Relationship Between Sarcopenia and Intensive Blood Pressure Control Efficacy and Safety: A Secondary Analysis of SPRINT.

BACKGROUND: Sarcopenia and hypertension are independently associated with worse cardiovascular disease (CVD) risk and survival. While individuals with sarcopenia may benefit from intensive blood pressure (BP) control, the increased vulnerability of this population raises concerns for potential harm. This study aimed to evaluate clinical and safety outcomes with intensive (target <120 mm Hg) versus standard (<140 mm Hg) systolic BP targets in older hypertensive adults with sarcopenia compared with nonsarcopenic counterparts in the SPRINT (Systolic Blood Pressure Intervention Trial). METHODS: Sarcopenia was defined using surrogates of the lowest sex-stratified median of the sarcopenia index (serum creatinine/cystatin C×100) for muscle wasting and gait speed ≤0.8 m/s for muscle weakness. Outcomes included CVD events, all-cause mortality, and serious adverse events. RESULTS: Of 2571 SPRINT participants with sarcopenia index and gait speed data available (aged ≥75 years), 502 (19.5%) met the criteria for sarcopenia, which was associated with higher risks of CVD events (adjusted hazard ratio, 1.49 [95% CI, 1.15-1.94]; P=0.003) and all-cause mortality (adjusted hazard ratio, 1.46 [95% CI, 1.09-1.94]; P=0.010). In participants with sarcopenia, intensive (versus standard) BP control nearly halved the risk of CVD events (adjusted hazard ratio, 0.57 [95% CI, 0.36-0.88]; P=0.012) without increasing serious adverse events. Similar risk reduction was seen for all-cause mortality in participants with sarcopenia (adjusted hazard ratio, 0.66 [95% CI, 0.41-1.08]; P=0.102), but the effect was only significant in those without chronic kidney disease. CONCLUSIONS: Older hypertensive adults with sarcopenia randomized to intensive BP control experienced a lower risk of CVD without increased adverse events compared with standard BP control. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01206062.

Low-Density-Lipoprotein Cholesterol and Mortality Outcomes Among Healthy Older Adults: A Post Hoc Analysis of ASPREE Trial.

BACKGROUND: The prognostic implication of cholesterol levels in older adults remains uncertain. This study aimed to examine the relationship between low-density-lipoprotein cholesterol (LDL-c) and mortality outcomes in older individuals. METHODS: This post hoc analysis examined the associations of LDL-c levels with mortality risks from all-cause, cardiovascular disease (CVD), cancer, and combined non-CVD/noncancer conditions in a cohort of individuals aged ≥65 years from the ASPirin in Reducing Events in the Elderly trial (NCT01038583). At baseline, participants had no diagnosed dementia, physical disability, or CVD, and were not taking lipid-lowering agents. Outcome analyses were performed using multivariable Cox models. RESULTS: We analyzed 12 334 participants (mean age: 75.2 years). Over a median 7-year follow-up, 1 250 died. Restricted cubic splines found a U-shaped relation for LDL-c and all-cause mortality, cancer mortality, and noncancer/non-CVE mortality (nadir: 3.3-3.4 mmol/L); the risk of CVD mortality was similar at LDL-c below 3.3 mmol/L and increased above 3.3 mmol/L. Similar trends were observed in analyses modeling LDL-c by quartiles. When modeling LDL-c as a continuous variable, the risk of all-cause mortality, cancer mortality, and noncancer/non-CVD mortality was decreased by 9%, 16%, and 18%, respectively, per 1-mmol/L higher LDL-c, and the risk of CVD mortality was increased by 19% per 1-mmol/L higher LDL-c. Reduced all-cause and non-CVD/noncancer mortality risks were only significant in males but not females (pinteraction < .05). CONCLUSIONS: There were U-shaped relationships between LDL-c and all-cause mortality, cancer mortality, and noncancer/non-CVD mortality in healthy older adults. Higher LDL-c levels were associated with an increased risk of CVD mortality. Future studies are warranted to confirm our results.

Health Characteristics and Aspirin Use in Participants at the Baseline of the ASPirin in Reducing Events in the Elderly - eXTension (ASPREE-XT) Observational Study.

BACKGROUND: Aspirin as a primary preventative in healthy older adults did not prolong disability-free survival in the ASPREE randomized trial. Observational studies following randomized trials allow assessment of benefits and harms which may not appear during the trial. We describe health characteristics, physical function, and aspirin use in the ASPREE-eXTension (ASPREE-XT) observational study cohort. METHODS: Descriptive statistics compared health characteristics of those consented to ASPREE-XT at their first post-trial baseline (XT01) to corresponding ASPREE baseline values, and to those not consented. Likelihood of an indication for aspirin was assessed in participants reporting aspirin use at XT01. RESULTS: 16,317 (93%) of the remaining and eligible 17,546 ASPREE participants were consented into ASPREE-XT; 14,894 completed XT01. Mean participant age had increased from 74.9 to 80.6 years. Overall health and physical function declined from the original ASPREE baseline; more participants were living alone, there was higher prevalence of chronic kidney disease, diabetes, and frailty, grip strength was lower and gait speed slower. Those not consented into ASPREE-XT were slightly older, and had lower cognitive scores and higher prevalence of age-related conditions than those who continued. 1015/11,717 (8.7%) participants without an apparent indication for aspirin reported using aspirin at XT01. CONCLUSIONS: The ASPREE-XT cohort was slightly less healthy at the XT01 visit than at ASPREE trial initiation, and rates of aspirin use without indication were similar to ASPREE baseline. Participants will be followed long-term to investigate aspirin's potential legacy towards dementia and cancer prevention and explore determinants of healthy aging.

Prediction of disability-free survival in healthy older people.

Prolonging survival in good health is a fundamental societal goal. However, the leading determinants of disability-free survival in healthy older people have not been well established. Data from ASPREE, a bi-national placebo-controlled trial of aspirin with 4.7 years median follow-up, was analysed. At enrolment, participants were healthy and without prior cardiovascular events, dementia or persistent physical disability. Disability-free survival outcome was defined as absence of dementia, persistent disability or death. Selection of potential predictors from amongst 25 biomedical, psychosocial and lifestyle variables including recognized geriatric risk factors, utilizing a machine-learning approach. Separate models were developed for men and women. The selected predictors were evaluated in a multivariable Cox proportional hazards model and validated internally by bootstrapping. We included 19,114 Australian and US participants aged ≥65 years (median 74 years, IQR 71.6-77.7). Common predictors of a worse prognosis in both sexes included higher age, lower Modified Mini-Mental State Examination score, lower gait speed, lower grip strength and abnormal (low or elevated) body mass index. Additional risk factors for men included current smoking, and abnormal eGFR. In women, diabetes and depression were additional predictors. The biased-corrected areas under the receiver operating characteristic curves for the final prognostic models at 5 years were 0.72 for men and 0.75 for women. Final models showed good calibration between the observed and predicted risks. We developed a prediction model in which age, cognitive function and gait speed were the strongest predictors of disability-free survival in healthy older people.Trial registration Clinicaltrials.gov (NCT01038583).

A multistate model of health transitions in older people: a secondary analysis of ASPREE clinical trial data.

BACKGROUND: Understanding the nature of transitions from a healthy state to chronic diseases and death is important for planning health-care system requirements and interventions. We aimed to quantify the trajectories of disease and disability in a population of healthy older people. METHODS: We conducted a secondary analysis of data from the ASPREE trial, which was done in 50 sites in Australia and the USA and recruited community-dwelling, healthy individuals who were aged 70 years or older (≥65 years for Black and Hispanic people in the USA) between March 10, 2010, and Dec 24, 2014. Participants were followed up with annual face-to-face visits, biennial assessments of cognitive function, and biannual visits for physical function until death or June 12, 2017, whichever occurred first. We used multistate models to examine transitions from a healthy state to first intermediate disease events (ie, cancer events, stroke events, cardiac events, and physical disability or dementia) and, ultimately, to death. We also examined the effects of age and sex on transition rates using Cox proportional hazards regression models. FINDINGS: 19 114 participants with a median age of 74·0 years (IQR 71·6-77·7) were included in our analyses. During a median follow-up of 4·7 years (IQR 3·6-5·7), 1933 (10·1%) of 19 114 participants had an incident cancer event, 487 (2·5%) had an incident cardiac event, 398 (2·1%) had an incident stroke event, 924 (4·8%) developed persistent physical disability or dementia, and 1052 (5·5%) died. 15 398 (80·6%) individuals did not have any of these events during follow-up. The highest proportion of deaths followed incident cancer (501 [47·6%] of 1052) and 129 (12·3%) participants transitioned from disability or dementia to death. Among 12 postulated transitions, transitions from the intermediate states to death had much higher rates than transitions from a healthy state to death. The progression rates to death were 158 events per 1000 person-years (95% CI 144-172) from cancer, 112 events per 1000 person-years (86-145) from stroke, 88 events per 1000 person-years (68-111) from cardiac disease, 69 events per 1000 person-years (58-82) from disability or dementia, and four events per 1000 person-years (4-5) from a healthy state. Age was significantly associated with an accelerated rate for most transitions. Male sex (vs female sex) was significantly associated with an accelerate rate for five of 12 transitions. INTERPRETATION: We describe a multistate model in a healthy older population in whom the most common transition was from a healthy state to cancer. Our findings provide unique insights into the frequency of events, their transition rates, and the impact of age and sex. These results have implications for preventive health interventions and planning for appropriate levels of residential care in healthy ageing populations. FUNDING: The National Institutes of Health.

Cardiovascular risk prediction in healthy older people.

Identification of individuals with increased risk of major adverse cardiovascular events (MACE) is important. However, algorithms specific to the elderly are lacking. Data were analysed from a randomised trial involving 18,548 participants ≥ 70 years old (mean age 75.4 years), without prior cardiovascular disease events, dementia or physical disability. MACE included coronary heart disease death, fatal or nonfatal ischaemic stroke or myocardial infarction. Potential predictors tested were based on prior evidence and using a machine-learning approach. Cox regression analyses were used to calculate 5-year predicted risk, and discrimination evaluated from receiver operating characteristic curves. Calibration was also assessed, and the findings internally validated using bootstrapping. External validation was performed in 25,138 healthy, elderly individuals in the primary care environment. During median follow-up of 4.7 years, 594 MACE occurred. Predictors in the final model included age, sex, smoking, systolic blood pressure, high-density lipoprotein cholesterol (HDL-c), non-HDL-c, serum creatinine, diabetes and intake of antihypertensive agents. With variable selection based on machine-learning, age, sex and creatinine were the most important predictors. The final model resulted in an area under the curve (AUC) of 68.1 (95% confidence intervals 65.9; 70.4). The model had an AUC of 67.5 in internal and 64.2 in external validation. The model rank-ordered risk well but underestimated absolute risk in the external validation cohort. A model predicting incident MACE in healthy, elderly individuals includes well-recognised, potentially reversible risk factors and notably, renal function. Calibration would be necessary when used in other populations.

A pilot study of aquatic prehabilitation in adults with knee osteoarthritis undergoing total knee arthroplasty - short term outcome.

BACKGROUND: Knee osteoarthritis (KOA) is increasingly more prevalent and significant number of patients require knee arthroplasty. Although knee arthroplasty is generally successful, it takes months to recover physical function. Preoperative physical function is known to predict postoperative outcomes and exercise can improve preoperative physical function. However, patients with KOA have difficulty exercise on land due to pain and stiffness, while water exercise can be better tolerated. We hypothesized that preoperative water exercise to improve preoperative physical function will improve postoperative outcomes after total knee arthroplasty (TKA). METHODS: We enrolled 43 participants who were scheduled for elective TKA in 4-8 weeks and scored at or below 50th percentile in mobility assessment tool-sf (MAT-sf). All enrolled participants were assessed on 1) clinical osteoarthritis symptom severity using Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), 2) physical function using Short Physical Performance Battery (SPPB), 3) self-reported mobility using Mobility Assessment Tool-short form (MAT-sf), 4) depression using Geriatric Depression Scale-short form (GDS-sf), 5) cognitive function using Montreal Cognitive Assessment (MoCA). Blood samples for high-sensitivity-C-reactive protein (hs-CRP), tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) were stored at - 80 °C then all samples were analyzed together. All the enrolled participants were randomly assigned to the aquatic exercise intervention (AEI) or usual care group. Sixty minute sessions of AEI was conducted three times a week for 4-8 weeks. Participants in both groups were evaluated within 1 week before their scheduled surgery, as well as 4 weeks after the surgery. RESULTS: The mean age was 67.1 (±6.2), 44% were female, 74% were White. There is no statistically significant difference in combined outcome of any complication, unscheduled ER visit, and disposition to nursing home or rehab facility by AEI. However, AEI was associated with more favorable outcomes: WOMAC scores (p < 0.01), chair-stand (p = 0.019), MAT-sf as well as improved depression (p = 0.043) and cognition (p = 0.008). CONCLUSION: 4-8 weeks of aquatic exercise intervention resulted in improved functional outcomes as well as improved depression and cognition in elderly patients undergoing TKA. A larger study is warranted to explore the role of water exercise in clinical and functional outcomes of TKA.

Blood Pressure Control Among Older Adults With Hypertension: Narrative Review and Introduction of a Framework for Improving Care.

Although antihypertensive medications are effective, inexpensive, and recommended by clinical practice guidelines, a large percentage of older adults with hypertension have uncontrolled blood pressure (BP). Improving BP control in this population may require a better understanding of the specific challenges to BP control at older age. In this narrative review, we propose a framework for considering how key steps in BP management occur in the context of aging characterized by heterogeneity in function, multiple co-occurring health conditions, and complex personal and environmental factors. We review existing literature related to 4 necessary steps in hypertension control. These steps include the BP measure which can be affected by the technique, device, and setting in which BP is measured. Ensuring proper technique can be challenging in routine care. The plan includes setting BP treatment goals. Lower BP goals may be appropriate for many older adults. However, plans must take into account the generalizability of existing evidence, as well as patient and family's health goals. Treatment includes the management strategy, the expected benefits, and potential risks of treatment. Treatment intensification is commonly needed and can contribute to polypharmacy in older adults. Lastly, monitor refers to the need for ongoing follow-up to support a patient's ability to sustain BP control over time. Sustained BP control has been shown to be associated with a lower rate of cardiovascular disease and multimorbidity progression. Implementation of current guidelines in populations of older adults may be improved when specific challenges to BP measurement, planning, treating, and monitoring are addressed.

Automated Frailty Screening At-Scale for Pre-Operative Risk Stratification Using the Electronic Frailty Index.

BACKGROUND: Frailty is associated with numerous post-operative adverse outcomes in older adults. Current pre-operative frailty screening tools require additional data collection or objective assessments, adding expense and limiting large-scale implementation. OBJECTIVE: To evaluate the association of an automated measure of frailty integrated within the Electronic Health Record (EHR) with post-operative outcomes for nonemergency surgeries. DESIGN: Retrospective cohort study. SETTING: Academic Medical Center. PARTICIPANTS: Patients 65 years or older that underwent nonemergency surgery with an inpatient stay 24 hours or more between October 8th, 2017 and June 1st, 2019. EXPOSURES: Frailty as measured by a 54-item electronic frailty index (eFI). OUTCOMES AND MEASUREMENTS: Inpatient length of stay, requirements for post-acute care, 30-day readmission, and 6-month all-cause mortality. RESULTS: Of 4,831 unique patients (2,281 females (47.3%); mean (SD) age, 73.2 (5.9) years), 4,143 (85.7%) had sufficient EHR data to calculate the eFI, with 15.1% categorized as frail (eFI > 0.21) and 50.9% pre-frail (0.10 < eFI ≤ 0.21). For all outcomes, there was a generally a gradation of risk with higher eFI scores. For example, adjusting for age, sex, race/ethnicity, and American Society of Anesthesiologists class, and accounting for variability by service line, patients identified as frail based on the eFI, compared to fit patients, had greater needs for post-acute care (odds ratio (OR) = 1.68; 95% confidence interval (CI) = 1.36-2.08), higher rates of 30-day readmission (hazard ratio (HR) = 2.46; 95%CI = 1.72-3.52) and higher all-cause mortality (HR = 2.86; 95%CI = 1.84-4.44) over 6 months' follow-up. CONCLUSIONS: The eFI, an automated digital marker for frailty integrated within the EHR, can facilitate pre-operative frailty screening at scale.

Effect of Aspirin on Activities of Daily Living Disability in Community-Dwelling Older Adults.

BACKGROUND: Cerebrovascular events, dementia, and cancer can contribute to physical disability with activities of daily living (ADL). It is unclear whether low-dose aspirin reduces this burden in aging populations. In a secondary analysis, we now examine aspirin's effects on incident and persistent ADL disability within a primary prevention aspirin trial in community-dwelling older adults. METHODS: The ASPREE (ASPirin in Reducing Events in the Elderly) trial of daily 100 mg aspirin versus placebo recruited 19 114 healthy adults aged 70+ years (65+ years if U.S. minority) in Australia and the United States. Six basic ADLs were assessed every 6 months. Incident ADL disability was defined as inability or severe difficulty with ≥1 ADL; persistence was confirmed if the same ADL disability remained after 6 months. Proportional hazards modeling compared time to incident or persistent ADL disability for aspirin versus placebo; death without prior disability was a competing risk. RESULTS: Over a median of 4.7 years, incident ADL disability was similar in those receiving aspirin (776/9525) and placebo (787/9589) with walking, bathing, dressing, and transferring the most commonly reported. Only 24% of incident ADL disability progressed to persistent. Persistent ADL disability was lower in the aspirin group (4.3 vs 5.3 events/1000 py; hazard ratio [HR] = 0.81, 95% confidence interval [CI]: 0.66-1.00), with bathing and dressing the most common ADL disabilities in both groups. Following persistent ADL disability, there were more deaths in the aspirin group (24 vs 12). DISCUSSION: Low-dose aspirin in initially healthy older people did not reduce the risk of incident ADL disability, although there was evidence of reduced persistent ADL disability.

Risky Behavior: Hospital Transfers Associated with Early Mortality and Rates of Goals of Care Discussions.

INTRODUCTION: Inter-hospital transfer (IHT) patients have higher in-hospital mortality, higher healthcare costs, and worse outcomes compared to non-transferred patients. Goals of care (GoC) discussions prior to transfer are necessary in patients at high risk for decline to ensure that the intended outcome of transfer is goal concordant. However, the frequency of these discussions is not well understood. This study was intended to assess the prevalence of GoC discussions in IHT patients with early mortality, defined as death within 72 hours of transfer, and prevalence of primary diagnoses associated with in-hospital mortality. METHODS: This was a retrospective study of IHT patients aged 18 and older who died within 72 hours of transfer to Wake Forest Baptist Medical Center between October 1, 2016-October 2018. Documentation of GoC discussions within the electronic health record (EHR) prior to transfer was the primary outcome. We also assessed charts for primary diagnosis associated with in-hospital mortality, code status changes prior to death, in-hospital healthcare interventions, and frequency of palliative care consults. RESULTS: We included in this study a total of 298 patients, of whom only 10.1% had documented GoC discussion prior to transfer. Sepsis (29.9%), respiratory failure (28.2%), and cardiac arrest (27.5%) were the top three diagnoses associated with in-hospital mortality, and 73.2% of the patients transitioned to comfort measures prior to death. After transfer, 18.1% of patients had invasive procedures performed with 9.7% undergoing major surgery. Palliative care consultation occurred in only 4.4%. CONCLUSION: The majority (89.9%) of IHT patients with early mortality did not have GoC discussion documented within EHR prior to transfer, although most transitioned to comfort measures prior to their deaths, highlighting that additional work is needed in this area.

A randomized pilot study to evaluate graft versus fistula vascular access strategy in older patients with advanced kidney disease: results of a feasibility study.

BACKGROUND: Although older adults encompass almost half of patients with advanced chronic kidney disease, it remains unclear which long-term hemodialysis vascular access type, arteriovenous fistula or arteriovenous graft, is optimal with respect to effectiveness and patient satisfaction. Clinical outcomes based on the initial AV access type have not been evaluated in randomized controlled trials. This pilot study tested the feasibility of randomizing older adults with advanced kidney disease to initial arteriovenous fistula versus graft vascular access surgery. METHODS: Patients 65 years or older with pre-dialysis chronic kidney disease or incident end-stage kidney disease and no prior arteriovenous vascular access intervention were randomized in a 1:1 ratio to undergo surgical placement of a fistula or a graft after providing informed consent. Trial feasibility was evaluated as (i) recruitment of ≥ 70% of eligible participants, (ii) ≥ 50 to 70% of participants undergo placement of index arteriovenous access within 90 to 180 days of enrollment, respectively, (iii) ≥ 80% adherence to study-related assessments, and (iv) ≥ 70% of participants who underwent index arteriovenous access placement will have a follow-up duration of ≥ 12 months after index surgery date. RESULTS: Between September 2018 and October 2019, 81% (44/54) of eligible participants consented and were enrolled in the study; 11 had pre-dialysis chronic kidney disease, and 33 had incident or prevalent end-stage kidney disease. After randomization, 100% (21/21) assigned to arteriovenous fistula surgery and 78% (18/23) assigned to arteriovenous graft surgery underwent index arteriovenous access placement within a median (1st, 3rd quartile) of 5.0 (1.0, 14.0) days and 13.0 (5.0, 44.3) days, respectively, after referral to vascular surgery. The completion rates for study-specific assessments ranged between 40.0 and 88.6%. At median follow-up of 215.0 days, 5 participants expired, 7 completed 12 months of follow-up, and 29 are actively being followed. Assessments of grip strength, functional independence, and vascular access satisfaction were completed by > 85% of patients who reached pre-specified post-operative assessment time point. CONCLUSIONS: Results from this study reveal it is feasible to enroll and randomize older adults with advanced kidney disease to one of two different arteriovenous vascular access placement surgeries. The study can progress with minor protocol adjustments to a multisite clinical trial. TRIAL REGISTRATION: Clinical Trials ID, NCT03545113.

The Moderate Alcohol and Cardiovascular Health Trial (MACH15): Design and methods for a randomized trial of moderate alcohol consumption and cardiometabolic risk.

BACKGROUND: Observational studies have documented lower risks of coronary heart disease and diabetes among moderate alcohol consumers relative to abstainers, but only a randomized clinical trial can provide conclusive evidence for or against these associations. AIM: The purpose of this study was to describe the rationale and design of the Moderate Alcohol and Cardiovascular Health Trial, aimed to assess the cardiometabolic effects of one alcoholic drink daily over an average of six years among adults 50 years or older. METHODS: This multicenter, parallel-arm randomized trial was designed to compare the effects of one standard serving (∼11-15 g) daily of a preferred alcoholic beverage to abstention. The trial aimed to enroll 7800 people at high risk of cardiovascular disease. The primary composite endpoint comprised time to the first occurrence of non-fatal myocardial infarction, non-fatal ischemic stroke, hospitalized angina, coronary/carotid revascularization, or total mortality. The trial was designed to provide >80% power to detect a 15% reduction in the risk of the primary outcome. Secondary outcomes included diabetes. Adverse effects of special interest included injuries, congestive heart failure, alcohol use disorders, and cancer. RESULTS: We describe the design, governance, masking issues, and data handling. In three months of field center activity until termination by the funder, the trial randomized 32 participants, successfully screened another 70, and identified ∼400 additional interested individuals. CONCLUSIONS: We describe a feasible design for a long-term randomized trial of moderate alcohol consumption. Such a study will provide the highest level of evidence for the effects of moderate alcohol consumption on cardiovascular disease and diabetes, and will directly inform clinical and public health guidelines.

Prognostic Awareness, Disease and Palliative Understanding Among Caregivers of Patients With Dementia.

BACKGROUND: Persons with dementia (PwD) often have significant cognitive deficits and functional limitations, requiring substantial caregiver assistance. Given the high symptom burden and terminal nature of dementia, good prognostic awareness and integration of palliative care (PC) is needed. OBJECTIVE: To evaluate prognostic awareness, disease, and PC understanding among caregivers of PwD and to assess for improvements in routine care. DESIGN: A cross-sectional study of 2 cohorts at a single-academic medical center. Surveys were mailed to 200 caregivers of PwD in 2012 (cohort 1). Surveys were sent to new subset of caregivers of PwD (n = 80) in 2018 (cohort 2) to assess trends over time. RESULTS: A total of 154 of caregivers completed the survey (response rate 55%). Compared to 2012, a higher proportion of caregivers in 2018 reported having conversations about prognosis with PwD's physicians (25% in 2012 vs 45% in 2018; P = .027). However, a large percentage (43% in 2012 and 40% in 2018) of caregivers reported no understanding of the PwD's prognosis. Despite most stating dementia was not curable, only 39% in 2012 and 52% in 2018 (P = .015) understood that dementia was a terminal disease. In addition, only 32% in 2012 and 40% in 2018 (P = .39) felt that they were knowledgeable about PC. CONCLUSIONS: Prognostic discussions between caregivers of PwD and the PwD's physicians may be occurring more often; however, a high percentage of caregivers report a poor understanding about the terminal nature of dementia and the role of PC.

Inflammatory biomarkers, geriatric assessment, and treatment outcomes in acute myeloid leukemia.

OBJECTIVES: To investigate changes in inflammatory biomarkers during induction therapy for older adults with acute myeloid leukemia (AML) and their associations with geriatric assessment (GA) measures and outcomes. METHODS: This was a single institution ancillary study to a prospective observational study (N = 20 consecutive adults aged ≥60 with newly diagnosed AML who received induction chemotherapy). Biomarkers (Interleukin-6 [IL-6], IL-6 soluble receptor [IL-6 sR], tumor necrosis factor alpha [TNFα], TNFα soluble receptor 1 [TNFα sR1], interleukin-3 [IL-3], C-reactive protein [CRP]) were collected at start of induction, weekly for three weeks, and post-induction and were compared over time using paired t-tests. GA was administered at baseline and post-induction, and correlated with biomarker levels using Spearman correlations. Survival was estimated using Kaplan-Meier and compared by categorized biomarker level using Wilcoxon tests. RESULTS: Biomarker levels were stable during induction, except for CRP and IL-6 sR. Declines in objectively measured physical function [Short Physical Performance Battery (SPPB); r = 0.71, p < 0.01] and increases in self-reported limitation in instrumental activities of daily living (r = 0.81, p < 0.01) were correlated with increased TNFα sR1. Declines in SPPB were correlated with increased CRP (r = -0.73, p < 0.01). Improvement in depression was correlated with increased IL-6 sR (r = -0.59 p = 0.02). Survival was shorter in those with baseline TNFα or CRP levels above the median (6.1 vs. 40.2 months and 5.5 vs. 27.6 months respectively, p = 0.04 for both). CONCLUSION: Among older adults with AML, the relationships between TNFα sR1, CRP, and IL-6 sR with change in physical and emotional health during treatment warrants further investigation.

A randomized pilot study comparing graft-first to fistula-first strategies in older patients with incident end-stage kidney disease: Clinical rationale and study design.

Timely placement of an arteriovenous (AV) vascular access (native AV fistula [AVF] or prosthetic AV graft [AVG]) is necessary to limit the use of tunneled central venous catheters (TCVC) in patients with end-stage kidney disease (ESKD) treated with hemodialysis (HD). National guidelines recommend placement of AVF as the AV access of first choice in all patients to improve patient survival. The benefits of AVF over AVG are less certain in the older adults, as age-related biological changes independently modulate patient outcomes. This manuscript describes the rationale, study design and protocol for a randomized controlled pilot study of the feasibility and effects of AVG-first access placement in older adults with no prior AV access surgery. Fifty patients age ≥65 years, with incident ESKD on HD via TCVC or advanced kidney disease facing imminent HD initiation, and suitable upper extremity vasculature for initial placement of an AVF or AVG, will be randomly assigned to receive either an upper extremity AVG-first (intervention) or AVF-first (comparator) access. The study will establish feasibility of randomizing older adults to the two types of AV access surgery, evaluate relationships between measurements of preoperative physical function and vascular access development, compare vascular access outcomes between groups, and gather longitudinal assessments of upper extremity muscle strength, gait speed, performance of activities of daily living, and patient satisfaction with their vascular access and quality of life. Results will assist with the planning of a larger, multicenter trial assessing patient-centered outcomes.

Frailty Screening Using the Electronic Health Record Within a Medicare Accountable Care Organization.

BACKGROUND: The accumulation of deficits model for frailty has been used to develop an electronic health record (EHR) frailty index (eFI) that has been incorporated into British guidelines for frailty management. However, there have been limited applications of EHR-based approaches in the United States. METHODS: We constructed an adapted eFI for patients in our Medicare Accountable Care Organization (ACO, N = 12,798) using encounter, diagnosis code, laboratory, medication, and Medicare Annual Wellness Visit (AWV) data from the EHR. We examined the association of the eFI with mortality, health care utilization, and injurious falls. RESULTS: The overall cohort was 55.7% female, 85.7% white, with a mean age of 74.9 (SD = 7.3) years. In the prior 2 years, 32.1% had AWV data. The eFI could be calculated for 9,013 (70.4%) ACO patients. Of these, 46.5% were classified as prefrail (0.10 < eFI ≤ 0.21) and 40.1% frail (eFI > 0.21). Accounting for age, comorbidity, and prior health care utilization, the eFI independently predicted all-cause mortality, inpatient hospitalizations, emergency department visits, and injurious falls (all p < .001). Having at least one functional deficit captured from the AWV was independently associated with an increased risk of hospitalizations and injurious falls, controlling for other components of the eFI. CONCLUSIONS: Construction of an eFI from the EHR, within the context of a managed care population, is feasible and can help to identify vulnerable older adults. Future work is needed to integrate the eFI with claims-based approaches and test whether it can be used to effectively target interventions tailored to the health needs of frail patients.

Effect of Aspirin on All-Cause Mortality in the Healthy Elderly.

BACKGROUND: In the primary analysis of the Aspirin in Reducing Events in the Elderly (ASPREE) trial, now published in the Journal, we report that the daily use of aspirin did not provide a benefit with regard to the primary end point of disability-free survival among older adults. A numerically higher rate of the secondary end point of death from any cause was observed with aspirin than with placebo. METHODS: From 2010 through 2014, we enrolled community-dwelling persons in Australia and the United States who were 70 years of age or older (or ≥65 years of age among blacks and Hispanics in the United States) and did not have cardiovascular disease, dementia, or disability. Participants were randomly assigned to receive 100 mg of enteric-coated aspirin or placebo. Deaths were classified according to the underlying cause by adjudicators who were unaware of trial-group assignments. Hazard ratios were calculated to compare mortality between the aspirin group and the placebo group, and post hoc exploratory analyses of specific causes of death were performed. RESULTS: Of the 19,114 persons who were enrolled, 9525 were assigned to receive aspirin and 9589 to receive placebo. A total of 1052 deaths occurred during a median of 4.7 years of follow-up. The risk of death from any cause was 12.7 events per 1000 person-years in the aspirin group and 11.1 events per 1000 person-years in the placebo group (hazard ratio, 1.14; 95% confidence interval [CI], 1.01 to 1.29). Cancer was the major contributor to the higher mortality in the aspirin group, accounting for 1.6 excess deaths per 1000 person-years. Cancer-related death occurred in 3.1% of the participants in the aspirin group and in 2.3% of those in the placebo group (hazard ratio, 1.31; 95% CI, 1.10 to 1.56). CONCLUSIONS: Higher all-cause mortality was observed among apparently healthy older adults who received daily aspirin than among those who received placebo and was attributed primarily to cancer-related death. In the context of previous studies, this result was unexpected and should be interpreted with caution. (Funded by the National Institute on Aging and others; ASPREE ClinicalTrials.gov number, NCT01038583 .).