Effects of Social Determinants and Pharmacogenetic Medication Interactions on 90-Day Hospital Readmissions.

Context: The present study builds on our prior work that demonstrated an association between pharmacogenetic interactions and 90-day readmission. Objective: Evaluate aggregate contribution of social determinants, comorbidity, and gene-x-drug interactions to moderate 90-day hospital readmission. Study Design and Analysis: Non-concurrent cohort study; Multivariable logistic regression Setting: Hospital/integrated healthcare delivery system in northern Illinois Population Studied: 19,999 adults tracked from 2010 through 2020 who underwent testing with a 13-gene pharmacogenetic panel Outcome Measure: 90-day hospital readmission (primary outcome) Results: Univariate logistic regression analyses demonstrated that strongest associations with 90 day hospital readmissions were the number of medications prescribed within 30 days of a first hospital admission that had Clinical Pharmacogenomics Implementation Consortium (CPIC) guidance (CPIC medications) (5+ CPIC medications, odds ratio (OR) = 7.66, 95% confidence interval 5.45-10.77) (p < 0.0001), major comorbidities (5+ comorbidities, OR 3.36, 2.61-4.32) (p < 0.0001), age (65 + years, OR = 2.35, 1.77-3.12) (p < 0.0001), unemployment (OR = 2.19, 1.88-2.64) (p < 0.0001), Black/African-American race (OR 2.12, 1.47-3.07) (p < 0.0001), median household income (OR = 1.63, 1.03-2.58) (p = 0.035), male gender (OR = 1.47, 1.21-1.80) (p = 0.0001), and one or more gene-x-drug interaction (defined as a prescribed CPIC medication for a patient with a corresponding actionable pharmacogenetic variant) (OR = 1.41, 1.18-1.70). Health insurance was not associated with risk of 90-day readmission. Race, income, employment status, and gene-x-drug interactions were robust in a multivariable logistic regression model. The odds of 90-day readmission for patients with one or more identified gene-x-drug interactions after adjustment for these covariates was attenuated by 10% (OR = 1.31, 1.08-1.59) (p = 0.006). Although the interaction between race and gene-x-drug interactions was not statistically significant, White patients were more likely to have a gene-x-drug interaction (35.2%) than Black/African-American patients (25.9%) who were not readmitted (p < 0.0001). Conclusions: These results highlight the major contribution of social determinants and medical complexity to risk for hospital readmission, and that these determinants may modify the effect of gene-x-drug interactions on rehospitalization risk.

Implementing Primary Care Mediated Population Genetic Screening Within an Integrated Health System.

INTRODUCTION: Genetic screenings can have a large impact on enabling personalized preventive care. However, this can be limited by the primary use of medical history-based screenings in determining care. The purpose of this study was to understand the impact of DNA10K, a population-based genetic screening program mediated by primary care physicians within an integrated health system to emphasize its contribution to preventive healthcare. METHODS: Construction of the patient experience as part of DNA10K shaped the context for PCP engagement within the program. A cross-sectional analysis of patient consents, orders, tests, and results of nearly 10,000 patients within the primary care specialties of family medicine, internal medicine or obstetrics/gynecology between April 1, 2019 and January 22, 2020 was conducted. RESULTS: Across all specialties, a median number of 7.5 cancer and cardiovascular disease variants per PCP was found. The average age of the study population was 49.6 years. Over 8% of these patients had at least one actionable genetic risk variant and almost 2% of patients had at least one CDC Tier 1 variant. The median numbers of patients per PCP with either hereditary breast and ovarian cancer, Lynch Syndrome, or Familial Hypercholesterolemia was 1 (Interquartile Range 0-2). DISCUSSION: The analysis of test results and the engagement of an integrated healthcare system in the implementation of a genetic screening program suggests that it can have a large impact on population health outcomes and minimal referral burden to PCPs if identified risks can lead to preventive care.

No association between germline variation in catechol-O-methyltransferase and colorectal cancer survival in postmenopausal women.

OBJECTIVE: Sex steroid hormones play a role in colorectal cancer (CRC) development, but little is known about their influence on tumor progression and metastasis. Because catechol-O-methyltransferase (COMT; 22q11.21) activity is an important component of estrogen-mediated carcinogenesis, we hypothesized that germline variation in COMT may be associated with CRC survival. METHODS: We identified 10 single nucleotide polymorphisms that tagged variation across two isoforms of COMT in 2,458 women with CRC from the Nurses' Health Study, Postmenopausal Hormones Supplementary Study to the Colon Cancer Family Registry, VITamins And Lifestyle Study, and Women's Health Initiative. All four studies participated in the Genetics and Epidemiology of Colorectal Cancer Consortium. RESULTS: During a median follow-up of 7 years across all studies, there were 799 deaths, including 566 deaths from CRC. Based on multiple comparisons, no associations between single nucleotide polymorphisms and CRC-specific or overall survival reached statistical significance, including the well-characterized Val108/158Met polymorphism (rs4680; CRC-specific survival: hazard ratio per minor allele, 1.04; 95% CI, 0.92-1.17; overall survival: hazard ratio per minor allele, 1.01; 95% CI, 0.90-1.14). CONCLUSIONS: In this large study of women with CRC, we find no evidence that common inherited variation in COMT is associated with survival time after diagnosis.

'Healers' understandings of indigenous names for HIV/AIDS in Harare, Zimbabwe.

Despite many years of HIV/AIDS education programming in Zimbabwe, there are still conflicting understandings of the disease, its genesis and its effects on the body. This is particularly true of traditional healers who, for better or worse, play a significant role in the education, care and treatment of people affected with the disease in Zimbabwe. Evidence from a sample of 50 urban-based healers illustrates the need for more thorough understandings of healers' explanatory frameworks as well as more integrative approaches to developing health promotion and education interventions targeting healers. Based on qualitative data, this article explores local understandings of HIV/AIDS, particularly as embodied in indigenous names for the disease.