Tobacco and nicotine use among active component U.S. military service members: a comparison of 2018 estimates from the Health Related Behaviors Survey and the Periodic Health Assessment.

This study compared estimates of the prevalence of and risk factors for tobacco and nicotine use obtained from the 2018 Health Related Behaviors Survey (HRBS) and Periodic Health Assessment (PHA) survey. The HRBS and the PHA are important Department of Defense sources of data on health behavior collected from U.S. military service members. While their collection methods differ, some survey questions are similar, which provides an opportunity to compare survey estimates. Active duty service members consistently reported a much lower prevalence of all types of tobacco and nicotine use on the PHA compared to the HRBS: cigarettes (11.1% vs. 18.4%), e-cigarettes (7.3% vs. 16.2%), chewing tobacco (9.7% vs. 13.4%), any tobacco or nicotine use (25.3% vs. 37.8%), and use of 2 or more tobacco or nicotine products (5.8% vs. 17.4%). Associations between tobacco and nicotine use as well as demographic and other behavioral variables were fairly similar, including age, sex, education, race and ethnicity, rank, and alcohol use. The associations with service branch, body mass index, and sleep were inconsistent. This results of this study suggest that the PHA can provide timely information on trends in military tobacco and nicotine use over time, but much higher estimates from the confidential, voluntary HRBS reported in this study suggest that the command-directed PHA may substantially underestimate the prevalence of all types of tobacco and nicotine use.

Coverage of HIV pre-exposure prophylaxis (PrEP) within the active duty U.S. military, 2023.

Estimates of HIV pre-exposure prophylaxis (PrEP) coverage in the U.S. military, defined as the proportion of the persons taking HIV PrEP out of the estimated number of persons who had indications for it, have never been published. The objective of this study was to provide an estimate of HIV PrEP coverage comparable to U.S. civilian estimates. The population with indications for HIV PrEP was obtained from the Department of Defense 2018 Health Related Behaviors Survey, a stratified random sample of members of all military service branches. The military PrEP coverage estimate of 31.6% in 2023 was lower than the national U.S. estimate of 36.0% in 2022. Among the military population of men who have sex with men (MSM), an estimated 24.6% of service members had indications for PrEP, similar to the national estimate of 24.7%. MSM comprised 66% of all military service members with HIV PrEP indications, compared to 40% in the U.S. general population. The U.S. military should continue deliberate, sustained, and effective actions to address sexual health inequities among MSM, aligned and coordinated with societal efforts including improved coverage of HIV PrEP to prevent HIV transmission.

Serologic Response to the Epstein-Barr Virus Peptidome and the Risk for Multiple Sclerosis.

Importance: It remains unclear why only a small proportion of individuals infected with the Epstein-Barr virus (EBV) develop multiple sclerosis (MS) and what the underlying mechanisms are. Objective: To assess the serologic response to all EBV peptides before the first symptoms of MS occur, determine whether the disease is associated with a distinct immune response to EBV, and evaluate whether specific EBV epitopes drive this response. Design, Setting, and Participants: In this prospective, nested case-control study, individuals were selected among US military personnel with serum samples stored in the US Department of Defense Serum Repository. Individuals with MS had serum collected at a median 1 year before onset (reported to the military in 2000-2011) and were matched to controls for age, sex, race and ethnicity, blood collection, and military branch. No individuals were excluded. The data were analyzed between September 1, 2022, and August 31, 2023. Exposure: Antibodies (enrichment z scores) to the human virome measured using VirScan (phage-displayed immunoprecipitation and sequencing). Main Outcome and Measure: Rate ratios (RRs) for MS for antibodies to 2263 EBV peptides (the EBV peptidome) were estimated using conditional logistic regression, adjusting for total anti-EBV nuclear antigen 1 (EBNA-1) antibodies, which have consistently been associated with a higher MS risk. The role of antibodies against other viral peptides was also explored. Results: A total of 30 individuals with MS were matched with 30 controls. Mean (SD) age at sample collection was 27.8 (6.5) years; 46 of 60 participants (76.7%) were male. The antibody response to the EBV peptidome was stronger in individuals with MS, but without a discernible pattern. The antibody responses to 66 EBV peptides, the majority mapping to EBNA antigens, were significantly higher in preonset sera from individuals with MS (RR of highest vs lowest tertile of antibody enrichment, 33.4; 95% CI, 2.5-448.4; P for trend = .008). Higher total anti-EBNA-1 antibodies were also associated with an elevated MS risk (top vs bottom tertile: RR, 27.6; 95% CI, 2.3-327.6; P for trend = .008). After adjusting for total anti-EBNA-1 antibodies, risk estimates from most EBV peptides analyses were attenuated, with 4 remaining significantly associated with MS, the strongest within EBNA-6/EBNA-3C, while the association between total anti-EBNA-1 antibodies and MS persisted. Conclusion and Relevance: These findings suggest that antibody response to EBNA-1 may be the strongest serologic risk factor for MS. No single EBV peptide stood out as being selectively targeted in individuals with MS but not controls. Larger investigations are needed to explore possible heterogeneity of anti-EBV humoral immunity in MS.

Imputation of Missing Data for Time-to-Event Endpoints Using Retrieved Dropouts.

We have explored several statistical approaches to impute missing time-to-event data that arise from outcome trials with relatively long follow-up periods. Aligning with the primary estimand, such analyses evaluate the robustness of results by imposing an assumption different from censoring at random (CAR). Although there have been debates over which assumption and which method is more appropriate to be applied to the imputation, we propose to use the collection of retrieved dropouts as the basis of missing data imputation. As retrieved dropouts share a similar disposition, such as treatment discontinuation, with subjects who have missing data, they can reasonably be assumed to characterize the distribution of time-to-event among subjects with missing data. In terms of computational intensity and robustness to violation of underlying distributional assumption, we have compared parametric approaches via MCMC or MLE multivariate sampling procedures to a non-parametric bootstrap approach with respect to baseline hazard function. Each of these approaches follows a process of multiple imputation ("proper imputations"), analysis of complete datasets, and final combination. The type-I error, and power rates are examined under a wide range of scenarios to inform the performance characteristics. A subset of a real unblinded phase III CVOT is used to demonstrate the application of the proposed approaches, compared to the Cox proportional hazards model and jump-to-reference multiple imputation.

Smoking and multiple sclerosis risk in black people: A nested case-control study.

BACKGROUND: Smoking is a well-established risk factor for MS; however, it is not known whether its effect on disease risk varies by race/ethnicity. METHODS: We conducted a nested case-control study among US military personnel who have serum samples stored at the Department of Defense Serum Repository. We measured serum cotinine levels, a marker of tobacco smoke exposure, in 157 Black and 23 White individuals who developed MS during follow-up. Controls were randomly selected and matched to each case by age, sex, race/ethnicity, dates of sample collection, and branch of military service. RESULTS: Smoking was not associated with an increased risk of MS in Black people (RR: 1.08, 95 % CI: 0.63-1.85). The results remained similar in analyses restricted to smoking status at baseline, to samples collected 5 years before symptom onset, and using different cut-off levels in cotinine to define smoking status. Smoking was not statistically significantly associated with MS risk in White people, but the point estimate was similar to what has previously been reported in other studies (RR: 1.85, 95 % CI: 0.56-6.16). CONCLUSIONS: Smoking was not associated with MS risk in Black people. Given the consistent association between smoking and MS risk in predominantly White populations, this may suggest that the association between smoking and MS varies by race/ethnicity.

Perceived Health Status and Medical Conditions Among US Active-Duty Service Members.

Purpose: This paper investigates the association between self-reported perceived health status and doctor-informed medical conditions among US active duty service members (ADSM). Methods: Data are from the 2018 Health-Related Behaviors Survey - a cross-sectional survey weighted to represent the US military (N = 17166). Perceived good health status was defined as having a response choice of "good", "very good", or "excellent" to the question: Would you say your overall physical health is ___? Medical conditions were based on self-reported presence of nine clinical conditions. Analysis included weighted prevalence and log-binomial regression models to explore relationships between ADSM characteristics with perceived good health status as well as concordance between perceived status and medical conditions. Results: ADSM rated their health to be excellent (14.6%), very good (37.7%), good (36.2%), fair (9.7%) and poor (1.7%). About 88.5% perceived a good (to excellent) health status. Perceived good health status was negatively associated with the number of medical conditions present (adjusted odds ratio (aOR): ranging from 0.78 to 0.92) as well as several health behaviors (aOR): ranging from 0.86 to 0.98) and other sociodemographic factors. Among all ADSMs, 51% perceived good health in the absence of medical conditions, while 8% perceived poor health status in the presence of medical conditions. Concordance between perceived health status and medical conditions was significantly lower among ADSM who were older (aOR: 0.61; 95% CI: 0.54-0.69), with dependent children (aOR: 0.89; 95% CI: 0.84-0.95), or had been deployed (aOR: 0.89, 95% CI: 0.84-0.95). Conclusion: The prevalence of perceived good health status among ADSMs was consistent with those documented in the general US population. The interrelationships between ADSM's perceptions, medical conditions and sociodemographic characteristics may have implications for their health literacy and utilization of health services. Study findings suggest that interventions promoting healthy behaviors, health literacy and treatment-seeking may influence perceived health status and mitigate medical conditions among ADSM, thus improving the US Military readiness, resilience and mission success.

Suicidal Behaviors Among Active-Duty US Service Members: Data from the 2018 Health-Related Behaviors Survey.

Background: This study aimed to 1) determine the prevalence of past-year suicidal ideation (SI) and attempts (SA) among active-duty SMs; 2) determine whether differences exist by age, sex, and race; and 3) assess whether prevalence estimates vary by risk profiles of mental health conditions and substance use. Methods: Data were from the 2018 Health-Related Behavior Survey (HRBS), a cross-sectional survey of active-duty SMs (n = 17,166). We used the logistic model to identify the factors of SI and SA and latent class analysis (LCA) to identify the risk profiles. Results: Among active duty SMs, 8.26% had SI and 1.25% had SA in the past year. Gender and age have been shown to influence how race might contribute to suicidal behaviors. Mental health conditions were associated with higher odds of SI and SA, as were younger ages; LGB identity; being separated, divorced, or widowed; use of e-cigarettes, dual use of e-cigarettes and cigarettes, or drugs; and history of deployment of less than 12 months. Frequencies of cigarette and e-cigarette use were also associated with SI and SA, indicating the odds were increasing by 0.3% for every additional cigarette or e-cigarette used. Five risk profiles were identified: class 1 (illegal drug use), class 2 (mental health needs with tobacco and alcohol use), class 3 (mental health conditions only), class 4 ("low risk" SMs with low levels of illegal drug use, mental health visits, tobacco use, and alcohol use), and class 5 (alcohol use). Compared to class 4 ("low risk"), all other risk profiles were associated with increased odds of suicidal behaviors. Conclusion: Despite the resources and increased access provided for mental health support, the prevalence of SI among active-duty SMs is greater than in the general population of the same age, likely due to additional military exposures and stressors.

Ertugliflozin and incident obstructive sleep apnea: an analysis from the VERTIS CV trial.

PURPOSE: The sodium-glucose transporter 2 inhibitor (SGLT2i) empagliflozin may reduce the incidence of obstructive sleep apnea (OSA) in patients with type 2 diabetes (T2D) and cardiovascular (CV) disease. This analysis of VERTIS CV, the CV outcome trial for the SGLT2i ertugliflozin conducted in a similar group of patients, explored the effects of ertugliflozin on reported incident OSA. METHODS: In VERTIS CV, patients ≥ 40 years with T2D and atherosclerotic CV disease (ASCVD) were randomized to ertugliflozin 5 or 15 mg or placebo. The primary endpoint was the composite of major adverse CV events. This exploratory analysis evaluated the impact of ertugliflozin (5 and 15 mg pooled) on incident OSA. Patients with prevalent OSA were excluded. Incident OSA events were based on investigator-reported events using the MedDRA SMQ term "sleep apnea syndrome." A multivariable Cox proportional hazards regression model was constructed to assess the association between ertugliflozin and incident OSA. RESULTS: Of 8246 patients enrolled, 7697 (93.3%) were without baseline OSA (placebo, n = 2561; ertugliflozin, n = 5136; mean age 64.4 years; BMI 31.7 kg/m2; HbA1c, 8.2%; 69.2% male; 88.3% White). The OSA incidence rate was 1.44 per 1000 person-years versus 2.61 per 1000 person-years among patients treated with ertugliflozin versus placebo, respectively, corresponding to a 48% relative risk reduction (HR 0.52; 95% CI 0.28-0.96; P = 0.04). CONCLUSIONS: In VERTIS CV, ertugliflozin reduced by nearly half the incidence of OSA in patients with T2D and ASCVD. These data contribute to the literature that SGLT2is may have a significant beneficial impact on OSA. CLINICALTRIALS: gov identifier: NCT01986881.

Unintended pregnancy among U.S. military active duty servicemembers: Estimates for 2018 and trends since 2005.

OBJECTIVES: To evaluate the prevalence of and factors associated with unintended pregnancy in the past 12 months among women and men in the United States (U.S.) military in 2018, as well as trends in unintended pregnancy between 2005 and 2018. STUDY DESIGN: This was a cross-sectional study using the 2018 Department of Defense Health Related Behaviors Survey of active duty servicemembers. We selected a stratified random sample from members of all military service branches and used weighted logistic regression models to identify associated independent factors. A 9.6% weighted response rate to the online survey resulted in 16,806 active duty servicemembers analyzed; 4993 women aged 17 to 44 years and 11,813 men aged 17 to 45+ years. We used data from five independent surveys: 2005, 2008, 2011, 2015, and 2018 to examine trends over time. RESULTS: A total of 5.6% (95% CI: 4.5%-6.7%) of servicewomen reported unintended pregnancy and 2.4% (95% CI: 1.9%-2.9%) of servicemen reported to have caused unintended pregnancy. Unintended pregnancy was associated with contraception nonuse, younger age, and being either married or cohabiting. CONCLUSION: The decrease in prevalence of unintended pregnancy among U.S. servicemembers since 2005 mirrors the general U.S. POPULATION: Differing contraception policies during basic training across military services may influence rates of unintended pregnancy. Unintended pregnancies place a large burden on the military healthcare system, as the majority of women serving in the military are of reproductive age, and thus require care before, during, and for years after giving birth. IMPLICATIONS: Unintended pregnancy among U.S. military servicewomen relatively mirrors that seen in the U.S. POPULATION: Contraceptive policies affect unintended pregnancy throughout servicemembers' duration of service. As they are more likely to live in states which restrict access to abortion services, servicewomen with unintended pregnancy may face increased obstacles to care.

COVID-19 Booster Vaccination in the U.S. Military, August 2021-January 2022.

INTRODUCTION: A booster dose of messenger RNA vaccine protects against severe COVID-19 outcomes. This study examined the incidence of COVID-19 booster vaccination among active-duty U.S. military servicemembers between August 2021 and January 2022, factors associated with vaccination uptake, and trends over time. METHODS: This was a retrospective cohort study of active-duty military personnel using data from the Defense Medical Surveillance System. Participants were included if they served in the active component from August 2021 through January 2022 and were eligible to receive a COVID-19 booster dose by January 2022. Adjusted hazard ratio estimates of time to booster vaccination were calculated using Cox proportional hazards regression. RESULTS: Lower booster vaccine uptake was seen in the U.S. military (25%) than among the general U.S. population at the same time (45%). Booster vaccination increased with older age, with greater education, with higher income, among women, and among those stationed overseas; it decreased with previous COVID-19 infection and use of the Janssen vaccine. There were no significant racial or ethnic disparities in booster vaccination. CONCLUSIONS: In the absence of a compulsory vaccination policy, lower booster vaccine uptake was seen among servicemembers than among the general U.S. population, particularly among members who were younger, were male, Marines, and had a previous history of infection. Low vaccination rates not only increase the risk of acute and long-term health effects from COVID-19 among servicemembers, but they also degrade the overall readiness of the U.S. military.

Quality and Integrated Service Delivery: A Cross-Sectional Study of the Effects of Malaria and Antenatal Service Quality on Malaria Intervention Use in Sub-Saharan Africa.

Using regionally linked facility and household surveys, we measured the quality of integrated antenatal care and malaria in pregnancy services in Kenya, Namibia, Senegal, and Tanzania. We examined country heterogeneities for the association of integrated antenatal and malaria service quality scores with insecticide-treated bed net (ITN) use in pregnant women and children under-five and intermittent preventive treatment in pregnancy (IPTp-2) uptake. Malaria in pregnancy service quality was low overall. Our findings suggest modest, positive associations between malaria in pregnancy quality and ITN use and IPTp-2 uptake across pooled models and for most studied countries, with evidence of heterogeneity in the strength of associations and relevant confounding factors. Antenatal care quality generally was not associated with the study outcomes, although a positive interaction with malaria in pregnancy quality was present for pooled ITN use models. The improved quality of malaria services delivered during formal antenatal care can help address low coverage and usage rates of preventive malaria interventions in pregnancy and childhood. Study findings may be used to target quality improvement efforts at the sub-national level. Study methods may be adapted to identify low-performing facilities for intervention and adaption to other areas of care, such as HIV/AIDS, child immunizations, and postnatal care.

Spatial and Spatio-Temporal Distribution of Human Respiratory Syncytial Virus, Human Parainfluenza Virus, and Human Adenoviruses Cases in Kenya 2007-2013.

Background: Human Respiratory Syncytial Virus (HRSV), Human Parainfluenza Virus (HPIV), and Human Adenovirus (HAdV) epidemics differ in geographical location, time, and virus type. Regions prone to infections can be identified using geographic information systems (GIS) and available methods for detecting spatial and time clusters. We sought to find statistically significant spatial and time clusters of HRSV, HPIV, and HAdV cases in different parts of Kenya. Methods: To analyse retrospective data, we used a geographical information system (GIS) and the spatial scan statistic. The information was gathered from surveillance sites and aggregated at the county level in order to identify purely spatial and Spatio-temporal clusters. To detect the presence of spatial autocorrelation, the local Moran's I test was used. To detect the spatial clusters of HRSV, HPIV, and HAdV cases, we performed the purely spatial scan statistic. Furthermore, space-time clusters were identified using space-time scan statistics. Both spatial and space-time analyses were based on the discrete Poisson model with a pre-specified statistical significance levelof p<0.05. Results: The findings showed that HRSV, HPIV, and HAdV cases had significant autocorrelation within the study areas. Furthermore, in the Western region of the country, the three respiratory viruses had local clusters with significant positive autocorrelation (p<0.05). Statistically, the Western region had significant spatial clusters of HRSV, HPIV, and HAdV occurrence. Furthermore, the space-time analysis revealed that the HPIV primary cluster persisted in the Western region from 2007 to 2013. However, primary clusters of HRSV and HAdV were observed in the Coastal region in 2009-11 and 2008-09, respectively. Conclusion: Human respiratory syncytial virus (HRSV), human parainfluenza virus (HPIV), and human adenovirus (HAdV) hotspots (clusters) occurred in Kenya's Western and Coastal regions from 2007 to 2013. The Western region appeared to be more prone to the occurrence of allthree respiratory viruses throughout the study period. Strategic mitigation should focus on these locations to prevent future clusters of HRSV, HPIV, and HAdV infections that could lead to epidemics.

Diagnosis of hepatitis C infection and cascade of care in the active component, U.S. Armed Forces, 2020.

Hepatitis C virus (HCV) infection rates are rising in the U.S. despite widely available tools to identify and effectively treat nearly all of these cases. This cross-sectional study aimed to use laboratory data to evaluate the prevalence of HCV diagnoses among active component U.S. military service members, describe the characteristics of those diagnosed with HCV, and evaluate the adherence of their care to current standards of practice. All service members in the active component U.S. military between 1 January and 31 December 2020 were included in the study population. The primary outcome was an HCV diagnosis at any time during military service, with secondary outcomes of HCV treatment and sustained virologic response (SVR). The initial case-finding algorithm used laboratory data to identify HCV patients seen in infectious disease and gastrointestinal disease clinics in military treatment facilities (MTFs) (direct care); this was supplemented with additional data to assess and correct for undercounting from cases occurring outside MTFs (purchased care). Thirty active component service members in 2020 had been diagnosed with HCV infection during their military service via direct care, or an estimate of 68 cases after correcting for additional cases from purchased care; this number represents only 12% of the expected number of infections based on previous studies. Of the 30 cases treated via direct care, 28 (93%) received HCV treatment, with 27 of those 28 (96%) achieving SVR. Changes to HCV screening policy for military accessions should be considered in order to effectively identify and treat asymptomatic HCV infections that would otherwise go undetected.

Cardiorenal outcomes with ertugliflozin assessed according to baseline glucose-lowering agent: An analysis from VERTIS CV.

AIM: To assess selected cardiorenal outcomes with ertugliflozin according to use of baseline glucose-lowering agent. MATERIALS AND METHODS: VERTIS CV was a cardiovascular (CV) outcome trial for ertugliflozin versus placebo, conducted in patients with type 2 diabetes and established atherosclerotic CV disease. The primary outcome was time to the first event of CV death, myocardial infarction or stroke (major adverse CV events [MACE]), with other CV outcomes also assessed. Outcomes were analysed using Cox proportional hazards models stratified by baseline use of metformin, insulin, sulphonylureas (SUs) and dipeptidyl peptidase-4 (DPP-4) inhibitors, with interaction testing to assess for treatment effect modification. Changes from baseline in glycaemic, metabolic and haemodynamic variables were also assessed. RESULTS: Of 8246 randomized patients, at baseline 6286 (76%) were on metformin, 3898 (47%) were on insulin, 3383 (41%) were on SUs and 911 (11%) were on DPP-4 inhibitors, alone or in combination therapy (67% used >1 glucose-lowering agent at baseline). For each glucose-lowering agent evaluated, no evidence for effect modification was observed for MACE by baseline use of metformin (with: hazard ratio [HR] 0.92, 95% confidence interval [CI] 0.790, 1.073; without: 1.13, 95% CI 0.867, 1.480), insulin (with: HR 0.91, 95% CI 0.765, 1.092; without: 1.06, 95% CI 0.867, 1.293), SUs (with: HR 1.11, 95% CI 0.890, 1.388; without: 0.90, 95% CI 0.761, 1.060) or DPP-4 inhibitors (with: HR 0.77, 95% CI 0.502, 1.173; without: 1.00, 95% CI 0.867, 1.147) (all Pinteraction  > 0.05). Similar results were observed for all secondary outcomes analysed. CONCLUSION: In VERTIS CV, the effects of ertugliflozin on cardiorenal outcomes were consistent across subgroups of patients stratified by baseline glucose-lowering agent. CLINICALTRIALS: gov identifier: NCT01986881.

Evaluation of the MSMR Surveillance Case Definition for Incident Cases of Hepatitis C.

The validity of military hepatitis C virus (HCV) surveillance data is uncertain due to the potential for misclassification introduced when using administrative databases for surveillance purposes. The objectives of this study were to assess the validity of the surveillance case definition used by the Medical Surveillance Monthly Report (MSMR) for HCV, the over and underestimation of cases from surveillance data, and the true burden of HCV disease in the U.S. military. This was a validation study of all potential HCV cases in the active component U.S. military from calendar year 2019 obtained using several different data sources: 1) outpatient, inpatient, and reportable medical event (RME) records in the Defense Medical Surveillance System, 2) Health Level 7 (HL7) laboratory data obtained from the Navy Marine Corps Public Health Center, and 3) chart review of the electronic medical records of all potential HCV cases, to include those from privately-sourced care. The sensitivity of the MSMR case definition was 83.6% and the positive predictive value (PPV) was 60.0%. This study suggests that the U.S. military should have confidence that the previous estimates derived using the MSMR surveillance case definition were moderately close to the true burden of incident chronic HCV infection (the true incidence of chronic disease being about 27% lower), but these reports likely dramatically overestimate the incidence of acute HCV. Since HCV was selected as an RME to guide public health action, it is most suitable to invest public health efforts in strengthening the use of confirmed RMEs as the surveillance case definition.