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American Journal of Preventive Medicine

Elsevier BV

Preprints posted in the last 7 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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Sociodemographic and health correlates of reimbursement authorizations for cannabis for medical purposes in Canadian veterans: A cross-sectional study linking the Life After Services Studies 2019 and Health Administrative Databases

Kendzerska, T.; Reyes, J.; Poirier, N.; Poirier, A.; Cull, A.; Murkar, A.; Saymeh, M.; Belanger, S.; Williams, M.; Shlik, J.; Jetly, R.; Robillard, R.

2026-06-12 epidemiology 10.64898/2026.06.10.26355368 medRxiv
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Background Evidence on factors associated with cannabis for medical purposes (CMP) authorizations among Veterans Affairs Canada (VAC) clients remains limited and inconsistent, particularly concerning mental health and posttraumatic stress disorder (PTSD), a leading indication for use. We investigated demographic, clinical and service characteristics associated with VAC authorizations for CMP reimbursement. Method We linked VAC administrative CMP program data with responses from the 2019 Life After Services Studies cross-sectional survey of Regular Force veterans released between 1998 and 2018. Multivariable logistic regressions examined associations between CMP reimbursement (yes/no) and demographic, clinical and well-being factors, with analyses stratified by PTSD status. Results Among 1,289 respondents (weighted n=33,131), 18.4% were authorized for CMP reimbursement. Younger age (<40 vs. [&ge;]60 years: OR 4.78, 95% CI: 2.24-10.21), unemployment with inability to work vs. employed (OR 3.10, 95% CI: 1.78-5.40), land service vs. air (OR 2.07, 95% CI: 1.22-3.50), PTSD (OR 2.81, 95% CI: 1.69-4.66), anxiety (OR 2.32, 95% CI: 1.45-3.70), and severe pain vs. no pain (OR 3.61, 95% CI: 1.97-6.60) were independently associated with authorization. Unemployment and severe pain were consistent correlates across PTSD strata. Among those without PTSD, younger age, multiple physical conditions, and frequent mental health visits were significant; among those with PTSD, shorter service, witnessing destruction, and suicidal ideation were additional factors. Conclusions CMP authorization patterns among Canadian veterans reflect the intersection of mental health, pain, and functional impairment, with variation by PTSD status. These findings underscore the need for longitudinal research on CMP mechanisms, effectiveness and safety.

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Alcohol Consumption Patterns and Sociodemographic Correlates Among US Adults with Cardiovascular Disease: A Cross-Sectional Analysis of All of Us and NHANES

yang, q.; yu, j.; zhao, h.; zou, m.; sun, y.

2026-06-09 public and global health 10.64898/2026.06.06.26355052 medRxiv
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This cross-sectional study aimed to examine the prevalence of alcohol use and its sociodemographic correlates among adults with cardiovascular disease (CVD). We analyzed data from two large US cohorts: the All of Us Research Program (2017-2023) and the National Health and Nutrition Examination Survey (NHANES, 1999-2016). Both CVD diagnosis and past-year alcohol consumption were self-reported. Risky drinking was defined as exceeding moderate drinking or binge drinking (All of Us), or moderate/heavy drinking (NHANES). Multivariable logistic regression was used to exam associations with sociodemographic and lifestyle factors. Among 32,788 current drinkers with CVD in the All of Us cohort, 15% exceeded moderate drinking thresholds and 26% reported binge drinking. Older age, female sex, and higher socioeconomic status were inversely associated with risky drinking, while smoking was positively associated. In NHANES, moderate drinking rose from 47.3% to 57.2% and heavy drinking from 6.7% to 7.2%. Moderate/heavy drinking was positively associated with age <65 but inversely with age [&ge;]65. Higher education and income were linked to moderate drinking, while current smoking was strongly associated with heavy drinking. These results highlight the need to integrate holistic screening for alcohol use, tobacco use, and social context into routine cardiovascular care.

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Local Influenza Forecasts Outperform State-Level Forecasts in the United States

Kim, D.; Pasco, R.; Johnson, K. E.; Fox, S. J.; Reich, N. G.; Meyers, L. A.

2026-06-08 infectious diseases 10.64898/2026.06.04.26354836 medRxiv
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Accurate outbreak forecasts are critical for timely and effective public health response. In the United States, however, most forecasts are produced at the state level, which can mask substantial sub-state heterogeneity and limit their utility for local planning. We generated and evaluated forecasts of the percentage of Emergency Department visits attributable to influenza across 173 large metropolitan Health Service Areas (HSAs) using a gradient boosting quantile regression (GBQR) model, and compared their accuracy to forecasts derived from state-level data alone. At a one-week, two-week and three-week horizon, local forecasts outperformed state-based forecasts in 98.8%, 90.8%, and 78.6% of HSAs, respectively, achieving mean weighted interval scores that were on average a 39.2% lower (95% range: 5.9% to 76.7%), 19.6% lower (-6.3% to 59.5%) , and 11.4% lower (-11.7% to 44.9%), respectively. The performance advantage of local forecasting was strongest in HSAs representing a smaller share of their state's population and increased with the proportion of the HSA population living in urban areas and the number of metropolitan areas within a state. These results, based on an analysis of HSAs with populations greater than 250,000, demonstrate that fine-scale modeling can substantially improve forecast accuracy and highlight the potential value of local forecasts for outbreak preparedness and response.

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Increasing influenza vaccination rates among care home staff: Economic evaluation of the FluCare intervention within a cluster-RCT

Wagner, A. P.; Risebro, H.; Clark, A.; Stirling, S.; Sims, E.; Bion, V.; Blacklock, J.; Birt, L.; Bryant, R.; Cook, L.; Dean, T.; Wyn Griffiths, A.; Guillard, C.; Holland, R.; Jones, A. P.; Jones, L.; Katangwe-Chigamba, T.; Pitcher, J.; Scott, S.; Wright, D.; Patel, A.

2026-06-09 health economics 10.64898/2026.06.06.26355050 medRxiv
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Introduction Care home (CH) influenza vaccination of staff improves resident health, yet uptake remains low at just over 11% (England, 2025/2026). We report an economic evaluation (EE) of "FluCare", an intervention to increase staff influenza vaccination through: vaccination clinics at CHs; promotional materials; and CH financial incentives. Method Seventy-five CHs were randomised to FluCare or control. A cost-consequence analysis took the influenza vaccination programme funder perspective, but also extended to the National Health Service (NHS) and CH perspective. Costs included: influenza vaccination; administration fee; FluCare components; CH resident NHS utilisation. Outcomes were: staff influenza vaccination rates; staff sickness; and resident mortality. Sensitivity analyses excluded intervention CHs that did not host vaccination clinics. Results Compared to control CHs, adjusted analysis found intervention homes with a mean absolute increase in vaccination rates of 1.8% (95% CI: -6.0%, 10.8%; p=0.572) at an increased cost of {pound}451 (95% CI: {pound}239, {pound}675; p<0.001) to the vaccination programme funders: {pound}249 per additional percentage point (PAPP) per CH. Vaccination clinics were delivered late in the influenza season, with 80% taking place from February 2023. Including only intervention CHs that hosted staff flu vaccination clinics (23/35), increases the mean difference to 10.1% (95% CI: 0.9%, 21.9%; p=0.018) and costs to {pound}805 (95% CI: {pound}603, {pound}1,079; p<0.001): {pound}79 PAPP per CH. Differences between trial arms in other costs and outcomes were marginal and generally non-significant. Conclusions FluCare delivered little improvement when staff flu vaccination clinics did not occur and had little impact on other costs/outcomes. Cost-effectiveness depends on willingness-to-pay for increased staff vaccination, but cost PAPP per CH improved from {pound}249 to {pound}79 when only CHs hosting clinics were considered. Late implementation, likely reduced impact by limiting clinic delivery, as reflected in sensitivity analysis. Future evaluations should implement FluCare earlier in the season.

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Modeling the Impact of Pediatric RSV Immunization in Massachusetts, 2024--2025

Jones, L.; Ergas, R.; Tibbs, A.; Russo, E. T.; Norville, J.; Bingay, B.; Brown, C. M.; Reich, N. G.; Pasco, R.

2026-06-10 epidemiology 10.64898/2026.06.05.26354236 medRxiv
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Background Pediatric immunizations for Respiratory Syncytial Virus (RSV), including monoclonal antibodies for infants and vaccines for pregnant people, have become broadly available and can prevent severe RSV outcomes in infants. However, quantifying the impact of RSV immunization in prevention of severe pediatric illness at the population-level is limited by lack of RSV case surveillance data. The Massachusetts Department of Public Health (DPH) conducted a modeling analysis using routine public health surveillance data to estimate the state-level impact of new RSV immunization products on Emergency Department (ED) visits and hospitalizations in Massachusetts for highest risk pediatric groups. Methods A scenario projection tool, called R.Scenario.Vax, was utilized to simulate RSV-associated ED hospital encounters by age group in the context of newly available immunizations. ED visit and hospitalization data from the National Syndromic Surveillance Program (NSSP) during the time period 10/08/2017--10/19/2024 were analyzed, scaled to account for changes in RSV testing practices over time and missing encounter volume in historic data, and utilized to inform model fit of a "typical" RSV season. RSV immunization data from the Massachusetts Immunization Information System (MIIS) for the 2023--2024 and 2024--2025 RSV seasons informed high and moderate pediatric RSV immunization coverage scenarios and their impact was compared to a counterfactual reference scenario of no new immunizations. Median projections were quantitatively and qualitatively compared to observed 2024--2025 season data. Percent reduction in hospital encounters and encounters averted per 10,000 population were calculated for each scenario as compared to the reference. Results Projections for the youngest at-risk age groups showed significantly lower RSV-associated ED visits and hospitalizations during the 2024--2025 season for both high and moderate immunization coverage scenarios. Median projections for infants under 6 months old in the highest coverage scenario, wherein nearly all infants were immunized, showed 72.6% lower ED visits and 73.4% lower hospitalizations when compared to the reference scenario, equating to 262 ED visits and 85 hospitalizations averted per 10,000 population. Conclusions Our results support the use of modeling methods for public health insights and suggest that RSV immunizations for infant populations result in significantly lower RSV-related ED encounters in Massachusetts.

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Medical discrimination and the selective erosion of institutional health trust: evidence from the Health Information National Trends Survey 6 and 7

Park, A.; Yin, L.; Wong, A.; Lee, C.; Choi, Y.

2026-06-09 public and global health 10.64898/2026.06.06.26355057 medRxiv
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Medical discrimination may alter how patients relate to health information sources following adverse care encounters. We examined whether discrimination experience is associated with selective erosion of institutional health trust and with compensatory digital health engagement, using nationally representative data from the Health Information National Trends Survey (HINTS) 6 (2022; n=6,252) and HINTS 7 (2024; n=7,278). Survey-weighted modified Poisson regression estimated prevalence ratios (PRs) for binary high-trust outcomes, and survey-weighted ordinary least squares estimated coefficients for continuous outcomes; jackknife replicate weights (50 replicates) provided variance estimates. Discrimination was associated with substantially lower probability of high trust in the healthcare system (PR=0.39; 95% CI 0.30-0.52) and physicians (PR=0.85; 95% CI 0.77-0.94), with no significant association for trust in scientists, government, family, or religious organisations. The clinical-institutional pattern replicated in HINTS 6, which additionally showed reduced trust in scientists for race/ethnicity-based discrimination. Contrary to a disengagement hypothesis, discrimination-exposed adults showed higher probability of online health information seeking (PR=1.06), health app use (PR=1.11), and online provider messaging (PR=1.13); these associations persisted after adjustment for trust in physicians. Discrimination was independently associated with lower health self-efficacy (b=-0.271). Medical discrimination selectively erodes trust in clinical institutions while leaving broader epistemic trust largely intact. Despite this, discrimination-exposed patients engage more actively with digital health channels, consistent with compensatory reorientation toward non-clinical information sources. These findings describe engaged but institutionally alienated patients, with implications for restoring clinical trust and for equity-centred digital health design.

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Influencers, not just adverts: social media influencer exposure and tobacco use among urban youth in Kampala and Nairobi - a comparative mixed methods study

Jawahar Kanth, J. S.; Anish, T. M. R.; Odhiambo, B.; Lwembawo, K. D.; Micheal, S.; Arinaitwe, J.; Nakiyingi, L.

2026-06-10 public and global health 10.64898/2026.06.06.26355037 medRxiv
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Tobacco control treaties were written for billboards and television, not for the people now selling lifestyles to young Africans. As mobile internet saturates East African cities, social media influencers have become an unmeasured channel, especially when it comes to tobacco promotion. We assessed the prevalence of tobacco use, its association with influencer exposure, and how urban youth interpret that exposure in two capitals with different tobacco laws. We conducted a comparative mixed-methods study among youth aged 18-29 years in Kampala, Uganda, and Nairobi, Kenya (January-August 2025), combining (i) a cross-sectional survey using systematic sampling at youth-dense venues (n=772), (ii) four online focus group discussions (FGDs; n=40), and (iii) content analysis of 30 tobacco-related posts from high-reach influencers (greater than 50,000 followers). We used chi-square tests and multivariable logistic regression, thematic analysis (Braun and Clarke), and descriptive engagement metrics. Ever tobacco use among urban youth in East Africa was 29.3% (226/772), similar in Kampala (30.7%) and Nairobi (28.0%; p=0.409). After adjustment, exposure to influencers promoting tobacco independently predicted ever use (adjusted odds ratio [aOR] 1.90, 95% confidence interval [CI] 1.29-2.82; p=0.001), alongside male sex (aOR 2.35) and age 26-29 years (aOR 1.99). Tertiary education (aOR 0.45) and never seeing tobacco content (aOR 0.26) were protective. Posts framed tobacco as aspirational lifestyle; 77% of sampled comments were positive and 47.5% expressed interest in trying the product. Influencer exposure behaved as a modifiable risk factor of a magnitude comparable to established demographic drivers. Tobacco control in the region must move from print-era advertising bans to platform governance, mandatory disclosure of paid promotion, and youth-led counter-marketing.

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Neighborhood socioeconomic status associated with post-stroke cognitive impairment: a retrospective cohort study

Siegel, M.; Corlin, L.; Miller, J.; Cote, K.; Leung, L. Y.

2026-06-11 epidemiology 10.64898/2026.06.09.26355320 medRxiv
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Background: Late complications after stroke (LCAS), including cognitive symptoms, impact quality of life and recovery. It is not known if neighborhood-level measures of socioeconomic status (SES) influence LCAS. This study assessed associations between SES measures, including neighborhood income inequality (Gini) and area deprivation index (ADI), and cognitive symptoms after acute ischemic stroke (AIS) in a hospital leveraging active surveillance of LCAS. Methods: This retrospective cohort study included 512 patients hospitalized with AIS at Tufts Medical Center with subsequent follow-up (between zero and three months or between three and twelve months) in the Stroke Clinic from 1/1/2018 - 12/31/2022. Using ZIP code data, patients were characterized as low Gini (low inequality) and high ADI (high deprivation) (Gini <= 0.4302, ADI >= 5) by state medians. These variables were combined, indicating patients who were living in both a low Gini and high ADI neighborhood to evaluate the effects of living in a homogeneously deprived area. There were 206 and 281 patients in the low Gini and high ADI groups respectively. 140 patients lived in a low Gini and high ADI neighborhood. The multivariable logistic analysis assessed the likelihood of cognitive symptoms, adjusting for age, race, ethnicity, sex, NIH Stroke Scale (NIHSS), thrombolysis, active LCAS surveillance, poverty, and ADI-Gini combination. Results: There were no associations between high ADI (OR: 1.03, 95% CI: 0.67 ? 1.57) or low Gini (OR: 1.74, 95% CI: 0.98 ? 3.07) alone and cognitive symptoms after AIS. However, the combined variable demonstrated increased likelihood of cognitive symptoms in the high ADI-low Gini group (OR: 1.82, 95% CI: 1.08 ? 3.06). Conclusions: This study suggests that individuals living in homogeneously deprived neighborhoods report higher likelihood of cognitive symptoms after AIS. Further studies with increased power are needed to investigate the underlying causes of these disparities and to develop interventions to reduce these complications.

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Healthcare professionals' perspectives on a multilevel cardiovascular risk management intervention (PROSPERA programme)

Bongaerts, V. A. M. C.; van Gestel, L. C.; van Peet, P. G.; Vuijk, M.-L. S.; Hageman, S. H. J.; Dorresteijn, J. A. N.; Bonten, T. N.; Numans, M. E.; van Os, H. J. A.; Vos, R. C.

2026-06-09 cardiovascular medicine 10.64898/2026.06.08.26355169 medRxiv
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Background: Two-thirds of Dutch cardiovascular risk management (CVRM) for patients at risk of cardiovascular disease is delivered in primary care practices. While individual risk scores are increasingly used during consultation, a population-level structure for risk-based patient outreach is not currently available. We therefore developed the PROSPERA programme, a multilevel intervention comprising population-level risk stratification and individual-level support tools. Aim: To assess anticipated and experienced barriers and facilitators among healthcare professionals (HCPs) to inform implementation in primary care. Methods: We conducted four focus groups and six interviews with nine primary care HCPs to explore anticipated and experienced barriers and facilitators. Inductive codes were thematically analysed and assigned to corresponding domains of the Theoretical Domains Framework (TDF) and the related Capability, Opportunity, Motivation model of Behaviour. Results: Barriers and facilitators were identified in 11 TDF domains. Population-level barriers included altered professional roles and limitations in technological infrastructure. Individual-level barriers were limited skills in interpreting risk calculations and difficulty integrating tools into clinical routine. Facilitators were related to beliefs on the importance of providing proactive care (population level), the use of U-Prevent for risk communication (individual level) and positive patient responses to the Lifestylecheck questionnaire (individual level). Conclusion: Addressing barriers and facilitators identified at both the population and individual levels can support implementation of the PROSPERA programme. Opportunities exist in education and training of HCPs in risk communication, as well as support in restructuring the physical and digital environment.

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General-purpose large language models can achieve physician-level accuracy in complex medical data extraction

Rajeev, M.; Narayan, A.

2026-06-10 gastroenterology 10.64898/2026.06.06.26354838 medRxiv
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Background: Unstructured data represent about 80% of total electronic health records (EHR) data. Structuring this free text is essential for advancing clinical research, including cohort selection for trials, retrospective studies, and the development of disease registries. While manual chart review (MCR) remains the gold standard for extracting this clinical data, the process is inherently slow, resource-intensive, and susceptible to errors from human fatigue. We evaluated the extraction accuracy, safety, and efficiency of the HeLIX (Hepatology Logic-Integrated Extraction) framework, a Large Language Model (LLM) protocol using Google Gemini 3 Pro, compared to a gold-standard Manual Chart Review (MCR). Methods: A prospective validation study was conducted using 50 high-complexity, simulated hepatology discharge summaries designed to replicate the real-world heterogeneity of EHRs. The HeLIX framework employed a Zero-Shot, Structured Chain-of-Thought (CoT) prompting strategy enforced by a three-layer architecture: Clinical Reasoning Trace, Schema Enforcement, and Evidence Verification. The model extracted 45 distinct clinical variables. Performance was benchmarked against a consensus MCR. Results: Across 2,250 evaluated data points, the model achieved an overall Extraction Accuracy of 99.24% (95% CI: 98.8%-99.5%), with perfect concordance in 35/45 (77.8%) variables. For binary diagnostic variables, the model demonstrated an overall F1-score of 0.98, Recall of 0.99 and substantial inter-rater reliability (Cohens {kappa} = 0.97). Hallucinations were exceptionally rare (2/2250; 0.08%). Critical errors affecting clinical management occurred in only 2 instances (<0.1% of total data), both involving etiological misattribution in complex multifactorial diagnoses. The AI workflow was 13.4-fold faster and 95.1% more cost-effective than manual extraction. Conclusion: The HeLIX framework demonstrates physician-level accuracy and reliability in extracting complex hepatology data. It offers a scalable, efficient, and economical alternative to manual chart review. Such frameworks could accelerate clinical research, enabling healthcare systems globally to build comprehensive patient registries for a fraction of the traditional cost.

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Cardiovascular-Kidney-Metabolic Syndrome Among US Adults, 1999-2023: National Trends and Projections Through 2050

Fu, F.; Wei, A.; Wang, G.; Fang, S.; Chen, J.; Liu, W.; Liu, H.; Gao, X.; Lei, Y.; Guo, N.; Chen, M.; Yu, J.; Wang, Y.; Li, S.; Mao, Y.; Yan, L.

2026-06-10 health systems and quality improvement 10.64898/2026.06.08.26355220 medRxiv
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Background Cardiovascular-kidney-metabolic (CKM) syndrome integrates adiposity, metabolic risk, kidney dysfunction, and cardiovascular disease in a prevention-oriented framework. National estimates across 1999-2023 NHANES and future burden remain limited. Methods We analyzed US adults aged 20 years from 11 NHANES cycles, 1999-2000 through August 2021-August 2023. CKM stage 0-4 was assigned using harmonized examination, laboratory, medication, and questionnaire data. Prevalence was survey-weighted and standardized to the 2010 US Census adult population. Decade trends used survey-weighted logistic regression adjusted for age, sex, and race and ethnicity. Exploratory 2040 and 2050 projections combined NHANES prevalence models with US Census projections under population-aging-only, trend-continuation, and risk-improvement scenarios. Results Among 62,890 eligible adults, 62,888 had sufficient CKM data. In 2021-2023, age-standardized prevalence was 87.9% (95% CI, 86.5%-89.4%) for CKM stage 1 and 62.0% (95% CI, 60.1%-63.8%) for stages 2-4. Stage 2 accounted for 50.1% (95% CI, 48.2%-51.9%) and stages 3-4 for 11.9% (95% CI, 11.0%-12.7%). From 1999-2000 to 2021-2023, any CKM increased by 4.6 percentage points (95% CI, 2.4 to 6.9; P<0.001), whereas stages 2-4 changed by 2.1 percentage points (95% CI, 5.1 to 0.8; P=0.156). In adjusted decade models, any CKM increased (OR, 1.28; 95% CI, 1.19-1.38; P<0.001), while stages 2-4 showed no significant linear trend (OR, 0.95; 95% CI, 0.89-1.01; P=0.084). Excess adiposity and diabetes increased, dyslipidemia declined, and hypertension, chronic kidney disease, and clinical cardiovascular disease were stable. With population aging alone, projected stages 2-4 burden rose from 164.8 million adults in 2023 to 193.7 million in 2050; under risk improvement, it was 147.7 million. Conclusions CKM syndrome remained highly prevalent among US adults. Although later stages did not increase significantly, population aging may expand the absolute care burden unless broad risk improvement occurs.

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Hanging on through Omicron, then what? A pre-exit baseline of the U.S. emergency nursing workforce, 2018 to 2022, with implications for the 2026 NSSRN cycle

Squire, K.

2026-06-08 nursing 10.64898/2026.06.07.26355097 medRxiv
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Background. The emergency department in the United States of America functions as a residual access point for healthcare and social services for populations including rural communities, the uninsured, mental health and addiction patients, and the unhoused. The workforce variable that determines unit function (experience density, the concentration of accumulated clinical judgment within a unit workforce) is not measured in hospital accounting systems. Objective. To document workforce composition changes in U.S. emergency nursing across the 2018 and 2022 cycles of the National Sample Survey of Registered Nurses (NSSRN), and to specify falsifiable predictions for the 2026 cycle. Methods. We analyzed NSSRN public-use files using a four-way ED definition extending Castner et al. (2024) and a hospital-bedside-restricted comparator. Variance estimation used jackknife replicate weights for 2018 and Successive Differences Replication for 2022. Burnout was operationalized using the Norful et al. (2023) leaving-reasons proxy across cycles, with sensitivity analysis using the 2022 direct burnout item. Results. A 15-year trajectory (2008-2022) documents progressive experience-density compression: the ED's 15+ year veteran cohort fell from 41.9% to 28.0% over the decade preceding the pandemic, a loss of nearly a third of the senior cohort and a 19.6% decline in mean experience density, before recovering modestly to 33.3% as veteran nurses remained through the pandemic acute phase, leaving the ED as the youngest hospital setting throughout. Hospital non-ED bedside nurses lost senior tenure between cycles (mean 15.65[-&gt;]14.06 years since first licensure; 15+ year share 43.5%[-&gt;]38.7%), while ED nurses retained their senior tail (mean 11.60[-&gt;]12.58). Burnout endorsement rose sharply in both populations (non-ED 27.3%[-&gt;]46.0%; ED 34.2%[-&gt;]61.2%), with the ED-vs-non-ED gap more than doubling. Controlling for tenure, ED status was not independently associated with burnout in 2018 (OR 1.15, 95% CI 0.83-1.59) but was strongly associated in 2022 (OR 1.92, 95% CI 1.44-2.55; p<.001). The direct burnout item showed a parallel pattern (OR 2.92, 95% CI 1.62-5.28). Conclusions. A pandemic-era setting-specific burnout effect emerged in emergency nursing that workforce-composition controls cannot explain. The 2022 cycle establishes a pre-exit baseline against which the 2026 NSSRN will serve as the falsifiable test of post-Omicron veteran exit. Nursing pipeline replacement lag exceeds the interval before 2026 data arrives; the consequences of inaction fall on populations dependent on ED-based residual access.

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Conversational Artificial Intelligence-Enabled Precision Oncology Reveals Context-Specific TGFβ and JAK/STAT Alterations in Pancreatic Cancer

Diaz, F. C.; Waldrup, B.; Carranza, F. G.; Manjarrez, S.; Velazquez-Villarreal, E.

2026-06-12 gastroenterology 10.64898/2026.06.10.26355398 medRxiv
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Background: Pancreatic ductal adenocarcinoma (PDAC) is characterized by extensive molecular complexity, profound stromal remodeling, and limited responsiveness to systemic therapies. Although gemcitabine-based regimens remain widely utilized, the molecular pathways that influence treatment-associated biological variation are incompletely understood. The TGF{beta} and JAK/STAT signaling networks are recognized regulators of tumor progression, immune modulation, and therapeutic resistance; however, their genomic architecture in clinically stratified PDAC populations remains poorly defined. Methods: We employed a conversational artificial intelligence-driven analytical framework to investigate TGF{beta} and JAK/STAT pathway alterations in a cohort of 184 PDAC patients. Clinical and molecular data were integrated to generate age- and treatment-stratified cohorts, enabling pathway-level and gene-level analyses according to gemcitabine exposure. Findings generated through AI-assisted interrogation were subsequently evaluated using conventional statistical approaches. Results: TGF{beta} pathway alterations were identified in approximately one-quarter to one-third of tumors across clinical subgroups and demonstrated relatively stable frequencies regardless of age at diagnosis or gemcitabine treatment status. Gene-level analyses revealed that pathway disruption was predominantly driven by recurrent alterations in SMAD4, with additional low-frequency events involving TGFBR1 and TGFBR2. Notably, TGFBR2 mutations were significantly more frequent among late-onset PDAC patients receiving gemcitabine compared with untreated late-onset patients (8.8% vs. 1.4%; p = 0.04), suggesting a potential treatment-associated enrichment. In contrast, JAK/STAT pathway alterations were rare throughout the cohort, with only isolated mutations observed in pathway components including JAK1, JAK2, JAK3, STAT1, STAT3, and related regulatory genes. No significant differences in JAK/STAT alteration frequencies were identified according to age or treatment exposure. Conclusions: TGF{beta} and JAK/STAT pathways exhibit distinct genomic architectures in PDAC. TGF{beta} pathway disruption represents a recurrent feature of disease biology, largely driven by SMAD4 alterations, while TGFBR2 enrichment in gemcitabine-treated late-onset tumors suggests a potential context-specific association worthy of further investigation. Conversely, genomic alterations within the JAK/STAT pathway are uncommon, indicating that pathway activity may be regulated predominantly through non-genomic mechanisms. These findings demonstrate the utility of conversational artificial intelligence agents for rapid, scalable, and clinically contextualized pathway interrogation and support future studies integrating multi-omic data to refine precision medicine strategies in PDAC.

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Association between depressive symptoms and physical function among participants with heart disease in the Reasons for Geographic And Racial Differences in Stroke (REGARDS) study.

Fasokun, M. E.; Safford, M. M.; Khodneva, Y.; Colantonio, L. D.; Goyal, P.; Alanaeme, C. J.; Hanif, A. A. M.; Enogela, E. M.; Bowling, C. B.; Levitan, E. B.

2026-06-11 epidemiology 10.64898/2026.06.09.26355319 medRxiv
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Background: Depression and heart disease frequently co-occur in the aging population and are associated with functional decline and poor health outcomes. Understanding how depressive symptoms relate to different aspects of physical function among adults with heart disease may help identify high-risk subgroups. Objective: To examine the association of depressive symptoms with self-reported and observed physical function measures among participants with heart disease in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study and assess whether associations differ by sex and race?sex groups. Methods: We conducted a cross-sectional analysis using data from REGARDS study second in-home visit (2013?2016). Depressive symptoms were measured with the 10-item Center for Epidemiologic Studies Depression scale (CES D 10), considering scores ?10 as clinically significant. Physical function measures were instrumental activities of daily living (IADL), activities of daily living (ADL), chair stand time (5 repetitions), and gait speed. Linear regression models estimated associations of depressive symptoms with function, adjusting for sociodemographic, health behavior, antidepressant medications, body mass index, and social support. Effect modification by sex and race?sex group was evaluated. Results: Among 3,055 participants, 11.7% had CES D 10 ?10. Compared to CES-D-10 scores <10, CES D 10 ?10 was associated with more limitations in IADL (1.84 points; 95% CI 1.62, 2.06), ADL (0.43 points; 95% CI 0.34, 0.52) and slower chair stand time (0.88 second; 95% CI 0.07, 1.69); associations with gait speed were modest (?0.04 meters/second; 95% CI ?0.08, -0.01). Women had a stronger association between CES-D-10 and ADL (0.49 points; 95% CI 0.35, 0.64) than men (0.33 points; 95% CI 0.21, 0.44; p for interaction = 0.01). Interaction between CES D 10 and race?sex groups was not statistically significant. Conclusions: Among adults with heart disease, clinically significant depressive symptoms were associated with lower physical function, particularly among women.

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Recognition and Treatment of Primary Aldosteronism in the Updated Guideline Era

Tsai, C.-H.; Chang, Y.-C.; Chang, C.-C.; Wu, W.-C.; Chang, Y.-Y.; Chen, U.-L.; Lee, B.-C.; Hung, C.-S.; Huang, K.-H.; Chueh, J. S.; Wu, V.-C.; Lin, Y.-H.

2026-06-10 cardiovascular medicine 10.64898/2026.06.08.26355219 medRxiv
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Background: Primary aldosteronism (PA) is increasingly recognized as a common cause of hypertension. The 2025 Endocrine Society guideline introduced a simplified diagnostic framework, but its real-world clinical implications remain unclear. Methods: We conducted a multicenter retrospective cohort study of hypertensive patients undergoing PA testing in Taiwan. PA was defined biochemically according to the 2025 Endocrine Society criteria. Multivariable logistic regression identified factors associated with PA diagnosis and aldosterone-targeted therapy. Among patients with suppressed renin (?1 ng/mL/h), restricted cubic splines evaluated the adjusted association between renin and PA probability. Results: Among 18,766 patients undergoing PA testing, 6,760 (36.0%) met diagnostic criteria for PA. PA was associated with older age, female sex, lower potassium, resistant hypertension, and a higher antihypertensive medication burden. Among patients with suppressed renin, lower renin remained significantly associated with higher adjusted PA probability. However, only 39.0% of patients with PA received aldosterone-targeted therapy, including 28.2% who received mineralocorticoid receptor antagonist therapy within 6 months and 9.4% who underwent adrenalectomy during follow-up. Lower renin, higher aldosterone, lower potassium, and resistant hypertension were associated with aldosterone-targeted therapy, while younger patients with fewer comorbidities were more likely to undergo adrenalectomy. Conclusions: Using the updated diagnostic framework, PA was highly prevalent among hypertensive patients undergoing PA testing. Nevertheless, many patients who met these biochemical criteria did not receive aldosterone-targeted therapy in routine care. These findings highlight the potential treatment implications of broader PA recognition and support the development of practical pathways to guide MRA therapy, adrenalectomy referral, and individualized management.

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Correlates of time to presentation for stroke care among patients at a tertiary hospital in Ondo State, Nigeria: A retrospective records review

Ogunsemoyin, O.; Fayehun, O.

2026-06-09 health policy 10.64898/2026.06.06.26355064 medRxiv
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Introduction: Early hospital presentation after stroke onset is necessary for rapid assessment and access to time-dependent acute management. This study examined the correlates of late presentation for stroke care among patients recorded at a tertiary hospital in Ondo State, Nigeria. Methods: A retrospective records review was conducted using secondary data from the Stroke Registry of the University of Medical Sciences Teaching Hospital, radiology department records, referral notes, and ambulance records. Records of stroke cases documented within the preceding 24 months were reviewed. Late presentation was defined as hospital presentation more than four hours after symptom onset. Frequencies, chi-square tests, and modified Poisson regression with robust standard errors were used to estimate adjusted prevalence ratios. Results: The analysis included 371 stroke cases. Of these, 317 (85.4%) presented after four hours, and the median time to presentation was 24 hours (interquartile range: 9-72 hours). Late presentation differed significantly by employment status, first-contact route, and pathway complexity at bivariate analysis. After adjustment, non-hospital first contact remained strongly associated with late presentation: patients whose first documented contact was non-hospital-based had almost 3 times the prevalence of delay compared with those whose first contact was hospital-based (adjusted prevalence ratio = 2.89; 95% confidence interval: 2.15-3.90; p < 0.001). Conclusion: Late presentation was pervasive in this tertiary hospital record cohort and was primarily associated with the initial direction of care-seeking. Stroke response interventions should emphasise immediate hospital presentation and strengthen urgent referral from non-hospital first-contact points.

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Structural Cardiac Abnormalities, Ventricular Dysfunction Phenotypes, and Heart Failure Risk among Antiretroviral Therapy-treated People Living with HIV in South Africa

Omar, Z.; PHIZA Study Team, ; Ahmed, A. A.; Wolfson, J.; Huang, Z.; Mgidlana, M.; Black, A.; Abd El Hadi, M.; Aremu, O. O.; Peterson, T. E.; Ntusi, N. A. B.; Meintjes, G.; Ntsekhe, M.; Baker, J. V.

2026-06-08 cardiovascular medicine 10.64898/2026.06.04.26354960 medRxiv
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Background: The manifestations of cardiovascular disease (CVD) among people with HIV (PWH) differ by region globally. While HIV disease is associated with increased atherosclerotic CVD risk in the global North, non-ischemic heart failure (HF) is more common in sub-Saharan Africa, the global HIV epicenter. We estimated the effect of treated HIV on the frequency and phenotype of HF and its cardiac precursors in South Africa (SA). Methods: In an observational study, we recruited PWH on antiretroviral therapy (ART), age [&ge;]40 years and people without HIV (PWoH) with similar distributions of age, sex, ethnicity, and hypertension, from a community clinic in Khayelitsha (Cape Town, SA). Procedures included a clinical assessment, echocardiography (Echo), and b-type natriuretic peptide (BNP) measure. Echo parameters defined structural abnormalities, left ventricle (LV) filling pressure, and LV systolic and diastolic dysfunction (DD). HF was defined by symptoms and/or BNP [&ge;]35pg/mL and LV dysfunction, subcategorized as reduced, mildly reduced, or preserved ejection fraction (HFrEF, HFmrEF, and HFpEF). Comparisons by HIV status were adjusted for age, sex, hypertension, smoking, obesity, diabetes, elevated LDL-cholesterol, and hazardous alcohol use. Results: Between September 2022 and August 2025, we enrolled 1008 PWH and 500 controls [median (Q1-Q3) age 48 years (43-53), 77% female]. Among PWH and controls respectively, 37% and 39% had hypertension, 21% and 25% were current smokers, 40% and 45% were obese, and 9% and 17% had diabetes. LV systolic dysfunction (1%) and HFrEF (1%) were rare, and undiagnosed HFpEF (8%) was the predominant HF phenotype. Compared to controls, PWH had higher odds of elevated LV mass index (LVMI) (OR 2.1; 95%CI 1.5-3.0) and DD (OR 1.4; 95%CI 1.0-2.0). Risk for elevated LVMI and DD was greatest among women with HIV, who also had an increased risk for undiagnosed HFpEF (OR 1.9; 95%CI 1.2-3.2), compared to women without HIV; effects which were not seen among men (p=0.051 for HIV*Sex interaction). Conclusions: In a peri-urban SA community with a high burden of cardiometabolic risk factors, the frequency of abnormal structural and functional cardiac precursors of HFpEF was greater amongst ART-treated PWH. This was most pronounced amongst women with HIV, who also had increased risk of undiagnosed HFpEF.

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Dementia and Frailty Impact Postoperative Care Trajectories and Burden among Older Adults Undergoing Radical Cystectomy for Bladder Cancer

Ernandez, J.; Xiang, L.; Adler, R.; Hsu, J.; Shah, S. K.; Kim, D.; Gershman, B.; Mossanen, M.; Weissman, J. S.

2026-06-06 urology 10.64898/2026.06.04.26354768 medRxiv
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OBJECTIVE: Bladder cancer (BC) is predominantly a disease of older, comorbid adults, and radical cystectomy (RC), which is the gold standard treatment, carries considerable morbidity. We sought to determine the impact of baseline dementia and frailty on the care trajectory beyond the immediate postoperative period. We hypothesized that frail patients and those with dementia undergoing RC for BC will have poorer care trajectories. METHODS AND MATERIALS: We identified Medicare beneficiaries [&ge;] 66 years old who underwent RC for BC in 2017 with 12 months of pre- and post-RC enrollment. Frailty and dementia were characterized using validated, claims-based measures. Associations between baseline frailty and dementia with postoperative care trajectory outcomes were determined using Fine-Gray competing risk models. RESULTS: We identified 3,600 beneficiaries of whom 11.6% were frail and 3.4% met criteria for dementia. Patients with dementia were more likely to be frail, comorbid, and not receive standard-of-care neoadjuvant chemotherapy. Frailty was independently associated with [&ge;] 2 transitions in care level after index discharge from RC and skilled nursing facility (SNF) admissions within 1 year of RC, exposure to intensive post-RC interventions, including dialysis and feeding tube placement, and poorer survival. Dementia remained associated with SNF admissions regardless of frailty level. CONCLUSIONS: Among a contemporary cohort of older adults undergoing RC for BC, preoperative dementia and frailty were independently associated with poorer care trajectory beyond the immediate postoperative period after RC. Our work highlights a role for preoperative geriatric assessment in identifying and optimizing patients at greatest risk.

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Impact of Early Treatment on Symptom Improvement and Procedural Events among Men with BPH and Bothersome Lower Urinary Tract Symptoms: A Contemporary Analysis of the American Urological Association Quality (AQUA) Registry

Ernandez, J.; Najafi, A.; Roehrborn, C. G.; Lerner, L. B.

2026-06-10 urology 10.64898/2026.06.08.26355194 medRxiv
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PURPOSE: As the armamentarium of BPH therapies continues to expand, it remains imperative to maximize patient satisfaction and minimize decisional regret. We sought to determine the impact of time from BPH diagnosis to index treatment on symptom improvement and subsequent procedural events. MATERIALS AND METHODS: We queried the American Urological Association Quality Registry for men [&ge;] 40 years old with BPH, available IPSS data, and no receipt of prior BPH treatment. Index treatment included medication, surgery, or minimally invasive surgical therapy (MIST). Outcomes included IPSS over 3 years of follow-up, change in percentage of mild lower urinary tract symptoms (LUTS) by 3 months, and time to procedural event. Patients were stratified by time from index diagnosis to treatment by <12 months, 1-3 years, and >3 years. Outcomes were compared across time-to-treatment cohorts with appropriate statistical tests with p < 0.05 as significant. RESULTS: 43,919 patients met criteria with 19,642 pursuing treatments. Patients pursued treatment at comparably lower baseline IPSS compared to prior prospective series. Patients undergoing surgery and MIST had significantly higher baseline IPSS, while medical comorbidities were significantly more common among men initiating pharmacotherapy. Early surgery and MIST were associated with significant improvement in IPSS within 6-12 months and an increase in mild LUTS by 3 months. All forms of early treatment were associated with delayed time to procedural events, including catheterization and fulguration. CONCLUSIONS: Early procedural intervention for BPH is associated with early symptom improvement and delayed time to procedural events among real-world, contemporary practice.

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Burden of Chronic Kidney Disease in China, 1990-2021: Findings from the 2021 Global Burden of Disease Study

Wang, M.; Zhao, T.; Wang, H.; Hou, S.; Fu, Y.

2026-06-09 epidemiology 10.64898/2026.06.06.26355056 medRxiv
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Introduction: To investigate the epidemiological characteristics of chronic kidney diseases (CKD) in China in 2021 and its trends between 1990 and 2021, in the context of significant population growth and lifestyle changes over the past 30 years that have likely influenced the CKD spectrum. Methods: Data on CKD prevalence, mortality, disability-adjusted life-years (DALY), and risk factors were obtained from the Global Burden of Disease Study 2021. The estimated decadal percentage changes were calculated to evaluate changes in trends in prevalence, mortality and disease burden. Results: In 2021, an estimated 118.4 (95% UI 109.4 to 127.5) million people in China were affected by CKD, contributing to 204 230 (95% UI 164 736 to 246 372) deaths and 6.13 (95% UI 5.18 to 7.21) million DALY. Although CKD due to diabetes mellitus and hypertension accounted for less than a quarter of all cases, they were responsible for over 90% of CKD-related deaths. Over the past three decades, CKD mortality and DALY rates have steadily increased, although the prevalence has stabilized in the last decade. Diabetes mellitus type 2 and hypertension have emerged as key drivers of CKD burden in China. Conclusions: The CKD burden in China shows a dual pattern of rising incidence and high mortality from diabetes and hypertension-related chronic kidney disease, alongside persistently high years lived with disability from glomerulonephritis and other causes.