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Browsing by Author "Beasley, T. Mark"
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Item Influence of Age on Warfarin Dose, Anticoagulation Control, and Risk of Hemorrhage(Wiley, 2018) Shendre, Aditi; Parmar, Gaurav M.; Dillon, Chrisly; Beasley, T. Mark; Limdi, Nita A.; Epidemiology, School of Public HealthObjective We assessed the influence of age on warfarin dose, percentage time in target range (PTTR), and risk of major hemorrhage. Design Warfarin users recruited into a large prospective inception cohort study were categorized into three age groups: young (younger than 50 yrs), middle aged (50–70 yrs), and elderly (older than 70 yrs). The influence of age on warfarin dose and PTTR was assessed using regression analysis; risk of major hemorrhage was assessed using proportional hazards analysis. Models were adjusted for demographic, clinical, and genetic factors. Setting Two outpatient anticoagulation clinics. Participants A total of 1498 anticoagulated patients. Outcomes Warfarin dose (mg/day), PTTR, major hemorrhage. Results Of the 1498 patients, 22.8% were young, 44.1% were middle aged, and 33.1% were elderly. After accounting for clinical and genetic factors, compared with young warfarin users, warfarin dose requirements were 10.6% lower among the middle aged and an additional 10.6% lower for the elderly. Compared with young patients, middle-aged and elderly patients spent more time in target international normalized ratio (INR) range (p<0.0001), despite having fewer INR assessments (p<0.0001). Compared with young warfarin users, absolute risk of hemorrhage was marginally higher among the middle aged (p=0.08) and significantly higher among the elderly (p=0.016). Compared with young warfarin users, after adjustment, the relative risk of hemorrhage increased by 31% for each age category (p=0.026). Conclusions In a real-world setting, despite achieving better anticoagulation control, elderly patients had a higher risk of major hemorrhagic events. As the population ages and the candidacy for oral anticoagulation increases, strategies that mitigate the elevated risk of hemorrhage need to be identified.Item Wood cookstove use is associated with gastric cancer in Central America and mediated by host genetics(Springer Nature, 2023-10) Rifkin, Samara B.; Miller, Anna K.; Montalvan‑Sanchez, Eleazar E.; Norwood, Dalton A.; Martinez, Enrique; Waterboer, Tim; Beasley, T. Mark; Dominguez, Ricardo L.; Williams, Scott M.; Morgan, Douglas R.; Medicine, School of MedicineBiomass cookstove food preparation is linked to aero-digestive cancers, mediated by ingested and inhaled carcinogens (e.g., heterocyclic amines, and polycyclic aromatic hydrocarbons). We investigated the association between gastric adenocarcinoma, wood cookstove use, H. pylori CagA infection and risk modification by variants in genes that metabolize and affect the internal dose of carcinogens. We conducted a population-based, case–control study (814 incident cases, 1049 controls) in rural Honduras, a high-incidence region with a homogeneous diet and endemic H. pylori infection, primarily with the high-risk CagA genotype. We investigated factors including wood cookstove use, H. pylori CagA serostatus, and 15 variants from 7 metabolizing genes, and the interactions between wood stove use and the genetic variants. Male sex (OR 2.0, 1.6–2.6), age (OR 1.04, 1.03–1.05), wood cookstove use (OR 2.3, 1.6–3.3), and CagA serostatus (OR 3.5, 2.4–5.1) and two SNPs in CYP1B1 (rs1800440 and rs1056836) were independently associated with gastric cancer in multivariate analysis. In the final multivariate model, a highly significant interaction (OR 3.1, 1.2–7.8) was noted between wood cookstove use and the rs1800440 metabolizing genotype, highlighting an important gene-environment interaction. Lifetime wood cookstove use associates with gastric cancer risk in the high-incidence regions of Central America, and the association is dependent on the rs1800440 genotype in CYP1B1. H. pylori CagA infection, wood cookstove use and the rs1800440 genotype, all of which are highly prevalent, informs who is at greatest risk from biomass cookstove use.