OBJECTIVES/GOALS: Using the covariate-rich Veteran Health Administration data, estimate the association between Proton Pump Inhibitor (PPI) use and severe COVID-19, rigorously adjusting for confounding using propensity score (PS)-weighting. METHODS/STUDY POPULATION: We assembled a national retrospective cohort of United States veterans who tested positive for SARS-CoV-2, with information on 33 covariates including comorbidity diagnoses, lab values, and medications. Current outpatient PPI use was compared to non-use (two or more fills and pills on hand at admission vs no PPI prescription fill in prior year). The primary composite outcome was mechanical ventilation use or death within 60 days; the secondary composite outcome included ICU admission. PS-weighting mimicked a 1:1 matching cohort, allowing inclusion of all patients while achieving good covariate balance. The weighted cohort was analyzed using logistic regression. RESULTS/ANTICIPATED RESULTS: Our analytic cohort included 97,674 veterans with SARS-CoV-2 testing, of whom 14,958 (15.3%) tested positive (6,262 [41.9%] current PPI-users, 8,696 [58.1%] non-users). After weighting, all covariates were well-balanced with standardized mean differences less than a threshold of 0.1. Prior to PS-weighting (no covariate adjustment), we observed higher odds of the primary (9.3% vs 7.5%; OR 1.27, 95% CI 1.13-1.43) and secondary (25.8% vs 21.4%; OR 1.27, 95% CI 1.18-1.37) outcomes among PPI users vs non-users. After PS-weighting, PPI use vs non-use was not associated with the primary (8.2% vs 8.0%; OR 1.03, 95% CI 0.91-1.16) or secondary (23.4% vs 22.9%;OR 1.03, 95% CI 0.95-1.12) outcomes. DISCUSSION/SIGNIFICANCE: The associations between PPI use and severe COVID-19 outcomes that have been previously reported may be due to limitations in the covariates available for adjustment. With respect to COVID-19, our robust PS-weighted analysis provides patients and providers with further evidence for PPI safety.

Sexual dimorphism is common in many extant animals, but it is difficult to demonstrate in fossil species. Working with material from the Late Cretaceous of the U.S. Coastal Plain, we herein analyze sexual dimorphism in ostracodes from the superfamily Cytheroidea, a group whose extant members have males that are relatively more elongate than females. We digitized outlines of more than 6000 individual ostracode valves or carapaces, extracted size (area) and shape (length-to-height ratio) information, and used finite mixture models to assess hypotheses of sexual dimorphism. Male and female clusters can be discerned in nearly all populations with sufficient data, resulting in estimates of size and shape dimorphism for 142 populations across 106 species; an additional nine samples are interpreted to consist only of females. Dimorphism patterns varied across taxa, especially for body size: males range from 30% larger to 20% smaller than females. Magnitudes of sexual dimorphism are generally stable within species across time and space; we can demonstrate substantial evolutionary changes in dimorphism in only one species, Haplocytheridea renfroensis. Several lines of evidence indicate that patterns of sexual dimorphism in these ostracodes reflect male investment in reproduction, suggesting that this study system has the potential to capture variation in sexual selection through the fossil record.