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Background Although analgesics are initiated on hospital discharge in millions of adults each year, studies quantifying the risks of opioids and nonsteroidal anti-inflammatory drugs (NSAIDs) among older adults during this transition are limited. We sought to determine the incidence and risk of post-discharge adverse events among older adults with an opioid claim in the week after hospital discharge, compared to those with NSAID claims only. Methods and findings We performed a retrospective cohort study using a national sample of Medicare beneficiaries age 65 and older, hospitalized in the United States hospitals in 2016. We excluded beneficiaries admitted from or discharged to a facility. We derived a propensity score that included over 100 factors potentially related to the choice of analgesic, including demographics, diagnoses, surgeries, and medication coadministrations. Using 3:1 propensity matching, beneficiaries with an opioid claim in the week after hospital discharge (with or without NSAID claims) were matched to beneficiaries with an NSAID claim only. Primary outcomes included death, healthcare utilization (emergency department [ED] visits and rehospitalization), and a composite of known adverse effects of opioids or NSAIDs (fall/fracture, delirium, nausea/vomiting, complications of slowed colonic motility, acute renal failure, and gastritis/duodenitis) within 30 days of discharge. After 3:1 propensity matching, there were 13,385 beneficiaries in the opioid cohort and 4,677 in the NSAID cohort (mean age: 74 years, 57% female). Beneficiaries receiving opioids had a higher incidence of death (1.8% versus 1.1%; RR 1.7 [1.3 to 2.3], p < 0.001, number needed to harm [NNH] 125), healthcare utilization (19.0% versus 17.4%; RR 1.1 [1.02 to 1.2], p = 0.02, NNH 59), and any potential adverse effect (25.2% versus 21.3%; RR 1.2 [1.1 to 1.3], p < 0.001, NNH 26), compared to those with an NSAID claim only. Specifically, they had higher relative risk of fall/fracture (4.5% versus 3.4%; RR 1.3 [1.1 to 1.6], p = 0.002), nausea/vomiting (9.2% versus 7.3%; RR 1.3 [1.1 to 1.4], p < 0.001), and slowed colonic motility (8.0% versus 6.2%; RR 1.3 [1.1 to 1.4], p < 0.001). Risks of delirium, acute renal failure, and gastritis/duodenitis did not differ between groups. The main limitation of our study is the observational nature of the data and possibility of residual confounding. Conclusions Older adults filling an opioid prescription in the week after hospital discharge were at higher risk for mortality and other post-discharge adverse outcomes compared to those filling an NSAID prescription only., Author(s): Shoshana J. Herzig 1,2,*, Timothy S. Anderson 1,2, Yoojin Jung 1, Long Ngo 1,2, Dae H. Kim 2,3,4, Ellen P. McCarthy 1,2,4 Introduction Pain is highly prevalent in the [...]

Objective: To determine whether previously reported racial differences in fall rates between White and Black/African American is explained by differences in health status and neighborhood characteristics. Design: Prospective cohort Setting: Community Participants: The study included 550 White and 116 Black older adults in the Greater Boston area (mean age: 78 years; 36% men) who were English-speaking, able to walk across a room, and without severe cognitive impairment. Measurements: Falls were prospectively reported using monthly fall calendars. The location of each fall and fall-related injuries were asked during telephone interviews. At baseline, we assessed risk factors for falls, including sociodemographic characteristics, physiologic risk factors, physical activity, and community-level characteristics. Results: Over the mean follow-up of 1,048 days, 1,539 falls occurred (incidence: 806/1,000 person-years). Whites were more likely than Blacks to experience any falls (867 versus 504 falls per 1,000 person-years; RR [95% CI]: 1.77 [1.33, 2.36]), outdoor falls (418 versus 178 falls per 1,000 person-years; 1.78 [1.08, 2.92]), indoor falls (434 versus 320 falls per 1,000 person-years; 1.44 [1.02, 2.05]), and injurious falls (367 versus 205 falls per 1,000 personyears; 1.79 [1.30, 2.46]). With exception of injurious falls, higher fall rates in Whites than Blacks were substantially attenuated with adjustment for risk factors and community-level characteristics: any fall (1.24 [0.81, 1.89]), outdoor fall (1.57 [0.86, 2.88]), indoor fall (1.08 [0.64, 1.81]), and injurious fall (1.77 [1.14, 2.74]). Conclusion: Our findings suggest that the racial differences in fall rates may be largely due to confounding by individual-level and community-level characteristics. [ABSTRACT FROM AUTHOR]

Both SGLT2i inhibitors (SGLT2i) and GLP-1 receptor agonists (GLP-1 RA) have shown cardiovascular (CV) benefits in CV outcome trials among patients with type 2 diabetes (T2D) and established CV disease (CVD). Whether these agents are associated with differential CV effects and mortality in real-world T2D patients with and without CVD is unclear. Using Medicare and 2 U.S. commercial claims datasets (4/2013-12/2016), we identified 1:1 propensity score-matched patients aged ≥18 years with T2D initiating a SGLT2i or a GLP-1 RA with and without CVD (32,064 and 101,210 matched pairs, respectively). We assessed a composite CV outcome [myocardial infarction (MI) or stroke], mortality, and hospitalization for heart failure (HHF), and estimated hazard ratios (HRs) and 95% CIs adjusting for >140 baseline covariates. Compared to GLP-1 RA, the HR for the composite CV outcome was 1.10 (95% CI 0.95-1.26) for SGLT2i initiators with CVD, and 1.23 (1.08-1.41) for initiators without CVD, over a mean 8.4-month follow-up (Table). Initiators of the two drugs with and without CVD had similar mortality risk, but SGLT2i users had 31-33% reductions in HHF risk [0.67 (0.55-0.81) and 0.69 (0.51-0.92)]. This study suggests robust reductions in rates of HHF associated with SGLT2i vs. GLP-1, but in primary prevention, where HHF was less common, benefits were offset by somewhat increased risk of MI and stroke. Disclosure: E. Patorno: Research Support; Self; National Institute on Aging. Other Relationship; Self; Boehringer Ingelheim International GmbH. A. Pawar: None. S. Schneeweiss: Consultant; Self; Aetion, WHISCON, LLC. R.J. Glynn: Research Support; Self; AstraZeneca, Kowa Pharmaceutical Europe Co. Ltd., Novartis Pharmaceuticals Corporation, Pfizer Inc. D.H. Kim: None. B.M. Everett: Advisory Panel; Self; American College of Cardiology. Consultant; Self; Abbott Laboratories, Amgen Inc., National Institute of Diabetes and Digestive and Kidney Diseases, Novartis Pharmaceuticals Corporation, Roche Diagnostic USA. Research Support; Self; Novartis Pharmaceuticals Corporation. Other Relationship; Spouse/Partner; Merck & Co., Inc. Other Relationship; Self; UpToDate. Other Relationship; Spouse/Partner; UpToDate. L.G. Bessette: None. S.C. Kim: Research Support; Self; Bristol-Myers Squibb Company, Genentech, Inc., Pfizer Inc. [ABSTRACT FROM AUTHOR]

Background: Frailty is a geriatric syndrome that diminishes the potential for functional recovery after a transcatheter aortic valve replacement (TAVR) or surgical aortic valve replacement (SAVR) procedure; however, its integration in clinical practice has been limited by a lack of consensus on how to measure it.Objectives: This study sought to compare the incremental predictive value of 7 different frailty scales to predict poor outcomes following TAVR or SAVR.Methods: A prospective cohort of older adults undergoing TAVR or SAVR was assembled at 14 centers in 3 countries from 2012 to 2016. The following frailty scales were compared: Fried, Fried+, Rockwood, Short Physical Performance Battery, Bern, Columbia, and the Essential Frailty Toolset (EFT). Outcomes of interest were all-cause mortality and disability 1 year after the procedure.Results: The cohort was composed of 1,020 patients with a median age of 82 years. Depending on the scale used, the prevalence of frailty ranged from 26% to 68%. Frailty as measured by the EFT was the strongest predictor of death at 1 year (adjusted odds ratio [OR]: 3.72; 95% confidence interval [CI]: 2.54 to 5.45) with a C-statistic improvement of 0.071 (p < 0.001) and integrated discrimination improvement of 0.067 (p < 0.001). Moreover, the EFT was the strongest predictor of worsening disability at 1 year (adjusted OR: 2.13; 95% CI: 1.57 to 2.87) and death at 30 days (adjusted OR: 3.29; 95% CI: 1.73 to 6.26).Conclusions: Frailty is a risk factor for death and disability following TAVR and SAVR. A brief 4-item scale encompassing lower-extremity weakness, cognitive impairment, anemia, and hypoalbuminemia outperformed other frailty scales and is recommended for use in this setting. (Frailty Assessment Before Cardiac Surgery & Transcatheter Interventions; NCT01845207). [ABSTRACT FROM AUTHOR]

Background: Traditional count-based measures of comorbidity are unlikely to capture the complexity of multiple chronic conditions (multimorbidity) in older adults with cancer. We aimed to define patterns of multimorbidity and their impact in older United States veterans with multiple myeloma (MM)., Methods: We measured 66 chronic conditions in 5076 veterans aged 65 years and older newly treated for MM in the national Veterans Affairs health-care system from 2004 to 2017. Latent class analysis was used to identify patterns of multimorbidity among these conditions. These patterns were then assessed for their association with overall survival, our primary outcome. Secondary outcomes included emergency department visits and hospitalizations., Results: Five patterns of multimorbidity emerged from the latent class analysis, and survival varied across these patterns (log-rank 2-sided P < .001). Older veterans with cardiovascular and metabolic disease (30.9%, hazard ratio [HR] = 1.33, 95% confidence interval [CI] = 1.21 to 1.45), psychiatric and substance use disorders (9.7%, HR = 1.58, 95% CI = 1.39 to 1.79), chronic lung disease (15.9%, HR = 1.69, 95% CI = 1.53 to 1.87), and multisystem impairment (13.8%, HR = 2.25, 95% CI = 2.03 to 2.50) had higher mortality compared with veterans with minimal comorbidity (29.7%, reference). Associations with mortality were maintained after adjustment for sociodemographic variables, measures of disease risk, and the count-based Charlson Comorbidity Index. Multimorbidity patterns were also associated with emergency department visits and hospitalizations., Conclusions: Our findings demonstrate the need to move beyond count-based measures of comorbidity and consider cancer in the context of multiple chronic conditions., (Published by Oxford University Press 2021.)

Aim: The goal of this study was to investigate the therapeutic potential of combining radiation therapy and cytotoxic RNase, ranpirnase (ONCONASE; ONC), in human lung tumor models in vitro and in vivo. As translational implications, the non-invasive monitoring response to individual therapy with ONC was also investigated to determine the underlying therapeutic mechanisms., Materials and Methods: A clonogenic survival assay was used to measure the effect of ONC and radiation on A549 human non-small cell lung carcinoma (NSCLC) cells. H&E staining, TUNEL staining and caspase-3-antibody labeling were used for in vivo analysis of apoptosis. A growth-delay assay was applied to detect the therapeutic potential of ONC as a radiation sensitizer in vivo. ONC-induced changes in blood flow and biochemical metabolites were measured by various noninvasive dynamic contrast enhanced magnetic resonance imaging (DCE MRI), non-localized 1H magnetic resonance spectroscopy (MRS), and near-infrared spectroscopy (NIRS) methods., Results: ONC at 5-10 microg/ml sensitized the radiation response of A549 tumor cells in vitro. Remarkable increases in ONC-induced apoptosis in vivo were observed in caspase-3 antibody labeling and TUNEL staining assays. ONC significantly increased the radiation-induced tumor growth delay of A549 tumors. It was observed, when using a DCE MRI method, that there were significant increases in K(trans) values at the rim of tumor regions at 1.5 h post-injection of ONC. When using non-localized 1H MRS, an approximately 20% decrease in lactate levels with ONC was found., Conclusion: ONC may be a new and promising drug in the treatment of NSCLC as a radiation therapy enhancer.