baseline. HbA1c was above 6.5% in 61.9% at baseline and ranged from 45.4 to 53.8% at subsequent yearly time points. At the 4-yr longitudinal analysis, in the DM group (n = 109), mean blood glucose decreased by 20.2 mg/dl at yr 4, mean HbA1c was 7.0 ± 1.5% at baseline vs. 6.8 ± 1.4%. Patients achieved IGF-I normalization in 52.1% and 57.4% of cases in the DM and no-DM groups, respectively at 1 year. The mean daily PEGV dose (mg/day) was higher in the DM group (18.2 vs. 15.3) while the absolute change of IGF-I values from baseline was similar in both groups. PEGV was well tolerated in both groups without any unexpected AEs. CONCLUSIONS: Patients with DM had a moderate decrease in mean fasting glucose values during PEGV treatment.

Factors predicting the near-final height in growth hormone-treated children and adolescents with chronic kidney disease.

CONTEXT: GH therapy is an accepted measure to increase adult height in young prepubertal patients suffering from growth failure related to chronic kidney disease (CKD). The impact of GH therapy on final height (FH) in CKD patients of pubertal age is unclear. OBJECTIVE: This study set out to analyze near-FH in a cohort of GH-treated CKD patients. DESIGN, SETTINGS, AND PATIENTS: Of 240 evaluable patients in the Pfizer International Growth Database (KIGS) with CKD, 39% were prepubertal and 61% were pubertal at baseline; 45% were on conservative treatment for CKD, 28% were on dialysis, and 27% were in the period after renal transplantation. MAIN OUTCOME MEASURES: Near-FH, relation to pubertal stage, and factors predictive of growth response were the main outcome measures. RESULTS: Mean height sd scores increased continuously during GH treatment until near-FH by 1.2 and 1.6 in boys and girls, respectively. Mean near-FH differed significantly from prepubertal patients showing severely delayed puberty (-3.6), late pubertal patients (-2.9), early pubertal patients (-2.2), and prepubertal patients with normal onset of puberty (-2.0). The initial degree of stunting, degree of bone age retardation, duration of GH therapy, time spent on conservative treatment/dialysis, pubertal delay (>2 sd), gender, and age at start of GH treatment were significant predictors of growth response to GH therapy, explaining between 33 and 61% of the overall variability. CONCLUSIONS: Long-term GH therapy of CKD patients in prepubertal and pubertal age results in an increased adult height, but response is diminished in patients on dialysis and/or with severely delayed puberty.

Final height in Swedish children with idiopathic growth hormone deficiency enrolled in KIGS treated optimally with growth hormone.

AIM: To assess final height in children with growth hormone deficiency (GHD) treated with human recombinant growth hormone (GH). METHODS: Final height data for 401 Swedish children with idiopathic GHD and treated with GH, included in KIGS (Pfizer International Growth Database) between 1987 and spring 2006, were analysed retrospectively. Data were grouped according to sex, age and severity of GHD. Height at entry into KIGS, at the onset of puberty and near final height were analysed between groups. RESULTS: Groups were heterogeneous for GHD, which ranged from partial to severe. For all groups, mean final height corrected for mid-parental height was within the normal Swedish height range. In patients with severe GHD, mean final height was almost identical to mean normal Swedish height. About 16% of patients showed disproportionality (short legs) at final height and were significantly shorter than other patients. The parents of these children also demonstrated short stature. CONCLUSION: Children with idiopathic GHD receiving GH replacement therapy can achieve a final height that as a group is within the normal range and all achieve a height within their genetic potential.

Racial/Ethnic Disparities in US Pediatric Growth Hormone Treatment.

BACKGROUND/AIMS: To compare racial/ethnic proportions of subjects receiving growth hormone (GH) treatment to the expected proportions, and secondarily, to assess racial/ethnic differences in subject characteristics at GH treatment initiation. METHODS: Race/ethnicity-based expected frequencies of height <-2.25 SD were determined by applying relative risks for short stature, calculated from a regional population of 189,280 pediatric primary care patients, to US census data, and compared to racial/ethnic proportions of US subjects enrolled in the Pfizer International Growth Study (KIGS) using the χ2 test. Characteristics of white and black subjects at GH treatment initiation were presented as medians and compared by the Wilcoxon rank sum test (significant p < 0.01). RESULTS: White subjects exceeded the expected frequency (63%) for all indications (83%) and each separately, ranging from 73% for congenital GH deficiency (GHD) to 85% for idiopathic short stature (p < 0.001). Compared to white subjects, black subjects treated for idiopathic GHD had greater height deficits relative both to the population (-2.97 vs. -2.56 SD) and to their mid-parental heights (-2.47 vs. -1.89 SD), lower stimulated GH peak levels (4.9 vs. 6.0 ng/mL), and lower birth weights (-0.86 vs. -0.48 SD). Black subjects with congenital GHD had lower stimulated GH peaks (2.1 vs. 3.2 ng/mL) and started GH treatment at younger ages (2.9 vs. 4.8 years), while those with acquired GHD had lower birth weights (-1.12 vs. -0.08 SD). Male predominance did not differ by race for any or all indications. CONCLUSION: Overrepresentation of white children among those receiving GH treatment in the US KIGS registry reflects racial/ethnic treatment biases, not just differences in growth rates.