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Abstract Background There is a reported association between proton pump inhibitor (PPI) exposure and increased risk of Clostridium difficile infection (CDI), but less is known about how this class of medications taken during treatment might influence mortality after CDI. Here we examine 180-day mortality rates in a cohort of CDI elders and its association with exposure to PPIs. We conducted a retrospective cohort study of elderly patients (> 65 years of age) diagnosed and treated for CDI in the years 2014–2016 (n = 874) in the Umass Memorial Health Care system, which represents both academic and community healthcare. Patient characteristics and medication use was extracted from the electronic medical record (EMR) and 6 month mortality data was obtained via the Center for Disease Control National Death Index. A Cox proportional hazards model was used to estimate hazard ratios associated with medication exposures and other relevant variables. Results Of the 874 elderly adults treated for CDI, 180-day all-cause mortality was 12.4%. Exposure to a PPI was associated with a 55% reduced risk of mortality (adjusted hazard ratio (aHR) 0.45; 95% confidence interval (CI) 0.28–0.72). In our Cox model, increasing age (aHR 1.45; 95% CI 1.14–1.84), those with severe CDI infections (aHR 1.87; 95% CI 1.22–2.88), and those with hospital acquired CDI (aHR 3.01; 95% CI 1.81–4.99) also had increased 180 day mortality risk. There were similar associations noted with both 90 day and 1-year mortality. Conclusion Use of PPIs during CDI treatment in elderly patients is associated with decreased 180-day mortality. Although use of PPIs has been associated with an increased risk of CDI, it appears to be protective against mortality when used during the treatment phase.

Abstract Background As we continue the fourth year of the COVID-19 epidemic, SARS-CoV-2 infections still cause high morbidity and mortality in the United States. During 2020–2022, COVID-19 was one of the leading causes of death in the United States and by far the leading cause among infectious diseases. Vaccination uptake remains low despite this being an effective burden reducing intervention. The development of COVID-19 therapeutics provides hope for mitigating severe clinical outcomes. This modeling study examines combined strategies of vaccination and treatment to reduce the burden of COVID-19 epidemics over the next decade. Methods We use a validated mathematical model to evaluate the reduction of incident cases, hospitalized cases, and deaths in the United States through 2033 under various levels of vaccination and treatment coverage. We assume that future seasonal transmission patterns for COVID-19 will be similar to those of influenza virus and account for the waning of infection-induced immunity and vaccine-induced immunity in a future with stable COVID-19 dynamics. Due to uncertainty in the duration of immunity following vaccination or infection, we consider three exponentially distributed waning rates, with means of 365 days (1 year), 548 days (1.5 years), and 730 days (2 years). We also consider treatment failure, including rebound frequency, as a possible treatment outcome. Results As expected, universal vaccination is projected to eliminate transmission and mortality. Under current treatment coverage (13.7%) and vaccination coverage (49%), averages of 81,000–164,600 annual reported deaths, depending on duration of immunity, are expected by the end of this decade. Annual mortality in the United States can be reduced below 50,000 per year with 52–80% annual vaccination coverage and below 10,000 annual deaths with 59–83% annual vaccination coverage, depending on duration of immunity. Universal treatment reduces hospitalizations by 88.6% and deaths by 93.1% under current vaccination coverage. A reduction in vaccination coverage requires a comparatively larger increase in treatment coverage in order for hospitalization and mortality levels to remain unchanged. Conclusions Adopting universal vaccination and universal treatment goals in the United States will likely lead to a COVID-19 mortality burden below 50,000 deaths per year, a burden comparable to that of influenza virus.