Evaluating area-based socioeconomic status predictors of pediatric health outcomes in Manitoba

Introduction Socioeconomic gradients in health exist in Canada. Although multiple Canadian area-based socioeconomic measures (ABSM) have been developed, none have been specifically validated against relevant pediatric outcomes. Our objective was to use key pediatric health outcomes and compare the strength of association with a number of ABSM, including income quintile. Objectives and Approach This is a retrospective cross-sectional assessment of the association between socioeconomic status (SES) measured by ABSM and key pediatric health outcomes at the population level. Data from the Manitoba Population Research Data Repository was used for residents aged 0-19y. The timeframe was 2010-2015. Outcomes included preterm births, birth weight, mortality, vaccination rates and teen pregnancy. Regressions used each outcome against various ABSM (e.g. CAN-Marg, SEFI2, INSPQ) or income quintile. Best model for each outcome was assessed by goodness of fit measure (AIC). Measures of inequality included SII (Slope Index of Inequality) and RII (Relative Index of Inequality, both RIImean and RIIratio). Results In our regression models, the 4 Can-Marg subcomponents consistently had about 15% lower AICs (best fit) across all 16 key pediatric outcomes compared to INSPQ (Raymond-Pampalon), income quintile or SEFI2 (Socioeconomic Factor Index - Version 2). Sex differences were small and inconsequential. Whether ABSMs were treated as continuous or categorical predictors was of little statistical consequence. Of note, 15 of the 16 outcomes had socioeconomic gradients identified by SII or RII on at least one of the ABSMs. Income quintile detected 12 of 15, CAN-Marg material deprivation detected 9; the combination of CAN-Marg material deprivation and ethnicity detected 13 of 15. SEFI2 detected only 3 and the National INSPQ detected 6. Conclusion/Implications There are significant health inequalities in pediatric outcomes in Manitoba (15 of 16 studied). Combining CAN-Marg measures of poverty (material deprivation) and ethnic concentration identified 13/15 cases of documented inequality and was the best ABSM for capturing pediatric health gradients; it was similar to income quintile alone

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:Atotal 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/m2 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 \u3c .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 patient\u27s clinical course, including a VF at diagnosis

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

Glucocorticoid-related changes in body mass index among children and adolescents with rheumatic diseases

Objective To examine the temporal and dose-related effects of glucocorticoids (GCs) on body mass index (BMI) in children with rheumatic diseases. Methods Children initiating GCs for a rheumatic disease (n = 130) were assessed every 3 months for 18 months. BMI, weight, and height Z score trajectories were described according to GC starting dosage in prednisone equivalents: high (≥1.0 mg/kg/day), low (\u3c0.2 mg/kg/day to a maximum of 7.5 mg/day), and moderate (between high and low) dosage. The impact of GC dosing, underlying diagnosis, pubertal status, physical activity, and disease activity on BMI Z scores and on percent body fat was assessed with longitudinal mixed-effects growth curve models. Results The GC starting dose was high in 59% and moderate in 39% of patients. The peak BMI Z score was +1.29 at 4 months with high-dose GCs and +0.69 at 4.2 months with moderate-dose GCs (P \u3c 0.001). Overall, 50% (95% confidence interval 41-59%) of the children returned to within +0.25 SD of their baseline BMI Z score. Oral GC dose over the preceding 3 months was the most significant determinant of BMI Z score and percent body fat. The proportion of days in receipt of GCs, disease activity, and a diagnosis of systemic-onset juvenile idiopathic arthritis were also associated with BMI Z scores. The correlation between changes in BMI and changes in percent body fat was 0.09. Conclusion In children with rheumatic diseases starting moderate and high doses of GCs, BMI Z scores peaked at 4 months, and only half returned to within +0.25 SD of their baseline BMI Z score after 18 months. Copyright © 2013 by the American College of Rheumatology

High incidence of vertebral fractures in children with acute lymphoblastic leukemia 12 months after the initiation of therapy

Purpose: Vertebral fractures due to osteoporosis are a potential complication of childhood acute lymphoblastic leukemia (ALL). To date, the incidence of vertebral fractures during ALL treatment has not been reported. Patient and Methods: We prospectively evaluated 155 children with ALL during the first 12 months of leukemia therapy. Lateral thoracolumbar spine radiographs were obtained at baseline and 12 months. Vertebral bodies were assessed for incident vertebral fractures using the Genant semiquantitative method, and relevant clinical indices such as spine bone mineral density (BMD), back pain, and the presence of vertebral fractures at baseline were analyzed for association with incident vertebral fractures. Results: Of the 155 children, 25 (16%; 95% CI, 11% to 23%) had a total of 61 incident vertebral fractures, of which 32 (52%) were moderate or severe. Thirteen (52%) of the 25 children with incident vertebral fractures also had fractures at baseline. Vertebral fractures at baseline increased the odds of an incident fracture at 12 months by an odds ratio of 7.3 (95% CI, 2.3 to 23.1; P = .001). In addition, for every one standard deviation reduction in spine BMD Z-score at baseline, there was 1.8-fold increased odds of incident vertebral fracture at 12 months (95% CI, 1.2 to 2.7; P = .006). Conclusion: Children with ALL have a high incidence of vertebral fractures after 12 months of chemotherapy, and the presence of vertebral fractures and reductions in spine BMD Z-scores at baseline are highly associated clinical features. © 2012 by American Society of Clinical Oncology

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

Objective. 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. Methods. Children with rheumatic diseases initiating GC were enrolled in a prospective observational study. Annual spine radiographs were evaluated using the Genant semiquantitative method. Spine areal bone mineral density (aBMD) was measured every 6 months. Clinical features, including cumulative GC dose, back pain, disease and physical activity, calcium and vitamin D intake, and spine aBMD Z scores, were analyzed for association with IVF. Results. Seven (6%) of 118 children (95% confidence interval 2.9-11.7%) had IVF. Their diagnoses were: juvenile dermatomyositis (n = 2), systemic lupus erythematosus (n = 3), systemic vasculitis (n = 1), and mixed connective tissue disease (n = 1). One child was omitted from the analyses after 4 months because of osteoporosis treatment for symptomatic IVF. Children with IVF received on average 50% more GC than those without (P = 0.030), had a greater increase in body mass index (BMI) at 6 months (P = 0.010), and had greater decrements in spine aBMD Z scores in the first 6 months (P = 0.048). Four (67%) of 6 children with IVF and data to 12 months had spine aBMD Z scores less than-2.0 at 12 months compared to 16% of children without IVF (P = 0.011). Conclusion. The incidence of VF 12 months following GC initiation was 6%; most children were asymptomatic. Children with IVF received more GC, had greater increases in BMI, and had greater declines in spine aBMD Z scores in the first 6 months. © 2012, American College of Rheumatology

Significant benefits of AIP testing and clinical screening in familial isolated and young-onset pituitary tumors

Context Germline mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene are responsible for a subset of familial isolated pituitary adenoma (FIPA) cases and sporadic pituitary neuroendocrine tumors (PitNETs). Objective To compare prospectively diagnosed AIP mutation-positive (AIPmut) PitNET patients with clinically presenting patients and to compare the clinical characteristics of AIPmut and AIPneg PitNET patients. Design 12-year prospective, observational study. Participants & Setting We studied probands and family members of FIPA kindreds and sporadic patients with disease onset ≤18 years or macroadenomas with onset ≤30 years (n = 1477). This was a collaborative study conducted at referral centers for pituitary diseases. Interventions & Outcome AIP testing and clinical screening for pituitary disease. Comparison of characteristics of prospectively diagnosed (n = 22) vs clinically presenting AIPmut PitNET patients (n = 145), and AIPmut (n = 167) vs AIPneg PitNET patients (n = 1310). Results Prospectively diagnosed AIPmut PitNET patients had smaller lesions with less suprasellar extension or cavernous sinus invasion and required fewer treatments with fewer operations and no radiotherapy compared with clinically presenting cases; there were fewer cases with active disease and hypopituitarism at last follow-up. When comparing AIPmut and AIPneg cases, AIPmut patients were more often males, younger, more often had GH excess, pituitary apoplexy, suprasellar extension, and more patients required multimodal therapy, including radiotherapy. AIPmut patients (n = 136) with GH excess were taller than AIPneg counterparts (n = 650). Conclusions Prospectively diagnosed AIPmut patients show better outcomes than clinically presenting cases, demonstrating the benefits of genetic and clinical screening. AIP-related pituitary disease has a wide spectrum ranging from aggressively growing lesions to stable or indolent disease course