Epidemiological approaches to multivariable models of health inequity: A study of race, rurality, and occupation during the COVID-19 pandemic.

PURPOSE: Methods for assessing the structural mechanisms of health inequity are not well established. This study applies a phased approach to modeling racial, occupational, and rural disparities on the county level. METHODS: Rural counties with disparately high rates of COVID-19 incidence or mortality were randomly paired with in-state control counties with the same rural-urban continuum code. Analysis was restricted to the first six months of the pandemic to represent the baseline structural reserves for each county and reduce biases related to the disruption of these reserves over time. Conditional logistic regression was applied in two phases-first, to examine the demographic distribution of disparities and then, to examine the relationships between these disparities and county-level social and structural reserves. RESULTS: In over 200 rural county pairs (205 for incidence, 209 for mortality), disparities were associated with structural variables representing economic factors, healthcare infrastructure, and local industry. Modeling results were sensitive to assumptions about the relationships between race and other social and structural variables measured at the county level, particularly in models intended to reflect effect modification or mediation. CONCLUSIONS: Multivariable modeling of health disparities should reflect the social and structural mechanisms of inequity and anticipate interventions that can advance equity.

Iron homeostasis during risperidone treatment in children and adolescents.

OBJECTIVE: Previous cross-sectional evidence has linked antipsychotic-related weight gain to reduced body iron concentration. Using longitudinal data, we examined the association between changes in weight following risperidone initiation or discontinuation and ferritin concentration. METHOD: Study 1: Between April 2004 and September 2007, participants were enrolled from outpatient settings in a prospective randomized clinical trial comparing the efficacy of risperidone monotherapy to the combination of risperidone and behavior therapy in targeting disruptive behavior in 4- to 13-year-old children with DSM-IV-TR-based autism spectrum disorder. Study 2: Medically healthy 7- to 17-year-old participants in long-term open-label risperidone treatment at study entry returned for follow-up 1.5 years later, between July 2007 and July 2011. Available blood samples were used to measure ferritin. Linear multivariable regression analysis tested the association between ferritin concentration and change in age-sex-specific body mass index (BMI) z score between study entry and endpoint, adjusting for relevant confounders. RESULTS: Study 1 sample consisted of 73 participants (85% males, mean age: 7.7 ± 2.4 years). After 18.0 ± 2.0 weeks on risperidone, their BMI z score increased by 0.93 ± 0.70 points and ferritin concentration declined by 6.8 ± 13.3 µg/L. After adjusting for age and sex, change in BMI z score was inversely correlated with percent change in ferritin concentration (ß = -18.3, P < .003). Study 2 participants had all been receiving risperidone at study entry. At follow-up, 1.5 ± 0.3 years later, risperidone was discontinued in 26 of the 96 who were included in the analysis. Neither change in BMI z score nor in ferritin concentration was different between those who continued versus discontinued risperidone. However, a reduction in BMI z score between study entry and follow-up was associated with higher ferritin concentration at follow-up in participants who discontinued risperidone compared to those who continued it (P = .01). CONCLUSIONS: Risperidone-related weight gain is associated with a reduction in body iron reserves, which appears to improve with weight loss following risperidone discontinuation. Preliminary evidence suggests that risperidone may also directly inhibit iron absorption. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00080145.

759C/T Variants of the Serotonin (5-HT2C) Receptor Gene and Weight Gain in Children and Adolescents in Long-Term Risperidone Treatment.

BACKGROUND: Great inter-individual variability exists in the susceptibility to gain weight during antipsychotic treatment. Thus, we examined whether the -759C/T variants in the promoter region of the 5HT2C receptor gene were differentially associated with weight gain in children and adolescents in long-term risperidone treatment. METHODS: Medically healthy 7 to 17 year-olds, treated with risperidone for ≥ six months, were enrolled. Anthropometric measurements, laboratory tests, and treatment history were obtained upon enrollment and from medical records. The effect of the genotype on the trajectory of age-sex-adjusted weight and body mass index (BMI) z scores before and after the onset of risperidone treatment was investigated. RESULTS: In 124 subjects (90% males, mean age: 11.8 years) treated with risperidone for a mean of 2.8 years, weight and BMI z scores significantly increased after starting risperidone. This change was similar across the two genotype groups as were changes in several cardiometabolic variables. CONCLUSION: In contrast to other reports, the T allele failed to confer protection against excessive weight gain or cardiometabolic abnormalities in this group of children and adolescents chronically treated with risperidone.