Benefits and Harms of Standard Versus Reduced-Dose Direct Oral Anticoagulant Therapy for Older Adults With Multiple Morbidities and Atrial Fibrillation.

Background Dose reduction of direct oral anticoagulant (DOAC) medications is inconsistently applied to older adults with multiple morbidities, potentially due to perceived harms and unknown benefits of standard dosing. Methods and Results Using 2013 to 2017 US Medicare claims linked to Minimum Data Set records, we conducted a retrospective cohort study. We identified DOAC initiators (apixaban, dabigatran, rivaroxaban) aged ≥65 years with nonvalvular atrial fibrillation residing in a nursing home. We estimated inverse-probability of treatment weights for DOAC dose using propensity scores. We examined safety (hospitalization for major bleeding) and effectiveness outcomes (all-cause mortality, thrombosis [myocardial infarction, stroke, systemic embolism, venous thromboembolism]). We estimated hazard ratios (HRs) and 95% CIs using cause-specific hazard-regression models. Of 21 878 DOAC initiators, 48% received reduced dosing. The mean age of residents was 82.0 years, 66% were female, and 31% had moderate/severe cognitive impairment. After estimating inverse-probability of treatment weights, standard dosing was associated with a higher rate of bleeding (HR, 1.18 [95% CI, 1.03-1.37]; 9.4 versus 8.0 events per 100 person-years). Standard-dose therapy was associated with the highest rates of bleeding among those aged >80 years (9.1 versus 6.7 events per 100 person-years) and with a body mass index <30 kg/m2 (9.4 versus 7.4 events per 100 person-years). There was no association of dosing with mortality (HR, 0.99 [95% CI, 0.96-1.06]) or thrombotic events (HR, 1.16 [95% CI, 0.96-1.41]). Conclusions In this nationwide study of nursing home residents with nonvalvular atrial fibrillation, we found a higher rate of bleeding and little difference in effectiveness of standard versus reduced-dose DOAC treatment. Our results support the use of reduced-dose DOACs for many older adults with multiple morbidities.

National Cohort Study of Homebound Persons Living With Dementia: Antibiotic Prescribing Trends and Opportunities for Antibiotic Stewardship.

Background: Over 7 million older Americans are homebound. Managing infections in homebound persons presents unique challenges that are magnified among persons living with dementia (PLWD). This work sought to characterize antibiotic use in a national cohort of PLWD who received home-based primary care (HBPC) through the Veterans Health Administration. Methods: Administrative data identified veterans aged ≥65 years with ≥2 physician home visits in a year between 2014 and 2018 and a dementia diagnosis 3 years before through 1 year after their initial HBPC visit. Antibiotics prescribed orally, intravenously, intramuscularly, or by enema within 3 days of an HBPC visit were assessed from the initial HBPC visit to death or December 31, 2018. Prescription fills and days of therapy (DOT) per 1000 days of home care (DOHC) were calculated. Results: Among 39 861 PLWD, the median age (interquartile range [IQR]) was 85 (78-90) years, and 15.0% were Black. Overall, 16 956 (42.5%) PLWD received 45 122 prescription fills. The antibiotic use rate was 20.7 DOT per 1000 DOHC. Telephone visits and advanced practice provider visits were associated with 30.9% and 42.0% of fills, respectively. Sixty-seven percent of fills were associated with diagnoses for conditions where antibiotics are not indicated. Quinolones were the most prescribed class (24.3% of fills). The overall median length of therapy (IQR) was 7 (7-10) days. Antibiotic use rates varied across regions. Within regions, the median annual antibiotic use rate decreased from 2014 to 2018. Conclusions: Antibiotic prescriptions were prevalent in HBPC. The scope, appropriateness, and harms of antibiotic use in homebound PLWD need further investigation.

Association of Beta Blocker Use With Bone Mineral Density in the Framingham Osteoporosis Study: A Cross-Sectional Study.

Some, but not all, prior observational studies have shown that beta blocker (BB) use is associated with lower fracture risk and higher bone mineral density (BMD). Rodent studies show the mechanism to involve the reduction in the effects of beta-adrenergic signaling on bone remodeling. Because previous studies did not have detailed information on dose, duration, and beta-1 selectivity, we examined these in a cross-sectional analysis of the association between BB use and hip and spine BMD using DXA with the Offspring Cohort of the Framingham Heart Study. The sample size was n = 1520, and 397 individuals used BBs. We used propensity score modeling to balance a comprehensive set of covariates using inverse probability of treatment weighting (IPTW) to minimize bias due to treatment indication. We found significant differences in BMD between BB users and non-users for three of four BMD measurements (femoral neck: 3.1%, 95% CI, 1.1% to 5.0%; total femur: 2.9%, 95% CI, 0.9% to 4.9%; femoral trochanter: 2.4%, 95% CI, -0.1% to 5.0%; and lumbar spine: 2.7%, 95% CI, 0.2% to 5.0%). Results were found to be similar between sexes although the magnitude of association was larger for women. Similar differences were estimated for beta-1 selective and nonselective BBs compared with no BB use. We modeled dose in categories (no BB use, low-dose, high-dose) and as a continuous variable and found an increasing dose response that levels off at higher doses. Finally, associations were similar for short-term versus long-term (≤4 years versus >4 years) use. In summary, this large comprehensive study shows that BB use is associated with higher BMD in a dose-related manner regardless of beta-1 specificity and duration of use, which supports the conduct of a randomized clinical trial of BBs for achieving improvements in BMD for individuals at risk of bone loss with aging. © 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research.

Frailty Confers High Mortality Risk across Different Populations: Evidence from an Overview of Systematic Reviews and Meta-Analyses.

We performed an overview of systematic reviews and meta-analyses to summarize available data regarding the association between frailty and all-cause mortality. Medline, Embase, CINAHL, Web of Science, PsycINFO, and AMED (Allied and Complementary Medicine) databases were searched until February 2020 for meta-analyses examining the association between frailty and all-cause mortality. The AMSTAR2 checklist was used to evaluate methodological quality. Frailty exposure and the risk of all-cause mortality (hazard ratio [HR] or relative risk [RR]) were displayed in forest plots. We included 25 meta-analyses that pooled data from between 3 and 20 studies. The number of participants included in these meta-analyses ranged between <2000 and >500,000. Overall, 56%, 32%, and 12% of studies were rated as of moderate, low, and critically low quality, respectively. Frailty was associated with increased risk of all-cause mortality in 24/24 studies where the HR/RRs ranged from 1.35 [95% confidence interval (CI) 1.05-1.74] (patients with diabetes) to 7.95 [95% CI 4.88-12.96] (hospitalized patients). The median HR/RR across different meta-analyses was 1.98 (interquartile range 1.65-2.67). Pre-frailty was associated with a significantly increased risk of all-cause mortality in 7/7 studies with the HR/RR ranging from 1.09 to 3.65 (median 1.51, IQR 1.38-1.73). These data suggest that interventions to prevent frailty and pre-frailty are needed.

Global Incidence of Frailty and Prefrailty Among Community-Dwelling Older Adults: A Systematic Review and Meta-analysis.

Importance: Frailty is a common geriatric syndrome of significant public health importance, yet there is limited understanding of the risk of frailty development at a population level. Objective: To estimate the global incidence of frailty and prefrailty among community-dwelling adults 60 years or older. Data Sources: MEDLINE, Embase, PsycINFO, Web of Science, CINAHL Plus, and AMED (Allied and Complementary Medicine Database) were searched from inception to January 2019 without language restrictions using combinations of the keywords frailty, older adults, and incidence. The reference lists of eligible studies were hand searched. Study Selection: In the systematic review, 2 authors undertook the search, article screening, and study selection. Cohort studies that reported or had sufficient data to compute incidence of frailty or prefrailty among community-dwelling adults 60 years or older at baseline were eligible. Data Extraction and Synthesis: The methodological quality of included studies was assessed using The Joanna Briggs Institute's Critical Appraisal Checklist for Prevalence and Incidence Studies. Meta-analysis was conducted using a random-effects (DerSimonian and Laird) model. Main Outcomes and Measures: Incidence of frailty (defined as new cases of frailty among robust or prefrail individuals) and incidence of prefrailty (defined as new cases of prefrailty among robust individuals), both over a specified duration. Results: Of 15 176 retrieved references, 46 observational studies involving 120 805 nonfrail (robust or prefrail) participants from 28 countries were included in this systematic review. Among the nonfrail individuals who survived a median follow-up of 3.0 (range, 1.0-11.7) years, 13.6% (13 678 of 100 313) became frail, with the pooled incidence rate being 43.4 (95% CI, 37.3-50.4; I2 = 98.5%) cases per 1000 person-years. The incidence of frailty was significantly higher in prefrail individuals than robust individuals (pooled incidence rates, 62.7 [95% CI, 49.2-79.8; I2 = 97.8%] vs 12.0 [95% CI, 8.2-17.5; I2 = 94.9%] cases per 1000 person-years, respectively; P for difference < .001). Among robust individuals in 21 studies who survived a median follow-up of 2.5 (range, 1.0-10.0) years, 30.9% (9974 of 32 268) became prefrail, with the pooled incidence rate being 150.6 (95% CI, 123.3-184.1; I2 = 98.9%) cases per 1000 person-years. The frailty and prefrailty incidence rates were significantly higher in women than men (frailty: 44.8 [95% CI, 36.7-61.3; I2 = 97.9%] vs 24.3 [95% CI, 19.6-30.1; I2 = 8.94%] cases per 1000 person-years; prefrailty: 173.2 [95% CI, 87.9-341.2; I2 = 99.1%] vs 129.0 [95% CI, 73.8-225.0; I2 = 98.5%] cases per 1000 person-years). The incidence rates varied by diagnostic criteria and country income level. The frailty and prefrailty incidence rates were significantly reduced when accounting for the risk of death. Conclusions and Relevance: Results of this study suggest that community-dwelling older adults are prone to developing frailty. Increased awareness of the factors that confer high risk of frailty in this population subgroup is vital to inform the design of interventions to prevent frailty and to minimize its consequences.