Racial and Ethnic Differences in Antiseizure Medications Among People With Epilepsy on Medicaid: A Case of Potential Inequities.

Background and Objectives: Being on a newer, second-, and third-generation antiseizure medication (ASM) may represent an important marker of quality of care for people with epilepsy. We sought to examine whether there were racial/ethnic differences in their use. Methods: Using Medicaid claims data, we identified the type and number of ASMs, as well as the adherence, for people with epilepsy over a 5-year period (2010-2014). We used multilevel logistic regression models to examine the association between newer-generation ASMs and adherence. We then examined whether there were racial/ethnic differences in ASM use in models adjusted for demographics, utilization, year, and comorbidities. Results: Among 78,534 adults with epilepsy, 17,729 were Black, and 9,376 were Hispanic. Overall, 25.6% were on older ASMs, and being solely on second-generation ASMs during the study period was associated with better adherence (adjusted odds ratio: 1.17, 95% confidence interval [CI]: 1.11-1.23). Those who saw a neurologist (3.26, 95% CI: 3.13-3.41) or who were newly diagnosed (1.29, 95% CI: 1.16-1.42) had higher odds of being on newer ASMs. Importantly, Black (0.71, 95% CI: 0.68-0.75), Hispanic (0.93, 95% CI: 0.88-0.99), and Native Hawaiian and Other Pacific Island individuals (0.77, 95% CI: 0.67-0.88) had lower odds of being on newer ASMs when compared with White individuals. Discussion: Generally, racial and ethnic minoritized people with epilepsy have lower odds of being on newer-generation ASMs. Greater adherence by people who were only on newer ASMs, their greater use among people seeing a neurologist, and the opportunity of a new diagnosis point to actionable leverage points for reducing inequities in epilepsy care.

A framework for health equity in people living with epilepsy.

Epilepsy is a disease where disparities and inequities in risk and outcomes are complex and multifactorial. While most epilepsy research to date has identified several key areas of disparities, we set out to provide a multilevel life course model of epilepsy development, diagnosis, treatment, and outcomes to highlight how these disparities represent true inequities. Our piece also presents three hypothetical cases that highlight how the solutions to address inequities may vary across the lifespan. We then identify four key domains (structural, socio-cultural, health care, and physiological) that contribute to the persistence of inequities in epilepsy risk and outcomes in the United States. Each of these domains, and their core components in the context of epilepsy, are reviewed and discussed. Further, we highlight the connection between domains and key areas of intervention to strive towards health equity. The goal of this work is to highlight these domains while also providing epilepsy researchers and clinicians with broader context of how their work fits into health equity.

Inconsistent Medicaid Coverage is Associated with Negative Health Events for People with Epilepsy.

OBJECTIVE: Examine the association between gaps in Medicaid coverage and negative health events (NHEs) for people with epilepsy (PWE). METHODS: Using five years of Medicaid claims for PWE, we identified gaps in Medicaid coverage. We used logistic regression to evaluate the association between a gap in coverage and being in the top quartile of NHEs and factors associated with having a gap. These models adjusted for: demographics, residence, medication adherence, disease severity, and comorbidities. RESULTS: Of 186,616 PWE, 21.7% had a gap in coverage. The odds of being in the top quartile of NHEs per year were 66% higher among those with a gap (OR: 1.66; 95% CI: 1.61, 1.70). Being female, younger, and having psychiatric comorbidities increased the odds of having a gap. CONCLUSIONS: Gaps in Medicaid coverage are associated with being a high utilizer during covered periods. Specific groups could be targeted with interventions to reduce churning.

Burden of Chronic and Acute Conditions and Symptoms in People With Epilepsy.

BACKGROUND AND OBJECTIVES: People with epilepsy, one-third of whom in the United States are on Medicaid, experience a wide range of chronic and physical comorbidities that influence their care and outcomes. In this study, we examine the burden and racial/ethnic disparities of chronic and acute conditions, injuries, and symptoms in a large and diverse group of people with epilepsy on Medicaid. METHODS: Using 5 years of Medicaid claims data, we identified adults with epilepsy and used all available claims and diagnoses to identify each person's Clinical Classification Codes groups diagnosed during the study period. Using association rule mining, we identified the top combinations of conditions and stratified these by race/ethnicity to identify potential prevalence disparities. We examined the top combinations of conditions in high utilizers; that is, individuals in the top quartile of hospitalizations and emergency department visits. RESULTS: Among 81,963 patients, the most common conditions were anxiety and mood disorders (46.5%), hypertension (36.9%), back problems (35.2%), developmental disorders (31.6%), and headache (29.5%). When examining combinations of conditions, anxiety and mood disorders continued to have an outsized prevalence, appearing in nearly every combination. There were notable disparities in disease burden, with American Indians and Alaskan Natives having a substantially higher prevalence of developmental disorders, while Black individuals had a higher prevalence of hypertension. These disparities persisted to the higher-order combinations that included these conditions. High utilizers had a much higher disease burden, with 75.8% having an anxiety or mood disorder, as well as a higher burden of injuries. DISCUSSION: This study shows a high prevalence of psychiatric and physical conditions and identifies racial and ethnic disparities affecting people with epilepsy. Targeting interventions to consider the comorbidities, race, and ethnicity has potential to improve clinical care and reduce disparities.

Elevated Dietary Inflammation Among Supplemental Nutrition Assistance Program Recipients Provides Targets for Precision Public Health Intervention.

INTRODUCTION: The Supplemental Nutrition Assistance Program was designed to prevent food insecurity among low-income Americans and has been linked to improvements in pregnancy health, long-term child development, and criminal recidivism. However, the pursuit of food security does not ensure nutritional sufficiency, and the program has not improved diet quality or cardiometabolic mortality (i.e., heart disease, stroke, diabetes). In this study, longitudinal cohort data are used to identify by Supplemental Nutrition Assistance Program status the proinflammatory characteristics that predispose to chronic disease. METHODS: Between 2015 and 2018, annual 24-hour dietary recalls were conducted with 409 residents from low-income, urban neighborhoods in Columbus and Cleveland, Ohio (statistical analysis started in 2019). The Dietary Inflammatory Index was calculated. It provides empirically validated estimates of the internal inflammation that each diet should produce; higher Dietary Inflammatory Index scores have been associated with elevated inflammatory biomarkers. Finally, associations between Supplemental Nutrition Assistance Program and Dietary Inflammatory Index were evaluated, and dietary components that differed by Supplemental Nutrition Assistance Program status were identified. RESULTS: Supplemental Nutrition Assistance Program recipients had higher Dietary Inflammatory Index scores (+0.40, 95% CI=0.09, 0.70) and a consistently lower intake of 4 anti-inflammatory nutrients (dietary fiber, ß-carotene, magnesium, vitamin E) than nonrecipients. Vitamin D intake did not differ by Supplemental Nutrition Assistance Program status but was well below the Recommended Daily Allowance in this sample. CONCLUSIONS: Supplemental Nutrition Assistance Program recipients had elevated Dietary Inflammatory Index scores, implying higher diet-driven inflammation. This was due, in part, to low intake of 4 anti-inflammatory food components, which were higher yet still nutritionally insufficient among nonrecipients. Findings highlight specific nutritional targets for improving public health through dietary change.

Low Omega-3 intake is associated with high rates of depression and preterm birth on the country level.

Low circulating levels of long chain omega-3 polyunsaturated fatty acids (LC omega-3 PUFA) have been linked to major depressive disorder (MDD) and preterm birth (PTB), and prenatal depression associates with PTB. We therefore hypothesized that low Omega-3 intake would associate with higher MDD and PTB rates on the country-level. To test this hypothesis, we obtained country-level estimates for omega-3 intake, MDD prevalence, PTB rate, and per capita income for 184 countries in 2010. We then estimated the LC omega-3 PUFA levels that these intakes produce by accounting for direct consumption and the endogenous conversion of ingested plant-based precursors. Penalized splines indicated that MDD and PTB rates decreased linearly with increasing LC omega-3 PUFA, up to ~ 1000 mg/day for MDD and up to ~ 550 mg/day for PTB. Adjusted linear regression models below these thresholds revealed that a one standard deviation increase in LC omega-3 PUFA (380 mg/day) was associated with an MDD decrease of 5 cases/1000 people and a PTB decrease of 15 cases/1000 livebirths. In light of the extensive prior evidence on the individual-level, these findings indicate that low intake of LC omega-3 PUFA and its precursors may be elevating MDD and PTB rates in 85% of the countries studied.

Evolutionary triangulation: informing genetic association studies with evolutionary evidence.

Genetic studies of human diseases have identified many variants associated with pathogenesis and severity. However, most studies have used only statistical association to assess putative relationships to disease, and ignored other factors for evaluation. For example, evolution is a factor that has shaped disease risk, changing allele frequencies as human populations migrated into and inhabited new environments. Since many common variants differ among populations in frequency, as does disease prevalence, we hypothesized that patterns of disease and population structure, taken together, will inform association studies. Thus, the population distributions of allelic risk variants should reflect the distributions of their associated diseases. Evolutionary Triangulation (ET) exploits this evolutionary differentiation by comparing population structure among three populations with variable patterns of disease prevalence. By selecting populations based on patterns where two have similar rates of disease that differ substantially from a third, we performed a proof of principle analysis for this method. We examined three disease phenotypes, lactase persistence, melanoma, and Type 2 diabetes mellitus. We show that for lactase persistence, a phenotype with a simple genetic architecture, ET identifies the key gene, lactase. For melanoma, ET identifies several genes associated with this disease and/or phenotypes related to it, such as skin color genes. ET was less obviously successful for Type 2 diabetes mellitus, perhaps because of the small effect sizes in known risk loci and recent environmental changes that have altered disease risk. Alternatively, ET may have revealed new genes involved in conferring disease risk for diabetes that did not meet nominal GWAS significance thresholds. We also compared ET to another method used to filter for phenotype associated genes, population branch statistic (PBS), and show that ET performs better in identifying genes known to associate with diseases appropriately distributed among populations. Our results indicate that ET can filter association results to improve our ability to discover disease loci.

Neighborhood socio-economic characteristics, African ancestry, and Helicobacter pylori sero-prevalence.

PURPOSE: The authors recently reported high Helicobacter pylori sero-prevalence among African-Americans of high African ancestry. We sought to determine whether neighborhood-level socio-economic characteristics are associated with H. pylori prevalence and whether this helps explain the link between African ancestry and H. pylori. METHODS: Antibodies to H. pylori proteins were assessed in the serum of 336 African-American and 329 white Southern Community Cohort Study participants. Prevalence odds ratios (ORs) and 95 % confidence intervals (CIs) for CagA+ and CagA- H. pylori were calculated using polytomous logistic regression in relation to 10 Census block group-level measures of socio-economic status. RESULTS: After adjusting for individual-level characteristics, three neighborhood-level factors were significantly inversely related to CagA+ H. pylori: percent completed high school; median house values; and percent employed (comparing highest to lowest tertile, OR, 0.47, 95 % CI, 0.26-0.85; OR, 0.56, 95 % CI, 0.32-0.99; and OR, 0.59, 95 % CI, 0.34-1.03, respectively). However, accounting for these measures did not attenuate the association between African ancestry and CagA+ H. pylori, with African-Americans of low, medium, and high African ancestry maintaining two-, seven-, and ninefold increased odds, respectively, compared to whites. CONCLUSIONS: Neighborhood-level measures of education, employment, and house values are associated with CagA+ H. pylori sero-prevalence, but do not explain the persistent strong relationship between African ancestry level and CagA+ H. pylori. The findings suggest that neighborhood socio-economic status can help to highlight high-risk areas for prevention and screening efforts and that the link between African ancestry and H. pylori may have a biological basis.

Common variation in vitamin D pathway genes predicts circulating 25-hydroxyvitamin D Levels among African Americans.

Vitamin D is implicated in a wide range of health outcomes, and although environmental predictors of vitamin D levels are known, the genetic drivers of vitamin D status remain to be clarified. African Americans are a group at particularly high risk for vitamin D insufficiency but to date have been virtually absent from studies of genetic predictors of circulating vitamin D levels. Within the Southern Community Cohort Study, we investigated the association between 94 single nucleotide polymorphisms (SNPs) in five vitamin D pathway genes (GC, VDR, CYP2R1, CYP24A1, CYP27B1) and serum 25-hydroxyvitamin D (25(OH)D) levels among 379 African American and 379 Caucasian participants. We found statistically significant associations with three SNPs (rs2298849 and rs2282679 in the GC gene, and rs10877012 in the CYP27B1 gene), although only for African Americans. A genotype score, representing the number of risk alleles across the three SNPs, alone accounted for 4.6% of the variation in serum vitamin D among African Americans. A genotype score of 5 (vs. 1) was also associated with a 7.1 ng/mL reduction in serum 25(OH)D levels and a six-fold risk of vitamin D insufficiency (<20 ng/mL) (odds ratio 6.0, p = 0.01) among African Americans. With African ancestry determined from a panel of 276 ancestry informative SNPs, we found that high risk genotypes did not cluster among those with higher African ancestry. This study is one of the first to investigate common genetic variation in relation to vitamin D levels in African Americans, and the first to evaluate how vitamin D-associated genotypes vary in relation to African ancestry. These results suggest that further evaluation of genetic contributors to vitamin D status among African Americans may help provide insights regarding racial health disparities or enable the identification of subgroups especially in need of vitamin D-related interventions.

Correcting away the hidden heritability.

In the age of high-density genome-wide association (GWAS) data, correcting for multiple comparisons is a substantial issue for genetic epidemiological studies. However, the current manuscript review process generally requires both stringent correction and independent replication. The result of this stringency is that studies that are published suffer from inflated Type 2 error rates (false negatives), thereby removing many likely real signals from follow-up. Elimination of these alleles, if they are truly associated, from further study will slow research progress in studies of complex disease. We argue that this method of correction is overly conservative, especially in an age when high-density follow-up experiments are possible and reasonably inexpensive.

Report on the 6th African Society of Human Genetics (AfSHG) Meeting, March 12-15, 2009, Yaounde, Cameroon.

The African Society of Human Genetics (AfSHG), founded in 2003 with its inaugural meeting in Accra, Ghana,1 has the stated missions of (1) disseminating information about human genetics research in Africa, (2) establishing a mentorship network providing educational resources, including the development of appropriate technology transfer, (3) providing advocacy for human genetic research in Africa, and (4) encouraging collaborative research. Despite its young age, the AfSHG has developed a strong cadre of active researchers, both within and outside of Africa, with more than 400 members (from 16 countries across Africa as well as 8 other countries), and has held six successful meetings, five in Africa and one in the United States.