On the Value of Measuring Recent Drug Use by Self-Reports and Urinalysis in Clinical Trials.

Background: Valid measurement of drug use in patients enrolled in clinical trials that treat substance use disorder is vital to determine the trial's outcome. Self-reports are often used but their validity has been studied with mixed results. Urinalysis may sometimes be employed as an alternative or supplement to self-reports. Objectives: This study examined how estimating drug use by either method would affect the results from a randomized clinical trial conducted in a methadone treatment program. At the initial Baseline interview and four follow-up interviews, participants were asked about their drug use history and provided a urine specimen for drug testing. Results: In most cases, the urinalyses detected more drugs than the patients had reported using. A major exception was heroin, whose use was an eligibility criterion for enrollment in the study and methadone treatment. Conclusions: The patients' self-reports would have led us to conclude that the use of heroin and fentanyl had declined from the initial Baseline interview to the final follow-up interview, while the urinalysis results indicated no change in exposure to heroin and an increase in exposure to fentanyl. Clinical trials would be well served to employ the use of biological tests in addition to self-reports to measure recent drug use and to accurately estimate the efficacy of the experimental protocols and patients' exposure to drugs.

Disparities in COVID-19 vaccination receipt by race, ethnicity, and social determinants of health among a large patient population in a network of community-based healthcare centers.

BACKGROUND: There are known disparities in U.S. COVID-19 vaccination but there is limited information on national vaccine uptake in a large, racially diverse, all-age population. Here, we describe COVID-19 vaccination coverage in a large U.S. population accessing care in OCHIN (not an acronym), a national network of community-based healthcare organizations. METHODS: Within OCHIN, we identified patients aged 6 months and older with ≥1 completed clinical encounter since becoming age-eligible for the COVID-19 vaccine between December 13, 2020 and December 31, 2022. Patients' COVID-19 vaccination status was assessed from OCHIN's Epic® electronic health record which includes data from state immunization information systems. Patients were considered vaccinated if they received ≥1 dose of a monovalent vaccine product; coverage was categorized by age groups (6 months-4 years; 5-11 years, 12-15 years, 16+ years). Multivariate analyses assessed factors associated with COVID-19 vaccination across age groups. RESULTS: The cohort included 3.3 million Hispanic (37 %), non-Hispanic (NH) White (31 %), NH Black (15 %), and NH Asian (7 %) patients; 45 % of whom were Medicaid-enrolled, 19 % uninsured, and 53 % with a household income below 100 % of the federal poverty level. The proportion with ≥1 COVID-19 vaccine dose increased with age, from 11.7 % (6 months through 4 years) to 72.3 % (65 years and older). The only factors associated with significantly higher COVID-19 vaccine coverage across age groups were prior receipt of an influenza vaccine and having private insurance. In adjusted modeling, when compared to NH whites, COVID-19 vaccine coverage was significantly higher among Hispanic, NH Asian, and NH multiple-race patients aged ≥5 years and significantly lower among NH Black and NH Native Hawaiian/Other Pacific Islander patients aged 6 months-4 years old. CONCLUSIONS: We identified disparities in primary series COVID-19 vaccine coverage by age, race and ethnicity, household income, insurance status, and prior influenza vaccination within this large, diverse population accessing care in community-based healthcare organizations.

Tinnitus after COVID-19 vaccination: Findings from the vaccine adverse event reporting system and the vaccine safety datalink.

PURPOSE: To assess the occurrence of tinnitus following COVID-19 vaccination using data mining and descriptive analyses in two U.S. vaccine safety surveillance systems. METHODS: Reports of tinnitus after COVID-19 vaccination to the Vaccine Adverse Event Reporting System (VAERS) from 2020 through 2024 were examined using empirical Bayesian data mining and by calculating reporting rates. In the Vaccine Safety Datalink (VSD) population, ICD-10 coded post-vaccination medical visits were examined using tree-based data mining, and tinnitus visit incidence rates during post-vaccination days 1-140 were calculated by age group for COVID-19 vaccines and for comparison, influenza vaccine. RESULTS: VAERS data mining did not find disproportionate reporting of tinnitus for any COVID-19 vaccine. VAERS received up to 84.82 tinnitus reports per million COVID-19 vaccine doses administered. VSD tree-based data mining found no signals for tinnitus. VSD tinnitus visit incidence rates after COVID-19 vaccines were similar to those after influenza vaccine except for the group aged ≥65 years (Moderna COVID-19 vaccine, 165 per 10,000 person-years; Pfizer-BioNTech COVID-19 vaccine, 154; influenza vaccine, 135). CONCLUSIONS: Overall, these findings do not support an increased risk of tinnitus following COVID-19 vaccination but cannot definitively exclude the possibility. Descriptive comparisons between COVID-19 and influenza vaccines were limited by lack of adjustment for potential confounding factors.

Lack of Evidence for Vaccine-Associated Enhanced Disease From COVID-19 Vaccines Among Adults in the Vaccine Safety Datalink.

PURPOSE: Vaccine-associated enhanced disease (VAED) is a theoretical concern with new vaccines, although trials of authorized vaccines against SARS-CoV-2 have not identified markers for VAED. The purpose of this study was to detect any signals for VAED among adults vaccinated against coronavirus disease 2019 (COVID-19). METHODS: In this cross-sectional study, we assessed COVID-19 severity as a proxy for VAED among 400 adults hospitalized for COVID-19 from March through October 2021 at eight US healthcare systems. Primary outcomes were admission to an intensive care unit (ICU) and severe illness (score ≥6 on the World Health Organization [WHO] Clinical Progression Scale). We compared the risk of outcomes among those who had completed a COVID-19 vaccine primary series versus those who were unvaccinated. We incorporated inverse propensity weights for vaccination status in a doubly robust regression model to estimate the causal average treatment effect. RESULTS: The causal risk ratio in vaccinated versus unvaccinated was 0.36 (95% confidence interval [CI], 0.15-0.94) for ICU admission and 0.46 (95% CI, 0.25-0.76) for severe illness. CONCLUSION: Among hospitalized patients, reduced disease severity in those vaccinated against COVID-19 supports the absence of VAED.

COVID-19 Vaccination in the First Trimester and Major Structural Birth Defects Among Live Births.

Importance: COVID-19 vaccination is recommended throughout pregnancy to prevent pregnancy complications and adverse birth outcomes associated with COVID-19 disease. To date, data on birth defects after first-trimester vaccination are limited. Objective: To evaluate the associated risks for selected major structural birth defects among live-born infants after first-trimester receipt of a messenger RNA (mRNA) COVID-19 vaccine. Design, Setting, and Participants: This was a retrospective cohort study of singleton pregnancies with estimated last menstrual period (LMP) between September 13, 2020, and April 3, 2021, and ending in live birth from March 5, 2021, to January 25, 2022. Included were data from 8 health systems in California, Oregon, Washington, Colorado, Minnesota, and Wisconsin in the Vaccine Safety Datalink. Exposures: Receipt of 1 or 2 mRNA COVID-19 vaccine doses in the first trimester, as part of the primary series. Main Outcomes and Measures: Selected major structural birth defects among live-born infants, identified from electronic health data using validated algorithms, with neural tube defects confirmed via medical record review. Results: Among 42 156 eligible pregnancies (mean [SD] maternal age, 30.9 [5.0] years) 7632 (18.1%) received an mRNA COVID-19 vaccine in the first trimester. Of 34 524 pregnancies without a first-trimester COVID-19 vaccination, 2045 (5.9%) were vaccinated before pregnancy, 13 494 (39.1%) during the second or third trimester, and 18 985 (55.0%) were unvaccinated before or during pregnancy. Compared with pregnant people unvaccinated in the first trimester, those vaccinated in the first trimester were older (mean [SD] age, 32.3 [4.5] years vs 30.6 [5.1] years) and differed by LMP date. After applying stabilized inverse probability weighting, differences in baseline characteristics between vaccinated and unvaccinated pregnant persons in the first trimester were negligible (standardized mean difference <0.20). Selected major structural birth defects occurred in 113 infants (1.48%) after first-trimester mRNA COVID-19 vaccination and in 488 infants (1.41%) without first-trimester vaccine exposure; the adjusted prevalence ratio was 1.02 (95% CI, 0.78-1.33). In secondary analyses, with major structural birth defect outcomes grouped by organ system, no significant differences between infants vaccinated or unvaccinated in the first trimester were identified. Conclusions and Relevance: In this multisite cohort study, among live-born infants, first-trimester mRNA COVID-19 vaccine exposure was not associated with an increased risk for selected major structural birth defects.

COVID-19 Vaccination Coverage and Factors Associated With Vaccine Uptake Among People With HIV.

Importance: People with HIV (PWH) may be at increased risk for severe outcomes with COVID-19 illness compared with people without HIV. Little is known about COVID-19 vaccination coverage and factors associated with primary series completion among PWH. Objectives: To evaluate COVID-19 vaccination coverage among PWH and examine sociodemographic, clinical, and community-level factors associated with completion of the primary series and an additional primary dose. Design, Setting, and Participants: This retrospective cohort study used electronic health record data to assess COVID-19 vaccination information from December 14, 2020, through April 30, 2022, from 8 health care organizations of the Vaccine Safety Datalink project in the US. Participants were adults diagnosed with HIV on or before December 14, 2020, enrolled in a participating site. Main Outcomes and Measures: The percentage of PWH with at least 1 dose of COVID-19 vaccine and PWH who completed the COVID-19 vaccine primary series by December 31, 2021, and an additional primary dose by April 30, 2022. Rate ratios (RR) and 95% CIs were estimated using Poisson regression models for factors associated with completing the COVID-19 vaccine primary series and receiving an additional primary dose. Results: Among 22 058 adult PWH (mean [SD] age, 52.1 [13.3] years; 88.8% male), 90.5% completed the primary series by December 31, 2021. Among 18 374 eligible PWH who completed the primary series by August 12, 2021, 15 982 (87.0%) received an additional primary dose, and 4318 (23.5%) received a booster dose by April 30, 2022. Receipt of influenza vaccines in the last 2 years was associated with completion of the primary series (RR, 1.17; 95% CI, 1.15-1.20) and an additional primary dose (RR, 1.61; 95% CI, 1.54-1.69). PWH with uncontrolled viremia (HIV viral load ≥200 copies/mL) (eg, RR, 0.90 [95% CI, 0.85-0.95] for viral load 200-10 000 copies/mL vs undetected or <200 copies/mL for completing the primary series) and Medicaid insurance (eg, RR, 0.89 [95% CI, 0.87-0.90] for completing the primary series) were less likely to be fully vaccinated. By contrast, greater outpatient utilization (eg, RR, 1.07 [95% CI, 1.05-1.09] for ≥7 vs 0 visits for primary series completion) and residence in counties with higher COVID-19 vaccine coverage (eg, RR, 1.06 [95% CI, 1.03-1.08] for fourth vs first quartiles for primary series completion) were associated with primary series and additional dose completion (RRs ranging from 1.01 to 1.21). Conclusions and Relevance: Findings from this cohort study suggest that, while COVID-19 vaccination coverage was high among PWH, outreach efforts should focus on those who did not complete vaccine series and those who have uncontrolled viremia.

Correlates of Staff Acceptability of a Novel Telemedicine-Delivered Medications for Opioid Use Disorder Program in a Rural Detention Center.

Opioid overdose death is significantly increased immediately following incarceration. Evidence-based medications are underutilized in rural jails and detention centers. We have reported our efforts to address this gap through telemedicine-based medications for opioid use disorder treatment (tele-MOUD) for incarcerated patients. Staff acceptance and perceptions are critically important factors in the assurance of program validation. We assessed tele-MOUD acceptability and perceptions of effectiveness and stigma in one detention center. Overall, we found that jail staff's general acceptability of the program was rather low, as was perceived effectiveness of MOUD, while stigmatizing beliefs were present. Furthermore, tele-MOUD acceptability was positively correlated with perceptions of MOUD effectiveness and negatively correlated with stigmatizing notions of MOUD (p's < 0.001). Findings suggest the need for educational interventions. Future research investigating the potential moderating effects of training on staff acceptability of jail-based tele-MOUD will support the implementation and sustainability of these life-saving programs.

Coronavirus Disease 2019 (COVID-19) Vaccination and Stillbirth in the Vaccine Safety Datalink.

OBJECTIVE: Coronavirus disease 2019 (COVID-19) vaccination is recommended in pregnancy to reduce the risk of severe morbidity from COVID-19. However, vaccine hesitancy persists among pregnant people, with risk of stillbirth being a primary concern. Our objective was to examine the association between COVID-19 vaccination and stillbirth. METHODS: We performed a matched case-control study in the Vaccine Safety Datalink (VSD). Stillbirths and live births were selected from singleton pregnancies among persons aged 16-49 years with at least one prenatal, delivery, or postpartum visit at eight participating VSD sites. Stillbirths identified through diagnostic codes were adjudicated to confirm the outcome, date, and gestational age at fetal death. Confirmed antepartum stillbirths that occurred between February 14, 2021, and February 27, 2022, then were matched 1:3 to live births by pregnancy start date, VSD site, and maternal age at delivery. Associations among antepartum stillbirth and COVID-19 vaccination in pregnancy, vaccine manufacturer, number of vaccine doses received, and vaccination within 6 weeks before stillbirth (or index date in live births) were evaluated using conditional logistic regression. RESULTS: In the matched analysis of 276 confirmed antepartum stillbirths and 822 live births, we found no association between COVID-19 vaccination during pregnancy and stillbirth (38.4% stillbirths vs 39.3% live births in vaccinated individuals, adjusted odds ratio [aOR] 1.02, 95% CI, 0.76-1.37). Furthermore, no association between COVID-19 vaccination and stillbirth was detected by vaccine manufacturer (Moderna: aOR 1.00, 95% CI, 0.62-1.62; Pfizer-BioNTech: aOR 1.00, 95% CI, 0.69-1.43), number of vaccine doses received during pregnancy (1 vs 0: aOR 1.17, 95% CI, 0.75-1.83; 2 vs 0: aOR 0.98, 95% CI, 0.81-1.17), or COVID-19 vaccination within the 6 weeks before stillbirth or index date compared with no vaccination (aOR 1.16, 95% CI, 0.74-1.83). CONCLUSION: No association was found between COVID-19 vaccination and stillbirth. These findings further support recommendations for COVID-19 vaccination in pregnancy.

Post-COVID conditions following COVID-19 vaccination: a retrospective matched cohort study of patients with SARS-CoV-2 infection.

COVID-19 vaccinations protect against severe illness and death, but associations with post-COVID conditions (PCC) are less clear. We aimed to evaluate the association between prior COVID-19 vaccination and new-onset PCC among individuals with SARS-CoV-2 infection across eight large healthcare systems in the United States. This retrospective matched cohort study used electronic health records (EHR) from patients with SARS-CoV-2 positive tests during March 2021-February 2022. Vaccinated and unvaccinated COVID-19 cases were matched on location, test date, severity of acute infection, age, and sex. Vaccination status was ascertained using EHR and integrated data on externally administered vaccines. Adjusted relative risks (RRs) were obtained from Poisson regression. PCC was defined as a new diagnosis in one of 13 PCC categories 30 days to 6 months following a positive SARS-CoV-2 test. The study included 161,531 vaccinated COVID-19 cases and 161,531 matched unvaccinated cases. Compared to unvaccinated cases, vaccinated cases had a similar or lower risk of all PCC categories except mental health disorders (RR: 1.06, 95% CI: 1.02-1.10). Vaccination was associated with ≥10% lower risk of sensory (RR: 0.90, 0.86-0.95), circulatory (RR: 0.88, 0.83-0.94), blood and hematologic (RR: 0.79, 0.71-0.89), skin and subcutaneous (RR: 0.69, 0.66-0.72), and non-specific COVID-19 related disorders (RR: 0.53, 0.51-0.56). In general, associations were stronger at younger ages but mostly persisted regardless of SARS-CoV-2 variant period, receipt of ≥3 vs. 1-2 vaccine doses, or time since vaccination. Pre-infection vaccination was associated with reduced risk of several PCC outcomes and hence may decrease the long-term consequences of COVID-19.

Obstetric Complications and Birth Outcomes After Antenatal Coronavirus Disease 2019 (COVID-19) Vaccination.

OBJECTIVE: To evaluate the association between antenatal messenger RNA (mRNA) coronavirus disease 2019 (COVID-19) vaccination and risk of adverse pregnancy outcomes. METHODS: This was a retrospective cohort study of individuals with singleton pregnancies with live deliveries between June 1, 2021, and January 31, 2022, with data available from eight integrated health care systems in the Vaccine Safety Datalink. Vaccine exposure was defined as receipt of one or two mRNA COVID-19 vaccine doses (primary series) during pregnancy. Outcomes were preterm birth (PTB) before 37 weeks of gestation, small-for-gestational age (SGA) neonates, gestational diabetes mellitus (GDM), gestational hypertension, and preeclampsia-eclampsia-HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome. Outcomes in individuals vaccinated were compared with those in propensity-matched individuals with unexposed pregnancies. Adjusted hazard ratios (aHRs) and 95% CIs were estimated for PTB and SGA using a time-dependent covariate Cox model, and adjusted relative risks (aRRs) were estimated for GDM, gestational hypertension, and preeclampsia-eclampsia-HELLP syndrome using Poisson regression with robust variance. RESULTS: Among 55,591 individuals eligible for inclusion, 23,517 (42.3%) received one or two mRNA COVID-19 vaccine doses during pregnancy. Receipt of mRNA COVID-19 vaccination varied by maternal age, race, Hispanic ethnicity, and history of COVID-19. Compared with no vaccination, mRNA COVID-19 vaccination was associated with a decreased risk of PTB (rate: 6.4 [vaccinated] vs 7.7 [unvaccinated] per 100, aHR 0.89; 95% CI, 0.83-0.94). Messenger RNA COVID-19 vaccination was not associated with SGA (8.3 vs 7.4 per 100; aHR 1.06, 95% CI, 0.99-1.13), GDM (11.9 vs 10.6 per 100; aRR 1.00, 95% CI, 0.90-1.10), gestational hypertension (10.8 vs 9.9 per 100; aRR 1.08, 95% CI, 0.96-1.22), or preeclampsia-eclampsia-HELLP syndrome (8.9 vs 8.4 per 100; aRR 1.10, 95% CI, 0.97-1.24). CONCLUSION: Receipt of an mRNA COVID-19 vaccine during pregnancy was not associated with an increased risk of adverse pregnancy outcomes; this information will be helpful for patients and clinicians when considering COVID-19 vaccination in pregnancy.

Attitudes Toward COVID-19 Vaccines Among Pregnant and Recently Pregnant Individuals.

Importance: Pregnant people and infants are at high risk of severe COVID-19 outcomes. Understanding changes in attitudes toward COVID-19 vaccines among pregnant and recently pregnant people is important for public health messaging. Objective: To assess attitudinal trends regarding COVID-19 vaccines by (1) vaccination status and (2) race, ethnicity, and language among samples of pregnant and recently pregnant Vaccine Safety Datalink (VSD) members from 2021 to 2023. Design, Setting, and Participants: This cross-sectional surveye study included pregnant or recently pregnant members of the VSD, a collaboration of 13 health care systems and the US Centers for Disease Control and Prevention. Unvaccinated, non-Hispanic Black, and Spanish-speaking members were oversampled. Wave 1 took place from October 2021 to February 2022, and wave 2 took place from November 2022 to February 2023. Data were analyzed from May 2022 to September 2023. Exposures: Self-reported or electronic health record (EHR)-derived race, ethnicity, and preferred language. Main Outcomes and Measures: Self-reported vaccination status and attitudes toward monovalent (wave 1) or bivalent Omicron booster (wave 2) COVID-19 vaccines. Sample- and response-weighted analyses assessed attitudes by vaccination status and 3 race, ethnicity, and language groupings of interest. Results: There were 1227 respondents; all identified as female, the mean (SD) age was 31.7 (5.6) years, 356 (29.0%) identified as Black race, 555 (45.2%) identified as Hispanic ethnicity, and 445 (36.3%) preferred the Spanish language. Response rates were 43.5% for wave 1 (652 of 1500 individuals sampled) and 39.5% for wave 2 (575 of 1456 individuals sampled). Respondents were more likely than nonrespondents to be White, non-Hispanic, and vaccinated per EHR. Overall, 76.8% (95% CI, 71.5%-82.2%) reported 1 or more COVID-19 vaccinations; Spanish-speaking Hispanic respondents had the highest weighted proportion of respondents with 1 or more vaccination. Weighted estimates of somewhat or strongly agreeing that COVID-19 vaccines are safe decreased from wave 1 to 2 for respondents who reported 1 or more vaccinations (76% vs 50%; χ21 = 7.8; P < .001), non-Hispanic White respondents (72% vs 43%; χ21 = 5.4; P = .02), and Spanish-speaking Hispanic respondents (76% vs 53%; χ21 = 22.8; P = .002). Conclusions and Relevance: Decreasing confidence in COVID-19 vaccine safety in a large, diverse pregnant and recently pregnant insured population is a public health concern.

Overview of U.S. COVID-19 vaccine safety surveillance systems.

The U.S. COVID-19 vaccination program, which commenced in December 2020, has been instrumental in preventing morbidity and mortality from COVID-19 disease. Safety monitoring has been an essential component of the program. The federal government undertook a comprehensive and coordinated approach to implement complementary safety monitoring systems and to communicate findings in a timely and transparent way to healthcare providers, policymakers, and the public. Monitoring involved both well-established and newly developed systems that relied on both spontaneous (passive) and active surveillance methods. Clinical consultation for individual cases of adverse events following vaccination was performed, and monitoring of special populations, such as pregnant persons, was conducted. This report describes the U.S. government's COVID-19 vaccine safety monitoring systems and programs used by the Centers for Disease Control and Prevention, the U.S. Food and Drug Administration, the Department of Defense, the Department of Veterans Affairs, and the Indian Health Service. Using the adverse event of myocarditis following mRNA COVID-19 vaccination as a model, we demonstrate how the multiple, complementary monitoring systems worked to rapidly detect, assess, and verify a vaccine safety signal. In addition, longer-term follow-up was conducted to evaluate the recovery status of myocarditis cases following vaccination. Finally, the process for timely and transparent communication and dissemination of COVID-19 vaccine safety data is described, highlighting the responsiveness and robustness of the U.S. vaccine safety monitoring infrastructure during the national COVID-19 vaccination program.

Influenza vaccination accuracy among adults: Self-report compared with electronic health record data.

OBJECTIVE: To assess the validity of electronic health record (EHR)-based influenza vaccination data among adults in a multistate network. METHODS: Following the 2018-2019 and 2019-2020 influenza seasons, surveys were conducted among a random sample of adults who did or did not appear influenza-vaccinated (per EHR data) during the influenza season. Participants were asked to report their influenza vaccination status; self-report was treated as the criterion standard. Results were combined across survey years. RESULTS: Survey response rate was 44.7% (777 of 1740) for the 2018-2019 influenza season and 40.5% (505 of 1246) for the 2019-2020 influenza season. The sensitivity of EHR-based influenza vaccination data was 75.0% (95% confidence interval [CI] 68.1, 81.1), specificity 98.4% (95% CI 92.9, 99.9), and negative predictive value 73.9% (95% CI 68.0, 79.3). CONCLUSIONS: In a multistate research network across two recent influenza seasons, there was moderate concordance between EHR-based vaccination data and self-report.

Mortality risk after COVID-19 vaccination: A self-controlled case series study.

BACKGROUND: Although previous studies found no-increased mortality risk after COVID-19 vaccination, residual confounding bias might have impacted the findings. Using a modified self-controlled case series (SCCS) design, we assessed the risk of non-COVID-19 mortality, all-cause mortality, and four cardiac-related death outcomes after primary series COVID-19 vaccination. METHODS: We analyzed all deaths between December 14, 2020, and August 11, 2021, among individuals from eight Vaccine Safety Datalink sites. Demographic characteristics of deaths in recipients of COVID-19 vaccines and unvaccinated individuals were reported. We conducted SCCS analyses by vaccine type and death outcomes and reported relative incidences (RI). The observation period for death spanned from the dates of emergency use authorization to the end of the study period (August 11, 2021) without censoring the observation period upon death. We pre-specified a primary risk interval of 28-day and a secondary risk interval of 14-day after each vaccination dose. Adjusting for seasonality in mortality analyses is crucial because death rates vary over time. Deaths among unvaccinated individuals were included in SCCS analyses to account for seasonality by incorporating calendar month in the models. RESULTS: For Pfizer-BioNTech (BNT162b2), RIs of non-COVID-19 mortality, all-cause mortality, and four cardiac-related death outcomes were below 1 and 95 % confidence intervals (CIs) excluded 1 across both doses and both risk intervals. For Moderna (mRNA-1273), RI point estimates of all outcomes were below 1, although the 95 % CIs of two RI estimates included 1: cardiac-related (RI = 0.78, 95 % CI, 0.58-1.04) and non-COVID-19 cardiac-related mortality (RI = 0.80, 95 % CI, 0.60-1.08) 14 days after the second dose in individuals without pre-existing cancer and heart disease. For Janssen (Ad26.COV2.S), RIs of four cardiac-related death outcomes ranged from 0.94 to 0.98 for the 14-day risk interval, and 0.68 to 0.72 for the 28-day risk interval and 95 % CIs included 1. CONCLUSION: Using a modified SCCS design and adjusting for temporal trends, no-increased risk was found for non-COVID-19 mortality, all-cause mortality, and four cardiac-related death outcomes among recipients of the three COVID-19 vaccines used in the US.

Abnormal uterine bleeding diagnoses and care following COVID-19 vaccination.

BACKGROUND: There is evidence suggesting that COVID-19 vaccination may be associated with small, transitory effects on uterine bleeding, possibly including menstrual timing, flow, and duration, in some individuals. However, changes in health care seeking, diagnosis, and workup for abnormal uterine bleeding in the COVID-19 vaccine era are less clear. OBJECTIVE: This study aimed to assess the impact of COVID-19 vaccination on incident abnormal uterine bleeding diagnosis and diagnostic evaluation in a large integrated health system. STUDY DESIGN: Using segmented regression, we assessed whether the availability of COVID-19 vaccines was associated with changes in monthly, population-based rates of incident abnormal uterine bleeding diagnoses relative to the prepandemic period in health system members aged 16 to 44 years who were not menopausal. We also compared clinical and demographic characteristics of patients diagnosed with incident abnormal uterine bleeding between December 2020 and October 13, 2021 by vaccination status (never vaccinated, vaccinated in the 60 days before diagnosis, vaccinated >60 days before diagnosis). Furthermore, we conducted detailed chart review of patients diagnosed with abnormal uterine bleeding within 1 to 60 days of COVID-19 vaccination in the same time period. RESULTS: In monthly populations ranging from 79,000 to 85,000 female health system members, incidence of abnormal uterine bleeding diagnosis per 100,000 person-days ranged from 8.97 to 19.19. There was no significant change in the level or trend in the incidence of abnormal uterine bleeding diagnoses between the prepandemic (January 2019-January 2020) and post-COVID-19 vaccine (December 2020-December 2021) periods. A comparison of clinical characteristics of 2717 abnormal uterine bleeding cases by vaccination status suggested that abnormal bleeding among recently vaccinated patients was similar or less severe than abnormal bleeding among patients who had never been vaccinated or those vaccinated >60 days before. There were also significant differences in age and race of patients with incident abnormal uterine bleeding diagnoses by vaccination status (Ps<.02). Never-vaccinated patients were the youngest and those vaccinated >60 days before were the oldest. The proportion of patients who were Black/African American was highest among never-vaccinated patients, and the proportion of Asian patients was higher among vaccinated patients. Chart review of 114 confirmed postvaccination abnormal uterine bleeding cases diagnosed from December 2020 through October 13, 2021 found that the most common symptoms reported were changes in timing, duration, and volume of bleeding. Approximately one-third of cases received no diagnostic workup; 57% had no etiology for the bleeding documented in the electronic health record. In 12% of cases, the patient mentioned or asked about a possible link between their bleeding and their recent COVID-19 vaccine. CONCLUSION: The availability of COVID-19 vaccination was not associated with a change in incidence of medically attended abnormal uterine bleeding in our population of over 79,000 female patients of reproductive age. In addition, among 2717 patients with abnormal uterine bleeding diagnoses in the period following COVID-19 vaccine availability, receipt of the vaccine was not associated with greater bleeding severity.

Postmenopausal bleeding after COVID-19 vaccination.

BACKGROUND: There is a growing literature base regarding menstrual changes following COVID-19 vaccination among premenopausal people. However, relatively little is known about uterine bleeding in postmenopausal people following COVID-19 vaccination. OBJECTIVE: This study aimed to examine trends in incident postmenopausal bleeding diagnoses over time before and after COVID-19 vaccine introduction, and to describe cases of new-onset postmenopausal bleeding after COVID-19 vaccination. STUDY DESIGN: For postmenopausal bleeding incidence calculations, monthly population-level cohorts consisted of female Kaiser Permanente Northwest members aged ≥45 years. Those diagnosed with incident postmenopausal bleeding in the electronic medical record were included in monthly numerators. Members with preexisting postmenopausal bleeding or abnormal uterine bleeding, or who were at increased risk of bleeding due to other health conditions, were excluded from monthly calculations. We used segmented regression analysis to estimate changes in the incidence of postmenopausal bleeding diagnoses from 2018 through 2021 in Kaiser Permanente Northwest members meeting the inclusion criteria, stratified by COVID-19 vaccination status in 2021. In addition, we identified all members with ≥1 COVID-19 vaccination between December 14, 2020 and August 14, 2021, who had an incident postmenopausal bleeding diagnosis within 60 days of vaccination. COVID-19 vaccination, diagnostic procedures, and presumed bleeding etiology were assessed through chart review and described. A temporal scan statistic was run on all cases without clear bleeding etiology. RESULTS: In a population of 75,530 to 82,693 individuals per month, there was no statistically significant difference in the rate of incident postmenopausal bleeding diagnoses before and after COVID-19 vaccine introduction (P=.59). A total of 104 individuals had incident postmenopausal bleeding diagnosed within 60 days following COVID-19 vaccination; 76% of cases (79/104) were confirmed as postvaccination postmenopausal bleeding after chart review. Median time from vaccination to bleeding onset was 21 days (range: 2-54 days). Among the 56 postmenopausal bleeding cases with a provider-attributed etiology, the common causes of bleeding were uterine or cervical lesions (50% [28/56]), hormone replacement therapy (13% [7/56]), and proliferative endometrium (13% [7/56]). Among the 23 cases without a clear etiology, there was no statistically significant clustering of postmenopausal bleeding onset following vaccination. CONCLUSION: Within this integrated health system, introduction of COVID-19 vaccines was not associated with an increase in incident postmenopausal bleeding diagnoses. Diagnosis of postmenopausal bleeding in the 60 days following receipt of a COVID-19 vaccination was rare.

Incidence of Adolescent Syncope and Related Injuries Following Vaccination and Routine Venipuncture.

PURPOSE: Vaccination is associated with syncope in adolescents. However, incidence of vaccine-associated syncope and resulting injury, and how it compares to syncope incidence following other medical procedures, is not known. Here, we describe the incidence of syncope and syncope-related injury in adolescents following vaccination and routine venipuncture. METHODS: We identified all Kaiser Permanente Northwest members ages 9-18 years with a vaccination or routine venipuncture and a same-day International Classification of Diseases diagnosis of syncope from 2013 through 2019. All cases were chart reviewed to establish chronology of events (vaccination, venipuncture, syncope, and injury, as applicable) and to attribute cause to vaccination or venipuncture. Incidence rates for vaccine-associated and venipuncture-associated syncope were calculated overall, by sex and age group. Syncope events resulting in injury were assessed for each event type. RESULTS: Of 197,642 vaccination and 12,246 venipuncture events identified, 549 vaccination and 67 venipuncture events had same-day syncope codes. Chart validation confirmed 59/549 (10.7%) events as vaccine-associated syncope, for a rate of 2.99 per 10,000 vaccination events (95% confidence interval (CI): 2.27-3.85) and 20/67 (29.9%) events as venipuncture-associated syncope, for a rate of 16.33 per 10,000 venipuncture events (95% CI: 9.98-25.21). The incidence rate ratio of vaccine-associated to venipuncture-associated syncope events was 0.18 (95% CI: 0.11-0.31). The incidence of vaccine-associated syncope increased with each additional simultaneously administered vaccine, from 1.51 per 10,000 vaccination events (95% CI: 0.93-2.30) following a single vaccine to 9.94 per 10,000 vaccination events (95% CI: 6.43-14.67) following three or more vaccines. Syncope resulted in injury in about 15% of both vaccine and venipuncture events. DISCUSSION: Syncope occurs more commonly following venipuncture than vaccination. The number of simultaneously administered vaccines is a risk factor for postvaccination syncope in adolescents.

Racial and ethnic disparities in influenza vaccination coverage among pregnant women in the United States: The contribution of vaccine-related attitudes.

OBJECTIVE: Racial and ethnic disparities in influenza vaccination coverage among pregnant women in the United States have been documented. This study assessed the contribution of vaccine-related attitudes to coverage disparities. METHODS: Surveys were conducted following the 2019-2020 and 2020-2021 influenza seasons in a US research network. Using electronic health record data to identify pregnant women, random samples were selected for surveying; non-Hispanic Black women and influenza-unvaccinated women were oversampled. Regression-based decomposition analyses were used to assess the contribution of vaccine-related attitudes to racial and ethnic differences in influenza vaccination. Data were combined across survey years, and analyses were weighted and accounted for survey design. RESULTS: Survey response rate was 41.2% (721 of 1748) for 2019-2020 and 39.3% (706 of 1798) for 2020-2021. Self-reported influenza vaccination was higher among non-Hispanic White respondents (79.4% coverage, 95% CI 73.1%-85.7%) than Hispanic (66.2% coverage, 95% CI 52.5%-79.9%) and non-Hispanic Black (55.8% coverage, 95% CI 50.2%-61.4%) respondents. For all racial and ethnic groups, a high proportion (generally >80%) reported being seen for care, recommended for influenza vaccination, and offered vaccination. In decomposition analyses, vaccine-related attitudes (e.g., worry about vaccination causing influenza; concern about vaccine safety and effectiveness) explained a statistically significant portion of the observed racial and ethnic disparities in vaccination. Maternal age, education, and health status were not significant contributors after controlling for vaccine-related attitudes. CONCLUSIONS: In a setting with relatively high influenza vaccination coverage among pregnant women, racial and ethnic disparities in coverage were identified. Vaccine-related attitudes were associated with the disparities observed.

Influenza vaccination coverage among persons ages six months and older in the Vaccine Safety Datalink in the 2017-18 through 2022-23 influenza seasons.

BACKGROUND: In the United States, annual vaccination against seasonal influenza is recommended for all people ages ≥ 6 months. Vaccination coverage assessments can identify populations less protected from influenza morbidity and mortality and help to tailor vaccination efforts. Within the Vaccine Safety Datalink population ages ≥ 6 months, we report influenza vaccination coverage for the 2017-18 through 2022-23 seasons. METHODS: Across eight health systems, we identified influenza vaccines administered from August 1 through March 31 for each season using electronic health records linked to immunization registries. Crude vaccination coverage was described for each season, overall and by self-reported sex; age group; self-reported race and ethnicity; and number of separate categories of diagnoses associated with increased risk of severe illness and complications from influenza (hereafter referred to as high-risk conditions). High-risk conditions were assessed using ICD-10-CM diagnosis codes assigned in the year preceding each influenza season. RESULTS: Among individual cohorts of more than 12 million individuals each season, overall influenza vaccination coverage increased from 41.9 % in the 2017-18 season to a peak of 46.2 % in 2019-20, prior to declaration of the COVID-19 pandemic. Coverage declined over the next three seasons, coincident with widespread SARS-CoV-2 circulation, to a low of 40.3 % in the 2022-23 season. In each of the six seasons, coverage was lowest among males, 18-49-year-olds, non-Hispanic Black people, and those with no high-risk conditions. While decreases in coverage were present in all age groups, the declines were most substantial among children: 2022-23 season coverage for children ages six months through 8 years and 9-17 years was 24.5 % and 22.4 % (14 and 10 absolute percentage points), respectively, less than peak coverage achieved in the 2019-20 season. CONCLUSIONS: Crude influenza vaccination coverage increased from 2017 to 18 through 2019-20, then decreased to the lowest level in the 2022-23 season. In this insured population, we identified persistent disparities in influenza vaccination coverage by sex, age, and race and ethnicity. The overall low coverage, disparities in coverage, and recent decreases in coverage are significant public health concerns.