American Journal of Preventive Medicine

Background: The impact of the Inflation Reduction Act (IRA) upon late-stage developments has been assumed to be limited. The Congressional Budget Office's IRA analysis excluded post-approval innovation, potentially overlooking substantial economic risks to drug developers and declines in the availability of treatments in areas of high unmet medical need such as oncology. Methods: A total of 1148 secondary trials from 364 FDA-approved medicines, published from 2018 to 2025, were obtained from Biomedtracker and clinicaltrials.gov. Using fractional multinomial logit, we model the share distribution of secondary indication studies across 19 disease groups and assess the change in this distribution post-IRA. We also assessed the number of secondary treatment studies pre- vs. post-IRA using multiple linear regression. Results: After the IRA's introduction, small molecule follow-on studies in oncology exhibited a statistically significant 35% decline (R2 = .48, p < 0.014) and lead indication small molecule oncology approvals exhibited a statistically significant 27% decline (R2 = .70, p < 0.002). We also find a statistically significant 14% decline in the share of orphan oncology studies pre- vs. post-IRA (p<0.001). Research Conclusions: This study's results refute claims that the IRA would have minimal negative effects on patient access or late-stage biopharmaceutical R&D. We hope this study reinvigorates debate about the law's unintended consequences and encourages thoughtful policy solutions, as the IRA manifestly creates disincentives that negatively impact patients seeking needed new medicines, particularly those requiring cures addressing metastatic late-stage cancers.

IntroductionAlthough prior studies suggest e-cigarette use is associated with worse mental health, it remains unclear whether these associations persist independent of diagnosed depression and how tobacco use and depression jointly affect health-related quality of life. Although the long-term health risks of vaping are still unknown, self-reported health is a reliable measure of quality of life. This study provides the first health utility estimates of the independent and combined effects of cigarette use, e-cigarette use, and depression on health-related quality of life. MethodsWe analyzed 2022-2023 Behavioral Risk Factor Surveillance System data on health-related quality of life as measured by self-reported physically or mentally unhealthy days in the past 30 days. The average number of unhealthy days was estimated by age, gender, smoking status (current versus non-smoking), depression status (received a prior diagnosis), and current e-cigarette use status (every day or some day use). We converted the number of overall healthy days into EQ-5D utility scores by age-specific percentile matching of BRFSS and MEPS distributions, a method developed by Jia and Lubetkin. ResultsCigarette use, e-cigarette use, and depression were each associated with worse health-related quality of life. Mentally unhealthy days increased with the accumulation of these conditions. Associations with physically unhealthy days followed a similar pattern, particularly among younger adults, although the magnitude of association was smaller. E-cigarette use alone was associated with 2.0-4.2 (95% CI: 2.0-4.6) additional mentally unhealthy days per month across all age groups. Notably, e-cigarette use was independently associated with poorer mental health among adults aged 18-64 with or without diagnosed depression. After accounting for smoking and depression status, e-cigarette use was associated with disutility scores of 0.011 in men and 0.015 in women among young adults, with the largest losses observed when multiple conditions co-occurred. ConclusionE-cigarette use is associated with poorer health-related quality of life, particularly among younger adults, and these effects are amplified when combined with cigarette use and depression. Quantifying these joint impacts as health utility losses highlights the importance of addressing e-cigarette use within integrated tobacco control and mental health policies, especially for young populations.

Introduction: Even though state minimum wage (MW) is a policy lever that affects income and poverty and can prevent of violence, no prior study has comprehensively evaluated its impact in the United States (US). In this study, we estimated the impact of at least a $1 USD increase in state MW above the federal MW on overall, firearm, and non-firearm homicide mortality and examined its impact on racialized inequities. Methods: We conducted a quasi-experimental study using controlled interrupted time series (CITS) and synthetic controlled interrupted time series (SCITS) approaches to examine immediate and sustained impact of state MW increases. We used state-month level homicide victimization mortality data from 2010-2019. Homicide victimization death was identified using International Classification of Disease codes, 10th revision. State MW data was obtained from the Bureau of Labor Statistics. Results: Demographic and social variables from intervention, never-exposed, and always-exposed states were similar to each other and representative of the total US population from all 50 states. The CITS results show that after MW increases in the intervention states, these states experienced a sustained decline of -0.22 (-0.37, -0.07) homicide victimizations/ 100,000 person-years/ year relative to the never-exposed states and -0.39 (-0.59, -0.18) relative to always-exposed states. This resulted in 5,657 fewer homicide victimization deaths in the intervention states over four years of post-MW increase period compared to the never-exposed states. SCITS results were similar to the CITS results, and the majority of sustained declines were observed in firearm-related deaths and among Black population. Conclusion: MW increase was associated with a reduction in homicide victimization rates, which were robust in multiple sensitivity analyses, more pronounced for firearm-related homicide deaths, and reduced homicide victimization inequities for Black Americans.

Objective: Hispanic/Latinx populations in the U.S. experience higher rates of chronic disease linked to physical inactivity, yet digital health interventions remain largely inaccessible to more than 16 million Hispanic/Latinx adults with limited English proficiency. While large language models (LLMs) offer scalable personalization, their use in non-English behavioral coaching is unexplored. This study introduces MHC-Coach-ES, a Spanish-language LLM fine-tuned on the Transtheoretical Model (TTM) of behavior change. Materials and Methods: We fine-tuned Llama 3-70B-Instruct using a two-stage pipeline. First, the model was adapted to Spanish health and motivational language using a 2.21-million-token corpus. Second, it was instruction-tuned on 3,268 translated human written messages to align the model with the Transtheoretical Model (TTM) of Behavioral Change. We compared MHC-Coach-ES with Llama 3-70B-Instruct and translated human-expert messages using a forced-choice preference survey (N = 77) and blinded expert review (N = 2). Results: Spanish-speaking participants significantly preferred MHC-Coach-ES messages over translated human-expert messages (81% preference, P<0.001). Linguistic analysis showed that MHC-Coach-ES produced more temporally anchored messages than the base model (65% vs. 20%), while maintaining readability. In blinded evaluation, clinical experts rated MHC-Coach-ES higher for alignment with Transtheoretical Model stages than human-expert messages (4.83 vs. 4.38 out of 5). The base model also outperformed translated expert messages across preference and expert ratings. Conclusions: Generative AI can operationalize behavioral science frameworks in Spanish, offering a scalable approach to reducing health disparities. The strong performance of both MHC-Coach-ES and the base model highlights the promise of generative and personalized approaches over translation-based localization for theory-driven behavioral interventions.

IntroductionSmoking 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. MethodsWe 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. ResultsAfter 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. ConclusionsIn 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.

ObjectiveTo characterize the magnitude and geographic distribution of commercially negotiated hospital facility rates for fourteen common interventional radiology (IR) procedures using publicly posted Hospital Price Transparency Machine-Readable Files (MRFs), and to describe the relationships between state-level commercial pricing, population rurality, and within-system rate uniformity. MethodsIn this cross-sectional observational analysis, we examined hospital-weighted commercial rate observations from U.S. hospital MRFs for fourteen IR procedures spanning image-guided drainage, embolization, peripheral vascular intervention, dialysis access maintenance, and percutaneous spine. The unit of analysis was one observation per distinct negotiated rate per state-CPT cell, deduplicating multi-facility same-system reporting in which two or more hospitals posted identical rate, range, and payer-count tuples. Outliers were excluded using transparent absolute and CMS-relative bounds. State-level statistics were computed where [&ge;]5 distinct hospital-system observations were reported. Commercial rates were compared to CY 2026 CMS Outpatient Prospective Payment System (OPPS) facility payments. Relationships between state-level commercial rate and 2020 U.S. Census percent-rural population were assessed by Spearman rank correlation. ResultsAcross 14 procedures, state-level commercial median rates varied 3.7-to 8.3-fold between the highest- and lowest-priced states. The largest spreads were observed for fem-pop angioplasty (CPT 37224, 8.3-fold), fem-pop atherectomy (37225, 8.1-fold), and iliac stenting (37221, 7.1-fold). National median commercial rates ranged from 1.34x (PAE/GAE) to 3.60x (paracentesis) the corresponding CMS OPPS facility payment. Across all 14 procedures, the relationship between state percent-rural and median commercial rate was negative (mean Spearman {rho} = -0.46, range -0.33 to -0.80; 14 of 14 codes negative), with the most-rural quartile of states showing a median commercial rate 42% below the most-urban quartile. Deduplication identified 660 multi-facility groups in which a single negotiated rate was applied across two or more affiliated hospitals within a state. DiscussionSubstantial state-level variation in commercially negotiated facility rates exists for common IR procedures, with consistently lower rates in more rural states. Within-system rate uniformity is a frequent feature: many regional health systems post identical commercial rates across multiple owned facilities. The findings are consistent with prior literature linking commercial pricing to market structure and support continued investment in price transparency as a precondition for informed decision-making.

Background: Xylazine and medetomidine are veterinary sedatives increasingly detected as adulterants in the U.S. illicit drug supply. In response, several states have scheduled xylazine. Whether these policies are associated with subsequent changes in xylazine and medetomidine detections remains unclear. Methods: We conducted a state-level, semiannual, serial cross-sectional study using National Forensic Laboratory Information System (NFLIS) data from 1999 to 2025. The primary outcomes were xylazine and medetomidine reports per 100,000 NFLIS drug reports. We used staggered difference-in-differences event-study models to estimate changes in report rates after xylazine scheduling. Sensitivity analyses excluded Florida and expanded the treatment definition to include states that criminalized xylazine without formal scheduling. Falsification analyses examined steroid and antidepressant reports as negative-control outcomes. Results: NFLIS recorded 101,987 xylazine reports and 12,085 medetomidine reports. Xylazine scheduling was not associated with a significant change in xylazine report rates (ATT, 2,872.29 per 100,000; 95% CI, -2,024.63 to 7,769.21; p=.250). In contrast, xylazine scheduling was associated with a significant increase in medetomidine report rates (ATT, 1,536.51 per 100,000; 95% CI, 211.14 to 2,861.88; p=.023). Sensitivity analyses produced similar findings. Negative-control outcomes showed no significant changes. Conclusions: State xylazine scheduling was associated with increases in medetomidine reports but no significant change in xylazine reports. These findings suggest that scheduling may be followed by changes in adulterant composition rather than reductions in overall 2-adrenergic agonist involvement. Our study highlights the importance of monitoring the unintended effects of xylazine scheduling and supporting continued investment in public health surveillance, drug checking, and harm reduction services.

Background Chinas rapidly ageing population has increased the demand for long-term care insurance (LTCI), while the sustainability of current financing arrangements remains uncertain. Understanding willingness to pay (WTP) for improved LTCI services among LTCI beneficiaries or primary family caregivers may provide empirical evidence for discussions on acceptable and sustainable contribution mechanisms. Methods We conducted a contingent valuation survey among 278 LTCI beneficiaries or primary family caregivers in Panjin City, Liaoning Province, China. An iterative bidding game with randomized starting bids was used to elicit monthly WTP for a predefined LTCI service improvement scenario. Tobit regression models with heteroskedasticity-robust standard errors were used to estimate factors associated with WTP, including household income, disability severity, satisfaction with current services, and demographic characteristics. Results The mean monthly WTP for improved LTCI services was approximately CNY 300, compared with the current average monthly premium of approximately CNY 120. The median WTP was CNY 250. Higher household income was positively associated with WTP. Compared with participants with monthly household income below CNY 5,000, those in the highest income group above CNY 30,000 reported an additional WTP of CNY 178.9. More severe disability was also associated with higher WTP, whereas greater satisfaction with current LTCI services was associated with lower WTP. These associations were generally consistent across alternative model specifications. Conclusions LTCI beneficiaries or primary family caregivers in this Chinese pilot city reported a willingness to contribute more for improved LTCI services, particularly among those with higher income, greater care needs, or lower satisfaction with current services. These findings may inform discussions on differentiated contribution arrangements and service quality improvements in LTCI financing reform. However, the results should be interpreted cautiously because the study was conducted in a single pilot city and relied on stated-preference data.

IntroductionMonitoring 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. MethodsUsing 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. ResultsThe 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. ConclusionENDS-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. What this paper addsWhat is already known on this topic: O_LITransitions in cigarette and ENDS use have changed over time, with youth more likely to adopt ENDS and less likely to adopt cigarettes than older age groups. C_LI What this study adds O_LIWe found that ENDS initiation among youth peaked around 2019 and was higher for those 15-17 years than 12-14 years. There were few significant differences between the two age groups for other transitions. C_LIO_LICigarette initiation among youth declined over this period. Cessation rates for both ENDS and cigarettes have remained relatively stable. C_LI How this study might affect research, practice or policy O_LITobacco control efforts should prioritize preventing all tobacco and nicotine product initiation among youth. C_LI

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.

ImportanceThe rapid rise of online sports gambling in the U.S. has been associated with financial harms, raising concern that it may adversely affect population mental health. ObjectiveTo estimate the causal effect of state legalization of online sports gambling on population mental health, including a range of self-reported and registry-based outcomes. Design, Setting, and ParticipantsRepeated cross-sectional study using nationally representative Behavioral Risk Factor Surveillance System (BRFSS) data from 2014-2025 and registry-based mortality records from 2012-2024. We leveraged state-level variation in the legalization of online sports gambling and applied a stacked difference-in-differences with event study design. The analytic sample included 4,660,948 BRFSS respondents and mortality records for virtually all state-years. We estimated effects on all adults and several higher-risk subgroups, including men, young men, and men with lower educational attainment. ExposureState legalization of online sports gambling. Main Outcomes and MeasuresSelf-reported outcomes included poor mental health days, depressive disorder diagnoses, ever binge drinking, number of binge drinking episodes, and marijuana use. Registry-based outcomes included suicide mortality and alcohol-induced mortality per 100,000. ResultsAmong 4,660,948 BRFSS respondents, 48.7% were men, 40.2% had no more than a high school education, and the mean age was 47.6 years. Legalization of online sports gambling had no discernible effect on poor mental health days of all U.S. adults (-0.01 days; 95% CI, -0.16 to 0.14; P=0.88), depressive disorder diagnoses (0.1 percentage points; 95% CI, -0.7 to 0.9; P=0.84), binge drinking, binge drinking episodes, or marijuana use. Meanwhile, mean suicide mortality was 14.1 per 100,000 and mean alcohol-induced mortality was 12.2 per 100,000. Legalization did not affect adult suicides (0.13 deaths per 100,000; 95% CI, -0.71 to 0.97; P=0.76) or alcohol-induced mortality (1.08 deaths per 100,000; 95% CI, -0.58 to 2.73; P=0.21). Results were null among men and higher-risk subgroups of men. Conclusions and RelevanceThe legalization of online sports gambling has not produce detectable population-level changes in a range of mental health outcomes, including reported symptoms, diagnoses, substance use, and registry-based mortality due to suicide or alcohol, in up to 3 years of follow-up. These findings suggest that although online sports gambling may cause financial harm and severe distress for some individuals, legalization has not produced measurable average changes in population mental health over the observed follow-up period. Key pointsO_ST_ABSQuestionC_ST_ABSHas the legalization of online sports gambling affected population-level mental health, including symptoms, diagnoses, substance use, suicides, and alcohol-induced mortality? FindingsIn this repeated cross-sectional study that applied a difference-in-differences design to more than 4.6 million individual-level survey responses and mortality records, the legalization of online sports gambling from 2018-2024 did not affect reported poor mental health days, depressive disorders, binge drinking, marijuana use, suicide mortality, or alcohol-induced mortality. Results were similar among men and higher-risk subgroups of men. MeaningThe legalization of online sports gambling has not produced detectable population-level changes in a broad range of mental health outcomes in up to 3 years of follow-up.

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.

BackgroundNeighborhood social vulnerability may shape cardiovascular health (CVH), but its association with Lifes Essential 8 (LE8), and whether changes in vulnerability track with changes in CVH during midlife, are unclear. We examined cross-sectional and longitudinal associations of the Social Vulnerability Index (SVI) with LE8 and assessed differences by SVI domain, LE8 component, race, and sex. MethodsWe analyzed CARDIA participants at Year 15 (Y15; 2000-2001; n = 3,168; mean age 40 years) and Year 30 (Y30; 2015-2016; n = 2,267; mean age 55 years). Residential addresses were geocoded and linked to 2000 and 2016 SVI. Participants were stratified by SVI quartiles. CVH scores were calculated from LE8 metrics (range 0-100; higher is better CVH), excluding sleep. Using multivariable linear regression adjusted for age, sex, race, and educational attainment, we estimated LE8 differences across SVI quartiles and associations of 15-year SVI change/residential mobility with change in LE8. Cox models estimated incident CVD associations. ResultsHigher SVI was associated with lower LE8 at both exams. Adjusted Q4 vs Q1 differences in overall LE8 were -5.34 points (95% CI, -6.90 to -3.78) at Y15 and -4.60 points (95% CI, -6.51 to -2.69) at Y30. Among the four SVI domains, SES and household characteristics drove most of the disparity in LE8 scores (Y30 Q4 vs. Q1: SES {Delta} = -6.98; household {Delta} = -6.56 points). Component-level differences across quartiles of SVI were largest for nicotine exposure at Y15 (-13.09 points) and physical activity at Y30 (-13.09 points). Changes in SVI and residential mobility were not significantly associated with change in LE8. ConclusionHigher social vulnerability was associated with significantly lower CVH. Socioeconomic and household factors, along with behavioral gaps in nicotine exposure and physical activity, may be key targets for community-level interventions to improve cardiovascular health equity.

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.

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.

PurposeWhen emulating trials of medication initiation using real-world data, there may be ambiguity regarding the most suitable time zero event for the research question of interest. The time zero event must be strongly associated with the clinical indication for treatment, confer a high probability of actual treatment initiation, and be measurable with sufficient temporal precision in the source data. When it is uncertain whether a candidate event will satisfy these three conditions simultaneously, empirical identification of predictors of medication initiation can provide valuable guidance. The objective of this study was to empirically identify predictors of incident atorvastatin initiation to inform the definition of time zero for future target trial emulations. MethodsA retrospective cohort study was conducted using Medicare claims data (study period January 1, 2018 - December 31, 2019). The cohort included statin naive beneficiaries aged [&ge;] 65 years with [&ge;] 12 months of continuous enrollment, as of the study period start date, and at least one new or incident prescription claim after study period start date. Atorvastatin initiation was defined by the first dispensing (index date). Non-atorvastatin initiators (reference group) were sampled at 25%; their index date was a randomly selected date of a new medication dispensing. Candidate predictor variables were ascertained in the 6 months pre-index and included demographics, comorbidities (classified separately from inpatient and outpatient claims), healthcare utilization, and pharmacotherapy. We developed and applied an eight-step procedure to identify independent predictors of incident atorvastatin initiation. ResultsThe study cohort comprised 481,742 incident atorvastatin initiators and 896,575 non-atorvastatin initiators (25% random sample). The strongest predictors of atorvastatin initiation were inpatient admission for cerebral infarction (OR 11.51, 95% CI 10.79-12.27) and myocardial infarction (OR 5.32, 95% CI 5.03-5.62). For example, a White male with a recent inpatient diagnosis of cerebral infarction had a predicted probability of atorvastatin initiation of 82% (95% CI 81-83%). ConclusionThe empirically identified predictors of atorvastatin initiation (acute cardio/cerebrovascular events) align with ACC/AHA guidelines recommending prompt statin therapy for secondary prevention. These predictors satisfy the three key requirements for a valid time zero event and should mitigate selection bias, channeling bias, and residual confounding in future target trial emulations. KEY POINTSO_LIFindings: Acute myocardial infarction and cerebral infarction recorded during an inpatient admission were the strongest predictors of incident atorvastatin initiation among statin-naive Medicare beneficiaries age 65 years and older. C_LIO_LIClinical Context: These findings align with current American College of Cardiology/American Heart Association guidelines that recommend prompt statin therapy for secondary prevention after these acute cardiovascular events. C_LIO_LIImplications for Future Research: Anchoring the time zero event to an inpatient admission for myocardial/cerebral infarction satisfies the three key requirements for a valid time zero event when studying medication initiation: it is strongly associated with the clinical indication for treatment, carries a high probability of actual statin initiation, and can be identified with sufficient temporal precision in administrative data. This approach should reduce channeling bias, selection bias (e.g., immortal time bias) and residual confounding in future target trial emulations. C_LIO_LIBroader Significance: The study provides an empirically derived, high-probability time zero event that can strengthen future target trial emulations using real-world data to assess the safety of commonly used medicines in older adults, a population often underrepresented in randomized trials to obtain regulatory approval. C_LI PLAIN LANGUAGE SUMMARYThis study aimed to identify a clear starting point for future research on the safety of atorvastatin in older adults. Using Medicare claims data from 2018-2019, researchers examined more than 1.3 million beneficiaries aged 65 and older who had not previously taken statins in the last year. They developed a predictive model to determine which patient characteristics were most strongly linked to starting atorvastatin. The strongest predictors were a recent hospital admission for heart attack (myocardial infarction) or stroke (cerebral infarction). These events were associated with a much higher chance of promptly receiving atorvastatin, which aligns with American College of Cardiology and American Heart Association guidelines recommending statin therapy soon after such events for secondary prevention. By using hospital discharge after these acute events as the starting point for future studies, researchers can create comparisons that reduce bias and allow more reliable estimates of atorvastatins effects on potential harms in this vulnerable elderly population.

Background: Black patients and individuals with low socioeconomic status (SES) face significant disparities in accessing curative therapies for hepatocellular carcinoma (HCC), including liver transplantation. This study aimed to develop provider-co-created intervention prototypes in response to patient-identified barriers and recommendations. Methods: A human-centered design session with hepatology and transplant providers at a large academic medical center was conducted. Prior to the session, participants were presented with barriers and preliminary solutions identified through an earlier human-centered design session with Black and low-SES patients. Using structured ideation methods, including brainwriting, challenge mapping, and concept voting, providers co-created intervention prototypes. Final concepts were synthesized from patient insights, provider input, and design methods using affinity diagramming and concept modeling. Results: Nine providers participated in the session. They focused on three key areas for intervention: inefficiencies in transplant pre-evaluation, inadequate social support, and information overload. Solutions included: (1) a structured triage pathway to standardize referrals and reduce delays; (2) a peer navigator model to guide patients through the transplant process; and (3) a multimodal transplant education roadmap to improve comprehension and engagement. These prototypes addressed both patient- and system-level barriers. Conclusions: Protypes developed through provider-led design, grounded in patient-identified barriers and co-created ideas, can yield actionable, scalable strategies to advance equity in HCC care. Future work will refine these prototypes through patient feedback and pilot them in clinical settings.

OBJECTIVETo 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 METHODSA 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. RESULTSTotal 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. CONCLUSIONSA 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.

We examined the impact of COVID-19 pandemic onset (2020 April) on homicide mortality in the United States. We conducted a single interrupted time series analysis using homicide events from the National Vital Statistics System that occurred over six years (2017-2022), with COVID-19 onset as an interruption. Monthly homicide deaths rates were calculated per 100,000 person-years to create a monthly time series. We used autoregressive integrated moving average regression, adjusted for seasonality, to model the immediate and sustained trend changes in the homicide mortality rate ratios due to the pandemic. We stratified models by length of stay-at-home order, race and ethnicity, sex, age, and weapon used to examine effect measure modification. In Jan 2017, the US homicide mortality rate was 5.9/100,000 PY. While there were annual seasonal changes, the overall time trend before April 2020 was stable. However, with COVID-19 onset, the overall homicide mortality rate ratio increased by 32% (95% CI: 0.23, 0.41), which persisted through 2022 without additional trend changes, but with seasonal variations. Immediate increases with stable sustained trends in homicide rates were also observed in most stratified analyses. COVID-19 pandemic onset is associated with US homicide mortality rates immediately increasing and remaining stable and higher afterwards.

Objectives: This meta-review compares methodological and reporting approaches between systematic reviews examining alcohol dose and cardiovascular disease (CVD) and assesses whether alcohol industry involvement is associated with divergent conclusions. Methods: KSR Evidence was searched 6 May 2025 to update a cohort of 60 systematic reviews from previous review. Reviews were included if they examined any dose-response relationship between alcohol consumption and CVD. Two reviewers independently screened records and extracted data on review characteristics, and citations. Methodological quality was appraised using AMSTAR 2. For a matched sample of reviews with and without known alcohol industry funding, the overlap of included primary studies was compared using Corrected Covered Area (CCA) analysis. Results: Thirty additional systematic reviews met the inclusion criteria, yielding 90 systematic reviews (1996-2025). Most (60.0%, 54/90) concluded that alcohol had a cardioprotective effect, whereas 31.1% (28/90) concluded no evidence of protection, and 8.9% (8/90) were inconclusive. Twenty reviews (22.0%) had declared or inferred alcohol industry funding or author connection; all but one reported a protective effect at lower doses, the other was inconclusive. Industry-connected reviews were cited more often (mean 575.9 vs 193.0, p=0.0002) and more commonly examined overall CVD rather than specific conditions (such as hypertension or stroke). Study overlap was low (CCA 2.59%) and 99% of reviews were rated as critically low quality. Conclusions: The fragmented evidence base is of poor methodological quality with selective inclusion of studies. Alcohol industry connections are strongly associated, with conclusions favouring alcohol consumption, highlighting the need for independent high-quality systematic reviews.