The Successful Aging after Elective Surgery (SAGES) II Study was designed to examine the relationship between delirium and Alzheimer's disease and related dementias (AD/ADRD), by capturing novel fluid biomarkers, neuroimaging markers, and neurophysiological measurements. The goal of this paper is to provide the first complete description of the enrolled cohort, which details the baseline characteristics and data completion. We also describe the study modifications necessitated by the COVID-19 pandemic, and lay the foundation for future work using this cohort. SAGES II is a prospective observational cohort study of community-dwelling adults age 65 and older undergoing major non-cardiac surgery. Participants were assessed preoperatively, throughout hospitalization, and at 1, 2, 6, 12, and 18 months following discharge to assess cognitive and physical functioning. Since participants were enrolled throughout the COVID-19 pandemic, procedural modifications were designed to reduce missing data and allow for high data quality. About 420 participants were enrolled with a mean (standard deviation) age of 73.4 (5.6) years, including 14% minority participants. Eighty-eight percent of participants had either total knee or hip replacements; the most common surgery was total knee replacement with 210 participants (50%). Despite the challenges posed by the COVID-19 pandemic, which required the use of novel procedures such as video assessments, there were minimal missing interviews during hospitalization and up to 1-month follow-up; nearly 90% of enrolled participants completed interviews through 6-month follow-up. While there are many longitudinal studies of older adults, this study is unique in measuring health outcomes following surgery, along with risk factors for delirium through the application of novel biomarkers-including fluid (plasma and cerebrospinal fluid), imaging, and electrophysiological markers. This paper is the first to describe the characteristics of this unique cohort and the data collected, enabling future work using this novel and important resource.

Hospital admission and discharge are at high risk of drug-related problems (DRPs) in older patients with cancer. This study aimed to assess the clinical and economic impact of a comprehensive pharmaceutical care intervention (RECAP) to optimize drug therapy in patients with cancer ≥75 years admitted to oncology or geriatric wards. RECAP intervention was defined as follows: at admission and discharge, hospital pharmacists conducted comprehensive medication reconciliation and review, identified relevant DRPs and provided optimization recommendations to prescribers; at discharge, pharmacists also provided patient education and shared information with primary care providers. The impact of the intervention was assessed by the rate of implementation of recommendations by the prescribers and the evolution of polypharmacy rate; a peer review of the clinical significance of DRPs was performed by an expert panel of geriatric oncologists and pharmacists. A cost saving analysis compared cost avoided through resolution of DRPs to cost of pharmacist's time. From January 2019 and August 2020, 201 patients were included (median age 80 [75-97] years), 68.7% with solid tumors. DRPs requiring optimization were identified in 70.9% of patients at admission (mean 1.7 DRP/patient) and 47.7% at discharge (0.9 DRP/patient). Most pharmacist recommendations (70.8%) were followed by prescribers, allowing the correction of 1.2 DRP/patient at admission and 0.7 DRP/patient at discharge. Half of resolved DRPs were rated as clinically significant. However, polypharmacy rate was not reduced at discharge. Cost comparison showed $7.2 avoided for $1 invested, with an estimated total net benefit of $354,822 (mean $1766 per patient). The RECAP model significantly reduces DRPs in hospitalized older patients with cancer. The model was cost saving, confirming the value of implementing it in routine practice.

Total tau (t-tau), neurofilament light (NfL), and glial fibrillary acidic protein (GFAP) are neuronal cytoskeletal biomarkers that may indicate greater risk of poor outcomes in age-related conditions, including mortality. Health disparities experienced by some racial minority subgroups may influence biomarker expression and effects on longevity. We aimed to examine (a) associations of serum t-tau, NfL, and GFAP with overall and cardiovascular mortality and (b) differences in associations by racial background. Data came from 1327 older participants from the Chicago Health and Aging Project (CHAP), a longitudinal population-based study. Cox proportional hazards regression models were used to examine associations between concentrations of serum t-tau, NfL, and GFAP biomarker(s) and mortality (overall/cardiovascular mortality based on age at death). Interaction terms were used to examine differences between African-American and European-American participants. Models were adjusted for age, sex, education, the APOE-ε4 allele, body mass index, chronic health conditions, and cognitive and physical functioning. Models showed that fivefold higher concentrations of t-tau (HR = 1.46, 95% CI: 1.27, 1.68), NfL (HR = 2.13, 95% CI: 1.76, 2.58), and GFAP (HR = 1.43, 95% CI: 1.08, 1.90) were separately associated with increased risk of overall mortality, with higher risk in African Americans in t-tau or NfL. In models with all biomarkers, NfL (HR = 2.17, 95% CI: 1.65, 2.85) was associated with risk of overall mortality, with racial differences in t-tau. Higher concentrations of t-tau (HR = 1.32, 95% CI: 1.02, 1.70), NfL (HR = 1.95, 95% CI: 1.40, 2.72), and GFAP (HR = 1.87, 95% CI: 1.18, 2.98) were separately associated with risk of cardiovascular mortality, with racial differences in t-tau, NfL, or GFAP. In combined models, NfL (HR = 1.73, 95% CI: 1.08, 2.78) was associated with cardiovascular mortality. Serum t-tau, NfL, and GFAP may be early indicators for mortality outcomes among older adults, with racial differences among associations.

Age is a major risk factor for venous thromboembolism (VTE), yet patients aged ≥90 years are under-represented in clinical trials of anticoagulant therapy. The objectives were to describe and compare patient clinical characteristics, treatments, and outcomes (VTE recurrence, bleeding, and mortality) during the first 3 months of anticoagulation between VTE patients aged ≥90 years and those aged <90 years. We analyzed data from the Registro Informatizado Enfermedad TromboEmbὀlica (RIETE), an ongoing global observational registry of patients with objectively confirmed acute VTE. From January 2001 to October 2022, 96,701 patients were registered in RIETE, of whom 3262 (3.4%) were aged ≥90 years. Patients aged ≥90 years were less likely to be men, and to have experienced cancer or recent surgery, but more likely to manifest immobility, chronic heart failure, anemia, renal insufficiency, or dementia than those aged <90 years. Most (99.6%) patients aged ≥90 years were receiving anticoagulant therapy. During the first 3 months, 26 patients aged ≥90 years developed VTE recurrences, 116 experienced major bleeding, and 564 died. Among patients initially presenting with pulmonary embolism (PE), deaths due to PE exceeded those due to fatal bleeding (76 vs. 19). Among those initially presenting with isolated deep-vein thrombosis (DVT), it was the reverse (2 vs. 11 deaths). In patients aged ≥90 years, the difference in the outcome of anticoagulant treatment depending on the initial presentation of VTE could suggest a need for different management approaches. Clinical trials evaluating the optimal duration of anticoagulation according to initial VTE presentation are warranted to limit excess deaths in this particular population.

Higher levels of frailty, quantified by a frailty index (FI), may be linked to fatigue severity as tasks become more physically and mentally demanding. Fatigue, a component of frailty research, has been ambiguous and inconsistent in its operationalization. Fatigability-the quantification of vulnerability to fatigue in relation to specific intensity and duration of activities-offers a more sensitive and standardized approach, though the associationbetween frailty and fatigability has not been assessed. Using cross-sectional data from the Long Life Family Study at Visit 2 (2014-2017; N = 2524; mean age ± standard deviation (SD) 71.4 ± 11.2 years; 55% women; 99% White), we examined associations between an 83-item FI after excluding fatigue items (ratio of number of health problems reported (numerator) out of the total assessed (denominator); higher ratio = greater frailty) and perceived physical and mental fatigability using the Pittsburgh Fatigability Scale (PFS) (range 0-50; higher scores = greater fatigability). Participants had mean ± standard deviation FI (0.08 ± 0.06; observed range: 0.0-0.43), PFS Physical (13.7 ± 9.6; 39.5% more severe, ≥15), and PFS Mental (7.9 ± 8.9; 22.8% more severe, ≥13). The prevalence of more severe physical and mental fatigability was higher across FI quartiles. In mixed effects models accounting for family structure, a clinically meaningful 3%-higher FI was associated with 1.9 points higher PFS Physical score (95% confidence interval (CI) 1.7-2.1) and 1.7 points higher PFS Mental score (95% CI 1.5-1.9) after adjusting for covariates. Frailty was associated with perceived physical and mental fatigability severity. Understanding this association may support the development of interventions to mitigate the risks associated with greater frailty and perceived fatigability. Including measurements of perceived fatigability, in lieu of fatigue, in frailty indices has the potential to alleviate the inconsistencies and ambiguity surrounding the operationalization of fatigue and provide a more precise and sensitive measurement of frailty.

Geriatric emergency department (GED) guidelines endorse screening older patients for geriatric syndromes in the ED, but there have been significant barriers to widespread implementation. The majority of screening programs require engagement of a clinician, nurse, or social worker, adding to already significant workloads at a time of record-breaking ED patient volumes, staff shortages, and hospital boarding crises. Automated, electronic health record (EHR)-embedded risk stratification approaches may be an alternate solution for extending the reach of the GED mission by directing human actions to a smaller subset of higher risk patients. We define the concept of automated risk stratification and screening using existing EHR data. We discuss progress made in three potential use cases in the ED: falls, cognitive impairment, and end-of-life and palliative care, emphasizing the importance of linking automated screening with systems of healthcare delivery. Research progress and operational deployment vary by use case, ranging from deployed solutions in falls screening to algorithmic validation in cognitive impairment and end-of-life care. Automated risk stratification offers a potential solution to one of the most pressing problems in geriatric emergency care: identifying high-risk populations of older adults most appropriate for specific GED care. Future work is needed to realize the promise of improved care with less provider burden by creating tools suitable for widespread deployment as well as best practices for their implementation and governance.

This editorial comments on the article by Jones et al.