Canadian Medical Association Journal

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.

BackgroundMultimorbidity is common among U.S. skilled nursing facilities (SNFs) residents and complicates pharmacologic management, yet real-world evidence on treatment patterns in this population remains limited. This study evaluated medication order rates and identified resident- and facility-level factors among SNF residents with multimorbidity. MethodsRetrospective, observational study using electronic health record (EHR) data from PointClickCares Life Sciences database. Participants were 728,222 residents active in a U.S. SNF on April 30, 2025 with at least one documented diagnosis of hypertension, hyperlipidaemia, type 2 diabetes (T2D), depression, or Alzheimers disease and related dementias (ADRD). The outcome was presence of guideline-recommended medication order for each condition, modelled with modified Poisson regression to estimate adjusted prevalence risk ratios (RRs) and 95% confidence intervals. ResultsMedication order rates were 79% for ADRD, 79.1% for T2D, 87.7% for hypertension, 83.3% for hyperlipidaemia, and 90.8% for depression. Rates varied across comorbidity combinations: ADRD was associated with lower medication order prevalence, while cardiometabolic multimorbidity profiles associated with higher prevalence. Black/African American identity had the lowest likelihoods of a medication order for 3 of 5 conditions (RRs of 0.93 to 0.92), while having hypertension or hyperlipidaemia medication order was associated with higher likelihood of having orders for 3 of remaining 4 conditions (RRs of 1.02 to 1.19). ConclusionsMost SNF residents with multimorbidity had a medication order for common chronic conditions, although important variability and disparities remain. Differences by comorbidity profile and social context underscore the need for targeted strategies supporting equitable, integrated prescribing and person-centred care in SNFs.

Background: Individuals undergoing lung cancer screening (LCS) represent a population at high risk for atherosclerotic cardiovascular disease (ASCVD), yet opportunities for cardiovascular prevention during screening encounters may be underutilized. While prior studies have examined whether statins are prescribed in eligible patients, little is known about the timing of statin initiation following LCS, particularly among statin-naive individuals. Methods: We conducted a retrospective cohort study using electronic health record data from a large academic health system in Missouri. Adults aged 50-80 who underwent LCS between January 1, 2015, and December 31, 2023, were statin-naive, and met 2019 ACC/AHA criteria for primary prevention were included. The primary outcome was time-to-statin initiation following LCS. Kaplan-Meier methods and Cox proportional hazards models were used to evaluate timing and predictors of statin initiation across demographic, clinical, and socioeconomic subgroups. Results: Among 3,100 statin-eligible, statin-naive individuals who had undergone LCS, only 27.3% were prescribed a statin within one year of LCS. Uptake accrued gradually (10.5% by 90 days; 17.8% by 180 days; 23.2% by 270 days; 27.1% by 360 days). In adjusted models, earlier statin initiation was independently associated with a higher ASCVD risk category, a cardiology visit in the year preceding LCS, and former (versus current) smoking; older age and male sex were associated with slower initiation. Race, insurance type, and area deprivation were not independently associated with time-to-statin initiation. Conclusions: Despite high ASCVD risk, most statin-eligible patients undergoing LCS did not receive timely statin therapy. Earlier initiation tracked calculated ASCVD risk and specialty (cardiology) contact rather than race, sex, insurance, or area deprivation. Because most patients at high calculated risk still went untreated, integrating cardiovascular risk assessment and preventive decision support into LCS workflows may help reduce missed opportunities for ASCVD prevention.

Background. Coronary CT angiography (CCTA) and calcium scoring detect subclinical coronary atherosclerosis, but the results of community based screening in asymptomatic adults with cardiovascular risk factors are poorly described. Objective. To describe the results of the first phase of a county-funded CT screening program and their variation by demographics, health system, time, and ZIP code. Methods. Retrospective analysis of aggregate reports from the Broward County Florida Heart Project (May 2023 to September 2025). Eligible residents were those with insurance coverage, age 45 to 70 years (limited exceptions), free of known cardiovascular disease and symptoms, with at least one risk factor. Examinations at six hospitals in four health systems were classified by the program team as normal (Category 1), abnormal (Category 2), or very abnormal (Category 3), with a separate flag for other non coronary abnormality. We used Wilson confidence intervals and chi square, trend, and Mantel Haenszel tests. Results. Among 7,135 participants (58.3% men; 79.0% White, 8.0% Black, 17.2% Hispanic), 43.2% had Category 1, 45.4% Category 2, and 11.4% Category 3 results; 56.8% (95% CI, 55.7% to 58.0%) had abnormal or very abnormal results. The proportion rose from 39.3% at 45 to 55 years to 78.5% at 71 or older (trend P<0.001) and was higher in men than women (68.9% vs 39.8%; odds ratio [OR], 3.36; 95% CI, 3.05 to 3.71). Rates were lower in Black than White participants (38.9% vs 58.6%; hospital adjusted OR, 0.45; 95% CI, 0.38 to 0.54) and in Hispanic than non Hispanic participants (51.0% vs 57.8%). Abnormal results ranged from 39.5% to 60.3% across health systems (P<0.001). Variation across the 50 highest volume ZIP codes did not exceed chance (P=0.53). Conclusions. More than half of insured, asymptomatic adults with risk factors screened in this community program had abnormal results, with steep age and sex gradients and unexplained variation across health systems. Black, Hispanic, and female residents were under-represented relative to the county

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.

We develop an age- and immunity-structured COVID-19 model with setting-specific contacts, calibrated to Ontario incidence and hospital admissions before Omicron. We simulate counterfactual vaccination strategies and contact restrictions in schools, workplaces, and other community settings, evaluating projected severe-case demand against an illustrative healthcare-capacity benchmark. Vaccination combined with workplace and community contact restrictions keeps simulated demand within capacity. In contrast, relaxing restrictions in either setting produces large surges and repeated capacity threats, even when school restrictions remain. School-only changes produce smaller effects on severe disease. These findings highlight the value of vaccination and setting-specific contact restrictions that prioritize workplace and community settings for pathogens with adult-concentrated severe outcomes.

Background Hepatitis E virus infection is associated with renal manifestations in selected clinical populations. Whether serologic evidence of previous exposure is associated with kidney dysfunction in the general population remains uncertain. Methods We conducted a cross-sectional analysis of six National Health and Nutrition Examination Survey cycles from 2009-2018 and August 2021-August 2023. Adults aged [&ge;]20 years with valid hepatitis E virus immunoglobulin G levels, serum creatinine levels, urinary albumin-to-creatinine ratios, and covariate data were included. The outcomes included a reduced estimated glomerular filtration rate (<60 mL/min/1.73 m2), albuminuria (albumin-to-creatinine ratio [&ge;]30 mg/g [3.39 mg/mmol]), and their composite. Survey-weighted logistic regression models were unadjusted, adjusted for age and sex, and additionally adjusted for demographic and clinical covariates. Results Among 30,428 adults, 2,911 were seropositive; the weighted seroprevalence was 8.29%. The seropositive participants were older than the seronegative participants were (weighted mean, 60.7 versus 46.5 years). Seropositivity was associated with all three binary outcomes in unadjusted analyses, but the estimates approached the null after adjustment for age and sex. The fully adjusted odds ratios were 0.99 (95% confidence interval, 0.85-1.16) for a reduced filtration rate, 1.05 (0.91-1.22) for albuminuria, and 1.05 (0.93-1.19) for composite kidney dysfunction. In a secondary analysis, seropositivity was associated with a 1.57 mL/min/1.73 m2 higher adjusted mean filtration rate (95% confidence interval, 0.71-2.43). Conclusions Hepatitis E virus immunoglobulin G seropositivity was not significantly associated with binary kidney outcomes after adjustment. Attenuation occurred principally after adjustment for age and sex. These findings do not establish the absence of an association and do not address kidney injury during active or persistent infection.

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: 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.

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.

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.

Background: Percutaneous mechanical circulatory support (pMCS) is increasingly used in critically ill patients, yet its value in relation to cost and outcomes remains unclear. We evaluated national variation in utilization, outcomes, and cost, and introduced a value of care framework integrating risk-adjusted outcomes and expenditures. Methods: We performed a retrospective cohort study using the National Inpatient Sample to identify non-elective hospitalizations of critically ill patients undergoing intra-aortic balloon pump (IABP) or percutaneous left ventricular assist device (pLVAD) placement using ICD-10 codes. Multivariable logistic regression and generalized linear models were used to estimate expected outcomes and costs. Observed-to-expected (O/E) ratios were calculated, and a value index was derived to compare procedural strategies. Results: A total of 57,910 weighted hospitalizations were included (IABP 78%, pLVAD 22%). In-hospital mortality exceeded 30% across regions. Significant regional variation was observed, with the West demonstrating the highest costs and the Midwest the lowest (p<0.001). Mean hospital charges were higher for pLVAD compared with IABP ($403,731 vs $320,769). Both strategies achieved outcomes better than expected after risk adjustment (O/E 0.92); however, costs were higher than expected for both, with greater relative cost inflation observed for IABP (O/E 1.41) and higher absolute costs for pLVAD. In value-of-care analysis, IABP was associated with lower cost and comparable outcomes, while pLVAD demonstrated higher cost without proportional outcome improvement. Conclusion: Substantial variation exists in the cost, outcomes, and value of pMCS strategies. While both IABP and pLVAD achieve favorable risk-adjusted outcomes, pLVAD is associated with higher costs without commensurate clinical benefit.

Background: Primary malignant cardiac tumors (PMCTs) are rare and histologically heterogeneous. Objective: To compare demographics, specific ICD-O-3 morphologies, first-course treatment patterns, annual registered case counts, and unadjusted overall survival between soft-tissue and hematologic PMCTs. Methods: We identified 730 PMCT cases diagnosed from 2000 to 2021 in SEER 18 (ICD-O-3 topography C38.0). Histologic lineage was assigned from ICD-O-3 morphology. Comparative analyses included soft-tissue (n=458) and hematologic (n=212) tumors. First-course variables were primary-site surgery, chemotherapy (yes versus no/unknown), and radiotherapy (radiation versus none/unknown). Groups were compared with chi-square tests. Overall survival was estimated with Kaplan-Meier methods; follow-up was truncated at 120 months. Results: Soft-tissue PMCTs occurred predominantly at ages 45-64 years (67.9%), whereas hematologic PMCTs occurred predominantly at age [&ge;]65 years (63.2%; p<0.001). Men comprised 59.9% of hematologic and 49.3% of soft-tissue cases (p=0.014). The leading soft-tissue morphology was hemangiosarcoma/angiosarcoma (ICD-O-3 9120/3; 201/458, 43.9%); synovial sarcoma accounted for 20/458 cases (4.4%). Diffuse large B-cell lymphoma, NOS, accounted for 131/212 hematologic tumors (61.8%). Any primary-site surgery was recorded in 66.6% of soft-tissue versus 15.6% of hematologic cases (p<0.001). Chemotherapy was recorded in 67.5% versus 51.1% (p<0.001), and radiotherapy in 9.0% versus 20.5% (p<0.001). In exploratory Kaplan-Meier analyses, hematologic patients with recorded chemotherapy had higher unadjusted 120-month overall survival than those without recorded chemotherapy (42.0% versus 12.2%; log-rank p=7.5x10-). Radiation-associated survival differences were not statistically significant in either lineage. Conclusions: Soft-tissue and hematologic PMCTs have distinct age distributions, named histologies, and first-course treatment patterns in SEER. These findings describe registry coding and do not establish treatment effectiveness or population incidence.

This paper examines the impact of Cancer Care Ontario's regionalization of lung cancer surgery on blood transfusion use for thoracic surgery at The Ottawa Hospital. Using aggregate data scraped from the paper ''Changing trends in blood transfusion: an analysis of 244,013 hospitalizations'' by Shehata et al. (2014) we estimated the effect regionalization on the log mean number of blood transfusions among thoracic surgeons (who treat lung cancer), utilizing other surgical specialties as controls. We found that the average number of blood transfusions increased significantly among thoracic surgeons following the opening of a new cancer care centre at the hospital in December 2009, while control specialties showed no parallel change. Contextualizing these results in a modified ''population level'' treatment threshold model, it is argued that the main driver of this increase in blood transfusions among thoracic surgeons was due to the influx of less skilled thoracic surgeons to The Ottawa Hospital, and the closing of thoracic surgery units at smaller hospitals which was part of the broader regionalization process.

Improving primary care is a long-standing strategy to constrain health care spending. Yet, evaluations of primary care models focused on payment reform have shown minimal effects on total cost of care. We report the results from a large-scale, real-world evaluation of an advanced primary care model that restructures access through same-day and next-day appointments, on-demand video visits, asynchronous clinician messaging, and extended hours. Using a stacked-cohort difference-in-differences design with entropy balancing and inverse probability of censoring weighting, we analyzed multi-payer claims covering April 2022 through March 2025. Advanced primary care use was associated with an 8.6% reduction in total cost of care (-$729 per patient per year; P = 0.004), driven by lower specialist cost (-$939/year; P < 0.001) and, to a lesser degree, by reductions in inpatient (-$134/year; P < 0.001), urgent care (-$70/year; P < 0.001), and emergency department cost (-$16/year; P = 0.02), partially offset by higher primary care cost (+$350/year; P < 0.001). The specialist reduction was concentrated in knowledge-based consultative encounters (-$663/year; P < 0.001), while procedural specialist cost was largely unchanged (-$276/year; P = 0.09). Cost differences emerged in the first post-index month. These findings suggest that advanced primary care may reduce total health care spending, with observed savings driven primarily by lower spending on consultative specialty care.

Background: Non-medically attended (NMA) and outpatient medically attended (MA) influenza illnesses contribute substantially to influenza disease burden in the United States. We leveraged a household study to estimate out-of-pocket and lost productivity costs of NMA and MA influenza illness. Methods: The Respiratory Virus Transmission Network for Influenza was a 2024-2025 case-ascertained household study at 3 U.S. sites. Influenza-positive index patients and household contacts self-reported daily symptoms, over-the-counter (OTC) medication use, medical care-seeking, time missed from work or activities, and self-collected nasal swabs for PCR testing. We included participants with PCR-confirmed influenza infection and influenza-like-illness symptoms who ever (MA) or never (NMA) sought medical care during follow-up. We obtained costs of OTC medications from retail websites and productivity costs from published values. We calculated OTC medication and lost productivity costs in 2025 USD for MA and NMA influenza separately and household-level lost productivity costs among caregivers for MA and NMA household members. Results: Median out-of-pocket OTC medication costs were $6.38 (interquartile range [IQR] $2.92-$11.60) among 594 MA and $3.72 (IQR $1.50-$7.05) among 153 NMA influenza illnesses. Among participants [&ge;]15 years of age, median lost productivity was $315 ($149-$743) for MA and $248 ($0-$624) for NMA illnesses. Median household-level lost productivity for caregiving was $148 (households with 1 ill child), $379 (multiple ill children), and $0 ([&ge;]1 ill adult). Conclusions: Influenza causes substantial lost productivity costs within households. These estimates can inform future economic burden and cost effectiveness analyses.

Background: It is unclear if sex differences exist in cognitive impairment and dementia associated with atrial fibrillation (AF) and whether this relationship is influenced by oral anticoagulation (OAC) therapy. Methods: We identified patients [&ge;]40 years with incident non-valvular AF (NVAF) and without previous history of cognitive impairment or dementia, stroke/transient ischemic attack or contraindication to OAC between April 1st, 2012 and March 31st, 2024, using linked administrative databases in Alberta, Canada. Outcomes included cognitive impairment, Alzheimer's disease, vascular dementia, and all-cause mortality. Survival models were used to estimate association between sex and outcomes, and between OAC therapy and outcome stratified by sex. Results: Of 66,885 patients, 43% were female. Compared to males, females were older (74 vs 68 years), frailer (14.7% vs 10.1%), and more likely to have CHA2DS -VA score [&ge;]2 (73% vs 65%). OAC was initiated in 60% of both sexes within 120 days of diagnosis. Females had a higher risk for cognitive impairment (aHR 1.14 [95% CI 1.07-1.20], p<0.0001), but a lower risk of vascular dementia (aHR 0.75 [95% CI 0.63-0.90], p=0.0016) and all-cause mortality (aHR 0.91 [95% CI 0.88-0.94], p<0.001), with no difference in risk of Alzheimer's disease (aHR 1.01 [95% CI 0.88-1.17], p=0.8496) between the sexes. Non-vitamin-K OAC (NOAC) use was associated with a lower risk of cognitive impairment compared to either warfarin or no OAC in both sexes, but a lower risk of Alzheimer's and vascular dementia in males only. Conclusion: In this large population-based study, we found females have a higher risk of cognitive impairment, but a lower risk of vascular dementia and all-cause mortality compared to males. For both sexes, NOAC use was associated with a lower risk of cognitive impairment compared to no OAC and a lower risk of Alzheimer's and vascular dementia in males only.

Pubertal growth spurt characteristics vary substantially across populations, but no study has characterized these parameters in Vietnamese children using the SITAR (SuperImposition by Translation And Rotation) framework, despite Vietnam rapid ongoing nutritional transition. We fitted sex specific SITAR models to longitudinal height data from 15,491 children (9,047 boys, 6,444 girls, 2018 to 2025) to estimate population and individual age at peak height velocity (APHV) and peak height velocity (PHV), and used multivariable linear mixed effects and logistic regression models to identify prepubertal predictors of pubertal timing and intensity. Population mean APHV was 12.2 years in boys and 9.2 years in girls, with PHV of 9.3 and 7.0 cm/year, respectively. This is earlier than previously reported Korean, Colombian, Ethiopian and US cohorts. Individual variability in pubertal timing was nearly twice as large in girls as in boys. After multivariable adjustment, higher baseline BMI-for-age z-score independently predicted earlier pubertal timing in both sexes, whereas height-for-age z-score and prepubertal height velocity showed opposite direction associations (earlier timing in boys but later timing in girls). A significant secular trend toward earlier puberty was observed in girls (~1 year per decade) but not in boys. Logistic models predicting early pubertal timing achieved acceptable discrimination in boys (AUC=0.76) and modest discrimination in girls (AUC=0.70). This first SITAR-based characterization study reveals earlier pubertal timing in these Vietnamese urban schoolchildren than comparator populations, pronounced sex-specific associations between prepubertal BMI status and height status, and a marked secular trend in earlier puberty in girls warranting further surveillance. Keywords: puberty, growth spurt, SITAR, peak height velocity, adolescent growth, Vietnam, BMI, secular trend

Background: The optimal P2Y12 inhibitor after percutaneous coronary intervention (PCI) remains debated. A recent frequentist network meta-analysis (NMA) concluded prasugrel provided optimal efficacy-safety balance. We update our previous Bayesian NMA with recent trials and contrast our findings with the frequentist NMA. Methods: We extended our 2023 systematic review by adding two trials published after our search cutoff. The primary efficacy endpoint was a composite of all-cause mortality, a recurrent non-fatal myocardial infarction, or non-fatal stroke (MACE). The primary safety endpoint was study-reported major bleeding events. Bayesian network meta-analysis with a primary binomial complementary log-log model with log(time) offset and random effects was performed. A statistical workflow with prior and posterior predictive checks, convergence diagnostics, model comparisons, sensitivity analyses and probabilities for a range of practical equivalence (ROPE: HR 0.90-1.11) are also reported. Results: 19 RCTs (n = 60,619) were identified. For MACE, prasugrel's probability of a clinical efficacy benefit (hazard ratio (HR) <0.9) was 70% compared to clopidogrel (HR 0.87, 95% credible interval (CrI )0.76-1.03) and 54% compared to ticagrelor. (HR 0.89, 95% CrI 0.73-1.12). For the ticagrelor versus clopidogrel comparison 76% of the posterior probability (HR 0.98, 95%CrI 0.82-1.18) lies in the ROPE. Ticagrelor (HR 1.26, 95%CrI 1.01-1.63) and prasugrel (HR 1.1, 95%CrI 0.88-1.26) showed 86% and 51% probabilities respectively of meaningful bleeding harm (HR > 1.1) versus clopidogrel. Conclusions: Despite 19 RCTs and approximately 60,000 patients, the Bayesian framework revealed clinically important uncertainties and identified probable regions of equivalence among the different P2Y12 inhibitors that were under appreciated with the previous frequentist publication.