Benefit-risk assessment for the Novavax COVID-19 vaccine (NVX-CoV2373).

A benefit-risk assessment of NVX-CoV2373, a vaccine to prevent COVID-19, was conducted to determine if the benefits of vaccination outweigh the risks of myocarditis/pericarditis. This analysis used data on myocarditis/pericarditis cases observed in the NVX-CoV2373 clinical studies, real-world data of mRNA COVID vaccine effectiveness against predominant SARS-CoV-2 strains in early 2023, and recent COVID-19 burden of disease data from the United States. The benefits of NVX-CoV2373 vaccination were estimated as the number of COVID-19 cases, hospitalizations, and deaths prevented. The risks of myocarditis/pericarditis cases and related hospitalizations and deaths occurring within 7 days of vaccination were also estimated. In our analysis, vaccination with NVX-CoV2373, per 100,000 vaccinated, resulted in an estimated 1805 COVID-19 cases prevented compared with an estimated 5.3 excess myocarditis/pericarditis cases. The number of COVID-19 hospitalizations and deaths prevented were also greater than vaccine-associated myocarditis/pericarditis hospitalizations and deaths. Our analysis indicates a positive benefit-risk balance for NVX-CoV2373.

Predictors of Influenza and Pneumococcal Vaccination Among Participants in the Women's Health Initiative.

OBJECTIVE: Older adults typically experience higher rates of severe disease and mortality than the general population after contracting an infectious disease. Vaccination is critical for preventing disease and severe downstream outcomes; however, vaccination rates among older adults are suboptimal. We assessed predictors associated with pneumococcal and seasonal influenza vaccination among older women. METHODS: We used data from the Women's Health Initiative, a nationwide cohort of women. We ascertained seasonal influenza and pneumococcal vaccination status through a questionnaire administered in 2013. We limited analyses to women aged ≥65 years at questionnaire administration. We used logistic regression to estimate associations between demographic, lifestyle, and health-related factors and vaccination and explored stratification by race. RESULTS: Of participants who responded to each question, 84.3% (n = 60 578) reported being vaccinated for influenza and 85.5% (n = 59 015) for pneumonia. The odds of reporting influenza vaccination were significantly lower among non-Hispanic Black participants than among non-Hispanic White participants (odds ratio [OR] = 0.53; 95% CI, 0.49-0.58), women with no health insurance versus private health insurance (OR = 0.61; 95% CI, 0.54-0.68), and women living in rural versus urban settings (OR = 0.84; 95% CI, 0.73-0.96). Current smoking, lower education levels, and having comorbid conditions were associated with lower likelihood of being vaccinated for influenza (than not); past pneumonia diagnosis and being currently married were associated with a higher likelihood. We observed similar associations for pneumococcal vaccination coverage. CONCLUSIONS: These findings reinforce the need to enact policy and implement programs to improve access to, education and awareness about, and provider recommendations for these critical disease-prevention tools. Results from our study should guide strategies for SARS-CoV-2 vaccination.

Patterns of use of recombinant zoster vaccine among commercially-insured immunocompetent and immunocompromised adults 50-64 years old in the United States.

PURPOSE: The Centers for Disease Control and Prevention (CDC) recommends recombinant zoster vaccination (RZV) for adults ≥ 50 years to prevent herpes zoster (HZ) and its sequelae. Initially, no distinct recommendation was made for immunocompromised adults, who experience higher HZ rates and more severe outcomes. We characterized receipt of first RZV dose (initiation) and both doses (completion) over time, and the impact of immune function on RZV uptake among adults aged 50-64 years in the United States. METHODS: We identified RZV claims from the IBM MarketScan database between 1/1/2018 and 12/31/2019. We characterized immunocompromised enrollees as having malignancy, HIV, solid organ transplant, primary immunosuppression, or medication-induced immunosuppression using inpatient, outpatient, and prescription claims in the 6 months prior to study start. We evaluated patterns of vaccine uptake by demographic and healthcare access characteristics and immune status. RESULTS: The cumulative incidence of RZV initiation during the study period was 10.0%. Incidence increased with age and number of medical office visits, and was higher among women, urban residents, high-deductible insurance beneficiaries, and those who were immunocompromised compared to immunocompetent. Among immunocompromised adults, RZV initiation was highest among those with HIV and primary immunodeficiencies. Of those who initiated RZV, 89.5% received both doses. RZV completion was highest among those who received the first dose at a pharmacy. Most enrollees (88.6%) who completed RZV vaccination did so within the recommended dosing schedule. CONCLUSIONS: RZV uptake was low in the two years since the CDC recommendation, and differed by demographic, healthcare access, and clinical characteristics. Initiation rates were higher among immunocompromised adults compared to immunocompetent adults, despite no CDC recommendation for vaccination in these groups during the study period. The CDC has since recommended RZV for immunocompromised individuals, and our findings may inform efforts to increase RZV uptake in individuals at higher risk of severe disease.

Systematic Review and Meta-Analysis to Estimate the Treatment Effect and Inform a Noninferiority Margin for a Phase 3 Noninferiority Trial in Uncomplicated Urogenital Gonorrhea.

BACKGROUND: Active-controlled noninferiority studies are used to investigate novel agents for uncomplicated urogenital gonorrhea (uUGC) as placebo-controlled trials are unethical. A systematic literature review and meta-analysis were conducted to estimate the ceftriaxone and proxy-for-placebo microbiological treatment effect and determine an appropriate noninferiority margin for phase 3 trials. METHODS: Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. To account for interstudy variability, a weighted, noniterative random-effects model was fitted using "R" software to estimate the microbiological response rate and 95% confidence intervals (CIs) for ceftriaxone and proxy-for-placebo (treatment with an antibiotic the isolate was subsequently confirmed resistant to, or spontaneous resolution without treatment). I2 , τ2 , and P values were computed and included in the meta-analysis forest plot. RESULTS: Seventeen studies were included in the meta-analysis; 14 reported ceftriaxone response in micro-intent-to-treat and microbiologically evaluable populations, and 3 reported proxy-for-placebo treatment response in uUGC (microbiologically evaluable population only). Microbiological treatment effect was estimated by subtracting the upper end of the CI for placebo from the lower end of the CI for ceftriaxone. Overall microbiological response was 98% (95% CI, 97-99) for ceftriaxone and 44% (95% CI, 34-54) for proxy-for-placebo, resulting in a microbiological treatment effect of 43%. A noninferiority margin of 15% preserved 65% of the ceftriaxone treatment effect, exceeding the 50% recommended per US Food and Drug Administration guidance for noninferiority studies. CONCLUSIONS: Results of this systematic literature review and meta-analysis could help inform the design, conduct, and analysis of future clinical studies in uUGC.

Database selection matters: A case study in child restraint use and injury patterns using North Carolina motor vehicle traffic crash report and trauma registry data.

OBJECTIVE: While proper restraint use is protective against motor traffic vehicle crash (MVTC)-associated morbidity and mortality, it is inconsistently measured across health and MVTC data sources. This project addresses this gap by assessing differences in child restraint measures between two North Carolina (NC) datasets and comparing the utility of these sources to evaluate patterns of child restraint use and associated health outcomes. METHODS: We analyzed 2018 NC MVTC and NC Trauma Registry (NCTR) data for children ≤15 years old, both separately and as linked MVTC-NCTR records. We calculated mean and standard deviation for continuous variables and frequency and proportion for categorical variables. Among linked records, we compared reported restraint use and performed age-adjusted logistic regression to estimate associations between restraint use and severe injury. RESULTS: A lower proportion of pediatric MVTC victims were reported as unrestrained in the MVTC (14.7%) versus NCTR (25.8%) data. Among linked MVTC-NCTR records, only 41.3% featured perfect concordance of restraint information between datasets. Among linked records, child restraint was reported for 31.3% of children, while the NCTR data allowed more granular coding of child restraint (30.3% overall), including child booster seat (13.5%), child car seat (8.7%), infant car seat (4.8%), and unrestrained in child car seat (3.4%). Age-adjusted regression analyses of the linked data revealed that lap/shoulder seatbelt use was significantly associated with lower likelihood of severe injury compared to being unrestrained whether informed by MVTC (OR = 0.39; 95% CI: 0.16, 0.93) or NCTR (OR = 0.38; 95% CI: 0.15, 0.96) data. While the association between reported use of a child car seat and severe injury was not statistically significant in the MVTC data (OR = 0.50; 95% CI: 0.19, 1.32), child car seat use reported in the NCTR data revealed a significant association (OR = 0.16; 95% CI: 0.03, 0.93). CONCLUSIONS: Linked crash and trauma center data allow for identifying important patterns of restraint use among pediatric passengers in MVTCs. Dataset-dependent differences in measuring restraint use have critical public health implications and illustrate the importance of careful dataset selection prior to analysis, as the use of different data sources may impact overall study conclusions.

Linking Emergency Medical Services and Emergency Department Data to Improve Overdose Surveillance in North Carolina.

INTRODUCTION: Linking emergency medical services (EMS) data to emergency department (ED) data enables assessing the continuum of care and evaluating patient outcomes. We developed novel methods to enhance linkage performance and analysis of EMS and ED data for opioid overdose surveillance in North Carolina. METHODS: We identified data on all EMS encounters in North Carolina during January 1-November 30, 2017, with documented naloxone administration and transportation to the ED. We linked these data with ED visit data in the North Carolina Disease Event Tracking and Epidemiologic Collection Tool. We manually reviewed a subset of data from 12 counties to create a gold standard that informed developing iterative linkage methods using demographic, time, and destination variables. We calculated the proportion of suspected opioid overdose EMS cases that received International Classification of Diseases, Tenth Revision, Clinical Modification diagnosis codes for opioid overdose in the ED. RESULTS: We identified 12 088 EMS encounters of patients treated with naloxone and transported to the ED. The 12-county subset included 1781 linkage-eligible EMS encounters, with historical linkage of 65.4% (1165 of 1781) and 1.6% false linkages. Through iterative linkage methods, performance improved to 91.0% (1620 of 1781) with 0.1% false linkages. Among statewide EMS encounters with naloxone administration, the linkage improved from 47.1% to 91.1%. We found diagnosis codes for opioid overdose in the ED among 27.2% of statewide linked records. PRACTICE IMPLICATIONS: Through an iterative linkage approach, EMS-ED data linkage performance improved greatly while reducing the number of false linkages. Improved EMS-ED data linkage quality can enhance surveillance activities, inform emergency response practices, and improve quality of care through evaluating initial patient presentations, field interventions, and ultimate diagnoses.

Gender differences in respiratory health outcomes among farming cohorts around the globe: findings from the AGRICOH consortium.

Purpose: Respiratory hazards of farming have been identified for centuries, with little focus on gender differences. We used data from the AGRICOH consortium, a collective of prospective cohorts of agricultural workers, to assess respiratory disease prevalence among adults in 18 cohorts representing over 200,000 farmers, farm workers, and their spouses from six continents.Methods: Cohorts collected data between 1992 and 2016 and ranged in size from 200 to >128,000 individuals; 44% of participants were female. Farming practices varied from subsistence farming to large-scale industrial agriculture. All cohorts provided respiratory outcome information for their cohort based on their study definitions. The majority of outcomes were based on self-report using standard respiratory questionnaires; the greatest variability in assessment methods was associated with chronic obstructive pulmonary disease (COPD).Results: For all three respiratory symptoms (cough, phlegm, and wheeze), the median prevalence in men was higher than in women, with the greatest difference for phlegm (17% vs. 10%). For asthma, women had a higher prevalence (7.8% vs 6.5%), with the difference associated with allergic asthma. The relative proportion of allergic asthma varied among cohorts. In two of eight cohorts for women and two of seven cohorts for men, allergic asthma was more common than non-allergic asthma.Conclusions: These findings indicate that respiratory outcomes are common among farmers around the world despite differences in agricultural production. As women in the general population are at higher risk of asthma, exploring gender differences in occupational studies is critical for a deeper understanding of respiratory disease among agricultural workers.

Association between Gut Microbiome Composition and Rotavirus Vaccine Response among Nicaraguan Infants.

Rotavirus is the leading cause of childhood deaths due to diarrhea. Although existing oral rotavirus vaccines are highly efficacious in high-income countries, these vaccines have been demonstrated to have decreased efficacy in low- and middle-income countries. A possible explanation for decreased efficacy is the impact of gut microbiota on the enteric immune system's response to vaccination. We analyzed the gut microbiome of 50 children enrolled in a prospective study evaluating response to oral pentavalent rotavirus vaccination (RV5) to assess associations between relative abundance of bacterial taxa and seroconversion following vaccination. Stool samples were taken before the first RV5 dose, and microbiome composition characterized using 16S rRNA amplicon sequencing and Quantitative Insights Into Microbial Ecology software. Relative abundance of bacterial taxa between seroconverters following the first RV5 dose, those with ≥ 4-fold increase in rotavirus-specific IgA titers, and nonseroconverters were compared using the Wilcoxon-Mann-Whitney test. We identified no significant differences in microbiome composition between infants who did and did not respond to vaccination. Infants who responded to vaccination tended to have higher abundance of Proteobacteria and Eggerthella, whereas those who did not respond had higher abundance of Fusobacteria and Enterobacteriaceae; however, these differences were not statistically significant following a multiple comparison correction. This study suggests a limited impact of gut microbial taxa on response to oral rotavirus vaccination among infants; however, additional research is needed to improve our understanding of the impact of gut microbiome on vaccine response, toward a goal of improving vaccine efficacy and rotavirus prevention.

A bibliometric analysis of an international research ethics trainee program.

We used bibliometric analysis to evaluate the citations associated with publications by trainees in the Fogarty International Center's International Research Ethics Education and Curriculum Development program. Papers published between 2004 and 2008 were identified for analysis. The outcome measures were total citations, h-index, and i-10. A total of 328 manuscripts were identified, with a yearly average of 66 publications and 363 citations. The median number of citations per paper is 3 (IQR Q1-Q3:6). 12.6% (n = 53) of papers were cited over 10 times and the h-index is 22, indicating that 22 papers had been cited at least 22 times. The data indicate that trainees have been productive and contributed to the scholarly literature. Future studies to benchmark this performance with other bioethics education programs are required to make interpretation of citation analysis more meaningful.