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.

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.

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.

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.

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.

OBJECTIVES To quantify socioeconomic inequalities in antibiotic prescribing for common infections in primary care, and assess whether these inequalities arise from differences in consultation frequency, prescribing behaviour, or variation in vaccination uptake, smoking, and body mass index. DESIGN Population based cohort study. SETTING Primary care data from Clinical Practice Research Datalink, England. PARTICIPANTS 17,195,399 children and adults estimated to have been registered with a general practice in 2019. MAIN OUTCOME MEASURES Antibiotic prescribing rates (prescriptions per person-year), consultation rates (consultations per person-year), and probability of receiving an antibiotic prescription following consultation. RESULTS Higher deprivation was associated with higher antibiotic prescribing rates for most respiratory tract indications. In children, prescribing rates were 44.8% (95% confidence interval [CI] 41.9% to 47.7%) higher for upper respiratory tract infections and 47.6% (95% CI 44.2% to 51.3%) higher for lower respiratory tract infections in the most versus least deprived twentile. In adults, prescribing rates for lower respiratory tract infections were 22.7% (95% CI 21.4% to 24.1%) higher in the most deprived twentile. Prescribing rates for other indications showed weak, U-shaped, or negative associations with deprivation. Prescribing inequalities were primarily driven by inequalities in consultation rates rather than probability of receiving antibiotics once consulted. Lower influenza vaccination uptake partly accounted for higher consultation rates for respiratory infections among more deprived children, while smoking prevalence contributed to inequalities among adults. CONCLUSIONS Socioeconomic inequalities in antibiotic prescribing vary by indication type and are largely explained by consultation frequency. Reducing inequalities may require interventions that decrease the need to consult, e.g. improving influenza vaccination coverage in children and reducing smoking among adults, rather than focussing solely on prescribing behaviour.

Background: Self-reported confidence in health information seeking does not reliably predict accurate health knowledge, yet the population-level distribution of this discordance and its demographic predictors have received limited direct study. This study aimed to identify and characterize a Confident-Incorrect phenotype among U.S. adults: individuals with high perceived health information competence who simultaneously hold inaccurate or fatalistic beliefs about cancer. Methods: Cross-sectional analysis of HINTS 7 (N = 7,278). A Confidence Index (3-item digital literacy composite (Cronbach's = 0.674) and an Evidence-Consistent Knowledge Score (factual cancer knowledge minus a cancer fatalism composite; fatalism subscale = 0.563) were computed and combined into a discordance framework. Median-split classification produced four phenotypes. Gaussian Mixture Model clustering with four components provided moderate independent validation (inter-method agreement = 65.2%). Survey-weighted multinomial logistic regression (n = 5,771; McFadden pseudo-R2 = 0.129) examined phenotype predictors. Results: An estimated 20.3% of U.S. adults were classified as Confident-Incorrect. They reported confidence levels similar to Well-Informed adults (z = 0.72 vs. 0.82) but scored 2.8-fold lower on objective cancer knowledge (0.74 vs. 2.06 out of 4) and exhibited the highest cancer fatalism of any phenotype (3.17 vs. 1.65 out of 4). Only 14.3% correctly identified alcohol as a cancer risk factor (vs. 58.8% of Well-Informed adults). Cancer screening rates did not differ meaningfully across phenotypes. Lower education (OR = 0.754), Hispanic ethnicity (OR = 1.788), non-Hispanic Black race (OR = 1.893), higher social media use (OR = 1.097), and lower trust in scientists (OR = 0.749) independently predicted Confident-Incorrect membership. Conclusions: An estimated one in five U.S. adults is overconfident in health information competence while holding substantially inaccurate beliefs about cancer prevention. Cancer screening rates did not follow the expected gradient across phenotypes, a null finding that cautions against inferring immediate behavioral impact from observed belief gaps. Interventions targeting specific factual errors and cancer fatalism are more likely to reach this group than general health literacy programs.

Introduction Stroke is a leading cause of disability and death in adults with type 2 diabetes (T2D). We evaluated the comparative stroke risk in Veterans with T2D initiated on either of two glucose-lowering medications: GLP-1 receptor agonists (GLP-1RA) or SGLT-2 inhibitors (SGLT2i). Patients and Methods We conducted a retrospective cohort study on diabetic Veterans aged 40 and older with no prior history of stroke or transient ischemic attack, who started on a GLP-1RA or SGLT2i between 2014 and 2021. Patients with contraindications or prior exposure to medication were excluded. Using national Veteran health data, we identified 195,072 [SS1.1]eligible individuals and followed them from treatment initiation until stroke, death, loss to follow up, or end of follow up, whichever came first. Primary outcome was incident stroke, and secondary outcomes included ischemic and hemorrhagic stroke. We applied Kaplan-Meier methods and Cox proportional hazards models. Adjusted associations were estimated using inverse probability weighting. Results Both unadjusted and adjusted analyses suggest GLP-1RA users have reduced stroke incidence compared SGLT-2i users[HS2.1] (HR = 0.[HS3.1]67, 95% CI 0.64-0.69; HR = 0.72, 95% CI 0.69-0.75). Similar results were found in secondary outcome and stratified analyses, with GLP-1RA users having reduced stroke risk compared to SGLT2i users for all age groups, chronic kidney disease stages, and hemoglobin A1c levels. Discussion and Conclusion GLP-1RA treatment was associated with a lower risk of stroke compared with SGLT2i treatment in Veterans with T2D. These findings were consistent for ischemic and hemorrhagic strokes, suggesting potential differences in stroke risk between the treatments.

Objectives: To examine COVID19 vaccine uptake among people diagnosed with sexually transmitted and bloodborne infections (STBBI) and reported methamphetamine users in Manitoba, Canada, during the acute phase of the COVID19 pandemic. Methods: We conducted a retrospective matched cohort study using linked population based administrative healthcare, laboratory, and vaccination databases in Manitoba. Individuals aged 16+ years with laboratory confirmed chlamydia/gonorrhea (CT/NG), syphilis, HIV, and/or documented methamphetamine use during the four years prior to March 1, 2020 were included in eight exposed cohorts. Each cohort was matched to unexposed comparators on age, sex, geographic region, and income quintile. The primary outcome was receipt of 2+ COVID19 vaccine doses between December 1, 2020 and March 31, 2022. Poisson regression models estimated adjusted rate ratios (aRRs) and 95% confidence intervals (95% CIs) for vaccine uptake. Results: Compared with matched comparators, most exposed cohorts were less likely to complete the COVID19 primary vaccine series. Individuals in the Syphilis Only (aRR: 0.87, 95% CI: 0.85 0.90), Syphilis Plus (aRR: 0.84, 95% CI: 0.81 0.86), CT/NG Only (aRR: 0.95, 95% CI: 0.94 0.96), CT/NG Plus (aRR: 0.82, 95% CI: 0.80 0.85), Methamphetamine Only (aRR: 0.78, 95% CI: 0.76 0.80), and Methamphetamine + STBBI cohorts (aRR: 0.74, 95% CI: 0.72 0.77) had significantly lower vaccine uptake. The HIV Only cohort did not differ significantly from matched comparators (aRR: 0.98, 95% CI: 0.95 1.01). Lower uptake was concentrated among individuals living in lower-income areas. Conclusions: People diagnosed with STBBI and methamphetamine users in Manitoba experienced significant inequities in COVID19 vaccine uptake, particularly those with STBBI coinfections and concurrent substance use. Integrated vaccination approaches linked with HIV, harm reduction, and addiction services may improve vaccine equity during future public health emergencies.

Introduction Cardiovascular disease (CVD) remains Vietnam's leading cause of mortality, yet no comprehensive national analysis of burden trends and future projections exists. This study characterizes Vietnam's CVD burden from 1990 to 2023 and projects burden through 2050. Methods Using Global Burden of Disease 2023 data, we analyzed CVD prevalence, incidence, mortality, and disability-adjusted life years (DALYs) in Vietnam from 1990 to 2023, stratified by sex and age. Joinpoint regression quantified temporal trends. Decomposition analysis separated contributions of population growth, aging, and epidemiological change. ARIMA modeling, validated against pre-pandemic and COVID 19 periods, projected burden through 2050. Results Despite age-standardized CVD prevalence below global estimates, stroke mortality and DALYs rates exceeded global benchmarks. Age-standardized CVD mortality (ASMR) declined significantly (average annual percentage change [APC]:-1.34%), yet absolute deaths nearly doubled from 121,611 to 223,068. Population aging contributed 140.9% to observed mortality increases while epidemiological improvements averted over 102,000 deaths. Male age-standardized CVD mortality was approximately twice that of females. High systolic blood pressure remained the leading attributable risk factor, while high BMI and alcohol use showed the largest rank escalations. CVD incidence reversed its declining trend during 2019 - 2023 (APC:+0.69%). By 2050, ASMR are projected to decline by 51.0% (218.8 to 107.1 per 100,000 [95%CI: 64.1 - 150.2]), while absolute deaths are projected to increase by 43.4% (206,677 to 296,335 [95%CI: 272,323 - 320,348]). Conclusions Vietnam faces a demographic paradox of improving age-specific outcomes alongside a rising absolute burden driven by population aging, demanding urgent reorientation toward aging-specific prevention, hypertension control, and chronic cardiovascular care.

Background: Statewide immunization data are essential for monitoring vaccination trends and evaluating immunization program impact. In the United States, Immunization Information Systems (IIS) were established in the early 1990s to collect these data; however, operational, legal, and procedural details vary across states and over time. This study summarized differences in IIS characteristics, such as legal requirements and reporting procedures, across U.S. states and jurisdictions over time. Methods: We analyzed survey data from previous work in 2000 and the Centers for Disease Control and Prevention (CDC) in 2012, 2018, and 2024. Our review focused on legislation and reporting requirements for immunization registries across 50 states and 14 jurisdictions, including U.S. territories and Freely Associated States. Results: Between 2000 and 2024, legal frameworks and reporting practices for immunization registries expanded across U.S. states and jurisdictions. The number of states with laws or administrative rules authorizing immunization registries increased from 24 states in 2000 to all 50 states, the District of Columbia, five metropolitan areas, five U.S. territories, and three Freely Associated States in 2024. Over the same period, reporting requirements also became more widespread. The number of states and jurisdictions mandating providers to report immunization records increased from 12 in 2000 to 54 in 2024. Consent policies also changed over time. By 2024, most states and jurisdictions had adopted implicit consent for reporting children's immunization records (41; 64%), while a smaller proportion required explicit parental consent (7; 11%) or implemented mandatory reporting without consent (14; 22%). Discussion: IIS infrastructure and reporting requirements have expanded across U.S. states and jurisdictions over the past two decades, while heterogeneity in consent policies and reporting practices persists. These temporal changes may need to be considered when interpreting IIS data, particularly in longitudinal and cross-jurisdictional analyses.

Objectives In Quebec, Canada, vaccination against human papillomavirus (HPV) has been publicly-funded since January 2016 for gay, bisexual, and other men who have sex with men (GBM) aged [&le;]26 years. The study aimed to analyze data collected in Greater Montreal (Engage study) to evaluate the HPV vaccination program for GBM in Quebec. Study Design Engage is a cohort of sexually active GBM aged [&ge;]16 recruited via respondent-driven-sampling (RDS) in Canada. Participants completed a questionnaire and tested for sexually transmitted infections. Methods RDS-II weights were applied to adjust for recruitment. Subgroups were compared using standardized mean differences. Odds ratios of HPV vaccination and prevalence ratios of anal HPV infection adjusted for potential confounders were estimated using robust regression models. Results Of 1179 participants, 309 were eligible for free HPV vaccination. Vaccine coverage among eligible GBM was 42%. Among those who disclosed same-sex sexual activity and discussed HPV vaccination with their healthcare provider, coverage reached 82%. Anal HPV prevalence among eligible GBM was 26.5% for [&ge;]1 HPV-6/11/16/18 genotypes without significant difference between vaccinated and unvaccinated individuals. Among unvaccinated GBM aged [&le;]26 who were aware of the vaccine, 60% intended to get vaccinated within the next year. Conclusions One to two years after GBM aged [&le;]26 were included in the Quebec HPV vaccination program, 42% of eligible GBM in Greater Montreal had been vaccinated. Anal HPV prevalence was high among GBM. Vaccinees were more likely to self-report a prior STI diagnosis. Offering vaccination to all preadolescents in schools appears essential to maximize vaccination benefits.

Abstract Aims To examine which demographic groups nicotine pouch advertisers chose to target on social media, and which groups Meta's algorithms actually delivered the adverts to. Design Cross-sectional analysis of advert-level data from the Meta Ad Library. Setting Meta social media platforms (including Facebook and Instagram) in the UK. Cases A random sample of 741 nicotine pouch adverts shown in the 12 months up to December 2025, and a comparison sample of 1,125 general adverts. Analyses of reach were restricted to adverts eligible for all genders and adult ages (444 pouch adverts; 674 general). Measurements Outcomes were advertiser-set gender and age-group targeting criteria (i.e., groups eligible to be shown each advert) and estimated advert reach to each group (i.e., number of people who saw each advert). Male-to-female reach ratios within age groups, and reach ratios comparing age groups, were calculated per advert and summarised using geometric means. To assess whether patterns were pouch-specific, comparisons with general adverts were made using ratios of reach ratios (RRR). Findings Advertisers of nicotine pouches targeted a broad sample; most adverts (79.1%; 586/741) were eligible to be shown to all genders, the remainder were restricted to men only. All were restricted to adults (minimum age 18 years) and most (95.6%; 708/741) had no upper age limit. Despite this, of pouch adverts eligible to be shown to all adults, adverts were more likely to reach men, particularly among younger men. Among 18-24-year-olds, pouch adverts reached around ten times as many men as women (RR 10.0, 95% CI 8.7-11.5), compared with a slight skew towards women for general adverts (RR 0.81, 95% CI 0.71-0.94), corresponding to an RRR of 12.3 (95% CI 10.0-15.1). Pouch adverts also showed a skew in reach towards younger age groups. Relative to those aged 35-44 years, reach was higher among 18-24-year-olds for nicotine pouch adverts (RR 1.33, 95% CI 1.17-1.51) but much lower for general adverts (RR 0.19, 95% CI 0.17-0.21), corresponding to an RRR of 7.0 (95% CI 6.0-8.2). Conclusions Nicotine pouch adverts on social media are often eligible to be shown broadly to all demographic groups but are disproportionately delivered to young men.

Background: Dihydropyridine calcium channel blockers (DHP-CCB) are widely prescribed antihypertensives whose adverse effects may trigger unnecessary prescribing of additional medications, termed prescribing cascades (PC). We aimed to identify potential DHP-CCB-induced PCs using high-throughput sequence symmetry analysis (HTSSA). Methods: Using Medicare claims data (2011-2020), we identified new users aged [&ge;]66 years with continuous enrollment [&ge;]360 days before and [&ge;]180 days after DHP-CCB initiation. We screened for initiation of 446 "marker" drug classes within {+/-}90 days of DHP-CCB initiation. Sequence ratios compared marker drug initiation after versus before DHP-CCB initiation. Adjusted sequence ratios (aSR), accounting for prescribing trends over time, were calculated with 95% CIs >1 considered statistically significant. Clinical experts classified statistically significant signals as potential PCs through consensus. Results: Among 388,862 DHP-CCB initiators (mean age 76.6 {+/-} 7.5 years; 62.5% women, 92.3% with hypertension), 82 of 446 marker drug classes had significantly elevated aSRs, of which 24 were classified as potential PCs. Strongest signals ranked by highest aSR included other systemic hemostatics (aSR 2.99; 95% CI, 1.10-8.16), other nasal preparations (aSR 1.99; 95% CI, 1.47-2.70), and drugs used in erectile dysfunction (aSR 1.85; 95% CI, 1.27-2.70). Other clinically relevant signals, ranked by number needed to harm (lowest to highest), included sulfonamides (NNTH 104; 95% CI, 98-111), electrolyte solutions (NNTH 216; 95% CI, 196-241), and osmotically acting laxatives (NNTH 710; 95% CI, 540-1056). Conclusion: Potential PCs identified in this Medicare cohort reflected known and underrecognized adverse effects of DHP-CCBs. Further studies are needed to evaluate the clinical consequences of these PCs.

Background: Non-communicable diseases (NCDs) account for approximately 75% of global deaths, with 79% occurring in low- and middle-income countries. Tobacco use remains a major modifiable risk factor, contributing to more than 8 million deaths annually. In Zambia, evidence on tobacco use among individuals with hypertension, diabetes mellitus, and cardiovascular disease remains limited. This study assessed the prevalence and determinants of tobacco use among adults with NCDs in Zambia. Methods: We conducted a secondary analysis of the 2017 Zambia STEPS survey. The analytic sample included 716 adults aged 18-69 years with self-reported hypertension, diabetes, and/or cardiovascular disease. Tobacco use was defined as current smoking or smokeless tobacco use. Multivariable logistic regression was used to estimate adjusted odds ratios (AORs), accounting for the complex survey design. Results: Among 716 participants, 65.5% had hypertension, 7.7% diabetes, and 26.8% cardiovascular disease; 89.5% had multimorbidity. The overall prevalence of tobacco use was 12.2%. Prevalence was 12.2% among those with hypertension, 5.5% among those with diabetes, and 14.1% among those with cardiovascular disease. Tobacco use was significantly higher among males. Female sex was associated with lower odds of tobacco use (AOR = 0.16, 95% CI: 0.05-0.54, p = 0.004). Secondary education (AOR = 0.15, 95% CI: 0.03-0.66) and higher education (AOR = 0.04, 95% CI: 0.01-0.44) were protective. Alcohol consumption increased the odds of tobacco use (AOR = 5.23, 95% CI: 1.17-23.28). Conclusion: Tobacco use remains common among adults with NCDs in Zambia. Integration of tobacco cessation interventions into routine NCD care is urgently needed.

Importance: Several professional medical societies have removed race and ethnicity from widely used clinical algorithms with implications for millions of patients. Yet the opinions of patients and the public regarding the tensions underlying these pivotal changes have not been systematically explored. Objective: To assess global public opinion on the use of race or ethnicity in clinical algorithms, including preferences for different approaches to algorithmic reform and perceptions of alternative predictors. Design: Cross-sectional survey study. Setting: Multinational opt-in online survey conducted via Prolific in January 2026. Participants: A volunteer convenience sample with quota sampling to achieve approximately equal participation by sex at birth and across ten categories of self-identified race and ethnicity. Main Outcomes and Measures: Self-reported comfort with demographic and social predictors in clinical calculators, with net comfort defined as percentage extremely or somewhat comfortable minus percentage extremely or somewhat uncomfortable; preferences for race-specific versus race-free algorithms; perceptions of algorithmic harm or benefit. Results: Of 1,050 responses, 994 (94.7%) met eligibility criteria. Participants resided in 43 countries with a median age of 32.0 years (IQR, 26-41). Net comfort with the use of race or ethnicity in a hypothetical cancer risk calculator was +62.4% (95% CI: +57.8% to +66.9%), compared with +14.5% (95% CI: +9.1% to +19.9%) for postal or ZIP code. Overall, 87.9% (95% CI: 85.9% to 90.0%) were comfortable with race or ethnicity if a clinician explained its use and only 12.8% agreed race and ethnicity should never be used clinically. Across spirometry, kidney function, and cardiovascular risk calculators, 40.0% to 47.6% preferred race-specific versions, whereas 16.7% to 28.2% preferred race-free alternatives. Furthermore, a substantial proportion disagreed that they were well-represented by race and ethnicity categories, ranging from 22.1% for osteoporotic fracture risk equations to 42.9% for cardiovascular risk equations. These findings were consistent across countries, self-identified race and ethnicity, and among participants reporting prior experiences of racism in healthcare. Conclusions and Relevance: In our diverse multinational survey study, respondents were comfortable with the use of race and ethnicity across application areas, but often did not feel represented by existing categories and were less comfortable with the use of alternatives based on postal or ZIP codes.

Background and Study Aims Fully covered, self expandable metal stents (FCSEMS) are used to treat biliary strictures. FCSEMS with transmural side holes may facilitate cystic duct drainage to mitigate risk of cholecystitis and impact other stent-related adverse events such as migration and occlusion. This study compared rates of premature stent occlusion and acute cholecystitis among patients with biliary strictures who underwent first time placement of a FCSEMS with or without transmural side holes. Patients and Methods This was a retrospective cohort study of adults who underwent endoscopic retrograde cholangiopancreatography (ERCP) with FCSEMS between April 2022 to April 2025 for malignant or benign extrahepatic bile duct strictures. Patients were followed for a minimum of 9 months or through planned stent removal. The primary outcome was premature bile duct occlusion. The secondary outcome was acute cholecystitis among patients with an intact gallbladder. Results Among 219 patients meeting enrollment criteria, 57 (26%) had side holes. The rate of premature stent occlusion was similar with transmural side holes (12%) vs. without (11%, HR 1.02, 95% CI 0.42 2.43, p = 0.96). Among patients with an intact gallbladder (n=129), acute cholecystitis rates were similar with side holes (6%) or without (4.8%, HR 1.01, 95% CI 0.22 4.5, p = 0.99). Conclusions FCSEMS stents with side holes do not reduce rates of premature bile duct stent occlusion or acute cholecystitis compared to FCSEMS without side holes.

While SARS-CoV-2 and influenza continue to place a significant burden on population health, within-household differences in decisions towards vaccination and seeking care across these two pathogens, and across sociodemographic groups, remain largely unexplored. By conducting a household-level survey in Illinois, we found that many individuals made inconsistent decisions about vaccination: among all adults, 29% were vaccinated for only one of COVID-19 or influenza, and among those with children in the home, 39% lived with a child whose influenza or COVID-19 vaccination status differed from their own. A higher proportion of adults were vaccinated against COVID-19 compared to influenza, while the opposite was true for those younger than 18 years old. These differences hold even when accounting for disparities in coverage by age, race/ethnicity, political affiliation, and socioeconomic status. While vaccinated individuals consistently reported wanting to protect themselves or others, those who declined vaccination reported highly heterogeneous reasons ranging from resource constraints to distrust or misconceptions about vaccination. These differences are even more pronounced for COVID-19, with larger partisan gaps and higher refusal driven by safety concerns, lack of trust, or religious reasons than those who decide not to get the influenza vaccine. In contrast to vaccination, the decision to seek medical care when sick showed opposite sociodemographic trends, that are likely attributable to illness severity. Our findings highlight that closing gaps in COVID-19 and influenza vaccination coverage will require an integrative strategy that accounts for diverse motivations, fears, and barriers to access, while addressing social inequalities common to both diseases.