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American Journal of Preventive Medicine

Elsevier BV

Preprints posted in the last 30 days, ranked by how well they match American Journal of Preventive Medicine's content profile, based on 11 papers previously published here. The average preprint has a 0.02% match score for this journal, so anything above that is already an above-average fit.

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Addition of Bupropion or Varenicline to Nicotine Replacement Therapy After Acute Coronary Syndrome: A Propensity-Matched Real-World Analysis

Qadeer, A.; Gohar, N.; Maniyar, P.; Shafi, N.; Juarez, L. M.; Mortada, I.; Pack, Q. R.; Jneid, H.; Gaalema, D. E.

2026-04-23 cardiovascular medicine 10.64898/2026.04.21.26351432 medRxiv
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Introduction: Smoking cessation after acute coronary syndrome (ACS) is a Class I recommendation, yet prescription pharmacotherapy use remains low and its real-world cardiovascular effectiveness when added to nicotine replacement therapy (NRT) is poorly characterized. Methods: We conducted a retrospective cohort study using the TriNetX US Collaborative Network (67 healthcare organizations). Adults hospitalized with ACS who received NRT within one month, serving as a proxy for active smoking status, were identified. Two co-primary propensity-matched (1:1, 50 covariates, caliper 0.10 SD) comparisons evaluated bupropion + NRT and varenicline + NRT individually versus NRT alone; a supportive analysis evaluated combined pharmacotherapy versus NRT alone. All-cause mortality was the primary endpoint. Secondary outcomes included MACE, heart failure exacerbations, major bleeding, TIA/stroke, emergency rehospitalizations, and cardiac rehabilitation utilization, assessed at 6 months and 1 year via Kaplan-Meier analysis. Hazard ratios (HRs) greater than 1.0 indicate higher hazard in the NRT-only group. Results: After matching, the combined analysis comprised 8,574 pairs, the bupropion analysis 4,654 pairs, and the varenicline analysis 2,126 pairs. At 1 year, the combined pharmacotherapy group had significantly lower all-cause mortality (HR 1.26, 95% CI 1.16-1.37), MACE (HR 1.16, 95% CI 1.12-1.21), heart failure exacerbations (HR 1.16, 95% CI 1.08-1.25), major bleeding (HR 1.18, 95% CI 1.08-1.28), and greater cardiac rehabilitation utilization (HR 0.82, 95% CI 0.74-0.92; all p < 0.001). TIA/stroke did not differ significantly. Six-month results were consistent. Both varenicline and bupropion individually showed lower mortality and MACE. A urinary tract infection falsification endpoint showed no between-group differences, supporting matching validity. The pharmacotherapy group had higher rates of new-onset depression, driven predominantly by bupropion recipients. Conclusions: In this propensity-matched real-world analysis, adding prescription smoking cessation pharmacotherapy to NRT after ACS was associated with lower mortality and fewer adverse cardiovascular events, supporting broader integration into post-ACS care pathways.

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Transitions in ENDS and cigarette use among youth in the PATH Study from 2015-2023: a multistate transition modeling analysis

Roberts, O. K.; Jeon, J.; Jimenez-Mendoza, E.; Land, S. R.; Freedman, N. D.; Torres-Alvarez, R.; Mistry, R.; Meza, R.; Brouwer, A. F.

2026-04-15 epidemiology 10.64898/2026.04.14.26349857 medRxiv
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Introduction: Monitoring trends in transitions in the use of electronic nicotine delivery systems (ENDS) and cigarettes among youth is important for understanding the potential public health impacts of these products. Methods: Using a weighted Markov multistate transition model accounting for complex survey design, we estimated transition rates and one-year transition probabilities between never, non-current, ENDS-only, and cigarette use (with or without dual use of ENDS) among 26,744 youth aged 12-17 years who participated in at least two consecutive waves from Waves 2-7.5 (approximately 2015-2023) of the nationally representative Population Assessment of Tobacco and Health (PATH) Study. We also estimated transitions stratified by ages 12-14 and 15-17 years. Results. The one-year probability of ENDS-only initiation from never use among youth peaked in 2017-19 (Waves 4-5) at 4.0% (95%CI: 3.6-4.3%) and was higher for 15-17-year-olds at 5.8% (95%CI: 5.2-6.4%) than 12-14-year-olds at 2.2% (95%CI: 1.8-2.6%). In the following years, ENDS-only initiation rates declined and plateaued, with 2.6% (95%CI: 2.3-3.0%) initiation in 2022-23. Cigarette initiation from never use decreased over 2015-23 from 0.8% (95%CI: 0.6-1.0%) in 2015-16 to 0.1% (95%CI: 0.0-0.2%) in 2022-23. There was an increase in the fraction of youth who transitioned from non-current product use to ENDS-only use from 13.7% (95%CI: 7.5-20.0%) in 2015-16 to 35.1% (95%CI: 25.4-44.8%) in 2022-23, paired with a decrease in non-current use to cigarette use from 20.9% (95%CI: 11.8-30.0%) to 6.3% (95%CI: 1.7-10.8%). Transitions from ENDS-only or cigarette use to non-current use remained relatively constant over time at around 25% and 15% per year, respectively. Conclusion. ENDS-only use initiation has changed over time, peaking around 2019 and subsequently decreasing and plateauing, but cessation rates for both ENDS and cigarettes have remained relatively stable. Thus, interruption of tobacco product initiation may be the most effective approach to reducing tobacco product use among youth.

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Patient Portal Activation Among Neurology Patients in Washington, DC

Streicher, N. S.

2026-04-11 health policy 10.64898/2026.04.08.26350061 medRxiv
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Background and ObjectivesPatient portals have become essential infrastructure for healthcare delivery following the 21st Century Cures Act, yet adoption remains inequitable. Understanding demographic and geographic determinants of portal activation is critical for addressing digital health disparities, particularly among neurology patients who face unique access barriers. We examined the demographic, geographic, and neighborhood-level factors associated with patient portal activation among neurology patients at multiple geographic scales in the Washington, DC metropolitan area. MethodsWe conducted a retrospective cohort study of 72,417 adult neurology patients seen at two academic medical centers sharing an electronic health record in Washington, DC (February 2021-February 2026). We examined portal activation using multivariable logistic regression and geographic analysis at four nested scales: the metropolitan catchment area, DCs eight wards, individual census tracts (via geocoded patient addresses), and individual DC residents. ResultsPortal activation was 64.7% overall. Activation varied by race/ethnicity (Non-Hispanic White 76.1%, Non-Hispanic Black 57.0%, Non-Hispanic Asian 57.6%, Hispanic 55.0%) and geography (DC Ward 2: 82.0% vs. Ward 7: 48.0%). Ward-level educational attainment (r = 0.948), broadband access (r = 0.889), and income (r = 0.811) were strongly correlated with activation. Within individual wards, Non-Hispanic White patients activated at 84-91% while Non-Hispanic Black patients activated at 48-64%, demonstrating that neighborhood resources alone do not explain disparities. DiscussionPatient portal activation is shaped by demographic, socioeconomic, and geographic factors operating at multiple levels. Persistent within-ward racial disparities indicate that geographically targeted interventions must be paired with culturally tailored approaches to achieve digital health equity.

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Trade-offs in Cardiovascular Risk Prediction Using Race and Social Determinants of Health

Hammarlund, N.; Wang, X.; Grant, D.; Purves, D.

2026-04-04 cardiovascular medicine 10.64898/2026.04.02.26350089 medRxiv
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Importance: Health systems are increasingly adopting race-neutral cardiovascular risk prediction tools, yet no study has examined how these choices redistribute preventive treatment at the point of clinical decision-making, particularly for Black individuals who already bear a disproportionate cardiovascular burden. Objective: To evaluate how including race, substituting social determinants of health (SDoH), or excluding both reshapes cardiovascular risk classification, calibration, fairness, and clinical decisions. Design: Retrospective cohort study with repeated cross-validation and integrated decision-focused evaluation, using CARDIA study data with baseline measures from 2010 and cardiovascular outcomes through 2021. Setting: Community-based longitudinal cohort recruited across multiple U.S. cities. Participants: 3,241 Black and White adults without known cardiovascular disease at baseline. Main Outcomes and Measures: Three models predicting 10-year incident cardiovascular disease were compared on predictive performance, calibration, fairness metrics, and realized clinical utility at the ACC/AHA 7.5% preventive treatment threshold. Results: Among 3,241 participants (46% Black, mean age 50 years, 6.9% CVD incidence), overall performance was similar across models (AUC 0.762 to 0.768). Predictor choice substantially reshaped clinical decisions at the guideline threshold. The SDoH-based model improved parity metrics but produced systematic underprediction and concentrated new overtreatment among Black participants. The clinical-only model further improved parity metrics but generated new undertreatment, with four cases of untreated CVD and none avoided. No single evaluative dimension captured the full equity consequences. Conclusions and Relevance: Parity metrics improved under both race-neutral models, yet both produced clinical harms concentrated among Black participants not apparent in population-average metrics. The case for race removal has rested on conceptual grounds, but comprehensive empirical evaluation is necessary before health systems can be confident their model choices truly serve those most at risk.

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Characteristics and Correlates of Older Smokers Experiences with E-Cigarette-Related Content on Social Media: Findings from a U.S.-Based Survey

Dycus, R.

2026-04-11 public and global health 10.64898/2026.04.07.26350354 medRxiv
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BackgroundDespite their potential to serve as a reduced-harm alternative to combustible tobacco, e-cigarette take-up remains low among older (45+) adult smokers, especially in the U.S. While social media is a known driver of vaping attitudes and behaviors in younger populations, its influence on older smokers is poorly understood. This paper provides the first focused analysis of e-cigarette-related social media exposure in this population, documenting its prevalence, characteristics, and attitudinal correlates. MethodsData come from an opt-in survey of U.S. adults (N = 974) recruited via Prolific, comprising three groups: (i) non-vaping smokers aged 45+ (N = 484), (ii) former-smoking vapers aged 45+ (N = 149), and (iii) any-vaping-status smokers aged 18-35 (N = 341). Descriptive statistics, weighted to U.S. population benchmarks, characterize self-reported exposure to e-cigarette-related content on social media. Logistic regressions estimate associations between exposure and intentions for future e-cigarette use, e-cigarette harm perceptions, and related attitudes. ResultsOlder smokers (35.3%) reported exposure to e-cigarette-related content on social media less frequently than both older vapers (44.0%) and younger smokers (72.0%). For older smokers, e-cigarette health risks were the most frequently reported topic of content viewed, followed by youth vaping and e-cigarette addiction. Among this group, exposure was positively associated with stated intentions for future e-cigarette use. Exposure was not significantly associated with perceived e-cigarette harms for any group. ConclusionsFindings provide suggestive evidence that social media exposure may promote e-cigarette adoption among older smokers. However, the cross-sectional design limits causal inference, and the observed associations may reflect selection bias or reverse causality. If a causal relationship exists, the patterns observed suggest that exposure influences e-cigarette adoption through mechanisms other than updating beliefs about e-cigarette risks. While these results tentatively support the potential of social media as a channel for older-smoker harm reduction, any policy applications must carefully weigh privacy concerns and risks to youth. Rigorous experimental studies are needed to confirm these findings and clarify how social media might be leveraged to improve public health outcomes among older smokers.

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Cannabis, ENDS, and Tobacco Co-use and Co-exposures Among ECHO Adolescents and Emerging Adults

Appleseth, H.; Felt, J.; Cohn, A. M.; Schmidt, R. J.; Croff, J. M.; Leffingwell, T. R.

2026-04-06 public and global health 10.64898/2026.04.03.26350120 medRxiv
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Importance: Understanding patterns of substance use and environmental exposures to tobacco, cannabis, and electronic nicotine delivery systems (ENDS) among youth is critical for developing targeted prevention strategies, particularly as co-use of tobacco, ENDS, and cannabis becomes more prevalent. Objective: To identify latent classes of tobacco, ENDS, and cannabis use, and environmental exposures to these products among adolescents and emerging adults. Design, Setting, and Participants: Data from the Environmental influences on Child Health Outcomes (ECHO) consortium (3rd data release, 2018 to 2022) were analyzed from March 2025 to January 2026. The sample (N=2,786) included early adolescents (ages 11 to 13; n=226, 7.9%), middle adolescents (ages 14 to 17; n=1,248, 43.4%), and late adolescents/emerging adults (ages 18 to 24; n=1,402, 48.7%) from 19 ECHO cohorts. Main Outcomes and Measures: The Youth Risk Behavior Survey, Substance Use module measured experimental and current use of cannabis, ENDS, and tobacco products, as well as daily environmental exposure to tobacco smoke, nicotine aerosols, and cannabis smoke within home and social contexts. A multiple group latent class analysis was used to identify distinct latent classes of substance use and environmental exposure to tobacco smoke, nicotine aerosols, and cannabis smoke and compared class prevalences across early, middle, and late adolescence. Results: Four latent classes were identified, including: No Use/No Exposure (53%), No Use, Polyexposure (10%), Experimental Use/Low Exposure (22%), and Polysubstance Use/High Polyexposure (14%). Cannabis was the most used substance (34% experimental or current use) and the most common source of environmental exposure (20%), followed by ENDS use (26% experimental or current use; 19% environmental exposure) and combustible tobacco (15% use; 19% environmental exposure). The No Use/No Exposure and No Use/Polyexposure classes were primarily made up of early and middle-aged adolescents, whereas the Experimental Use/Low Exposure and Polysubstance Use/High Polyexposure classes primarily consisted of late adolescents and emerging adults. Conclusions: Our study revealed distinct, developmentally patterned groupings of substance use and environmental exposure among US adolescents and emerging adults, highlighting the need for developmentally tailored interventions, messaging, and policies that address both active use and environmental exposure across adolescence.

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A Return-on-Investment Analysis of a Community-Based Diabetes Self-Management Program In New York City

Goldwater, J. C.; Harris, Y.; Das, S. K.; Fernandez Galvis, M. A.; Maru, D.; Jordan, W. B.; Sacaridiz, C.; Norwood, C.; Kim, S. S.; Neustrom, K.

2026-04-23 health economics 10.64898/2026.04.22.26351481 medRxiv
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OBJECTIVE: To evaluate the return on investment (ROI) of a community based Diabetes Self Management Program (DSMP) enhanced with health related social needs (HRSN) screening and referrals, implemented by the New York City (NYC) Department of Health and Mental Hygiene with three community based organizations in highly impacted, under resourced neighborhoods. RESEARCH DESIGN AND METHODS: A retrospective cost benefit analysis from a public sector payer perspective was conducted among 171 adults with type 2 diabetes who completed a six week, peer led DSMP delivered by community health workers (CHWs) in English, Spanish, and Korean during 2018 2019. A time driven, activity based costing model captured direct implementation costs, CHW workforce turnover, and administrative overhead. Monetized benefits included avoided diabetes related complications, reductions in self reported emergency department (ED) visits and hospitalizations, and quality adjusted life year (QALY) gains from improved medication adherence. Univariate sensitivity analyses tested robustness under conservative assumptions. RESULTS: Total program costs were $179,224; monetized benefits totaled $1,824,213, yielding a net benefit of $1,644,989 and an ROI of 918%, approximately $10 returned per $1 invested. Excluding QALY gains, ROI remained 551%. Self reported ED visits declined from 149 to 82 and hospitalizations from 93 to 24 in the six months following intervention. Over 80% of participants reported housing instability; 72% were Medicaid covered and 16% uninsured. Sensitivity analyses confirmed a positive ROI under all conservative scenarios. CONCLUSIONS: A CHW led, community based DSMP integrated with HRSN screening and referrals delivered substantial economic and public health value among adults facing housing instability and structural barriers to care. Findings support inclusion of DSMP as a covered benefit in Medicaid managed care, value based payment arrangements, and housing access initiatives to advance equitable diabetes outcomes.

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Missed Opportunities for Stroke Prevention in Hypertensive Patients: A Retrospective Case-Control Study

Yang, H.; Liu, Y.; Kim, C.; Huang, C.; Sawano, M.; Young, P.; McPadden, J.; Anderson, M.; Burrows, J. S.; Krumholz, H. M.; Brush, J. E.; Lu, Y.

2026-04-22 cardiovascular medicine 10.64898/2026.04.21.26351407 medRxiv
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BackgroundHypertension is the leading modifiable risk factor for ischemic stroke, yet the adequacy of preventative hypertension care in routine clinical practice remains suboptimal. Whether gaps in hypertension management represent missed opportunities for stroke prevention remains unclear. ObjectiveTo evaluate the association between hypertension care delivery and the risk of incident ischemic stroke. MethodsWe conducted a retrospective, matched, nested case-control study among adults with hypertension using electronic health record data from a large regional health system (2010-2024). Patients with a first-ever ischemic stroke were matched 1:2 to controls on age, sex, race and ethnicity, and calendar time. Three care metrics were assessed during follow-up: (1) outpatient visits with blood pressure (BP) measurement per year; (2) number of antihypertensive medication ingredients; and (3) medication intensification score. Conditional logistic regression estimated adjusted odds ratios (aORs). ResultsThe study included 13,476 cases and 26,952 matched controls (N = 40,428). Mean (SD) age was 64.8 (12.2) years, 54.1% were female, and mean follow-up was 2,497 (1,308) days. Cases had fewer BP visits per year (median, 2.50 vs. 3.01; p < 0.001), similar number of medication ingredients (2.00 vs 2.00), and lower treatment intensification scores (-0.211 vs - 0.125). In adjusted models, >5 BP visits per year was associated with lower stroke odds (aOR, 0.55; 95% CI, 0.51-0.59) compared with [&le;]1 visit. Use of 2-3 medication ingredients (vs 0) was also associated with reduced stroke odds (aOR, 0.80; 95% CI, 0.75-0.86), whereas >3 ingredients was not significant. The highest quartile of treatment intensification showed the strongest association (aOR, 0.47; 95% CI, 0.44-0.51). Findings were consistent across subgroup and sensitivity analyses, including strata defined by baseline SBP and follow-up SBP. ConclusionsGreater engagement in hypertension care was associated with lower odds of ischemic stroke, suggesting that gaps in routine management may represent missed opportunities for prevention.

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Area-Level Economic Opportunity Modifies the Income-Health Gradient in the United States

Mishra, A.; O'Brien, R.; Venkataramani, A. S.

2026-03-30 health economics 10.64898/2026.03.27.26349545 medRxiv
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Introduction: Economic opportunity is a core pillar of the American Dream but is not distributed equally across communities. Substantial evidence has identified economic opportunity as an independent social determinant of health, but relatively little is known about opportunity's relationship with other socioeconomic characteristics such as income. Here we address this gap in the literature to examine how area-level economic opportunity modifies the income-health gradient. Methods: We used multivariable ordinary least squares models to estimate the association between self-reported health and economic opportunity across household income levels for working age adults (ages 25-64). Our measures of income and health come from the 2010-2019 Current Population Survey Annual Social and Economic Supplements. Our measure of economic opportunity was drawn from Opportunity Insights and represents the county-averaged national income percentile rank attained in adulthood for individuals born to parents at the 25th percentile of the income distribution. We adjusted for a wide range of individual- and county-level demographic and socioeconomic characteristics. Results: We find that county-level economic opportunity modified the gradient in self-reported health and household income among working-age adults. Effects were particularly pronounced in the lowest income deciles -- an interdecile increase in economic opportunity was associated with closing almost 33% of the gap in health between the lowest and highest income deciles. The results were robust to sensitivity analyses. Conclusion: We show that local area economic opportunity flattens the relationship between household income and health, with lower-income individuals benefitting the most from living in high opportunity areas.

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Bridging the Coverage Gap: State Medicaid Limitations for Cardiac Rehabilitation Programs and the Risk to Disadvantaged Communities

Henson, J. C.; Spears, G. L.; Daughdrill, B. K.; Hagood, J. N.; Vallurupalli, S.

2026-04-05 health policy 10.64898/2026.04.03.26350136 medRxiv
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Background: Cardiac rehabilitation (CR) is a cost-effective, evidence-based intervention that improves outcomes for patients with heart failure (HF), yet access remains inequitable, particularly among Medicaid enrollees. This study evaluates the state-by-state variability in Medicaid coverage for CR services and examines the implications for health equity in vulnerable populations. Methods: We conducted a cross-sectional policy analysis of all 50 U.S. states to assess Medicaid coverage for outpatient CR services billed under CPT codes 93797 (without ECG monitoring) and 93798 (with ECG monitoring). Publicly available Medicaid documents were reviewed and supplemented with direct communication with state Medicaid agencies. States were categorized into full, partial/inconclusive, or no coverage. Geographic trends were visualized through heat maps and contextualized using state-level Medicaid enrollment data. Results: Marked disparities in CR coverage were identified. Only 41 states reimbursed for CPT 93797, and 43 for CPT 93798. Eight states lacked coverage for either code, predominantly in the South and Mountain West, including Arkansas, Georgia, Louisiana, Mississippi, Nevada, and Utah. States with the highest Medicaid enrollment (e.g., Louisiana, Arkansas) often provided no CR coverage, compounding access barriers for high-risk, low-income populations. Conclusions: The absence of standardized Medicaid coverage for CR contributes to systemic inequities in cardiovascular care, disproportionately impacting disadvantaged communities. Aligning Medicaid policies to ensure universal CR access--particularly through tele-rehabilitation and value-based care models--could reduce hospitalizations, improve survival, and promote health equity across the U.S.

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Assessing the Impact of Timing and Coverage of United States COVID-19 Vaccination Campaigns: A Multi-Model Approach

Nande, A.; Larsen, S. L.; Turtle, J.; Davis, J. T.; Bandekar, S. R.; Lewis, B.; Chen, S.; Contamin, L.; Jung, S.-m.; Howerton, E.; Shea, K.; Bay, C.; Ben-Nun, M.; Bi, K.; Bouchnita, A.; Chen, J.; Chinazzi, M.; Fox, S. J.; Hill, A. L.; Hochheiser, H.; Lemaitre, J. C.; Loo, S. L.; Marathe, M.; Meyers, L. A.; Pearson, C. A. B.; Porebski, P.; Przykucki, E.; Smith, C. P.; Venkatramanan, S.; Vespignani, A.; Willard, T. C.; Yan, K.; Viboud, C.; Lessler, J.; Truelove, S.

2026-04-08 public and global health 10.64898/2026.04.07.26349269 medRxiv
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Background Six years after its emergence, SARS-CoV-2 continues to have a substantial burden. The impact of vaccination and the optimal timing of its rollout remain uncertain given existing population immunity and variability in outbreak timing between summer and winter. Methods The US Scenario Modeling Hub convened its 19th round of ensemble projections for COVID-19 hospitalizations and deaths in the United States, where eight teams projected trajectories in each US state and nationally from April 2025 to April 2026 under five scenarios regarding vaccine recommendations and timing. Recommendations had two eligibility scenarios (high-risk individuals only and all-eligible) and two timing scenarios (classic start: mid-August, earlier start: late June). These were crossed to create four scenarios and were compared against a counterfactual scenario with no vaccination. Findings Compared to no vaccination, our ensemble projections estimated 90,000 (95% PI 53,000-126,000) hospitalizations averted in the high-risk and classic timing scenario across the US. Expanding to all-eligible age-groups averted an additional 26,000 (95% PI 14,000-39,000) hospitalizations, which when coupled with the early vaccination timing, was projected to further reduce national hospitalizations by 15,000 (95% PI -3,000-33,000). The majority of teams projected both summer and winter waves. Implications We project COVID-19 will cause significant hospitalizations and deaths in the US in the 2025-26 season and estimate significant benefits from a broad all-eligible vaccination recommendation. The results also suggest an additional benefit is likely to be gained from an earlier vaccination campaign. Funding Centers for Disease Control and Prevention; National Institute of Health (US), National Science Foundation (US)

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Depression Risk With PCSK9 Inhibitors Versus Statins in Hyperlipidemia

Lee, M.-J.; Li, C.-J.; Chang, R.; Lin, Y.-F.; Huang, C.-W.

2026-04-06 cardiovascular medicine 10.64898/2026.04.05.26350195 medRxiv
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Background Hyperlipidemia is a major risk factor for cardiovascular disease and is increasingly linked to depression, which is associated with adverse cardiovascular prognosis. As proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are increasingly used for lipid lowering, their neuropsychiatric safety profile compared with established therapies remains uncertain. Objectives This study aimed to compare the risk of incident depression associated with initiation of PCSK9 inhibitor therapy vs statin therapy among adults with hyperlipidemia. Methods In this population-based cohort study, we emulated a target trial using a new-user active-comparator design and real-world data from the TriNetX research network from July 1, 2020, to June 30, 2025. Adults with hyperlipidemia who newly initiated PCSK9 inhibitors or statins were included. The exposure was initiation of PCSK9 inhibitor therapy versus statin therapy. Propensity score matching was performed, yielding 17,805 patients in each group. The primary outcome was incident depression. Cumulative incidence was estimated using the Kaplan-Meier method, and hazard ratios (HRs) with 95% confidence intervals (Cis) were estimated using Cox proportional hazards models. Results Among 35 610 propensity score-matched patients, the mean age was 65.4 (10.6) years and 46.7% were female. During a mean follow-up of 35.0 (21.2) months, incident depression occurred in 546 patients (3.1%) initiating PCSK9 inhibitors and 981 patients (5.5%) initiating statins. The 5-year cumulative incidence of depression was 5.84% for PCSK9 inhibitor initiators and 7.91% for statin initiators. PCSK9 inhibitor initiation was associated with a lower risk of incident depression (HR, 0.74; 95% CI, 0.67-0.82), corresponding to a 5-year number needed to treat of 46. The association was observed for major depressive disorder (HR, 0.71; 95% CI, 0.63-0.80) but not for dysthymic disorder or adjustment disorder. Consistent associations were observed across prespecified subgroups and sensitivity analyses, and the lower depression risk associated with PCSK9 inhibitor initiation remained regardless of comparator statin intensity or lipophilicity. Conclusions In this real-world target trial emulation, initiation of PCSK9 inhibitor therapy was associated with a lower risk of incident depression compared with statin therapy among adults with hyperlipidemia. Further prospective studies are warranted to confirm these findings and clarify underlying mechanisms.

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Declining Pediatric Representation in NIH Artificial Intelligence and Machine Learning Funding, 2020-2024

Phillips, V.; Woodwal, P.

2026-04-11 health policy 10.64898/2026.04.08.26350420 medRxiv
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BackgroundArtificial intelligence and machine learning (AI/ML) are among the fastest-growing domains in NIH research funding, but whether children have shared equitably in this expansion is unknown. We characterized pediatric representation in NIH AI/ML funding from fiscal years (FY) 2020 to 2024. MethodsNIH grant data were obtained from Research Portfolio Online Reporting Tools Expenditures and Results bulk files for FY2020 to FY2024. AI/ML grants were identified using the NIH Research, Condition, and Disease Categorization "Machine Learning and Artificial Intelligence" category, and pediatric grants using the "Pediatric" category. Subprojects were excluded. Grants were deduplicated within each fiscal year by core project number for trend analyses and across all years retaining the most recent fiscal year for cross-sectional totals. Disease areas were identified by keyword searches of titles and abstracts. ResultsAcross FY2020 to FY2024, 5,624 unique NIH AI/ML grants totaling $3,371 million were identified. Of these, 836 grants (14.9%) were classified as pediatric, representing $401 million (11.9%) of total NIH AI/ML funding. Although this share was consistent with the historically reported overall NIH pediatric funding baseline of approximately 10% to 12%, it remained substantially below the US pediatric population share of approximately 22%. The pediatric share of NIH AI/ML funding declined from 12.3% in FY2020 to 10.8% in FY2024, despite growth in absolute pediatric funding. Indexed to FY2020, pediatric AI/ML funding grew approximately 2.6-fold compared with 3.0-fold growth in the total portfolio. Across disease areas, unadjusted adult/general-to-pediatric funding ratios ranged from 2.0-fold in mental health to 9.8-fold in cancer. ConclusionsPediatric representation in NIH AI/ML funding remained low and declined over time as the overall portfolio expanded. These findings suggest that growth in NIH AI/ML investment has not been matched by proportional gains for pediatric research.

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Patient perspectives on living with hypertension: Social media listening analysis across predominantly high-income countries

Di Somma, S.; Gervais, R.; Bains, M.; Carter-Williams, S.; Messner, S.; Onsongo, N.

2026-04-23 cardiovascular medicine 10.64898/2026.04.22.26351483 medRxiv
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Background: Chronic conditions such as hypertension can significantly disrupt daily life and emotional wellbeing. The interaction between patients' perceptions, adherence to antihypertensive medication and quality of life (QoL) remains underexplored outside structured clinical settings. Objectives: To capture unprompted patient perspectives and assess whether hypertension affects QoL and to investigate if patient reported experiences are associated with self-reported antihypertensive medication adherence. Methods: Social media listening (SML) study analyzing 86,368 anonymized posts from individuals with hypertension in 12 countries, collected between January 2022 and May 2024. Posts from 11 countries (n=81,368) were analyzed using artificial intelligence-enabled natural language processing. Posts from China (n=5,000) were analyzed separately using a harmonized framework. Quantitative and qualitative methods assessed variations by country, age, and gender, and associations between emotional expression and antihypertensive medication adherence. Results: Across the 11-country core sample, 45% of posts mentioned at least one QoL impact, most commonly worry/anxiety (11%). Impacts varied across countries. Among 8,096 posts with age identified, individuals <40 years reported emotional balance impacts in 28% of posts versus 22% among those aged 40+. Work/Education impacts were mentioned in 17% of posts by those <40 years vs 12% in 40+. Among 7968 posts explicitly referencing adherence, expressed worry was associated with stricter adherence (62% association score), as were structured routines (79% score), home monitoring (77%), dietary changes (77%), and exercise (71%). In contrast, sadness/depression was associated with inconsistent adherence (71%), as were forgetfulness (79%), side effects (73%), and cost/insurance concerns (65%). Conclusions: These results emphasize the importance of the psychological and emotional impact of hypertension, including on adherence to medication regimens, reinforcing the value of a holistic approach to patient care.

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County-level decarceration atlas: mechanisms, prevalence, and dynamics of decarceration across 2,870 U.S. counties, 1999-2019

Liu, Y. E.; Li, B.; Warren, J. L.; Gonsalves, G. S.; Wang, E. A.

2026-04-04 public and global health 10.64898/2026.04.02.26349309 medRxiv
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Decarceration, the process of reducing incarceration rates, is increasingly viewed as a strategy to improve population health and reduce health inequities. Yet, evidence on its health effects remains limited and may depend on how decarceration occurs. We developed a national decarceration "atlas" to characterize the mechanisms and dynamics of decarceration across more than 2,800 U.S. counties between 1999-2019. Using longitudinal county-level jail and prison data, we identified four operational types of decarceration: reduced pretrial detention, reduced jail time, reduced prison admissions, and reduced prison time. Nearly two-thirds of counties, including most rural counties, experienced at least one decarceration type during the study period. Declines typically followed periods of recent growth and were relatively modest in magnitude, with median reductions of 19% to 38% ten years after onset. The frequency and timing of decarceration types varied by urbanicity, state, and region, with many counties experiencing multiple mechanisms concurrently. Validation against documented case studies of state and local decarceration demonstrated alignment with known legislative and de facto drivers, while revealing substantial sub-state heterogeneity. This atlas provides a scalable framework and hypothesis-generating resource to support comparative studies of decarceration's heterogeneous health effects.

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Minor Consent state policies and COVID-19 vaccination in adolescents

Litchy, C.; Semprini, J.

2026-04-11 public and global health 10.64898/2026.04.10.26350608 medRxiv
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Background Ever since the COVID-19 vaccine became available, vaccinations in adolescents lagged behind adults. Whether adolescent vaccination rates were higher in states with "Minor Consent" policies remains unknown. Methods We accessed adolescent (aged 12-17) county-level vaccine administration data from the CDC (12/2020-05/2023). Our outcomes were COVID-19 vaccination counts for: 1) initial dose, 2) completed series doses, and 3) booster doses. Panel Poisson regression models with state and time random effects, seasonal fixed effects, log-population offsets, and adult vaccination rates were estimated to calculate incidence rate ratios (IRR), testing the association between residing in a state with a Minor Consent policy and COVID-19 vaccine uptake. Results Overall, for the initial dose and complete series, there was no difference in adolescent COVID-19 vaccination between states with or without Minor Consent policies. However, we found that Minor Consent policies were associated with lower COVID-19 booster doses (IRR = 0.582; 95% CI: 0.409, 0.828; p = 0.0026). This association was not found in urban counties (IRR = 0.867; CI = 0.722, 1.043; p = 0.1295), but only in rural counties (IRR = 0.541; CI = 0.401, 0.730; p < 0.0001). Conclusions Minor Consent policies were not associated with higher adolescent COVID-19 vaccination. Rather, we found that Minor Consent policies were associated with lower adolescent vaccination for booster doses in rural counties. Despite minimal evidence of impact, states continue to implement Minor Consent vaccination policies. Future research should investigate not just other vaccines, but also how Minor Consent policies impact parental trust in public health more broadly.

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Age-specific income losses due to HPV-attributable cancers in Singapore

Blythe, R.; Graves, N.; Iyer, N. G.; Peres, M. A.

2026-04-17 health economics 10.64898/2026.04.16.26351014 medRxiv
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Introduction The link between Human Papillomavirus (HPV) and cancer is well-established. In Singapore, bivalent HPV vaccines are subsidised for females, but not males. Economic analysis of HPV vaccination has generally assessed the costs to the health system, but this may not be as relevant to individual decision-making as potential lost income. We estimated the impact of bivalent HPV 16/18 vaccination on sick leave, unemployment, and premature mortality as a function of age and sex to understand the broader impact of HPV-related cancers. Methods We developed a population-level economic model to estimate lifetime income losses by diagnosis age, sex and cancer type. We applied sex- and cancer-specific Cox regressions to the Singapore Cancer Registry for annual predicted survival from 1992 to 2022. These were combined with census and employment data to estimate HPV-associated income losses in Singapore. Attributable fractions and vaccine effectiveness data for HPV 16/18 from the literature were used to estimate the effectiveness of bivalent HPV vaccination. Structural sensitivity analysis examined the role of 80% population coverage conferring herd immunity. Results The registry contained 17,294 individuals with an HPV-associated cancer diagnosis. Lost income was greatest for cervical cancer due to its high prevalence, however the losses per diagnosis were highest for oropharyngeal cancer. Bivalent HPV vaccination led to income benefits of $SGD1,397 [$895 to $1,838] in girls and -$62 [-$76 to -$48] in boys. A gender-neutral HPV vaccination of 80% of 15-year-old Singaporeans, conferring herd immunity, would have lifetime income protective benefits of $24.4m [$14.2m, $33.7m] per cohort, a five-fold return on investment. Conclusions In addition to avoiding healthcare costs and lost quality of life, parents should consider vaccination as a means of avoiding potential income losses. A national policy of gender-neutral HPV vaccination could deliver substantial income protection due to both individual vaccine protection and herd immunity.

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Religious beliefs and practices, political orientation, and distrust in healthcare predict attitudes toward mRNA vaccines in the United States

Solomon, E. D.; Chin, E. G.; Baldwin, K.; Baker, L. L.; DuBois, J. M.

2026-04-07 genetic and genomic medicine 10.64898/2026.04.06.26350267 medRxiv
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Religion has contributed to societal divides regarding COVID-19 mRNA vaccines. In this study, we conducted a secondary analysis of a survey of U.S. adults (N=4939) focused on how religious affiliations, beliefs, and practices impact attitudes toward genetic and genomic activities, one of which was mRNA vaccines. The dataset included large samples of participants from six religious groups in the U.S. (Black Protestant, Catholic, Evangelical Protestant, Jewish, Mainline Protestant, and Muslim), as well as individuals who were atheist, agnostic, or spiritual. ANCOVA results indicated that Evangelical Protestant participants showed significantly less support for mRNA vaccines than other groups, while atheist participants were the most supportive. Muslim participants had the highest concerns, whereas atheist participants had the lowest. Regression analyses indicated the strongest predictors of support for mRNA vaccines were more spiritual community support for community health, followed by higher acceptance of evolution, more liberal political orientation, less distrust toward the healthcare system, higher frequency of attending religious activities, higher income, lower fundamentalist religious beliefs, and more spiritual community support for liberal reproductive and end of life views. The strongest predictors of concerns about mRNA vaccines were more distrust toward the healthcare system and more conservative political orientation, followed by less spiritual community support for community health, stronger beliefs about God in the body, more fundamentalist religious beliefs, and lower knowledge of genetics. The large sample size, and examination of a broad array of religious variables alongside distrust and political orientation offer new insights. These findings add to the literature on the culture wars surrounding mRNA vaccines, and can perhaps aid in future efforts to build trust and relationships between public health and religious communities.

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Greater intergroup bias in vaccination attitudes among physicians than the general public

Murakami, M.; Ohtake, F.

2026-04-25 infectious diseases 10.64898/2026.04.23.26351641 medRxiv
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While vaccination conflicts have become apparent, physicians' attitudes toward those with differing views remain unclear. Through an online survey of 492 physicians and 5,252 members of the general public in Japan in February 2026, we investigated attitudes toward four vaccines (influenza, measles, HPV, and COVID-19). Intergroup bias was assessed as ingroup minus outgroup attitudes using a feeling thermometer. Multilevel regression examined associations with agreement group and physician status. Intergroup bias was significantly positive in both agreement and disagreement groups across all vaccine types, and was higher in the agreement group. Physicians exhibited higher intergroup bias than the general public. These findings indicate that vaccination conflict is bidirectional: physicians, often viewed as targets of hostility from vaccine-hesitant individuals, themselves exhibit greater intergroup bias toward those with opposing views. Interventions to raise physicians' awareness of their own bias, alongside communication strategies for vaccine-hesitant individuals, are needed.

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Closing the Survival Gap: Population-Level Impacts of Digitally-Coordinated Naloxone Distribution on Opioid-Involved Mortality in the Texas Gulf Coast

Goodman, M. L.; Maknojia, S.; Sciba, A.; Robertson, D.; Keiser, P.

2026-04-27 public and global health 10.64898/2026.04.24.26351679 medRxiv
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Background: Opioid-related mortality in Texas has escalated dramatically, increasingly driven by illicitly manufactured fentanyl. To address local surges in mortality, the Galveston County Health District deployed the Galveston County Opioid Defense Effort (GCODE) in July 2023, leveraging digitally integrated surveillance data from emergency medical services (EMS) and the Medical Examiner to provide targeted naloxone distribution in identified overdose hot spots. Methods: Using a segmented interrupted time series (ITS) design and Poisson regression with robust standard errors, we evaluated the population-level impact of GCODE on opioid-involved mortality through the end of 2025. Data were sourced from the Galveston Area Ambulance Authority (GAAA) and vital statistics (ICD-10 codes). We assessed mortality trajectory changes, the observed fatality ratio among EMS-detected opioid events (the Survival Gap), and demographic and geographic covariates. Results: The Poisson ITS model included 519 weekly observations (N = 14,827 tract-weeks across 101 census tracts). Pre-intervention, opioid mortality increased by 0.16% weekly (IRR = 1.0016; 95% CI: 1.000-1.003; p = 0.011). Following GCODE deployment, the mortality trajectory reversed to a sustained 0.55% weekly decrease (IRR = 0.9945; 95% CI: 0.990-0.999; p = 0.021). The observed fatality ratio among EMS-detected events declined from 7.59% (preintervention mean; SD = 0.111) to 1.71% (post-intervention; SD = 0.042; Chi^2 = 19.824; p = 0.0001). Opioid decedents were significantly younger than the general mortality population (OR = 0.945 per year of age; p < 0.001), and were descriptively more likely to lack documented race/ethnicity data (41.23% vs. 8.27% Unknown; p < 0.001), limiting equity analysis. Conclusions: The findings are consistent with GCODE having meaningfully reduced opioid mortality by substantially lowering event-level lethality. These results suggest that targeted, digitally coordinated harm reduction can decouple overdose incidence from fatal outcomes, with implications for harm reduction program design in structurally constrained environments.