Evaluation of potential adverse events following COVID-19 mRNA vaccination among adults aged 65 years and older: Two self-controlled studies in the U.S.

BACKGROUND: Our near-real-time safety monitoring of 16 adverse events (AEs) following COVID-19 mRNA vaccination identified potential elevation in risk for six AEs following primary series and monovalent booster dose administration. The crude association with AEs does not imply causality. Accordingly, we conducted robust evaluation of potential associations. METHODS: We conducted two self-controlled case series studies of COVID-19 mRNA vaccines (BNT162b2 and mRNA-1273) in U.S. Medicare beneficiaries aged ≥ 65 years. Adjusted incidence rate ratio (IRRs) and 95 % confidence intervals (CIs) were estimated following primary series doses for acute myocardial infarction (AMI), pulmonary embolism (PE), immune thrombocytopenia (ITP), disseminated intravascular coagulation (DIC); and following monovalent booster doses for AMI, PE, ITP, Bell's Palsy (BP) and Myocarditis/Pericarditis (Myo/Peri). RESULTS: The primary series study included 3,360,981 individuals who received 6,388,542 primary series doses; the booster study included 6,156,100 individuals with one monovalent booster dose. The AMI IRR following BNT162b2 primary series and booster was 1.04 (95 % CI: 0.91 to 1.18) and 1.06 (95 % CI: 1.003 to 1.12), respectively; for mRNA-1273 primary series and booster, 1.01 (95 % CI: 0.82 to 1.26) and 1.05 (95 % CI: 0.998 to 1.11), respectively. The hospital inpatient PE IRR following BNT162b2 primary series and booster was 1.19 (95 % CI: 1.03 to 1.38) and 0.86 (95 % CI: 0.78 to 0.95), respectively; for mRNA-1273 primary series and booster, 1.15 (95 % CI: 0.94 to 1.41) and 0.87 (95 % CI: 0.79 to 0.96), respectively. The studies' results do not support that exposure to COVID-19 mRNA vaccines elevate the risk of ITP, DIC, Myo/Peri, and BP. CONCLUSION: We did not find an increased risk for AMI, ITP, DIC, BP, and Myo/Peri and there was not consistent evidence for PE after exposure to COVID-19 mRNA primary series or monovalent booster vaccines. These results support the favorable safety profile of COVID-19 mRNA vaccines administered in the U.S. elderly population.

Use of Immunization Information Systems in Ascertainment of COVID-19 Vaccinations for Claims-Based Vaccine Safety and Effectiveness Studies.

Importance: Safety and effectiveness studies of COVID-19 vaccines are being conducted using clinical data, including administrative claims. However, claims data only partially capture administered COVID-19 vaccine doses for numerous reasons, such as vaccination at sites that do not generate claims for reimbursement. Objective: To evaluate the extent to which Immunization Information Systems (IIS) data linked to claims data enhances claims-based COVID-19 vaccine capture for a commercially insured population and to estimate the magnitude of misclassification of vaccinated individuals as having unvaccinated status in the linked IIS and claims data. Design, Setting, and Participants: This cohort study used claims data from a commercial health insurance database and obtained vaccination data from IIS repositories in 11 US states. Participants were individuals younger than 65 years who resided in 1 of 11 states of interest and who were insured in health plans from December 1, 2020, through December 31, 2021. Main Outcomes and Measures: Estimated proportion of individuals with at least 1 dose of any COVID-19 vaccine and proportion of individuals with a completed vaccine series based on general population guidelines. Vaccination status estimates were calculated and compared using claims data alone and linked IIS and claims data. Remaining misclassification of vaccination status was assessed by comparing linked IIS and claims data estimates with estimates from external surveillance data sources (Centers for Disease Control and Prevention [CDC] and state Department of Health [DOH]) and capture-recapture analysis. Results: This cohort study included 5 112 722 individuals (mean [SD] age, 33.5 [17.6] years; 2 618 098 females [51.2%]) from 11 states. Characteristics of those who received at least 1 vaccine dose and those who completed a vaccine series were similar to the overall study population. The proportion with at least 1 vaccine dose increased from 32.8% using claims data alone to 48.1% when the data were supplemented with IIS vaccination records. Vaccination estimates using linked IIS and claims data varied widely by state. The percentage of individuals who completed a vaccine series increased from 24.4% to 41.9% after the addition of IIS vaccine records and varied across states. The percentages of underrecording using linked IIS and claims data were 12.1% to 47.1% lower than those using CDC data, 9.1% to 46.9% lower than the state DOH, and 9.2% to 50.9% lower than capture-recapture analysis. Conclusion and Relevance: Results of this study suggested that supplementing COVID-19 claims records with IIS vaccination records substantially increased the number of individuals who were identified as vaccinated, yet potential underrecording remained. Improvements in reporting vaccination data to IIS infrastructures could allow frequent updates of vaccination status for all individuals and all vaccines.

Fatherhood status in relation to prostate cancer risks in two large U.S.-based prospective cohort studies.

BACKGROUND: Despite the high incidence and mortality of prostate cancer (PCa) in the Unites States, few risk factors have been consistently linked with these PCa outcomes. Assessing proxies of reproductive factors may offer insights into PCa pathogenesis. In this study, we examined fatherhood status as a proxy of fertility in relation to total, nonaggressive, aggressive, and fatal PCa. METHODS: We examined participants of two cohorts, the NIH-AARP Diet and Health (NIH-AARP) Study and Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. We used Cox proportional hazards regression to estimate hazard ratios (HRs) and 95% confidence intervals of associations between fatherhood status and number of children sired in relation to PCa incidence. RESULTS: Fatherhood status (one or more children vs. childless) was positively associated with total PCa risk in NIH-AARP or PLCO, but was not statistically significant (p = 0.06 and 0.55, respectively). Number of children sired indicated a slightly elevated risk of total PCa, but HRs were rarely significant and were of a fairly constant magnitude with no discernable trend relative to the childless referent group. Associations were similar for nonaggressive and aggressive PCa. The trend test for fatal PCa was statistically significant in NIH-AARP (ptrend  < 0.01), despite none of the individual categorical point estimates reaching this threshold. CONCLUSION: This study provides tentative evidence that fathering children is associated with a slightly increased PCa risk. Future research should strive to assess better proxies of reproductive function in relation to aggressive and fatal PCa to provide more specific evidence for this putative relationship.