Robert Couch

Incident vertebral fractures among children with rheumatic disorders 12 months after glucocorticoid initiation: a national observational study.

To determine the frequency of incident vertebral fractures (IVF) 12 months after glucocorticoid (GC) initiation in children with rheumatic diseases and to identify children at higher risk.

Effect of bacille Calmette-Guérin vaccination on C-peptide secretion in children newly diagnosed with IDDM

OBJECTIVE To determine whether administration of bacille Calmette-Guerin (BCG) vaccination to newly diagnosed IDDM patients can help preserve C-peptide secretion over the subsequent 18 months. RESEARCH DESIGN AND METHODS Twenty-six IDDM patients, all of whom had been diagnosed within the previous year, had basal C-peptide levels >0.06 nmol/1, and had negative reactions to Mantouxs test, were randomized pairwise as they presented and were given either 0.1 ml (100 μg) BCG vaccine or 0.1 ml saline intradermally. Both the patients and the investigators were blinded to the treatment. Fasting and glucagon-induced C-peptide levels and HbA1c were measured in all patients at enrollment and at 1, 3, 6, 9, 12, and 18 months after vaccination, and insulin dose was recorded at each visit. RESULTS At enrollment, there was no significant difference in age, duration of diabetes, insulin dose, HbA1c, or fasting C-peptide levels between the BCG-vaccinated and control groups. The mean basal and stimulated C-peptide levels in the BCG-treated group did not differ significantly from those in the control group at any time during the 18 months of followup, and there was no difference in insulin dose or HbA1c at any time between the groups. CONCLUSIONS BCG vaccination in children who have been recently diagnosed with IDDM does not affect the progressive decline in C-peptide levels or alter the clinical course of the disease.

Incident vertebral fractures and risk factors in the first three years following glucocorticoid initiation among pediatric patients with rheumatic disorders

Vertebral fractures are an important yet underrecognized manifestation of osteoporosis in children with chronic, glucocorticoid‐treated illnesses. Our goal was to determine the incidence and clinical predictors of vertebral fractures in the 3 years following glucocorticoid initiation among pediatric patients with rheumatic disorders. Incident vertebral fractures were evaluated according to the Genant semiquantitative method on lateral radiographs at baseline and then annually in the 3 years following glucocorticoid initiation. Extended Cox models were used to assess the association between vertebral fractures and clinical risk predictors. A total of 134 children with rheumatic disorders were enrolled in the study (mean ± standard deviation (SD) age 9.9 ± 4.4 years; 65% girls). The unadjusted vertebral fracture incidence rate was 4.4 per 100 person‐years, with a 3‐year incidence proportion of 12.4%. The highest annual incidence occurred in the first year (6.0%; 95% confidence interval (CI) 2.9% to 11.7%). Almost one‐half of the patients with fractures were asymptomatic. Every 0.5 mg/kg increase in average daily glucocorticoid (prednisone equivalents) dose was associated with a twofold increased fracture risk (hazard ratio (HR) 2.0; 95% CI 1.1 to 3.5). Other predictors of increased vertebral fracture risk included: (1) increases in disease severity scores between baseline and 12 months; (2) increases in body mass index Z‐scores in the first 6 months of each 12‐month period preceding the annual fracture assessment; and (3) decreases in lumbar spine bone mineral density Z‐scores in the first 6 months of glucocorticoid therapy. As such, we observed that a clinically significant number of children with rheumatic disorders developed incident vertebral fractures in the 3 years following glucocorticoid initiation. Almost one‐half of the children were asymptomatic and thereby would have been undiagnosed in the absence of radiographic monitoring. In addition, discrete clinical predictors of incident vertebral fractures were evident early in the course of glucocorticoid therapy.

Incident Vertebral Fractures in Children With Leukemia During the Four Years Following Diagnosis

OBJECTIVES The purpose of this article was to determine the incidence and predictors of vertebral fractures (VF) during the 4 years after diagnosis in pediatric acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS Children were enrolled within 30 days of chemotherapy initiation, with incident VF assessed annually on lateral spine radiographs according to the Genant method. Extended Cox models were used to assess the association between incident VF and clinical predictors. RESULTS A total of 186 children with ALL completed the baseline evaluation (median age, 5.3 years; interquartile range, 3.4-9.7 years; 58% boys). The VF incidence rate was 8.7 per 100 person-years, with a 4-year cumulative incidence of 26.4%. The highest annual incidence occurred at 12 months (16.1%; 95% confidence interval [CI], 11.2-22.7), falling to 2.9% at 4 years (95% CI, 1.1-7.3). Half of the children with incident VF had a moderate or severe VF, and 39% of those with incident VF were asymptomatic. Every 10 mg/m(2) increase in average daily glucocorticoid dose (prednisone equivalents) was associated with a 5.9-fold increased VF risk (95% CI, 3.0-11.8; P < .01). Other predictors of increased VF risk included VF at diagnosis, younger age, and lower spine bone mineral density Z-scores at baseline and each annual assessment. CONCLUSIONS One quarter of children with ALL developed incident VF in the 4 years after diagnosis; most of the VF burden was in the first year. Over one third of children with incident VF were asymptomatic. Discrete clinical predictors of a VF were evident early in the patients clinical course, including a VF at diagnosis.

The choice of normative pediatric reference database changes spine bone mineral density Z-scores but not the relationship between bone mineral density and prevalent vertebral fractures.

OBJECTIVES Our objectives were to assess the magnitude of the disparity in lumbar spine bone mineral density (LSBMD) Z-scores generated by different reference databases and to evaluate whether the relationship between LSBMD Z-scores and vertebral fractures (VF) varies by choice of database. PATIENTS AND DESIGN Children with leukemia underwent LSBMD by cross-calibrated dual-energy x-ray absorptiometry, with Z-scores generated according to Hologic and Lunar databases. VF were assessed by the Genant method on spine radiographs. Logistic regression was used to assess the association between fractures and LSBMD Z-scores. Net reclassification improvement and area under the receiver operating characteristic curve were calculated to assess the predictive accuracy of LSBMD Z-scores for VF. RESULTS For the 186 children from 0 to 18 years of age, 6 different age ranges were studied. The Z-scores generated for the 0 to 18 group were highly correlated (r ≥ 0.90), but the proportion of children with LSBMD Z-scores ≤-2.0 among those with VF varied substantially (from 38-66%). Odds ratios (OR) for the association between LSBMD Z-score and VF were similar regardless of database (OR = 1.92, 95% confidence interval 1.44, 2.56 to OR = 2.70, 95% confidence interval 1.70, 4.28). Area under the receiver operating characteristic curve and net reclassification improvement ranged from 0.71 to 0.75 and -0.15 to 0.07, respectively. CONCLUSIONS Although the use of a LSBMD Z-score threshold as part of the definition of osteoporosis in a child with VF does not appear valid, the study of relationships between BMD and VF is valid regardless of the BMD database that is used.

Hypothalamic-Pituitary-Thyroid Axis Changes in Children after Cardiac Surgery

INTRODUCTION Hypothalamic-pituitary-thyroid axis changes in critical illness result in nonthyroidal illness syndrome (NTIS) characterized by abnormal TSH and thyroid hormone levels. It is unclear whether NTIS is adaptive or maladaptive. Some have suggested that NTIS adversely affects outcome, but there are limited data in children. OBJECTIVE Our objective was to determine the natural history of NTIS in children undergoing cardiac bypass surgery and to correlate these changes with outcome and illness severity. METHODS Thyroid function was measured in 21 patients, aged 1-11 yr, preoperatively and postoperatively twice daily on postoperative days (POD) 0-3 and daily thereafter until POD 7. Pediatric Logistic Organ Dysfunction and inotrope scores and pediatric intensive care unit, hospital, and ventilation days were measured and statistically analyzed in relation to thyroid function. RESULTS All patients exhibited NTIS within the first day postoperatively. TSH recovered by POD 4. Total T(3), free T(3) index, and T(3) uptake were still below preoperative levels on POD 7. NTIS changes correlated to prolonged hospital stays with increased pediatric intensive care unit and mechanical ventilation days and also showed strong relations with Pediatric Logistic Organ Dysfunction and inotrope scores. The T(3) measures drawn within 6-14 h from surgery were predictive of clinical outcome. Alterations in illness severity preceded changes in thyroid function. CONCLUSION NTIS was present in this population of critically ill children with some of the biochemical changes not corrected by 8 d postoperatively. The degree of NTIS was related to and predictive of clinical outcome and illness severity.

High Incidence of IDDM Over 6 Years in Edmonton, Alberta, Canada

OBJECTIVE To determine the incidence of IDDM among children 0–14 years of age in Edmonton, Alberta, between 1990 and 1995 by means of a population-based registry. RESEARCH DESIGN AND METHODS Children <15 years of age diagnosed with IDDM between January 1990 and December 1995 were registered according to criteria of the World Health Organization (WHO) Multinational Project for Childhood Diabetes. The primary source of case ascertainment consisted of office records of pediatricians and endocrinologists. The secondary source consisted of inpatient records from the main city hospitals. RESULTS Between 1990 and 1995, 211 IDDM patients <15 years of age were detected by the two sources. All but 15 of them were of European ancestry. The ascertainment-corrected incidence rates of this ethnic group (constituting 77% of the population) for the 6 years were 38.6, 23.5, 23.3, 24.2, 22.0, and 24.3 per 100,000, respectively, with case ascertainment rates of 75–95%. The age-adjusted rate over the 6-year period was 25.7 per 100,000 with a case ascertainment rate of 84.3%. No sex difference was observed. The highest incidence occurred in the 10- to 14-year-old age-group, and more cases were detected between January and March than at other periods in the year. CONCLUSIONS The incidence of IDDM among the European-derived population in Edmonton between 1990 and 1995 is the highest rate over a 6-year period to be reported in North America, comparable to that in Prince Edward Island, Canada, and to the highest rates in the world.

Prader-Willi syndrome, excessive daytime sleepiness, and narcoleptic symptoms: a case report

IntroductionSleep abnormalities, including narcolepsy and cataplexy, are a common feature of Prader-Willi syndrome. Long-term treatment with the central nervous system stimulant modafinil has not been reported. In this case report we present a longitudinal perspective of sleep abnormalities in a nine-year-old Caucasian girl with Prader-Willi syndrome from age two to age nine, and detail the response to treatment with the central nervous system stimulant modafinil.Case presentationOur patient presented at two years of age with hypersomnia and narcoleptic episodes with cataplectic features. Initial polysomnograph testing revealed adequate sleep efficiency, but increased sleep fragmentation especially during rapid eye movement sleep. The narcoleptic episodes continued and a repeat polysomnograph at age five years confirmed features consistent with narcolepsy. Further sleep studies at six years, including a multiple sleep latency test, demonstrated signs of excessive daytime sleepiness. Treatment with modafinil was initiated at age seven years six months due to persistent hypersomnia and narcoleptic symptoms. Two polysomnograph studies were performed following treatment with modafinil, at age eight years six months and nine years three months. These studies showed excellent sleep efficiency and improvement of rapid eye movement sleep parameters, supporting the beneficial effects of long-term modafinil therapy.ConclusionsLong-term modafinil therapy may ameliorate the sleep disturbances of Prader-Willi syndrome and should be the focus of future clinical trials.

Glucocorticoid-Related Changes in Body Mass Index Among Children and Adolescents With Rheumatic Diseases

To examine the temporal and dose‐related effects of glucocorticoids (GCs) on body mass index (BMI) in children with rheumatic diseases.

Postnatal virilization mimicking 21-hydroxylase deficiency in 3 very premature infants.

Premature infants are known to have elevated 17-hydroxyprogesterone and adrenal androgen concentrations immediately after birth, but the levels decrease rapidly. Virilization of normal premature female infants as a result of these high androgens has not been described. Three premature female infants born at 24 to 25 weeks’ gestation, with birth weights 550 to 880 g and significant neonatal complications were noted to develop clitoromegaly 2 weeks to 3 months after birth. All 3 had elevated 17-hydroxyprogesterone >100 nmol/L and testosterone >3 nmol/L concentrations. All were treated as simple virilizing 21-hydroxylase deficiency, but subsequent genetic analysis revealed no CYP21 mutations. Follow-up after discontinuation of treatment revealed no recurrent virilization and normal adrenal steroid levels. Postnatal virilization in sick premature girls may occur, and investigations may suggest 21-hydroxylase deficiency. Genetic analysis of CYP21 should be performed before the diagnosis is confirmed. Further studies are needed to better document the natural history and possible causes of postnatal adrenal androgen secretion in sick premature infants.