Journal of the American Geriatrics Society

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.

Biological aging, the decline in physiological resilience that increases our vulnerability to disease and death as we grow older, can be measured from standard clinical-laboratory panels. Measurement of biological aging from laboratory data embedded in electronic health records (EHRs) could enhance precision healthcare. However, suitability of EHR-embedded laboratory records for this purpose is uncertain. We evaluated feasibility of EHR biological age measurement in a cohort of n=4,313 cardiothoracic-surgery patients at a large US Hospital and tested whether measured biological aging was associated with patient outcomes. Patients who were biologically older prior to surgery more often died or experienced adverse outcomes as compared to those measured to be biologically younger. Postoperative biological-aging trajectories were associated with length of intensive-care-unit (ICU) stays and in-hospital death. EHR laboratory data provide an opportunity for scalable implementation of biological aging measurement within healthcare systems, with potential to enhance patient monitoring and risk stratification.

Importance: The ASPREE randomized trial found no overall benefit of low-dose aspirin for disability-free survival among older adults. However, individual estimates in pre-specified subgroups indicated potential benefit among racial and ethnic minoritized participants in the United States (US). Objective: To evaluate whether the effect of low-dose aspirin vs placebo on disability-free survival differed across US Black and Hispanic ASPREE participants using individualized treatment-effect estimation. Design, Setting, and Participants: Post hoc clinical trial analysis of ASPREE, a randomized, double-blind, placebo-controlled clinical trial of daily low-dose aspirin vs placebo. This analysis included US ASPREE participants who self-identified as non-Hispanic Black or Hispanic, were aged 65 years or older, and had complete baseline predictor and outcome data. Interventions: Randomization to daily 100-mg aspirin or placebo. Main Outcomes and Measures: The primary outcome was loss of disability-free survival, defined as death, persistent physical disability, or dementia. Individualized treatment effects were estimated post hoc using a Random Survival Forest X-learner. Heterogeneity was evaluated on the relative scale with Cox proportional hazards models and on the absolute scale with 5-year risk differences. Results: Among 2411 US ASPREE participants, 1270 were included in the Black and Hispanic analytic cohort (897 non-Hispanic Black and 373 Hispanic participants; mean age, 71.8 years). Aspirin was associated with lower risk of disability-free survival loss compared with placebo (hazard ratio [HR], 0.65; 95% CI, 0.45-0.93). In model-derived tertiles, aspirin was associated with lower risk in the greatest predicted-benefit group (HR, 0.36; 95% CI, 0.19-0.71; 5-year absolute risk difference [ARD], -11.1 percentage points; 95% CI, -22.0 to -0.1) but not in the lowest predicted-benefit group (HR, 1.26; 95% CI, 0.70-2.27; ARD, +3.9 percentage points; 95% CI, -5.9 to 13.6). Conclusions and Relevance: In these analyses of US Black and Hispanic ASPREE participants, aspirin effects on disability-free survival appear to be heterogeneous, with benefit concentrated in a subset of participants. Because these findings are from post-hoc models, they should be externally validated before being incorporated into clinical decision-making. Trial Registration: ClinicalTrials.gov Identifier: NCT01038583; https://clinicaltrials.gov/study/NCT01038583

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: Preclinical and human observational studies suggest that metformin may decrease age-related pathology, including frailty. Objective: Determine whether metformin reduces frailty progression and biological age in older adults with glucose intolerance, a population at increased risk of becoming frail. Design, Setting and Participants: Randomized, double-blind, placebo-controlled trial of metformin in 145 non-frail or pre-frail older adults. Participants (72 +/-5 years, 48% female, 94% White, 35% Hispanic) were randomized to metformin vs. placebo for two years. Main Outcomes and Measures: Effect on frailty was primarily determined using generalized estimating equations by change in the Fried frailty phenotype score (based on weight loss, exhaustion, physical activity, gait speed, and grip strength). Because metformin can cause significant weight loss, effects on the Fried score were assessed with and without the weight loss criterion. Frailty also was assessed by change in the frailty index (composite of 95 deficits). Biological age was estimated by DNA methylation-based epigenetic clocks in blood. Results: Metformin led to a non-linear response in the Fried score rate of change, with an upward trajectory in year 1 (0.72 +/-0.22 per year vs. placebo, p=0.0011) and stabilization in year 2 (-0.33 +/-0.17 per year vs. placebo, p=0.056). Metformin led to more weight loss than placebo (-5.7 +/-5.2 vs. -2.3 +/-5.4 kg, p=0.0002); thus, when assessing effect on Fried score without the weight loss criterion, no difference was observed, indicating that weight loss in year 1 accounted for the change in Fried score. Notably, metformin caused a steady improvement in the frailty index (-0.006 +/-0.0026 per year vs. placebo, p=0.0222) that persisted with covariates adjustment including body mass index. Metformin reduced biological age estimated by PC-Horvath2 (-0.40 +/-0.16 per year, p=0.014) and PC-Hannum (-0.33 +/-0.16 per year, p=0.047) clocks. Metformin was well tolerated. Conclusions and Relevance: Metformin halts the progression of the deficit accumulation frailty index and reduces biological age, suggesting potential benefit for extending healthspan. Trial Registration: ClinicalTrials.gov: NCT02570672.

Objectives: To evaluate change in physical function and probable sarcopenia following a 36-week community multicomponent exercise programme (Vivifrail model) across two consecutive cycles, and to assess the consistency of this change between cohorts. Study design: Quasi-experimental, single-arm, repeated-measures service evaluation. Ninety-two older adults (2025-2026 cohort; mean age 75.9 years, 88.0% women) completed baseline and post-intervention assessments; an independent 2024-2025 cohort (n = 86) was analysed jointly for replication (n = 178). Main outcome measures: Short Physical Performance Battery (SPPB) score (primary); Timed Up and Go (TUG), handgrip strength, 6-metre walk time and Mini-Mental State Examination (MMSE) (secondary); probable sarcopenia (EWGSOP2), SPPB-based frailty category, and a fall-risk indicator computed identically in both cohorts. Results: SPPB improved by a mean of 1.33 points (Cohen's d = 0.96; p < .001), with concordant improvement in all four secondary outcomes (all q < .005). 72.8% reached the substantial minimal clinically important difference. Probable sarcopenia fell from 17.4% to 5.4% (p = .006), and frailty category shifted toward higher functional levels (p < .001). Effect sizes were consistent between cohorts for SPPB, handgrip and 6-metre walk; the Time x Cohort interaction was significant for TUG only. In the pooled sample, elevated fall risk fell from 19.7% to 11.2% (p = .002). Conclusions: A 36-week multicomponent exercise programme was associated with clinically meaningful, reproducible improvement in physical function and a reduction in probable sarcopenia across two independent cohorts. The single-arm design precludes causal inference.

Background Emerging evidence has linked frailty to individual chronic diseases, but whether it predicts a broad disease spectrum and accelerates multimorbidity accumulation over time remains unknown. This study aimed to systematically evaluate the associations of physical frailty with the burden of incident disease across a wide range of chronic conditions, and with the long-term rates of multimorbidity accumulation. Methods In this prospective cohort study of 466,864 UK Biobank participants , frailty status was assessed using the Fried frailty phenotype and categorized as robust, pre-frailty, or frailty. Chronic diseases were defined based on International Classification of Diseases (ICD)-10 codes, and disease patterns were identified using network analysis. Cox proportional hazards models were used to examine the associations of frailty status with incident chronic diseases, and linear mixed models were used to assess the annual rate of chronic disease accumulation. Results During a median follow-up of 13.8 years (IQR: 13.1-14.5), 536 incident chronic diseases across multiple systems were recorded. Physical frailty was associated with a significantly increased risk of 458 incident diseases (Bonferroni-corrected P < 0.05/536). In the overall cohort, compared with robust participants, those with pre-frailty ({beta} = 0.266, 95% confidence interval [CI]: 0.264-0.267) and frailty ({beta} = 0.941, 95% CI: 0.936-0.946) exhibited significantly faster rates of multimorbidity accumulation. This accelerated multimorbidity accumulation was consistently observed across strata of baseline disease burden, including participant with 0 ({beta} = 0.644, 95% CI: 0.635-0.653), 1 ({beta} =0.748, 95% CI: 0.727-0.768), [&ge;] 2 ({beta} =0.940, 95% CI: 0.933-0.947) chronic conditions at baseline. Similar associations were also found across distinct disease patterns, including neurodegenerative, metabolic, and psychiatric patterns. Conclusions Physical frailty predicts a broad range of incident diseases and is associated with accelerated multimorbidity accumulation. Incorporating frailty assessment into prevention strategies may help mitigate the growing burden of multimorbidity.

Background: Cardiovascular (CV) screening is critical for personnel deploying to Antarctica, where geographic isolation and limited medical care make the management of acute cardiovascular events challenging. The utility of contemporary risk prediction tools such as the AHA PREVENT equations in this unique population remains uncertain. Methods: We retrospectively analyzed 154 individuals referred for enhanced CV evaluation before deployment to the U.S. Antarctic Program (USAP). Participants were evaluated across three temporal cohorts (2018-2020, 2021-2023, and 2024-2026). Demographics, CV risk factors, cardiac testing, and deployment clearance outcomes were collected. Risk was estimated using the Framingham Risk Score (FRS), AHA/ACC Pooled Cohort Equations (PCE), and AHA PREVENT risk models. Results: The cohort was predominantly male (79.9%; mean age 44.6 {+/-} 14.6 years), and abnormal ECG was the most common referral trigger (70.8%). Median 10-year risk was low by PREVENT and FRS and borderline elevated by PCE (PREVENT 2.7% [IQR 1.1-6.6], FRS 2.3% [IQR 0.5-7.1], and PCE 6.1% [IQR 2.4-9.2]). Among 72 participants with all scores, 51% were classified discordantly; PREVENT ASCVD agreed closely with FRS (=0.77) but poorly with PCE (=0.24-0.35), which consistently estimated higher risk. PCE was calculable in 52.6% versus 70.8% for PREVENT. Overall, 132 participants (85.7%) were cleared for deployment, while 8 (5.2%) were not physically qualified (NPQ); 6 of these NPQs were due to cardiovascular causes. Of 22 cardiac medical evacuations during the study period, 21 involved individuals without prior advanced cardiovascular screening. One screened individual was evacuated for symptoms subsequently found to have no cardiac cause. Conclusions: Risk calculators disagree substantially in the fitness-selected population. We recommend PREVENT as the primary risk-stratification tool as it is the most contemporary derivation, incorporates renal function, is race-agnostic, extends to heart failure, applies from age 30, and agrees closely with FRS, easing transition. Targeted imaging, including coronary artery calcium scoring, may supplement intermediate-risk candidates.

Background Whether adiposity is protective against or detrimental to skeletal muscle health in older adults remains unresolved. The conflicting associations between adiposity and sarcopenia, ranging from apparently protective to harmful effects, have been described as the "obesity paradox". We investigated whether this paradox could be explained by heterogeneity in muscle functional capacity, hypothesising that the adiposity-sarcopenia relationship is modified by relative grip strength (RGS). Methods We conducted a cross-sectional analysis of the China Health and Retirement Longitudinal Study (CHARLS; n=15,701), with independent external validation in the US National Health and Nutrition Examination Survey (NHANES; n=10,730). RGS was defined as maximal grip strength divided by body weight. To minimise selective reporting, we performed a prespecified systematic screen of 536 interaction terms derived from 10 anthropometric exposures, 33 functional modifiers, and two sarcopenia outcomes. Core findings were evaluated through cross-metric and cross-outcome replication, sensitivity analyses addressing concerns regarding diagnostic circularity and mathematical coupling, and mediation analyses exploring potential biological pathways. Findings Among 536 tested interactions, 36 met the Bonferroni-corrected significance threshold, and 32 (89%) involved grip-related modifiers. The interaction between waist circumference and RGS for possible sarcopenia was highly significant (p=6.19 x 10(-24)). Stratified analyses showed that higher adiposity was associated with lower odds of sarcopenia, but the magnitude of this association differed substantially by RGS. For BMI, the inverse association was approximately 10-fold stronger among individuals with high RGS than among those with low RGS (OR 0.64, 95% CI 0.60-0.69 vs OR 0.97, 95% CI 0.96-0.98). Similar effect modification patterns were observed across four anthropometric measures and both sarcopenia outcomes, and were independently replicated in NHANES (p<1.0 x 10(-16)). The interaction was no longer evident after restricting analyses to participants with preserved grip strength (p=0.65). Mediation analyses suggested that the association was predominantly direct, with triglycerides accounting for 10.5% of the total effect. Interpretation The association between adiposity and sarcopenia is strongly modified by relative grip strength and appears to be concentrated among individuals with preserved muscle functional capacity. These findings provide a potential explanation for heterogeneity underlying the obesity paradox and suggest that integrating grip strength assessment into adiposity evaluation may improve risk stratification for sarcopenia in older adults.

Background: Sarcopenia and obesity often coexist in older adults and are associated with high-er functional decline, disability, and reduced quality of life. Although physical activity (PA) is protective, prescription and adherence to exercise programs remains low in this population. Pragmatic and scalable interventions are therefore needed. Thus, we evaluated the effects of a 12-week unsupervised PA prescription program on physical performance in overweight/obese frail geriatric outpatients. Methods: A single-arm interventional study was conducted among geriatric outpatients aged over 60 years. Thirty-seven overweight/obese participants (20 women) completed the 12-week home-based PACE prescription which included individualized functional and resistance exercises with walking. Physical performance [i.e. functional capacity (SPPB), walking speed, Timed Up and Go (TUG), lower-limb muscle endurance (30-STS) and function (5-STS)], clinical status (probable sarcopenia, fall risk, walking speed) and clinically meaningful changes were assessed. Results: Participants achieved 238 min/week of PA on average, with 65% meeting recommended PA guidelines. Significant improvements were observed in lower-limb muscle function (p=0.033) and endurance (p=0.006) and in absolute (p=0.038) or relative (p=0.045) estimated muscle power. The prevalence of probable sarcopenia decreased significantly following the intervention (p=0.011). Clinically meaningful improvements were observed in muscle endurance (p<0.001) and functional status (p=0.040). Conclusion: In overweight/obese frail geriatric outpatients, the prescription of PACE achieved high PA adherence and improved lower-limb muscle function. Integrating this pragmatic and personalized PA strategy into routine geriatric care may support healthy aging and help prevent sarcopenia-obesity related functional decline.

Objective: To determine whether plasma neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) are elevated in hospitalised patients with delirium relative to patients with dementia and primary psychiatric disorders (PPD). Methods and analysis: This was a cross-sectional observational study conducted at the Royal Melbourne Hospital, Melbourne, Australia, between April and October 2024, with comparator samples from a research biobank. In Phase 1 (Delirium Discovery Cohort), we measured plasma NfL and GFAP using the Single molecule array (Simoa) platform in hospitalised patients with delirium and compared them with dementia and PPD groups. Biomarker concentrations were the primary outcome and were compared using general linear models adjusted for age, sex, and estimated glomerular filtration rate, with bootstrapped confidence intervals. Discriminative performance was assessed as a secondary outcome using receiver operating characteristic (ROC) curve analysis. In Phase 2, we applied this threshold to independent dementia and PPD groups. Results: In Phase 1 (n =176), inpatients with delirium showed higher concentrations of both NfL and GFAP than patients with dementia ({beta} = 0.78; 95% CI [0.37, 1.20] and {beta} = 0.39 [0.07, 0.73] respectively) or PPD groups ({beta} = 1.17; [0.69, 1.66] and {beta} = 0.83 [0.51, 1.24] respectively). ROC curve analysis for differentiating delirium from dementia and PPD groups yielded an optimal NfL threshold of 24.1 pg/mL (AUC = 0.89, 96% sensitivity, 70% specificity). In comparison, GFAP showed lower accuracy (AUC = 0.85), and combining NfL with GFAP (AUC = 0.90) did not significantly improve performance. In Phase 2 (n = 154), the NfL threshold of > 24 pg/ml maintained strong performance (AUC = 0.95, 96% sensitivity, and 77% specificity). Conclusions: Plasma NfL shows promise as a biomarker for delirium in hospitalised patients, distinguishing it with high sensitivity from patients with dementia and PPD. Larger multicentre studies are needed to refine cut-offs, evaluate temporal dynamics, and determine integration into acute hospital delirium pathways.

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

Background: Preoperative risk assessment in vascular surgery relies on clinical scores and lipids that do not capture atherosclerotic disease activity. Circulating fatty acid synthase (cFAS) is a liver-derived enzyme whose concentration correlates with arterial plaque FAS content independent of LDL. The 5-item modified frailty index (mFI-5) is a validated predictor of postoperative mortality. Whether cFAS predicts outcomes after vascular surgery, and whether combining it with the mFI-5 improves risk discrimination, have not been examined. Methods: We studied 657 patients undergoing elective vascular surgery at a single center (2014 to 2023). cFAS was classified as non-detectable (n = 306) or, among detectable values, by tertiles (n = 117 each). Multivariable Cox models assessed associations with major adverse events (MAE), major adverse cardiovascular events (MACE), major adverse limb events (MALE), reintervention, and mortality, and Harrell's C-statistic quantified the incremental discrimination gained by adding cFAS and the mFI-5 to standard clinical covariates. Results: High serum cFAS was independently associated with 5-year MAE (adjusted hazard ratio [aHR] 1.94; 95% CI 1.31- 2.85), mortality (aHR 1.77; 1.05 to 3.00), MALE (aHR 4.53; 2.04 to 10.05), and reintervention (aHR 2.50; 1.37 to 4.57), but not MACE. Severe frailty (mFI-5 of 3 or higher) was associated with MACE (aHR 2.69; 1.29 to 5.58) and MAE (aHR 2.46; 1.30 to 4.65) but not limb endpoints at 1 year. Adding cFAS raised the 1-year MALE C-statistic from 0.649 to 0.764; the combined model yielded the highest discrimination. Conclusions: cFAS and mFI-5 were independently and additively associated with adverse outcomes after elective vascular surgery. cFAS was associated with limb events and mortality, the mFI-5 with cardiovascular events. Combining them improved discrimination over standard covariates.

Frailty is a common consequence of aging that makes individuals increasingly susceptible to adverse health outcomes. Frailty screening can identify pre-frail and frail individuals to prescribe interventions or inform clinical decision making to prevent or slow additional frailty progression. Objective, scalable, and automated frailty assessments may expedite and improve clinical frailty screening. Here, we leveraged human pose estimation for video-based gait analysis in older adults who were non-frail, pre-frail, and frail. We focused on gait because slow walking speed is key diagnostic criteria of frailty, and many gait deviations are often observed in older adults with frailty. We collected videos of 68 older adults (25 non-frail, 25 pre-frail, 18 frail) walking at both self-selected and fast paces and used an established pose estimation-based gait analysis approach to measure and compare gait parameters across frailty statuses. Pose estimation-based step time measurements were strongly correlated with manual annotations (self-selected: R2=0.93, fast: R2=0.80) and showed tight Bland-Altman limits of agreement (self-selected: -0.082 to 0.052s, fast: -0.114 to 0.110s), establishing validity of this video-based gait analysis approach in older adults. We then identified a series of cross-sectional differences in spatiotemporal gait parameters among non-frail, pre-frail, and frail older adults, demonstrating that video-based gait analysis can be useful for measuring gait differences across frailty statuses. This study demonstrates the potential of video-based pose estimation for scalable gait tracking across frailty statuses in older adults.

The COVID-19 pandemic led to significant disruptions in cardiovascular care and reductions in physical activity, but little is known about how exercise patterns changed after this period. This study assessed changes in weekly aerobic and strength training activity between 2020 and 2022 amongst adults aged 18 years or older who reported one or more cardiovascular diseases or risk factors. This study used National Health Interview Survey data from 2020 and 2022. Adjusted differences for moderate-to-vigorous physical activity (MVPA) were calculated using a linear regression model and for strength sessions using a Poisson regression, adjusting for sex and age. Changes in these outcomes were then stratified by age and sex subgroups. The weighted study population included 182,783,008 (standard error, +/-3,334,337) adults in 2020 and 185,388,060 (SE, +/-3,285,161) adults in 2022. Between 2020 and 2022, the overall weekly MVPA increased from 244.2 (SE, +/-4.5) minutes to 266.3 (SE, +/-5.7) minutes (adjusted difference, +22.1 [SE, +/-6.92] minutes). There were no statistically significant changes in the number of strength session per week overall or among sex and age subgroups. Across sex and age subgroups, increases in weekly MVPA were entirely concentrated among males and younger adults. The recovery from pandemic era reductions in aerobic and strength exercise training was uneven amongst demographic subgroups, which aligns with concurrent persistent disruptions in cardiovascular care.

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.

Objective: To develop and validate a supervised text-embedded transformer matching model to identify fall injuries in Medicare data, and evaluate the model's performance -- alongside a validated rule-based algorithm-- against "ground truth" from an external reference standard (self-reported fall injuries leading to medical attention). Materials and Methods: Text embeddings of ICD-10-CM and CPT codes in Medicare claims/encounters from participants in the Strategies to Reduce Injuries and Develop Confidence in Elders (STRIDE) trial served as model inputs. Trained on annotated claims/encounters occurring within +/- one month of self-reported fall injuries leading to medical attention, the transformer model generated a continuous 0-1 probability that each claim/encounter was for a fall injury. The model was then applied to all claims/encounters in STRIDE and compared alongside the rule-based algorithm to the external reference standard. Results: The model achieved an area under the curve (AUC) of > 0.96 against annotated claims/encounters in 9 out of 10 holdout folds and 0.85 in the remaining fold. In the full STRIDE dataset, the model achieved a peak AUC of 0.86 (95% CI, 0.84-0.87) against the external reference standard, with results comparable to the rule-based algorithm. Discussion: Relative to rule-based approaches, which typically generate binary outcomes, the continuous event probability generated by the transformer model could support clinical endpoint adjudication, with high-probability predictions treated as events, moderate-probability predictions being adjudicated, and low-probability predictions treated as non-events. Conclusion: A text-embedded transformer model identified fall injuries with comparable accuracy to a rule-based algorithm, demonstrating "proof of concept" for use in endpoint adjudication.

Abstract Background: Respiratory failure (RF) and atrial fibrillation/flutter (AF/AFL) often occur together in older adults, but long-term national mortality trends for the two conditions combined have not been described. We examined trends and disparities in deaths with co-listed RF and AF/AFL among U.S. adults aged 65 years and older from 1999 to 2024, and projected rates through 2035. Methodology: We used the CDC WONDER Multiple Cause of Death database to identify deaths with ICD 10 codes J96 (RF) and I48 (AF/AFL) listed together. Age-adjusted mortality rates (AAMRs) per 100,000 were standardized to the 2000 U.S. population and stratified by sex, race/ethnicity, census region, urbanization, state, and place of death. Joinpoint regression was used to estimate annual percent changes (APCs) and average annual percent changes (AAPCs). Forecasts for 2025 to 2035 were generated with an exponential smoothing (ETS) model. Results: A total of 433,598 deaths were recorded. The overall AAMR rose from 12.8 in 1999 to 66.7 in 2024 (AAPC 8.11%; 95% CI, 7.35 to 8.87; P < 0.0001). Three segments were identified: an increase from 1999 to 2018 (APC 7.73%), a sharp rise from 2018 to 2021 (APC 18.10%), and a decline from 2021 to 2024 (APC -5.25%). Males had a higher AAMR and a steeper increase than females (AAPC 8.44% vs 7.81%). Non-Hispanic White adults had the highest mean AAMR, Hispanic adults had the largest relative increase (AAPC 8.72%), and Non-Hispanic Asian/Pacific Islander adults had the smallest (AAPC 6.23%). The Midwest had the fastest regional growth (AAPC 9.35%). From 1999 to 2020, non-metropolitan areas increased faster than metropolitan areas (AAPC 10.09% vs 8.21%). State AAMRs ranged from 24.7 in Ohio to 85.1 in Louisiana. Most deaths occurred in hospital inpatient settings (64.1%), followed by nursing homes (14.1%) and the home (11.9%). The model projects an AAMR of 122.96 per 100,000 by 2035 (95% prediction interval, 85.42 to 160.50). Conclusions: Mortality involving RF with AF/AFL among older U.S. adults increased more than fivefold over 25 years, with a marked surge during the COVID 19 period and only a partial decline afterward. Differences by sex, race/ethnicity, region, and urbanization point to groups that may benefit from earlier detection and coordinated cardiopulmonary care.

Introduction: Rotating night shift work is associated with chronic circadian disruption and may contribute to higher cardiovascular disease (CVD) risk and mortality. The impact of rotating night shift work may vary by chronotype, particularly when an individual's circadian preference is misaligned with work schedules. Methods: In 2009, 69,458 women (mean age 54.4 years) free of CVD in the Nurses' Health Study II reported chronotype. Duration of rotating night shift work has been assessed biennially since 1989. Participants were followed from 2009 through June 2021 for incident CVD (myocardial infarction or stroke) and all-cause mortality. We used time-varying Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for outcomes in relation to rotating night shift work and chronotype and to evaluate whether the associations differed by chronotype. Primary models adjusted for key demographics, CVD risk factors, and workplace factors. Results: We documented 1,005 incident CVD events over 800,630 person-years and 1,777 deaths over 806,043 person-years. Each 5-year increase in rotating night shift work was associated with a modestly higher risk of incident CVD (HR 1.07; 95% CI 1.01, 1.14) and a 13% higher risk of all-cause mortality (HR 1.13; 95% CI 1.08, 1.17). Greater eveningness was associated with higher incident CVD risk (HR 1.17; 95% CI 1.06, 1.28) and all-cause mortality (HR 1.18; 95% CI 1.10, 1.26). For incident CVD, the increased risk per 5-year increment in rotating night shift work was observed only among definite morning types (HR 1.11; 95% CI 0.99, 1.23), but not among definite evening types (HR 0.99; 95% CI 0.86, 1.15; p-interaction=0.1732). For all-cause mortality, the increased risk associated with shorter-term rotating night shift work (<5 years) was more evident among definite morning types (HR 1.39; 95% CI 1.12, 1.73) than definite evening types (HR 1.37; 95% CI 0.98, 1.91). However, this difference was not observed for longer duration of shift work ([&ge;]5 years), and the overall interaction was not statistically significant (p-interaction=0.57). Similar patterns were observed when shift work duration was modeled continuously using restricted cubic spline analyses. Conclusion: Rotating night shift work was associated with a modest increase in CVD and all-cause mortality risk. The overall pattern of associations across chronotypes suggested that nurses with a morning chronotype may be more susceptible to the adverse effects of rotating night shift work.

Although physical activity is associated with better physical functioning, the effects of initiating regular physical activity among older adults with persistent inactivity remain unclear. We conducted a sequential target trial emulation using Health and Retirement Study (HRS) data to estimate the effect of physical activity initiation versus noninitiation on incident mobility difficulty. Participants were included in the analysis if they were aged [&ge;]65 years at the previous wave, reported no regular physical activity at the previous two waves, and had no mobility, activities of daily living (ADL), or instrumental activities of daily living (IADL) difficulties at baseline. Stabilized inverse probability of treatment weighting was applied to adjust for measured confounding. Weighted cumulative incidence was then estimated with death treated as a competing event, and risk differences were calculated at approximately 2, 4, and 6 years. At 2 years, the cumulative incidence of mobility difficulty was 32.75% among initiators and 39.73% among noninitiators, with a risk difference of -6.98 percentage points (95% CI, -13.11 to -0.88). At 4 and 6 years, risk differences were -2.90 percentage points (95% CI, -9.77 to 4.29) and -5.44 percentage points (95% CI, -12.27 to 1.99), respectively. Initiating regular moderate or vigorous physical activity was associated with a lower risk of incident mobility difficulty at approximately 2 years among older adults with persistent inactivity. This difference was less evident at later follow-up, and no clear differences were observed for incident ADL or IADL difficulty.