Canadian Medical Association Journal

Objectives: To estimate hyperlipidemia medication order prevalence and associated variables in U.S. skilled nursing facility (SNF) residents. Design: Retrospective, observational study. Setting and Participants: Electronic Health Record data from 447,080 SNF residents with a hyperlipidemia diagnosis identified in PointClickCare's Life Sciences clinical database (January-April 2025) were reviewed. Methods: The presence and absence of medication orders for hyperlipidemia treatments recommended by the American Heart Association were assessed. Descriptive analyses summarized demographic and clinical characteristics, and a modified Poisson regression model was used to estimate risk ratios for having a medication order, adjusting for demographic, clinical, and facility characteristics. Results: Overall, 83.3% of residents diagnosed with hyperlipidemia had at least one hyperlipidemia medication order. Statins were ordered by 96.2% of active order residents, while other medication classes i.e., omega-3 fatty acids, cholesterol absorption inhibitors, fibrates were less common (<8%). Risk ratios (RRs) for medication orders ranged from 0.87-1.16. Factors most strongly associated with having an order included hypertension medication orders (RR=1.16), unspecified hyperlipidemia diagnosis (RR=1.10), and active diabetes medication orders (RR=1.09); female sex (RR=0.95) and private (0.94) or other (0.87) payer types were associated with a lower likelihood of having an order. Conclusions and Implications: Most residents with a hyperlipidemia diagnosis had an active relevant medication order, but use of non-statin therapies was rare. Differences in treatment patterns by sex and payer type, along with limited uptake of newer agents, warrant further investigation into prescribing practices and access within SNFs.

Background Falls are increasingly recognized as adverse events in coronary heart disease (CHD) patients, yet their prognostic implications remain incompletely understood. This study examined the independent associations of falls with mortality and major adverse cardiovascular events, and the roles of functional status and frailty in these relationships. Methods This retrospective cohort study enrolled 2,139 CHD patients with median follow-up of 36 months. Falls were ascertained via telephone interviews every 3 months. Primary outcomes included major adverse cardiovascular events (MACE) and major adverse cardiovascular and cerebrovascular events (MACCE). Secondary outcomes comprised all-cause and cardiac mortality. Multivariable Cox models with stepwise adjustment for functional status indicators were constructed, with subgroup analyses stratified by frailty status. Results During follow-up, 171 patients (8.0%) experienced falls. Falls were associated with mortality in univariate analysis but not after adjusting for functional status, indicating mediation by functional decline. In contrast, falls remained independently associated with MACE (HR=1.73, 95%CI: 1.17-2.57, P=0.006) and MACCE (HR=1.67, 95%CI: 1.14-2.46, P=0.009) in fully adjusted models. Frailty significantly modified this association (P for interaction <0.001). Among robust patients, falls conferred substantially elevated risk (MACE: HR=4.08, 95%CI: 2.37-7.01; MACCE: HR=3.94, 95%CI: 2.30-6.76), whereas no significant association was observed in pre-frail or frail patients. Conclusions Falls independently predict long-term MACE and MACCE in CHD patients, with mortality effects mediated by functional status. Frailty significantly modifies the fall-cardiovascular event relationship--robust patients experiencing falls face substantially elevated cardiovascular risk and warrant comprehensive evaluation. These findings support integrating fall history into cardiovascular risk assessment and implementing frailty-stratified management.

Importance Tuberculosis preventive therapy is central to reducing tuberculosis, and foreign-born individuals account for most US tuberculosis cases. Current US Preventive Services Task Force guidance recommends testing and treating all foreign-born individuals regardless of age or time since immigration, yet the risks of disease progression and of treatment-related harm are not uniform across these groups. Objective To evaluate the cost-effectiveness and health outcomes of tuberculosis infection treatment strategies among immigrants from high-burden settings, stratified by age and time since immigration. Design Decision analytical model using individual-level microsimulation (Markov model) over a 30-year horizon, with deterministic and probabilistic (second-order Monte Carlo) sensitivity analyses. Costs and outcomes were discounted at 3%. Setting US federally funded tuberculosis clinic care (healthcare-sector perspective), using observed data from the Boston Medical Center/Boston Public Health Commission tuberculosis clinic and published literature. Participants A simulated cohort of 10000 IGRA-positive, foreign-born adults from high tuberculosis incidence settings (excluding immunosuppressed individuals), modeled as recent or remote (immigrated 25 years earlier) immigrants at ages 35 and 65 years. Interventions Rifampin daily for 4 months, isoniazid daily for 9 months, or no preventive therapy. Main Outcomes and Measures Costs, disability-adjusted life-years (DALYs), incident tuberculosis cases and deaths, treatment completion, and incremental cost-effectiveness ratios (ICERs), with the proportion of simulations in which each strategy was optimal at a willingness-to-pay threshold of $50000 per DALY averted. Results Among recent immigrants, rifampin was the dominant strategy at ages 35 and 65 years (optimal in 88.5% and 93.9% of simulations), yielding the fewest tuberculosis cases (119.44 and 82.31 per 10 000) and the highest treatment completion (71.4% and 67.7%). Among remote immigrants, rifampin remained the dominant strategy (optimal in 53.41% of simulations), followed by no treatment. In older remote immigrants, no treatment was optimal in 94.7% of simulations. ICERs for treatment vs no treatment were unfavorable ($193 600 and $412 857 per DALY averted for rifampin and isoniazid, respectively, at age 65). Conclusions and Relevance In this decision analytical model, rifampin was cost-effective for recent immigrants, whereas no treatment was optimal for older remote immigrants. Age and time since immigration may help risk-stratify tuberculosis infection treatment and reduce unnecessary treatment in lower-risk populations.

Objectives: To evaluate rates of pharmacological hypertension orders and identify resident- and facility-level predictors of pharmacologic care among skilled nursing facility (SNF) residents in the United States. Design: Retrospective, observational study. Setting and Participants: Electronic Health Record data from 1,285,062 long-term care residents in PointClickCare's Life Sciences database in facility on April 30, 2025 were reviewed, and 553,519 SNF residents with a documented hypertension diagnosis were identified. Methods: The presence and absence of medication orders for antihypertensive treatment recommended by the International Society of Hypertension was assessed. Descriptive analyses summarized demographic and clinical characteristics, and a modified Poisson regression model was used to estimate risk ratios (RRs) for having a medication order, adjusting for demographic, clinical, and facility characteristics. Results: Overall, 87.7% of residents diagnosed with hypertension had at least one antihypertensive medication order. Calcium channel blockers (44.3%) and beta blockers (43.5%) were the most frequently used classes. RRs ranged from 0.91 to 1.09. Higher likelihoods of antihypertensive orders were observed among residents prescribed hyperlipidemia and diabetes medication (RR = 1.09 and 1.05, respectively), while lower likelihoods of treatment were observed for other payer types (RR = 0.91), diabetes diagnoses (RR = 0.95), and hyperlipidemia diagnoses (RR = 0.98). Conclusions and Implications: Most residents with hypertension had orders for recommended pharmacologic therapy, although important gaps and disparities remain. The predominance of certain medication classes and persistent differences by comorbidity and facility type underscore the need for targeted strategies to improve equitable prescribing and access to evidence-based hypertension management in SNF settings.

Background: Prior analyses have demonstrated an inverse association between transcatheter aortic valve replacement (TAVR) procedural volume and short-term outcomes. However, less is known regarding the relationship between procedural volume and 1-year outcomes in the contemporary TAVR era. Objectives: To evaluate the association between annual hospital and operator TAVR procedural volumes and 1-year clinical outcomes in a contemporary national cohort. Methods: Clinical records from the Society of Thoracic Surgeons (STS)/American College of Cardiology (ACC) Transcatheter Valve Therapies (TVT) Registry for patients undergoing commercial TAVR between January 2020 and December 2022 were linked to Centers for Medicare & Medicaid Services administrative claims. Annualized hospital and operator TAVR volumes were modeled continuously and categorized into tertiles. Primary outcomes included 1-year all-cause mortality, stroke, the composite of mortality or stroke, and all-cause readmissions. Hierarchical risk-adjusted models accounting for patient clustering within sites were used to evaluate associations between procedural volume and outcomes. Results: Among 215,335 patients undergoing TAVR at 788 hospitals by 3,444 operators between 2020 and 2022, median annual hospital and operator volumes were 74 (IQR: 43-115) and 16 (IQR: 10-32), respectively. Volume was then categorized into tertiles (low, medium and high). Compared with high-volume hospitals ([&ge;]102/year), low-volume hospitals ([&le;]52/year) had higher adjusted rates of 1-year all-cause mortality (Odds Ratio (OR): 1.10 [95% CI: 1.05-1.16]), stroke (OR: 1.10 [95% CI: 1.01-1.19]), mortality or stroke (OR: 1.10 [95% CI: 1.05-1.15]), and all-cause readmissions (OR: 1.05 [95% CI: 1.00-1.09]). Compared with high-volume operators ([&ge;]25/year), low-volume operators ([&le;]11/year) had higher adjusted rates of stroke (OR: 1.16 [95% CI: 1.05-1.28]) and mortality or stroke (OR: 1.09 [95% CI: 1.03-1.15]) but not other endpoints. Conclusions: In a large, contemporary national TAVR registry, lower annual hospital ([&le;] 52/year) and operator ([&le;] 11/year) procedural volumes were independently associated with worse 1-year clinical outcomes. These findings suggest that procedural experience continues to influence outcomes despite maturation of contemporary TAVR practice.

Background: Longer follow-up periods in clinical trials for S. aureus bacteremia (SAB) may capture unrelated deaths, adding random noise that risks biasing trial results towards the null. Objective: To evaluate the timing and infection-relatedness of deaths within a large SAB clinical trial platform. Design: Blinded duplicate adjudication of trial deaths using a modified 7-point Likert-Scale. A third reviewer settled disagreements. Setting: 37 Canadian hospitals participating in the S. aureus Network Adaptive Platform (SNAP) Trial. Participants: 1515 adult patients recruited to SNAP between February 2022 and May 2026. Measurements: Timing and relatedness of 90-day deaths categorized as at least possibly SAB-related not likely to be SAB-related. Optimal follow-up cut-off was determined using Youden's index and graphically. Results: 247 deaths occurred; 97 (39.3%) were adjudicated as at least possibly SAB-related and 150 (60.7%) as not likely related. For probably/definitely related deaths, interrater agreement was 85.0% (Gwet's AC 0.73, substantial); for at least possibly related, it was 77.3% (Gwet's AC 0.55, moderate). Median survival was significantly shorter for SAB-related deaths (12 vs. 30.5 days; difference: 19 days earlier, 95% CI: 12-26, p<0.0001). Nearly 80% of SAB-related deaths occurred by day 30, whereas 50% of unrelated deaths occurred between days 30 and 90. Youden's index optimized follow-up at 20.5 days. Limitations: Potential for cause of death misclassification and data limited to Canadian sites. Conclusion: Deaths considered attributable to SAB cluster rapidly within the first month, while later deaths are predominantly unrelated. A 30-day all-cause mortality window may be more appropriate than 90 days for primary mortality outcomes in trials evaluating acute SAB therapies with longer follow up reserved for metastatic infection and recurrence.

Vitamin D sterols, phosphorus binders and calcimimetics are used to treat chronic kidney disease mineral and bone disorder (CKD-MBD) in hemodialysis. With few randomized trials, providers may titrate agents differently reflecting equipoise and opportunities for clinical trials. We studied patients initiating in-center hemodialysis at Dialysis Clinic, Inc facilities from 2006-2015 and who remained on hemodialysis for [&ge;]90 days (n=23,549). Multinomial logit models assessed titration among users of each medication at the start of the month considering static and dynamic CKD-MBD laboratories. Similarly parameterized logistic models assessed treatment initiation. Differences across facilities were quantified as random effects and corresponding median odds ratios. We observed patterns of titration associated with CKD-MBD laboratories including albumin-corrected serum calcium (Ca), serum phosphorus and parathyroid hormone (PTH) and minimal impact of patient characteristics. Best fit models incorporated 3 months of lagged Ca and phosphorus values and linear splines for current Ca, phosphorus and PTH values. Absolute titration probabilities for vitamin D sterols and calcimimetics were influenced by all three CKD-MBD parameters, such that Ca and phosphorus values altered the threshold PTH at which escalation and de-escalation probabilities crossed. Median odds ratios indicated the greatest facility variation for vitamin D sterol titration. Providers titrate CKD-MBD medications based largely on the full CKD-MBD laboratory phenotype, including the recent serum Ca, phosphorus and PTH history. Facility variation suggests equipoise in titration of vitamin D sterols with opportunities for clinical trials.

Introduction: Early childhood vision screening is critical for detecting amblyopia and other vision-threatening conditions. Despite screening recommendations during well-child visits, rates remain low. Red reflex assessment is recommended to identify serious ocular pathology, yet its use in primary care is not well described. We examined rates and drivers of vision screening in pediatric primary care. Methods: We conducted a retrospective review of electronic health records for children 3 to 5 years attending well-child visits in 2022 in one of three representative primary care clinics within a university health system. Outcomes were documented red reflex and functional vision tests. We evaluated associations with patient demographics and clinic site using multivariable logistic regression Results: Among 1,003 visits, 21.1% (n=212) had a documented red reflex assessment, and 60.8% (n=610) a functional vision test. Younger children (ages 3 and 4 vs. 5 years) had higher odds of red reflex assessment [adjusted odds ratio (aOR) 9.00 and 8.64], and lower odds of a functional vision (aOR 0.47 and 0.59) test. Females had higher odds of red reflex assessment (aOR 1.53). Other/Multiracial children had lower odds of red reflex assessment than Non-Hispanic White children (aOR 0.48). Screening rates varied significantly by clinic site Conclusions: Visual function and red reflex assessment are inconsistently performed in pediatric primary care, with particularly low rates of red reflex documentation. Screening rates varied between clinics and were affected by age. These findings highlight missed opportunities for early detection of vision-threatening conditions and identify targets for improving adherence to pediatric vision screening recommendations

Abstract Importance Acute otitis media is the most common infection in children and a major reason for antibiotic prescriptions, up to one third of which may be unnecessary. Sector of care may influence AOM management through differences in access to care, specialist involvement, parental expectations and financial foundation. Objective The objective is to examine differences in antibiotic prescribing practices between healthcare sectors. Design This is a nationwide register-based study comparing data from different healthcare sectors. Setting Finnish primary and secondary healthcare, covering both public- and private-sector visits. Prescriptions and sociodemographic information were linked from nationwide registers. Participants We included children under 18 years old who received a diagnosis of acute otitis media, defined by ICD-10 codes H65-H67, between January 1, 2017 and December 31, 2022. Exposures The exposure is the sector of care (public sector vs. private sector). Main Outcomes and Measures Primary outcomes were antibiotic prescribing, guideline adherence of the prescribed antibiotics, and rates of management failure. Secondary outcomes included antibiotic selection and guideline-adherent eligibility for tympanostomy tube placement. Associations were estimated using adjusted odds ratios (aORs) with 95% confidence intervals (CIs). Results The study included 295 064 children with 596 634 acute otitis media index visits, of which 77.6% resulted in an antibiotic prescription. Private-sector visits were associated with higher odds of antibiotic being prescribed (adjusted odds ratio [aOR]: 1.45; 95% CI: 1.41-1.49). Overall, 87.3% of antibiotic prescriptions were guideline adherent, but private-sector care was associated with lower odds of guideline-adherent prescribing (aOR: 0.64; 95% CI: 0.60-0.69). Compared with amoxicillin, the private sector showed higher odds of prescribing amoxicillin-clavulanic acid (32.8% vs. 8.3%; aOR: 3.00; 95% CI: 2.91-3.10). Management failure occurred in 7.0% of episodes and was more common in the private sector (aOR:1.52; 95% CI: 1.48-1.56). Only 48.7% of all tympanostomy tube insertions met the eligibility criteria. Conclusions and Relevance In this study overall adherence to guideline-recommended antibiotic treatment for AOM was high in Finland. Nevertheless, observed clinically meaningful sectoral differences in antibiotic selection, treatment failure, and tympanostomy eligibility adherence indicate a need for targeted antimicrobial stewardship and quality-improvement efforts, especially in the private sector.

Multi-Cancer Detection (MCD) tests can detect more than 50 different types of cancer using a blood test. Recently passed law in the U.S. guarantees that Medicare will pay for these tests when they are FDA approved and show evidence for clinical benefit. This manuscript provides estimates of the cost of MCD tests to Medicare under different assumptions of cost per test, eligibility, and screening uptake in the eligible population. This manuscript additionally estimates the cost of follow-up testing resulting from false positive results, which are considered avoidable costs caused by the screening test.

Introduction. Extracorporeal cardiopulmonary resuscitation (ECPR) can support patients who fail to respond to standard resuscitation for out-of-hospital cardiac arrest (OHCA) allowing further time for critical interventions and patient recovery. Although the majority of patients with refractory OHCA have coronary artery disease, the role of emergent percutaneous coronary intervention (PCI) is not clear. We evaluated the effect of PCI on survival to hospital discharge (SHD) in a contemporary cohort of patients with OHCA receiving ECPR. Methods. We performed a retrospective study using data from the Extracorporeal Life Support Organization (ELSO) registry. We included patients ?18 years with OHCA due to a presumed cardiac etiology or an initial shockable rhythm who received ECPR from January 2020 to December 2023. Our primary outcome was SHD. We used inverse probability weighted matching to estimate the average treatment effect of PCI on SHD. We also performed a sensitivity analysis of patients most likely to benefit from PCI (witnessed arrest and no return of spontaneous circulation after five minutes of cardiopulmonary resuscitation. Results. Of 1336 OHCA patients receiving ECPR, 1131 were included in the final analysis after exclusions for age (n=31) and presumed non-cardiac or initial non-shockable rhythm (n=174). The median age was 55 years (IQR 44-62) and most patients were male (n=901, 80%). Twenty-one percent (n=243) received PCI; those patients who received PCI were slightly older (58 [IQR 48-63] vs 53 [IQR 42-62]) and more often male (n=212 [87%] vs n=689 [78%]). In the primary analysis, we found no significant difference in SHD for patients who received PCI compared to those who did not receive PCI (-3.56%, 95% CI -10.31 to 3.19; p-value 0.301). In our sensitivity analysis, we also did not find a significant difference in SHD for patients who received PCI compared to those who did not receive PCI (-4.52%, 95% CI -12.42 to 2.46; p-value 0.246). Conclusion. In our registry-based study of refractory OHCA patients receiving ECPR, emergent PCI was not associated with a significant improvement in SHD.

BACKGROUND Transthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive, life-threatening disease. Sociodemographic factors may influence time to treatment initiation and resulting clinical outcomes, yet these relationships are poorly characterized. OBJECTIVE Assess the effects of sex and race on tafamidis initiation and subsequent outcomes and their interaction with factors such as ATTR-CM type and social deprivation measures. METHODS A retrospective cohort analysis was conducted using the US Komodo Healthcare Map (01/2016-06/2024) among patients with amyloidosis, identified by ICD-10-CM diagnosis codes. Cumulative incidence of treatment initiation and survival probabilities for cardiovascular-related hospitalization (CVH) or death were estimated by Kaplan-Meier, stratified by sex and race. Cox proportional hazards models were fitted for both endpoints to estimate hazard ratios, adjusting for demographics and clinical characteristics. RESULTS Of 11,311 patients identified, White and Black patients (n=9,223) were included in subsequent analyses. Within 12 months of diagnosis, White women had the lowest cumulative incidence of tafamidis initiation (11.4%), followed by Black women (22.0%), Black men (26.7%), and White men (31.0%). Event-free survival at 12 months was lowest in Black women (42.9%), followed by Black men (46.8%), White women (48.6%), and White men (54.4%). Median (95% CI) time to CVH or death was shortest for Black women (8.0 months [6.8-10.0]) followed by Black men (9.9 months [8.8-12.0]), White women (11.0 months [9.6-13.0]), and White men (15.0 months [14.0-16.0]). CONCLUSIONS In this large, real-world cohort of US patients with ATTR-CM, sex and race contributed to disparities in tafamidis initiation and survival, underscoring compounded disparities in both access and outcomes.

Background: High intensity statins are foundational after acute coronary syndrome (ACS), yet intensive care unit prescribing occurs while renal reserve, perfusion, and interacting therapies are changing. We tested a renal safety checkpoint integrating kidney status, hemodynamic instability, and drug interaction burden to identify when statin intensity may become nonexchangeable. Methods: We emulated an active-comparator target trial across MIMIC-IV, eICU, and MIMIC-III. Critically ill adults with ACS, acute myocardial infarction, or percutaneous coronary intervention who received high- or moderate-intensity statins within 24 hours were included. The primary outcome was 7-day KDIGO stage 2 or 3 acute kidney injury or incident renal replacement therapy. Eligibility, time zero, treatment assignment, and follow-up were aligned. Database-specific propensity scores, overlap weighting, and standardization addressed confounding and treatment overlap. Safety domains, longitudinal analyses, bootstrap resampling, source omission, and endpoint sensitivities assessed robustness. Results: Among 5,178 patients, 761 developed the primary outcome, including 223 who initiated renal replacement therapy. Standardized risks were 17.40% with high-intensity therapy and 15.01% with moderate-intensity therapy (risk difference, 2.39 percentage points [95% confidence interval (CI), -0.23 to 5.05]; risk ratio, 1.16 [95% CI, 0.99 to 1.39]). Risk separation was greatest with high hemodynamic instability (5.78 percentage points [95% CI, 1.56 to 9.74]) and high drug-interaction burden (6.24 percentage points [95% CI, -0.44 to 12.19]). Renal replacement therapy showed a 1.33-point risk difference (95% CI, 0.18 to 2.67). Conclusions: This study moves statin safety assessment beyond fixed dose label or isolated creatinine measurement. The findings support a clinically actionable monitoring strategy in which early statin intensity is reassessed against evolving perfusion, kidney status, and interaction burden. This approach preserves intensive lipid lowering for physiologically suitable patients while identifying a high risk window in which temporary moderation.

Background: The U.S. has the highest health care expenditure globally. Examining long-term national and state-level trends, and benchmarking them against other health systems, can provide important insights for public health planning and policy development. Aim: This study aimed to characterize temporal trends in the burden of bladder cancer, including prevalence, incidence, mortality, disability-adjusted life years (DALYs), years lived with disability (YLDs), and years of life lost (YLLs), and to evaluate state-level disparities and potential long-term effects of health policies. Methodology: Data were obtained from the Global Burden of Disease (GBD) 2021 study. Age- and sex-stratified trends were analyzed and visualized at both national and state levels across the study period. Burden estimates were additionally compared with those of other major health systems, including the European Union, countries with high socio-demographic index, and high-income settings. Results: In 2021, the U.S. recorded age-standardized rates of 8.35 for YLDs (0.33 lower), 3.41 for mortality (0.11 higher), 59.80 for YLLs (6.75 higher), 100.63 for prevalence (6.61 lower), 14.69 for incidence (0.51 lower), and 68.15 for DALYs (6.42 higher) compared to 1990 records. Lowest gender discrepancies across all measures were in 2021 were observed in District of Columbia with male:female ratio of DALYs: 2.4 [1.7, 3.2], mortality: 2.4 [1.8, 3.2], incidence: 2.5 [1.8, 3.4], prevalence: 2.4 [1.8, 3.2], YLDs: 2.4 [1.4, 4.1], and YLLs: 2.4 [1.7, 3.2]. In contrast, North and South Dakota had the highest gender discrepancies: DALYs: 3.9 [3.0, 5.2], incidence: 4.1 [3.1, 5.4], prevalence: 3.9 [3.0, 5.0], and YLLs: 4.0 [3.0, 5.2] and mortality: 4.2 [3.2, 5.6] and YLDs: 3.9 [2.3, 6.3]. Conclusion: Bladder cancer continues to impose a substantial and uneven burden across the U.S. State-level variations, driven by environmental factors, aging populations, and healthcare access gaps, require targeted prevention and improved early detection. Future research should assess the cost-effectiveness of prioritizing prevention over late-stage treatment to optimize healthcare spending.

Nickel has been studied for a long time as an environmental contaminant but less so in its connection to population health. It does not announce itself as loudly as its transition metal brethren like mercury and cadmium, but its chemical properties permit it to be deleterious as a low-dose, chronic exposure, particularly among those with immune systems sensitized to it. There is a growing evidence base and vocabulary to discuss nickel's affect on health. However, in the U.S., there are not recent, reliable estimates of the share of the population with a nickel allergy, let alone how much nickel Americans are exposed to through their diet. This paper seeks to close this evidence gap by creating a new dataset of dietary nickel and other heavy metal exposure and assessing how high levels of dietary nickel exposure shape local demand for health care services. We use soil data from the U.S. Geological Survey and data on agricultural product transport from FoodFlows.org to create a county-level dietary nickel exposure index. We then use a large electronic health record database and double machine learning to estimate how demand for primary care services varies across levels of dietary nickel exposure. We find that counties with high nickel exposure experience an increase in the share of primary care office visits for symptoms highly suggestive of nickel poisoning. This result survives multiple hypothesis test corrections and placebo tests. Our research suggests that nickel has harmful effects on individual health whose exposure can be measured at a population level, and is shaping primary care across the U.S.

Purpose: Population-level lung cancer screening programs require denominators that reflect age, smoking history, geography, and changing eligibility over time. We estimated annual prevalent and 20-year cumulative unique low-dose computed tomography screening eligibility for Maryland residents under alternative screening criteria. Methods: We built a deterministic cohort-cell stock-flow simulation using Maryland county-equivalent jurisdiction projections by age, sex, and race/ethnicity, with ACS socioeconomic/nativity covariates and smoking-history priors for ever-smoked status, pack-years, and quit-years. Scenarios included USPSTF 2013 legacy, USPSTF 2021, ACS 2023/2024, a risk-model-expanded sensitivity, and ever-smoked-only capacity stress tests. Cumulative unique eligibility counted people once at first eligibility rather than summing annual prevalent person-years. Results: Under USPSTF 2021, an estimated 238,346 Maryland residents were eligible in 2026 and 245,326 in 2045. The 20-year cumulative unique denominator was 768,668, whereas naively summing annual prevalent counts produced 4,850,735 person-years, a 6.31-fold overcount. ACS 2023/2024 expanded annual eligibility to 314,616 in 2026 and cumulative unique eligibility to 902,796 by adding remote former smokers. Ever-smoked-only adult eligibility was 1,957,699 in 2026 and 3,383,683 cumulative unique over 20 years. Conclusion: A Maryland statewide screening initiative should plan from cumulative unique eligibility and county-equivalent jurisdiction-specific burden rather than annual prevalence alone. Explicit pack-year and quit-year modeling materially changes statewide and county allocation compared with current-smoking proxy models.

Objective: To identify latent phenotypes of observed electronic health record (EHR) contact among patients with hypertension, evaluate their reproducibility across temporal resolutions and sensitivity to administrative censoring, and examine associations with treatment documentation and blood pressure (BP) control after adjustment for comorbidity burden and measurement opportunity. Methods: We conducted a retrospective cohort study of patients with hypertension and at least two recorded visits (N = 26,710). Latent class trajectory modelling of repeated binary visit indicators within a Bernoulli finite mixture framework was performed using 1-month and 3-month intervals over 36 months. Models were selected using the Bayesian Information Criterion and GRoLTS-recommended metrics. Multivariable linear regression examined associations between trajectory phenotypes and treatment documentation and BP control after adjustment for age, sex, race, baseline BP, and comorbidity burden. BP outcomes were also compared at 12, 24, and 36 months. Results: Four observed EHR contact trajectory groups were identified at both temporal resolutions (1-month: relative entropy 0.821, minimum APP 0.770, minimum OCC 6.49; 3-month: relative entropy 0.771, minimum APP 0.778, minimum OCC 5.39), with excellent bootstrap reproducibility (mean ARI 0.966 - 0.969). The four-group structure was replicated in the [&ge;] 24-month subgroup, although this represented only 20.8% of the cohort. Overall, 79.2% of patients had <24 months of follow-up, with censoring concentrated in the lowest-contact groups, indicating that these trajectories reflect observed EHR contact under variable administrative observation rather than patient disengagement. After adjustment, higher-contact groups had consistently higher treatment documentation rates than the low observed follow-up group, whereas differences in BP control were small and inconsistent. The highest-contact group did not achieve the lowest BP at any fixed time point despite the largest first-to-last BP reduction, demonstrating bias from differential observation window length. Conclusion: Four internally reproducible phenotypes of observed EHR contact were identified, but their trajectories were substantially influenced by administrative censoring and lack external validation. Contact phenotype was associated with treatment documentation but only weakly with BP control after adjustment.

Across 30 US states and the District of Columbia, eliminating the AIDS Drug Assistance Program is projected to save $6.45 billion in direct costs while generating $14.89 billion in downstream HIV care costs attributable to excess incident infections from 2026-2035. Costs are projected to surpass savings within six years.

Objective: To determine the absolute risk of starting dialysis versus mortality among adults with chronic kidney disease (CKD) treated at EsSalud from 2013 to 2022, utilizing data from the Renal Health Surveillance system (VISARE). Methods: This retrospective cohort study analyzed clinical records from the VISARE system (EsSalud). We estimated rates of dialysis initiation and death using Fine & Gray competitive risk models. Additionally, we calculated Restricted Mean Survival Time (RMST), adjusting for age, sex, clinical stage, and geographic region. Results: Among 142,770 adults with confirmed CKD and available glomerular filtration rate data, only 15.2% had albumin-to-creatinine ratio measurements, allowing KDIGO staging of 40,404 patients (28.3%). Mortality without having previously started dialysis exceeded the probability of starting renal replacement therapy (RRT) from G1, becoming more marked in G3 of chronic kidney disease (CKD); the possibility of dialysis is only greater, as expected, in G5. This outcome was most prevalent in regions with limited healthcare coverage. The combination of diabetes, hypertension, and age over 55 (the triad) was associated with reduced restricted mean survival time at both 5- and 10-year horizons across all enrollment cohorts. While Lima saw the highest rates of renal replacement therapy initiation, the Andean and Amazonian regions reported the lowest indicators. Conclusions Death without prior dialysis was the dominant outcome from G1 to G3 in this Peruvian cohort with national insurance, with direct implications for prognostic counseling, recalibration of renal failure risk equations, and equitable expansion of nephrology services in underserved regions. Keywords: Renal Insufficiency, Chronic; Competitive Risk; Diabetes Mellitus; Hypertension; Mortality; Mass Screening.

Importance Evolocumab reduces major adverse cardiovascular events (MACE) in patients with clinically evident atherosclerotic cardiovascular disease (ASCVD) and in patients at high cardiovascular (CV) risk but without a prior myocardial infarction (MI) or stroke. While evolocumab is shown to be cost-effective in clinically evident ASCVD, emerging CV outcomes evidence and newer guideline recommendations warrant assessment in patients at high CV risk without a prior MI or stroke. Objective To evaluate the cost-effectiveness of evolocumab added to standard therapy compared with standard therapy alone in patients at high CV risk without a prior MI or stroke, as represented by the VESALIUS-CV trial. Design, Setting, and Participants A previously published Markov cohort state-transition model was adapted to simulate VESALIUS-CV patients over a lifetime horizon. Health states included high-risk without a prior MI or ischemic stroke (IS), non-fatal MI, non-fatal IS, post-MI, post-IS, CV death, and non-CV death. Revascularization (RV) was modeled as a procedure with associated costs. The base case considered a US payer perspective and CV risk reduction inputs from evolocumab CV outcomes trials, including VESALIUS-CV, FOURIER, and FOURIER-OLE. Three scenario analyses were evaluated. Scenario 1 retained the US payer perspective and applied CV risk reduction estimates based on the Cholesterol Treatment Trialists' (CTT) Collaboration 2010 meta-analysis. Scenarios 2 and 3 adopted a US societal perspective, using evolocumab CV outcomes trial-based and 2010 CTT Collaboration-based risk reduction estimates, respectively. Main Outcomes and Measures The model outcomes included MACE (defined as MI, IS, or CV death), RV procedures, total costs, life-years (LYs), quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio (ICER). Results In the base case, at the current direct-to-patient price of $3,107 per year, evolocumab added to standard therapy was associated with lifetime reductions of 0.24 MACE and 0.17 RV procedures per person, incremental costs of $24,430, incremental QALYs of 0.34, and an ICER of $71,162 per QALY gained. Evolocumab remained cost-effective across all evaluated scenarios, with ICERs of $42,094, $51,160, and $20,152 per QALY in Scenarios 1, 2, and 3, respectively. Conclusions and Relevance In patients at high CV risk without a prior MI or stroke, evolocumab added to standard therapy was projected to improve CV outcomes and quality-adjusted survival. At the current direct-to-patient price of $3,107 per year, evolocumab was cost-effective in the base-case analysis, with an ICER of $71,162 per QALY gained, and remained cost-effective across scenario analyses, with ICERs ranging from $20,152 to $51,160 per QALY. These estimates were substantially below the $120,000 per QALY threshold defined in the 2025 American Heart Association/American College of Cardiology cost/value methodology statement.