Growth hormone therapy, muscle thickness, and motor development in Prader-Willi syndrome: an RCT.

OBJECTIVE: To investigate the effect of physical training combined with growth hormone (GH) on muscle thickness and its relationship with muscle strength and motor development in infants with Prader-Willi syndrome (PWS). METHODS: In a randomized controlled trial, 22 infants with PWS (12.9 ± 7.1 months) were followed over 2 years to compare a treatment group (n = 10) with a waiting-list control group (n = 12). Muscle thickness of 4 muscle groups was measured by using ultrasound. Muscle strength was evaluated by using the Infant Muscle Strength meter. Motor performance was measured with the Gross Motor Function Measurement. Analyses of variance were used to evaluate between-group effects of GH on muscle thickness at 6 months and to compare pre- and posttreatment (after 12 months of GH) values. Multilevel analyses were used to evaluate effects of GH on muscle thickness over time, and multilevel bivariate analyses were used to test relationships between muscle thickness, muscle strength, and motor performance. RESULTS: A significant positive effect of GH on muscle thickness (P < .05) was found. Positive relationships were found between muscle thickness and muscle strength (r = 0.61, P < .001), muscle thickness and motor performance (r = 0.81, P < .001), and muscle strength and motor performance (r = 0.76, P < .001). CONCLUSIONS: GH increased muscle thickness, which was related to muscle strength and motor development in infants with PWS. Catch-up growth was faster in muscles that are most frequently used in early development. Because this effect was independent of GH, it suggests a training effect.

Growth hormone combined with child-specific motor training improves motor development in infants with Prader-Willi syndrome: a randomized controlled trial.

Although severe motor problems in infants with Prader-Willi syndrome (PWS) are striking, motor development has never been studied longitudinally and the results of growth hormone (GH) treatment on motor development are contradictory. The authors studied whether GH treatment can enhance the effect of physical training on motor development in infants with PWS. Twenty-two infants were followed for two years during a randomized controlled trial. The treatment and control groups began GH after baseline or following a control period, respectively. Both groups followed a child-specific physical training program. Motor performance was measured every three months. Multi-level regression analysis revealed that motor development differed significantly between infants (p<.001), and this could be partially explained by baseline motor developmental level (p<.01). GH treatment enhanced the effects of child-specific physical training on both motor developmental rate and motor developmental potential. Moreover, this effect was more pronounced when GH treatment was initiated at a younger age.

Objective evaluation of muscle strength in infants with hypotonia and muscle weakness.

The clinical evaluation of an infant with motor delay, muscle weakness, and/or hypotonia would improve considerably if muscle strength could be measured objectively and normal reference values were available. The authors developed a method to measure muscle strength in infants and tested 81 typically developing infants, 6-36 months of age, and 17 infants with Prader-Willi Syndrome (PWS) aged 24 months. The inter-rater reliability of the measurement method was good (ICC=.84) and the convergent validity was confirmed by high Pearson's correlations between muscle strength, age, height, and weight (r=.79-.85). A multiple linear regression model was developed to predict muscle strength based on age, height, and weight, explaining 73% of the variance in muscle strength. In infants with PWS, muscle strength was significantly decreased. Pearson's correlations showed that infants with PWS in which muscle strength was more severely affected also had a larger motor developmental delay (r=.75).

Advanced medical life support procedures in vitally compromised children by a helicopter emergency medical service.

BACKGROUND: To determine the advanced life support procedures provided by an Emergency Medical Service (EMS) and a Helicopter Emergency Medical Service (HEMS) for vitally compromised children. Incidence and success rate of several procedures were studied, with a distinction made between procedures restricted to the HEMS-physician and procedures for which the HEMS is more experienced than the EMS. METHODS: Prospective study of a consecutive group of children examined and treated by the HEMS of the eastern region of the Netherlands. Data regarding type of emergency, physiological parameters, NACA scores, treatment, and 24-hour survival were collected and subsequently analysed. RESULTS: Of the 558 children examined and treated by the HEMS on scene, 79% had a NACA score of IV-VII. 65% of the children had one or more advanced life support procedures restricted to the HEMS and 78% of the children had one or more procedures for which the HEMS is more experienced than the EMS. The HEMS intubated 38% of all children, and 23% of the children intubated and ventilated by the EMS needed emergency correction because of potentially lethal complications. The HEMS provided the greater part of intraosseous access, as the EMS paramedics almost exclusively reserved this procedure for children in cardiopulmonary resuscitation. The EMS provided pain management only to children older than four years of age, but a larger group was in need of analgesia upon arrival of the HEMS, and was subsequently treated by the HEMS. CONCLUSIONS: The Helicopter Emergency Medical Service of the eastern region of the Netherlands brings essential medical expertise in the field not provided by the emergency medical service. The Emergency Medical Service does not provide a significant quantity of procedures obviously needed by the paediatric patient.

Sample size calculations for 3-level cluster randomized trials.

BACKGROUND: The first applications of cluster randomized trials with three instead of two levels are beginning to appear in health research, for instance, in trials where different strategies to implement best-practice guidelines are compared. In such trials, the strategy is implemented in health care units ('clusters') and aims at changing the behavior of health care professionals working in this unit ('subjects'), while the effects are measured at patient level ('evaluations'). PURPOSE: To guide the choice of number of clusters, number of subjects per cluster, and number of evaluations per subject. METHODS: We derive a sample size formula and investigate the influence of sample allocation on power or number of clusters required. RESULTS: The required sample size is the product of the sample size in absence of correlation and two variance inflation factors (VIFs) that describe the clustering of evaluations within subjects and of subjects within cluster, respectively. Because each VIF is expressed in terms of an interpretable Pearson correlation, subject matter knowledge can be incorporated. Moreover, these Pearson's correlations are related to intracluster correlations (ICCs) from comparable, but 2-level cluster randomized trials. Formulas are obtained to guide the sample allocation (number of clusters, subjects, and evaluations) for minimizing total sample size, minimizing the number of clusters, or maximizing power given a budget constraint. LIMITATIONS: Empirical estimates of variance components or ICCs from 3-level cluster trials are scarce which limits reliably powering. CONCLUSIONS: When parameterized in terms of Pearson correlations, the two variance inflation factors give quantitative insight into the impact of the number of clusters, subjects and evaluations on power. Moreover, subject matter knowledge as well as ICCs from 2-level cluster randomized trials can be incorporated in the sample size calculation, when empirical estimates of variance components or ICCs from a pilot or comparable 3-level study are lacking.