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Objectives: Little is known about frailty that develops following critical illness. We sought to describe the prevalence of newly acquired frailty, its clinical course, and the co-occurrence of frailty with disability and cognitive impairment in survivors of critical illness., Design: Longitudinal prospective cohort study., Setting: Medical and surgical ICUs at five U.S. centers., Patients: Adult patients treated for respiratory failure and/or shock., Measurements and Main Results: We measured frailty with the Clinical Frailty Scale at baseline (i.e., study enrollment) and at 3 and 12 months postdischarge. We constructed alluvial diagrams to describe the course of frailty and Venn diagrams to describe the overlap of frailty with disability in activities of daily living and cognitive impairment. We included 567 participants a median (interquartile range) of 61 years old (51-70 yr old) with a high severity of illness (Acute Physiology and Chronic Health Evaluation II of 23). Frailty (Clinical Frailty Scale scores ≥ 5) was present in 135 of 567 (24%) at baseline, 239 of 530 (45%) at 3 months, and 163 of 445 (37%) at 12 months. Of those with frailty at 3- or 12-month follow-up, 61% were not frail at baseline. Transition to a worse frailty state occurred in 242 of 530 of patients (46%) between baseline and 3 months and in 179 of 445 of patients (40%) between baseline and 12 months. There were 376 patients with frailty, disability, or cognitive impairment at 3-month follow-up. Of these, 53 (14%) had frailty alone. At 12 months, 276 patients had frailty, disability, or cognitive impairment, 37 (13%) of whom had frailty alone., Conclusions: Frailty is common among survivors of critical illness. In the majority, frailty is newly acquired. Roughly one in seven had frailty without co-occurring disability or cognitive impairment. Studies to understand outcomes of frailty that develops as the result of a critical illness and to identify modifiable risk factors for this potentially reversible syndrome are needed.

Forming pits on molybdenum disulfide (MoS 2 ) monolayers is desirable for (opto)electrical, catalytic, and biological applications. Thermal oxidation is a potentially scalable method to generate pits on monolayer MoS 2 , and pits are assumed to preferentially form around undercoordinated sites, such as sulfur vacancies. However, studies on thermal oxidation of MoS 2 monolayers have not considered the effect of adventitious carbon (C) that is ubiquitous and interacts with oxygen at elevated temperatures. Herein, the effect of adventitious C on the pit formation on MoS 2 monolayers during thermal oxidation is studied. The in situ environmental transmission electron microscopy measurements herein show that pit formation is preferentially initiated at the interface between adventitious C nanoparticles and MoS 2 , rather than only sulfur vacancies. Density functional theory (DFT) calculations reveal that the C/MoS 2 interface favors the sequential adsorption of oxygen atoms with facile kinetics. These results illustrate the important role of adventitious C on pit formation on monolayer MoS 2 ., (© 2020 Wiley-VCH GmbH.)

Background: Few prior studies have evaluated recovery after the onset of severe disability or have distinguished between the two subtypes of severe disability., Objectives: To identify the risk factors and intervening illnesses and injuries (i.e., events) that are associated with reduced recovery after episodes of progressive and catastrophic severe disability., Design: Prospective longitudinal study of 754 nondisabled community-living persons, aged 70 years or older., Setting: Greater New Haven, CT, March 1998 to December 2016., Participants: A total of 431 episodes of severe disability were evaluated from 385 participants: 116 progressive (115 participants) and 315 catastrophic (270 participants)., Measurements: Candidate risk factors were assessed every 18 months. Functional status and exposure to intervening events leading to hospitalization, emergency department visit, or restricted activity were assessed each month. Severe disability was defined as the need for personal assistance with three or more of four essential activities of daily living. Recovery was defined as return to independent function (no disability) within 6 months of developing severe disability., Results: Recovery occurred among 35.3% (95% confidence interval [CI] = 26.0%-48.0%) and 61.6% (95% CI = 53.5%-70.9%) of the 116 progressive and 315 catastrophic severe disability episodes, respectively. In the multivariable analyses, lives alone, frailty, and intervening hospitalization were each independently associated with reduced recovery from progressive disability, with adjusted hazard ratios (95% CIs) of 0.31 (0.15-0.64), 0.23 (0.12-0.45), and 0.27 (0.08-0.95), respectively, whereas low functional self-efficacy, intervening restricted activity, and intervening hospitalization were each independently associated with reduced recovery from catastrophic disability, with adjusted hazard ratios (95% CIs) of 0.56 (0.40-0.81), 0.55 (0.35-0.85), and 0.45 (0.31-0.66), respectively., Conclusions: Recovery of independent function is considerably more likely after the onset of catastrophic than progressive severe disability, the risk factors for reduced recovery differ between progressive and catastrophic severe disability, and subsequent exposure to intervening illnesses and injuries considerably diminishes the likelihood of recovery from both subtypes of severe disability., (© 2020 The American Geriatrics Society.)

Objective: This study aimed to answer 2 questions: first, to what degree does hospital operative volume affect mortality for adult patients undergoing 1 of 10 common emergency general surgery (EGS) operations? Second, at what hospital operative volume threshold will nearly all patients undergoing an emergency operation realize the average mortality risk?, Background: Nontrauma surgical emergencies are an underappreciated public health crisis in the United States; redefining where such emergencies are managed may improve outcomes. The field of trauma surgery established regionalized systems of care in part because studies demonstrated a clear relationship between hospital volume and survival for traumatic emergencies. Such a relationship has not been well-studied for nontrauma surgical emergencies., Methods: Retrospective cohort study of all acute care hospitals in California performing nontrauma surgical emergencies. We employed a novel use of an ecological analysis with beta regression to investigate the relationship between hospital operative volume and mortality., Results: A total of 425 acute care hospitals in California performed 165,123 EGS operations. Risk-adjusted mortality significantly decreased as volume increased for all 10 EGS operations (P < 0.001 for each); the relative magnitude of this inverse relationship differed substantially by procedure. Hospital operative volume thresholds were defined and varied by operation: from 75 cases over 2 years for cholecystectomy to 7 cases for umbilical hernia repair., Conclusions: Survival rates for nontrauma surgical emergencies were improved when operations were performed at higher-volume hospitals. The use of ecological analysis is widely applicable to the field of surgical outcomes research.

Background: The clinical trial of tiotropium in COPD, UPLIFT, enrolled adults with a mean age of 65 years and moderate-to-severe airflow obstruction, based on criteria from the Global Initiative for Chronic Obstructive Lung Disease (GOLD). For the UPLIFT cohort, however, GOLD-based criteria are not age-appropriate., Research Question: Will the use of more age-appropriate criteria for airflow obstruction from the Global Lung Function Initiative (GLI) modify the spirometric classification of the UPLIFT cohort and, in turn, the mortality effect of tiotropium in COPD?, Study Design and Methods: Baseline spirometric classifications were first cross-tabulated by GLI- and GOLD-based criteria. Next, in GLI- and GOLD-based airflow obstruction, modified intention-to-treat analyses evaluated differences in time to death over 4 years, comparing tiotropium vs placebo. Because treatment response may differ by COPD severity, the mortality effect also was evaluated within stratum defined by GLI- and GOLD-based moderate and severe airflow obstruction., Results: Of 5,898 participants with GOLD-based airflow-obstruction, staged as moderate in 2,739 (46.4%) and severe in 3,156 (53.5%), GLI-based criteria established airflow obstruction in 5,750 (97.5%), staged as moderate in 795 (13.5%) and severe in 4,947 (83.9%). Relative to placebo, tiotropium yielded statistically nonsignificant adjusted hazard ratios (adjHRs) (95% CI) for death of 0.91 (0.80-1.04) and 0.91 (0.79-1.03) in GLI- and GOLD-based airflow obstruction, respectively. However, statistically significant effect modification was observed, but only in GLI-based moderate and severe airflow-obstruction, with tiotropium yielding adjHRs for death of 0.53 (0.34-0.81) and 0.99 (0.86-1.13), respectively. The P value for interaction was .007., Interpretation: Mortality reduction by tiotropium was only statistically significant in GLI-based moderate airflow-obstruction, a group that was underrepresented in UPLIFT because of severity misclassification by the original GOLD-based enrollment criteria., (Copyright © 2020 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: Injuries from falls are major contributors to complications and death in older adults. Despite evidence from efficacy trials that many falls can be prevented, rates of falls resulting in injury have not declined., Methods: We conducted a pragmatic, cluster-randomized trial to evaluate the effectiveness of a multifactorial intervention that included risk assessment and individualized plans, administered by specially trained nurses, to prevent fall injuries. A total of 86 primary care practices across 10 health care systems were randomly assigned to the intervention or to enhanced usual care (the control) (43 practices each). The participants were community-dwelling adults, 70 years of age or older, who were at increased risk for fall injuries. The primary outcome, assessed in a time-to-event analysis, was the first serious fall injury, adjudicated with the use of participant report, electronic health records, and claims data. We hypothesized that the event rate would be lower by 20% in the intervention group than in the control group., Results: The demographic and baseline characteristics of the participants were similar in the intervention group (2802 participants) and the control group (2649 participants); the mean age was 80 years, and 62.0% of the participants were women. The rate of a first adjudicated serious fall injury did not differ significantly between the groups, as assessed in a time-to-first-event analysis (events per 100 person-years of follow-up, 4.9 in the intervention group and 5.3 in the control group; hazard ratio, 0.92; 95% confidence interval [CI], 0.80 to 1.06; P = 0.25). The rate of a first participant-reported fall injury was 25.6 events per 100 person-years of follow-up in the intervention group and 28.6 events per 100 person-years of follow-up in the control group (hazard ratio, 0.90; 95% CI, 0.83 to 0.99; P = 0.004). The rates of hospitalization or death were similar in the two groups., Conclusions: A multifactorial intervention, administered by nurses, did not result in a significantly lower rate of a first adjudicated serious fall injury than enhanced usual care. (Funded by the Patient-Centered Outcomes Research Institute and others; STRIDE ClinicalTrials.gov number, NCT02475850.)., (Copyright © 2020 Massachusetts Medical Society.)

Objectives: Medicare beneficiaries recovering from a critical illness are increasingly being discharged home instead of to post-acute care facilities. Rehabilitation services are commonly recommended for intensive care unit (ICU) survivors; however, little is known about the frequency and dose of home-based rehabilitation in this population., Design: Retrospective analysis of 2012 Medicare hospital and home health (HH) claims data, linked with assessment data from the Medicare Outcomes and Assessment Information Set., Setting: Participant homes., Participants: Medicare beneficiaries recovering from an ICU stay longer than 24 hours, who were discharged directly home with HH services within 7 days of discharge and survived without readmission or hospice transfer for at least 30 days (n = 3,176)., Measurements: Count of rehabilitation visits received during HH care episode., Results: A total of 19,564 rehabilitation visits were delivered to ICU survivors over 118,145 person-days in HH settings, a rate of 1.16 visits per week. One-third of ICU survivors received no rehabilitation visits during HH care. In adjusted models, those with the highest baseline disability received 30% more visits (rate ratio [RR] = 1.30; 95% confidence interval [CI] = 1.17-1.45) than those with the least disability. Conversely, an inverse relationship was found between multimorbidity (Elixhauser scores) and count of rehabilitation visits received; those with the highest tertile of Elixhauser scores received 11% fewer visits (RR = .89; 95% CI = .81-.99) than those in the lowest tertile. Participants living in a rural setting (vs urban) received 6% fewer visits (RR = .94; 95% CI = .91-.98); those who lived alone received 11% fewer visits (RR = .89; 95% CI = .82-.96) than those who lived with others., Conclusion: On average, Medicare beneficiaries discharged home after a critical illness receive few rehabilitation visits in the early post-hospitalization period. Those who had more comorbidities, who lived alone, or who lived in rural settings received even fewer visits, suggesting a need for their consideration during discharge planning. J Am Geriatr Soc 68:1512-1519, 2020., (© 2020 The American Geriatrics Society.)

Objective: The objectives of the current study were 2-fold: first, to evaluate the incidence and time to recovery of premorbid function within 6 months of major surgery and second, to identify factors associated with functional recovery among older persons who survive a major surgery with increased disability., Background: Most older persons would not choose a surgical treatment resulting in persistently increased postsurgical disability, even if survival was assured. Potential predictors of functional recovery after major surgery have, however, not been well-studied among geriatric patients., Methods: It is a prospective longitudinal study of 754 community-living persons 70 years or older. The analytic sample included 266 person-admissions in which participants survived major surgery with increased disability and were monitored on a monthly basis for 6 months., Results: Of the 266 person-admissions assessed, 174 (65.4%) recovered to their presurgical level of function, with median time to recovery of 2 months (interquartile range, 1-3), whereas 16 (6.0%) died. Two factors were significantly associated with an increased likelihood of functional recovery: being nonfrail (hazard ratio 1.60; 95% confidence interval 1.03-2.51; P = 0.038) and having elective surgery (hazard ratio 1.72; 95% confidence interval 1.14-2.59; P = 0.009). Three factors were associated with a reduced likelihood of functional recovery: hearing impairment, greater increase in postsurgical disability in the month after hospital discharge, and years of education., Conclusions: Among older persons, nonfrailty and elective surgery were positively associated with functional recovery, whereas hearing impairment, greater increases in postsurgical disability, and years of education were associated with higher risk of protracted disability.

Objective: Observational studies point to an inverse correlation between low-density lipoprotein (LDL) cholesterol levels and risk of intracerebral hemorrhage (ICH), but it remains unclear whether this association is causal. We tested the hypothesis that genetically elevated LDL is associated with reduced risk of ICH., Methods: We constructed one polygenic risk score (PRS) per lipid trait (total cholesterol, LDL, high-density lipoprotein [HDL], and triglycerides) using independent genomewide significant single nucleotide polymorphisms (SNPs) for each trait. We used data from 316,428 individuals enrolled in the UK Biobank to estimate the effect of each PRS on its corresponding trait, and data from 1,286 ICH cases and 1,261 matched controls to estimate the effect of each PRS on ICH risk. We used these estimates to conduct Mendelian Randomization (MR) analyses., Results: We identified 410, 339, 393, and 317 lipid-related SNPs for total cholesterol, LDL, HDL, and triglycerides, respectively. All four PRSs were strongly associated with their corresponding trait (all p < 1.00 × 10 -100 ). While one SD increase in the PRSs for total cholesterol (odds ratio [OR] = 0.92; 95% confidence interval [CI] = 0.85-0.99; p = 0.03) and LDL cholesterol (OR = 0.88; 95% CI = 0.81-0.95; p = 0.002) were inversely associated with ICH risk, no significant associations were found for HDL and triglycerides (both p > 0.05). MR analyses indicated that 1mmol/L (38.67mg/dL) increase of genetically instrumented total and LDL cholesterol were associated with 23% (OR = 0.77; 95% CI = 0.65-0.98; p = 0.03) and 41% lower risks of ICH (OR = 0.59; 95% CI = 0.42-0.82; p = 0.002), respectively., Interpretation: Genetically elevated LDL levels were associated with lower risk of ICH, providing support for a potential causal role of LDL cholesterol in ICH. ANN NEUROL 2020 ANN NEUROL 2020;88:56-66., (© 2020 American Neurological Association.)

Importance: Severe disability greatly diminishes quality of life and often leads to a protracted period of long-term care or death, yet the processes underlying severe disability have not been fully evaluated., Objective: To evaluate potential risk factors and precipitants associated with severe disability that develops progressively (during ≥2 months) vs catastrophically (from 1 month to the next)., Design, Setting, and Participants: Prospective cohort study conducted in greater New Haven, Connecticut, from March 1998 to December 2016, with 754 nondisabled community-living persons aged 70 years or older. Data analysis was conducted from November 2018 to May 2019., Main Outcomes and Measures: Candidate risk factors were assessed every 18 months. Functional status and potential precipitants, including illnesses or injuries leading to hospitalization, emergency department visit, or restricted activity, were assessed each month. Severe disability was defined as the need for personal assistance with at least 3 of 4 essential activities of daily living. The analysis was based on person-months within 18-month intervals., Results: The mean (SD) age for the 754 participants was 78.4 (5.3) years, 487 (64.6%) were women, and 683 (90.5%) were non-Hispanic white participants. The incidence of progressive and catastrophic severe disability was 3.5% and 9.7%, respectively, based on 3550 intervals. In multivariable analysis, 6 risk factors were independently associated with progressive disability (≥85 years: hazard ratio [HR], 1.6; 95% CI, 1.1-2.4; hearing impairment: HR, 1.7; 95% CI, 1.0-2.8; frailty: HR, 2.4; 95% CI, 1.6-3.7; cognitive impairment: HR, 2.0; 95% CI, 1.3-3.1; low functional self-efficacy: HR, 1.8; 95% CI, 1.2-2.8; low peak flow: HR, 1.7; 95% CI, 1.2-2.4), and 4 were independently associated with catastrophic disability (visual impairment: HR, 1.4; 95% CI, 1.1-1.8; hearing impairment: HR, 1.3; 95% CI, 1.0-1.7; poor physical performance: HR, 1.8; 95% CI, 1.3-2.5; low peak flow: HR, 1.3; 95% CI, 1.0-1.7). The associations of the precipitants were much more pronounced than those of the risk factors, with HRs as high as 321.4 (95% CI, 194.5-531.0) for hospitalization and catastrophic disability and 48.3 (95% CI, 31.0%-75.4%) for hospitalization and progressive disability. Elimination of an intervening hospitalization was associated with a decrease in the risk of progressive and catastrophic severe disability of 3.0% (95% CI, 3.0%-3.1%) and 12.3% (95% CI, 12.1%-12.5%), respectively. Risk differences were 0.6% (95% CI, 0.6%-0.6%) and 1.3% (95% CI, 1.3%-1.4%) for emergency department visit and 0.1% (95% CI, 0.1%-0.2%) and 0.4% (95% CI, 0.4%-0.4%) for restricted activity, and ranged from 0.1% (95% CI, 0.1%-0.1%) to 0.3% (95% CI, 0.3%-0.3%) for the independent risk factors, for progressive and catastrophic disability, respectively., Conclusions and Relevance: The findings of this study suggest that whether it develops progressively or catastrophically, severe disability among older community-living adults arises most commonly in the setting of an intervening illness or injury. To reduce the burden of severe disability, more aggressive efforts will be needed to prevent and manage intervening illnesses or injuries and to facilitate recovery after these debilitating events.

Objectives: The Strategies to Reduce Injuries and Develop Confidence in Elders (STRIDE) study is testing the effectiveness of a multifactorial intervention to prevent serious fall injuries. Our aim was to describe procedures that were implemented to optimize participant retention; report retention yields by age, sex, clinical site, and follow-up time; provide reasons for study withdrawals; and highlight the successes and lessons learned from the STRIDE retention efforts., Design: Pragmatic cluster randomized trial., Setting: A total of 86 primary care practices within 10 US healthcare systems., Participants: A total of 5451 community-living persons, 70 years of age or older, at high risk for serious fall injuries., Measurements: Study outcomes were collected every 4 months by a central call center. Reconsent was required to extend follow-up beyond the originally planned 36 months., Results: Over a median follow-up of 3.2 years (interquartile range = 2.8-3.7 y), 439 (8.1%) participants died and 600 (11.0%) withdrew their consent or did not reconsent to extend follow-up beyond 36 months, yielding rates (per 100 person-years) of deaths and withdrawals of 2.6 and 3.6, respectively. The withdrawal rate increased with advancing age, was comparable for men and women, and did not differ much by clinical site. The most common reasons for withdrawal were illness and unable to contact for reconsent at 36 months. Completion of the follow-up interviews was greater than 93% at each time point. Most participants completed all (71.8%) or all but one (9.2%) of the follow-up interviews. The most common reason for not completing a follow-up interview was unable to contact, with rates ranging from 2.8% at 40 months to 4.6% at 20 months., Conclusion: Completion of the thrice-yearly follow-up interviews in STRIDE was high, and retention of participants over 44 months exceeded the original projections. The procedures used in STRIDE, together with lessons learned, should assist other investigators who are planning or conducting large pragmatic trials of vulnerable older persons. J Am Geriatr Soc 68:1242-1249, 2020., (© 2020 The American Geriatrics Society.)

Background: The American College of Surgeons maintains that surgical care in the US has not reached optimal safety and quality. This can be driven partially by higher-risk, emergency operations in geriatric patients. We therefore sought to answer 2 questions: First, to what degree does standardized postoperative mortality vary in hospitals performing nonelective operations in geriatric patients? Second, can the differences in hospital-based mortality be explained by patient-, operative-, and hospital-level characteristics among outlier institutions?, Study Design: Patients 65 years and older who underwent 1 of 8 common emergency general surgery operations were identified using the California State Inpatient Database (2010 to 2011). Expected mortality was obtained from hierarchical, Bayesian mixed-effects logistic regression models. A risk-adjusted hospital-level standardized mortality ratio (SMR) was calculated from observed-to-expected in-hospital deaths. "Outlier" hospitals had an SMR 80% CI that did not cross the mean SMR of 1.0. High-mortality (SMR >1.0) and low-mortality (SMR <1.0) outliers were compared., Results: We included 24,207 patients from 107 hospitals. SMRs varied widely, from 2.3 (highest) to 0.3 (lowest). Eleven hospitals (10.3%) were poor-performing high-SMR outliers, and 10 hospitals (9.3%) were exceptional-performing low-SMR outliers. SMR was 3 times worse in the high-SMR compared with the low-SMR group (1.7 vs 0.6; p < 0.001). Patient-, operation-, and hospital-level characteristics were equivalent among outlier-hospitals., Conclusions: Significant hospital variation exists in standardized mortality after common general surgery operations done emergently in older patients. More than 10% of institutions have substantial excess mortality. These findings confirm that the safety of emergency operation in geriatric patients can be significantly improved by decreasing the wide variability in mortality outcomes., (Copyright © 2020 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Declines in bone, muscle and physical performance are associated with adverse health outcomes in older adults. However, few studies have described concurrent age-related patterns of change in these factors. The purpose of this study was to characterize change in four properties of muscle, physical performance, and bone in a prospective cohort study of older men., Methods: Using repeated longitudinal data from up to four visits across 6.9 years from up to 4681 men (mean age at baseline 72.7 yrs. ±5.3) participating in the Osteoporotic Fractures in Men (MrOS) Study, we used group-based trajectory models (PROC TRAJ in SAS) to identify age-related patterns of change in four properties of muscle, physical performance, and bone: total hip bone mineral (BMD) density (g/m 2 ) and appendicular lean mass/ht 2 (kg/m 2 ), by DXA; grip strength (kg), by hand dynamometry; and walking speed (m/s), by usual walking pace over 6 m. We also described joint trajectories in all pair-wise combinations of these measures. Mean posterior probabilities of placement in each trajectory (or joint membership in latent groups) were used to assess internal reliability of the model. The number of trajectories for each individual factor was limited to three, to ensure that the pair-wise determination of joint trajectories would yield a tractable number of groups as well as model fit considerations., Results: The patterns of change identified were generally similar for all measures, with three district groups declining over time at roughly similar rates; joint trajectories revealed similar patterns with no cross-over or convergence between groups. Mean posterior probabilities for all trajectories were similar and consistently above 0.8 indicating reasonable model fit to the data., Conclusions: Our description of trajectories of change with age in bone mineral density, grip strength, walking speed and appendicular lean mass found that groups identified by these methods appeared to have little crossover or convergence of change with age, even when considering joint trajectories of change in these factors.

Background: Angiotensin-converting enzyme inhibitors (ACEis) and angiotensin receptor blockers (ARBs) may protect against aging-related decline. This study directly compared ACEis and ARBs on associations with risk of mobility disability in older adults when combined with a physical activity intervention., Methods: This was a secondary analysis of the Lifestyle Interventions and Independence for Elders (LIFE) trial. Participants aged 70-89 years were randomized to a physical activity or health education intervention. Outcomes included incident and persistent major mobility disability, injurious falls, short physical performance battery, and gait speed. For this analysis, only participants who reported ACEi or ARB use at baseline were included. Baseline differences between ACEi and ARB groups were adjusted for using inverse probability of treatment weights. Weighted Cox proportional hazard models and analysis of covariance models were used to evaluate the independent effects of medications and interaction effects with the intervention on each outcome., Results: Of 1,635 participants in the Lifestyle Interventions and Independence for Elders study, 796 used either an ACEi (496, 62.3%) or ARB (300, 37.7%). Compared with ACEi users, ARB users had 28% lower risk (hazard ratio [HR] = 0.72 [0.60-0.85]) of incident major mobility disability and 35% (HR = 0.65 [0.52-0.82]) lower risk of persistent major mobility disability whereas no interaction between medication use and intervention was observed. Risk of injurious falls and changes in short physical performance battery or gait speed were not different between ARB and ACEi users., Conclusions: These results suggest that ARBs may protect from major mobility disability by other mechanisms than improving physical performance., (© The Author(s) 2019. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Walking independently is basic to human functioning. The Lifestyle Interventions and Independence for Elders (LIFE) studies were developed to assess whether initiating physical activity could prevent major mobility disability (MMD) in sedentary older adults., Methods: We review the development and selected findings of the LIFE studies from 2000 through 2019, including the planning phase, the LIFE-Pilot Study, and the LIFE Study., Results: The planning phase and the LIFE-Pilot provided key information for the successful implementation of the LIFE Study. The LIFE Study, involving 1635 participants randomized at eight sites throughout the United States, showed that compared with health education, the physical activity program reduced the risk of the primary outcome of MMD (inability to walk 400 m: hazard ratio = 0.82; 95% confidence interval = 0.69-0.98; P = .03), and that the intervention was cost-effective. There were no significant effects on cognitive outcomes, cardiovascular events, or serious fall injuries. In addition, the LIFE studies provided relevant findings on a broad range of other outcomes, including health, frailty, behavioral outcomes, biomarkers, and imaging. To date, the LIFE studies have generated a legacy of 109 peer-reviewed publications, 19 ancillary studies, and 38 independently funded grants and clinical trials, and advanced the development of 59 early career scientists. Data and biological samples of the LIFE Study are now publicly available from a repository sponsored by the National Institute on Aging (https://agingresearchbiobank.nia.nih.gov)., Conclusions: The LIFE studies generated a wealth of important scientific findings and accelerated research in geriatrics and gerontology, benefiting the research community, trainees, clinicians, policy makers, and the general public. J Am Geriatr Soc 68:872-881, 2020., (© 2020 The Authors. Journal of the American Geriatrics Society published by Wiley Periodicals, Inc. on behalf of The American Geriatrics Society.)

Objectives: To determine for each basic, instrumental, and mobility activity after hospitalization for acute medical illness: (1) disability prevalence immediately before and monthly for 6 months after hospitalization; (2) disability incidence 1 month after hospitalization; and (3) recovery time from incident disability during months 2 to 6 after hospitalization., Design: Prospective cohort study., Setting: New Haven, Connecticut., Participants: A total of 515 community-living persons, mean age 82.7 years, hospitalized for acute noncritical medical illness and alive within 1 month of hospital discharge., Measurements: Disability was defined monthly for each basic (bathing, dressing, walking, transferring), instrumental (shopping, housework, meal preparation, taking medications, managing finances), and mobility activity (walking a quarter mile, climbing flight of stairs, lifting/carrying 10 pounds, driving) if help was needed to perform the activity or if a car was not driven in the prior month., Results: Disability was common 1 and 6 months after hospitalization for activities frequently involved in leaving the home to access care including walking a quarter mile (prevalence 65% and 53%, respectively) and driving (65% and 61%). Disability was also common for activities involved in self-managing chronic health conditions including meal preparation (53% and 41%) and taking medications (41% and 31%). New disability was common and often prolonged. For example, 43% had new disability walking a quarter mile, and 30% had new disability taking medications, with mean recovery time of 1.9 months and 1.7 months, respectively. Findings were similar for the subgroup of persons residing at home (ie, not in a nursing home) at the first monthly follow-up interview after hospitalization., Conclusion: Disability in specific functional activities important to leaving home to access care and self-managing health conditions is common, often new, and present for prolonged time periods after hospitalization for acute medical illness. Post-discharge care should support patients through extended periods of vulnerability beyond the immediate transitional period. J Am Geriatr Soc 68:486-495, 2020., (© 2020 The American Geriatrics Society.)

Background: It has been theorized that a tiered, regionalized system of care for emergency general surgery (EGS) patients-akin to regional trauma systems-would translate into significant survival benefits. Yet data to support this supposition are lacking. The aim of this study was to determine the potential number of lives that could be saved by regionalizing EGS care to higher-volume, lower-mortality EGS institutions., Methods: Adult patients who underwent one of 10 common EGS operations were identified in the California Inpatient Database (2010-2011). An algorithm was constructed that "closed" lower-volume, higher-mortality hospitals and referred those patients to higher-volume, lower-mortality institutions ("closure" based on hospital EGS volume-threshold that optimized to 95% probability of survival). Primary outcome was the number of lives saved. Fifty thousand regionalization simulations were completed (5,000 for each operation) employing a bootstrap resampling method to proportionally redistribute patients. Estimates of expected deaths at the higher-volume hospitals were recalculated for every bootstrapped sample., Results: Of the 165,123 patients who underwent EGS operations over the 2-year period, 17,655 (10.7%) were regionalized to a higher-volume hospital. On average, 128 (48.8%) of lower-volume hospitals were "closed," ranging from 68 (22.0%) hospital closures for appendectomy to 205 (73.2%) for small bowel resection. The simulations demonstrated that EGS regionalization would prevent 9.7% of risk-adjusted EGS deaths, significantly saving lives for every EGS operation: from 30.8 (6.5%) deaths prevented for appendectomy to 122.8 (7.9%) for colectomy. Regionalization prevented 4.6 deaths per 100 EGS patient-transfers, ranging from 1.3 for appendectomy to 8.0 for umbilical hernia repair., Conclusion: This simulation study provides important new insight into the concept of EGS regionalization, suggesting that 1 in 10 risk-adjusted deaths could be prevented by a structured system of EGS care. Future work should expand upon these findings using more complex discrete-event simulation models., Level of Evidence: Therapeutic/Care Management, level IV.

Background and Purpose- Volumes of hemorrhage and perihematomal edema (PHE) are well-established biomarkers of primary and secondary injury, respectively, in spontaneous intracerebral hemorrhage. An automated imaging pipeline capable of accurately and rapidly quantifying these biomarkers would facilitate large cohort studies evaluating underlying mechanisms of injury. Methods- Regions of hemorrhage and PHE were manually delineated on computed tomography scans of patients enrolled in 2 intracerebral hemorrhage studies. Manual ground-truth masks from the first cohort were used to train a fully convolutional neural network to segment images into hemorrhage and PHE. The primary outcome was automated-versus-human concordance in hemorrhage and PHE volumes. The secondary outcome was voxel-by-voxel overlap of segmentations, quantified by the Dice similarity coefficient (DSC). Algorithm performance was validated on 84 scans from the second study. Results- Two hundred twenty-four scans from 124 patients with supratentorial intracerebral hemorrhage were used for algorithm derivation. Median volumes were 18 mL (interquartile range, 8-43) for hemorrhage and 12 mL (interquartile range, 5-30) for PHE. Concordance was excellent (0.96) for automated quantification of hemorrhage and good (0.81) for PHE, with DSC of 0.90 (interquartile range, 0.85-0.93) and 0.54 (0.39-0.65), respectively. External validation confirmed algorithm accuracy for hemorrhage (concordance 0.98, DSC 0.90) and PHE (concordance 0.90, DSC 0.55). This was comparable with the consistency observed between 2 human raters (DSC 0.90 for hemorrhage, 0.57 for PHE). Conclusions- We have developed a deep learning-based imaging algorithm capable of accurately measuring hemorrhage and PHE volumes. Rapid and consistent automated biomarker quantification may accelerate powerful and precise studies of disease biology in large cohorts of intracerebral hemorrhage patients.

NMDA receptors (NMDARs) play subunit-specific roles in synaptic function and are implicated in neuropsychiatric and neurodegenerative disorders. However, the in vivo consequences and therapeutic potential of pharmacologically enhancing NMDAR function via allosteric modulation are largely unknown. We examine the in vivo effects of GNE-0723, a positive allosteric modulator of GluN2A-subunit-containing NMDARs, on brain network and cognitive functions in mouse models of Dravet syndrome (DS) and Alzheimer's disease (AD). GNE-0723 use dependently potentiates synaptic NMDA receptor currents and reduces brain oscillation power with a predominant effect on low-frequency (12-20 Hz) oscillations. Interestingly, DS and AD mouse models display aberrant low-frequency oscillatory power that is tightly correlated with network hypersynchrony. GNE-0723 treatment reduces aberrant low-frequency oscillations and epileptiform discharges and improves cognitive functions in DS and AD mouse models. GluN2A-subunit-containing NMDAR enhancers may have therapeutic benefits in brain disorders with network hypersynchrony and cognitive impairments., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Older adults with acute myocardial infarction (AMI) have higher prevalence of functional impairments, including deficits in cognition, strength, and sensory domains, than their younger counterparts., Objective: To develop and evaluate the prognostic utility of a risk model for 6-month post-AMI mortality in older adults that incorporates information about functional impairments., Design: Prospective cohort study. (ClinicalTrials.gov: NCT01755052)., Setting: 94 hospitals throughout the United States., Participants: 3006 persons aged 75 years or older who were hospitalized with AMI and discharged alive., Measurements: Functional impairments were assessed during hospitalization via direct measurement (cognition, mobility, muscle strength) or self-report (vision, hearing). Clinical variables associated with mortality in prior risk models were ascertained by chart review. Seventy-two candidate variables were selected for inclusion, and backward selection and Bayesian model averaging were used to derive (n = 2004 participants) and validate (n = 1002 participants) a model for 6-month mortality., Results: Participants' mean age was 81.5 years, 44.4% were women, and 10.5% were nonwhite. There were 266 deaths (8.8%) within 6 months. The final risk model included 15 variables, 4 of which were not included in prior risk models: hearing impairment, mobility impairment, weight loss, and lower patient-reported health status. The model was well calibrated (Hosmer-Lemeshow P > 0.05) and showed good discrimination (area under the curve for the validation cohort = 0.84). Adding functional impairments significantly improved model performance, as evidenced by category-free net reclassification improvement indices of 0.21 (P = 0.008) for hearing impairment and 0.26 (P < 0.001) for mobility impairment., Limitation: The model was not externally validated., Conclusion: A newly developed model for 6-month post-AMI mortality in older adults was well calibrated and had good discriminatory ability. This model may be useful in decision making at hospital discharge., Primary Funding Source: National Heart, Lung, and Blood Institute of the National Institutes of Health.

The Precipitating Events Project (PEP Study) is an ongoing longitudinal study of 754 nondisabled community-living persons age 70 years or older who were members of a large health plan in greater New Haven, Connecticut, USA. The study was established to rigorously evaluate the epidemiology of disability in older persons and to elucidate the role of intervening illnesses and injuries on the disabling process. Of the eligible members, 75.2% agreed to participate and were enrolled between March 1998 and October 1999. Participants have completed comprehensive home-based assessments at 18-month intervals and have been interviewed monthly over the phone with a completion rate of 99%. Detailed participant-level data on health care utilization are obtained annually through linkages with Medicare claims. Through June 2019, 702 (93.1%) participants have died after a median of 109 months, while 43 (5.7%) have dropped out of the study after a median of 27 months. Death certificates are available for all decedents. To date, 117 original reports have been published using data from the PEP Study, including many focusing on other high priority areas such as end of life, frailty, depressive symptoms, aging stereotypes, pain, sleep, and methodologic research. The PEP Study welcomes proposals to access data for meritorious analyses from qualified investigators., Competing Interests: The authors have no conflict of interest.

Objective: To examine the epidemiology and key demographic and clinical correlates of patient-reported hypersomnia in persons with advanced age., Design: Cross-sectional design., Setting: Community., Participants: A total of 357 community-dwelling persons from the Yale Precipitating Events Project with a mean age of 84.2 years (range = 78-102 years)., Measurements: We studied patient-reported hypersomnia, defined categorically by an Epworth Sleepiness Scale (ESS) score of 10 or greater; as well as the severity of hypersomnia symptoms, defined continuously by an ESS score range of 0 to 24 (higher scores denote greater sleepiness). In multivariable regression models, we examined cross-sectional associations between key correlates and ESS score, expressed as categorical and continuous variables. Key correlates included: demographics, education, smoking status, body mass index, self-reported medical conditions, Center for Epidemiologic Studies Depression score, Mini-Mental State Examination score, Physical Activity Scale for the Elderly, restless legs syndrome (RLS), self-reported sleep-disordered breathing (SDB), medications, and Insomnia Severity Index., Results: Mean ESS score for all participants was 6.4. Patient-reported hypersomnia (ESS score ≥10) was established in 82 participants (23.0%)-their mean ESS score was 13.0. In multivariable models, male sex, nonwhite race, arthritis, depressive symptoms, low physical activity, RLS, SDB, central nervous system depressant medications, and insomnia severity were cross-sectionally associated with patient-reported hypersomnia (higher adjusted odds ratios, ranging from 1.93-2.86) and/or with the severity of hypersomnia symptoms (higher ESS scores, ranging from 0.11-2.86 points)., Conclusion: Patient-reported hypersomnia was prevalent in a sample of community-dwelling persons with advanced age. In addition, based on cross-sectional associations with the ESS score, key demographic and clinical characteristics were identified that may inform screening strategies for hypersomnia in advanced age. J Am Geriatr Soc 67:2545-2552, 2019., (© 2019 The American Geriatrics Society.)

Importance: Many older survivors of acute myocardial infarction (AMI) experience functional decline, an outcome of primary importance to older adults. Mobility impairment has been proposed as a risk factor for functional decline but has not been evaluated to date in older patients hospitalized for AMI., Objective: To examine the association of mobility impairment, measured during hospitalization, as a risk marker for functional decline among older patients with AMI., Design, Setting, and Participants: Prospective cohort study among 94 academic and community hospitals in the United States. Participants were 2587 hospitalized patients with AMI who were 75 years or older. The study dates were January 2013 to June 2017., Main Outcomes and Measures: Mobility was evaluated during AMI hospitalization using the Timed "Up and Go," with scores categorized as preserved mobility (≤15 seconds to complete), mild impairment (>15 to ≤25 seconds to complete), moderate impairment (>25 seconds to complete), and severe impairment (unable to complete). Self-reported function in activities of daily living (ADLs) (bathing, dressing, transferring, and walking around the home) and walking 0.4 km (one-quarter mile) was assessed at baseline and 6 months after discharge. The primary outcomes were worsening of 1 or more ADLs and loss of ability to walk 0.4 km from baseline to 6 months after discharge. The association between mobility impairment and risk of functional decline was evaluated with multivariable-adjusted logistic regression., Results: Among 2587 hospitalized patients with AMI, the mean (SD) age was 81.4 (4.8) years, and 1462 (56.5%) were male. More than half of the cohort exhibited mobility impairment during AMI hospitalization (21.8% [564 of 2587] had mild impairment, 16.0% [414 of 2587] had moderate impairment, and 15.2% [391 of 2587] had severe impairment); 12.8% (332 of 2587) reported ADL decline, and 16.7% (431 of 2587) reported decline in 0.4-km mobility. Only 3.8% (30 of 800) of participants with preserved mobility experienced any ADL decline compared with 6.9% (39 of 564) of participants with mild impairment (adjusted odds ratio [aOR], 1.24; 95% CI, 0.74-2.09), 18.6% (77 of 414) of participants with moderate impairment (aOR, 2.67; 95% CI, 1.67-4.27), and 34.7% (136 of 391) of participants with severe impairment (aOR, 5.45; 95% CI, 3.29-9.01). Eleven percent (90 of 800) of participants with preserved mobility declined in ability to walk 0.4 km compared with 15.2% (85 of 558) of participants with mild impairment (aOR, 1.51; 95% CI, 1.04-2.20), 19.0% (78 of 411) of participants with moderate impairment (aOR, 2.03; 95% CI, 1.37-3.02), and 24.6% (95 of 386) of participants with severe impairment (aOR, 3.25; 95% CI, 2.02-5.23)., Conclusions and Relevance: This study's findings suggest that mobility impairment assessed during hospitalization may be a potent risk marker for functional decline in older survivors of AMI. These findings also suggest that brief, validated assessments of mobility should be part of the care of older hospitalized patients with AMI to identify those at risk for this important patient-centered outcome.

Context: Prostate-specific antigen (PSA) changes during testosterone treatment of older hypogonadal men have not been rigorously evaluated., Design: Double-blinded, placebo-controlled trial., Setting: Twelve US academic medical centers., Participants: Seven hundred ninety hypogonadal men ≥65 years of age with average testosterone levels ≤275 ng/dL. Men at high risk for prostate cancer were excluded., Interventions: Testosterone or placebo gel for 12 months., Main Outcomes: Percentile changes in PSA during testosterone treatment of 12 months., Results: Testosterone treatment that increased testosterone levels from 232 ± 63 ng/dL to midnormal was associated with a small but substantially greater increase (P < 0.001) in PSA levels than placebo treatment. Serum PSA levels increased from 1.14 ± 0.86 ng/mL (mean ± SD) at baseline by 0.47 ± 1.1 ng/mL at 12 months in the testosterone group and from 1.25 ± 0.86 ng/mL by 0.06 ± 0.72 ng/mL in the placebo group. Five percent of men treated with testosterone had an increase ≥1.7 ng/mL and 2.5% of men had an increase of ≥3.4 ng/mL. A confirmed absolute PSA >4.0 ng/mL at 12 months was observed in 1.9% of men in the testosterone group and 0.3% in the placebo group. Four men were diagnosed with prostate cancer; two were Gleason 8., Conclusions: When hypogonadal older men with normal baseline PSA are treated with testosterone, 5% had an increase in PSA ≥1.7 ng/mL, and 2.5% had an increase ≥3.4 ng/mL., (Copyright © 2019 Endocrine Society.)

Background: Medication classes, polypharmacy, and hazardous alcohol and illicit substance abuse may exhibit stronger associations with serious falls among persons living with HIV (PLWH) than with uninfected comparators. We investigated whether these associations differed by HIV status., Setting: Veterans Aging Cohort Study., Methods: We used a nested case-control design. Cases (N = 13,530) were those who fell. Falls were identified by external cause of injury codes and a machine-learning algorithm applied to radiology reports. Cases were matched to controls (N = 67,060) by age, race, sex, HIV status, duration of observation, and baseline date. Risk factors included medication classes, count of unique non-antiretroviral therapy (non-ART) medications, and hazardous alcohol and illicit substance use. We used unconditional logistic regression to evaluate associations., Results: Among PLWH, benzodiazepines [odds ratio (OR) 1.24; 95% confidence interval (CI) 1.08 to 1.40] and muscle relaxants (OR 1.29; 95% CI: 1.08 to 1.46) were associated with serious falls but not among uninfected (P > 0.05). In both groups, key risk factors included non-ART medications (per 5 medications) (OR 1.20, 95% CI: 1.17 to 1.23), illicit substance use/abuse (OR 1.44; 95% CI: 1.34 to 1.55), hazardous alcohol use (OR 1.30; 95% CI: 1.23 to 1.37), and an opioid prescription (OR 1.35; 95% CI: 1.29 to 1.41)., Conclusion: Benzodiazepines and muscle relaxants were associated with serious falls among PLWH. Non-ART medication count, hazardous alcohol and illicit substance use, and opioid prescriptions were associated with serious falls in both groups. Prevention of serious falls should focus on reducing specific classes and absolute number of medications and both alcohol and illicit substance use.

Objectives: Late-life disability is highly dynamic but within-person short-term fluctuations have not been assessed previously. We analyze how substantial such late-life disability fluctuations are and whether they are associated with time-to-death, long-term disability trajectories, frailty, and sociodemographics., Methods: Monthly survey data (Precipitating Events Project Study) on activities of daily living/instrumental activities of daily living (ADL/IADL) disability (0-9) in the last years of life from 642 deceased respondents providing 56,308 observations were analyzed with a two-step approach. Observation-level residuals extracted from a Poisson mixed regression model (first step), which depict vertical short-term fluctuations from individual long-term trajectories, were analyzed with a linear mixed regression model (second step)., Results: Short-term disability fluctuations amounted to about one ADL/IADL limitation, increased in the last 4 years of life, and were closely associated with disability increases. Associations with frailty or sociodemographics characteristics were absent except for living alone., Discussion: Short-term disability fluctuations in late life were substantial, were linked to mortality-related processes, and represent a concomitant feature of disability increases in late life., (© The Author(s) 2019. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The lateral septum (LS) plays an important role in regulating aggression. It is well recognized that LS lesions lead to a dramatic increase in aggressive behaviors. A better understanding of LS neurophysiology and its functional output is therefore important to assess LS involvement in regulating aggression. The LS is a heterogeneous structure that maintains inputs and outputs with multiple brain regions, and is also divided into subregions that innervate one another. Thus, it is challenging to identify the exact cell type and projections for characterization. In this study, we determined the expression pattern of the calcium-activated chloride channel, TMEM16B, in the LS of both male and female mice. We then investigated the physiological contribution of the calcium-activated chloride channel to LS neuronal signaling. By performing whole-cell patch-clamp recording, we showed that TMEM16B alters neurotransmitter release at the hippocampal-LS synapse, and regulates spike frequency and spike frequency adaptation in subpopulations of LS neurons. We further demonstrated that loss of TMEM16B function promotes lengthened displays of aggressive behaviors by male mice during the resident intruder paradigm. In conclusion, our findings suggest that TMEM16B function contributes to neuronal excitability in subpopulations of LS neurons and the regulation of aggression in male mice. SIGNIFICANCE STATEMENT Aggression is a behavior that arose evolutionarily from the necessity to compete for limited resources and survival. One particular brain region involved in aggression is the lateral septum (LS). In this study, we characterized the expression of the TMEM16B calcium-activated chloride channel in the LS and showed that TMEM16B regulates the action potential firing frequency of LS neurons. We discovered that loss of TMEM16B function lengthens the displays of aggressive behaviors in male mice. These findings suggest that TMEM16B plays an important role in regulating LS neuronal excitability and behaviors associated with LS function, thereby contributing to our understanding of how the LS may regulate aggression., (Copyright © 2019 the authors.)

Background: Physical performance and activity have both been linked to fall risk, but the way they are jointly associated with falls is unclear. We investigated how these two factors are related to incident falls in older men., Methods: In 2,741 men (78.8 ± 5 years), we evaluated the associations between activity and physical performance and how they jointly contributed to incident falls. Activity was assessed by accelerometry. Physical performance was measured by gait speed, dynamic balance (narrow walk), chair stand time, grip strength, and leg power. Falls were ascertained by tri-annual questionnaires., Results: Men were grouped into four categories based on activity and performance levels. The greatest number of falls (36%-43%) and the highest fall rate (4.7-5.4/y among those who fell) (depending on the performance test) occurred in men with low activity/low performance, but most falls (57%-64%) and relatively high fall rates (3.0-4.35/y) occurred in the other groups (low activity/high performance, high activity/high performance and high activity/low performance; 70% of men were in these groups). There were interactions between activity, performance (gait speed, narrow walk), and incident falls (p = .001-.02); predicted falls per year were highest in men with low activity/low performance, but there was also a peak of predicted falls in those with high activity., Conclusions: In community-dwelling older men, many falls occur in those with the lowest activity/worst physical performance but fall risk is also substantial with better activity and performance. Activity/physical performance assessments may improve identification of older men at risk of falls, and allow individualized approaches to prevention., (© The Author(s) 2018. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Expected performance rates for various outcome metrics are a hallmark of hospital quality indicators used by Agency of Healthcare Research and Quality, Center for Medicare and Medicaid Services, and National Quality Forum. The identification of outlier hospitals with above- and below-expected mortality for emergency general surgery (EGS) operations is therefore of great value for EGS quality improvement initiatives. The aim of this study was to determine hospital variation in mortality after EGS operations, and compare characteristics between outlier hospitals., Methods: Using data from the California State Inpatient Database (2010-2011), we identified patients who underwent one of eight common EGS operations. Expected mortality was obtained from a Bayesian model, adjusting for both patient- and hospital-level variables. A hospital-level standardized mortality ratio (SMR) was constructed (ratio of observed to expected deaths). Only hospitals performing three or more of each operation were included. An "outlier" hospital was defined as having an SMR with 80% confidence interval that did not cross 1.0. High- and low-mortality SMR outliers were compared., Results: There were 140,333 patients included from 220 hospitals. Standardized mortality ratio varied from a high of 2.6 (mortality, 160% higher than expected) to a low of 0.2 (mortality, 80% lower than expected); 12 hospitals were high SMR outliers, and 28 were low SMR outliers. Standardized mortality was over three times worse in the high SMR outliers compared with the low SMR outliers (1.7 vs. 0.5; p < 0.001). Hospital-, patient-, and operative-level characteristics were equivalent in each outlier group., Conclusion: There exists significant hospital variation in standardized mortality after EGS operations. High SMR outliers have significant excess mortality, while low SMR outliers have superior EGS survival. Common hospital-level characteristics do not explain the wide gap between underperforming and overperforming outlier institutions. These findings suggest that SMR can help guide assessment of EGS performance across hospitals; further research is essential to identify and define the hospital processes of care which translate into optimal EGS outcomes., Level of Evidence: Epidemiologic Study, level III.

Frailty has long been an important concept in the practice of geriatric medicine and in gerontological research, but integration and implementation of frailty concepts into clinical practice in the United States has been slow. The National Institute on Aging (NIA) Intramural Research Program and the Johns Hopkins Older Americans Independence Center sponsored a symposium to identify potential barriers that impede the movement of frailty into clinical practice and to highlight opportunities to facilitate the further integration of frailty into clinical practice. Primary and subspecialty care providers, and investigators working to integrate and translate new biological aging knowledge into more specific preventive and treatment strategies for frailty provided the meeting content. Recommendations included a call for more specific language that clarifies conceptual differences between frailty definitions and measurement tools; the development of randomized controlled trials to test whether specific intervention strategies for a variety of conditions differently affect frail and non-frail individuals; development of implementation studies and therapeutic trials aimed at tailoring care as a function of pragmatic frailty markers; the use of deep learning and dynamic systems approaches to improve the translatability of findings from epidemiological studies; and the incorporation of advances in aging biology, especially focused on mitochondria, stem cells, and senescent cells, toward the further development of biologically targeted intervention and prevention strategies that can be used to treat or prevent frailty. J Am Geriatr Soc 67:1559-1564, 2019., (© 2019 The American Geriatrics Society.)

Background: There is a longstanding interest in the field of management science to study high performance organizations. Applied to medicine, research on hospital performance indicates that some hospitals are high performing, while others are not. The objective of this study was to identify a cluster of high-performing emergency general surgery (EGS) hospitals and assess whether high performance at one EGS operation was associated with high performance on all EGS operations., Methods: Adult patients who underwent one of eight EGS operations were identified in the California State Inpatient Database (2010-2011), which we linked to the American Hospital Association database. Beta regression was used to estimate a hospital's risk-adjusted mortality, accounting for patient- and hospital-level factors. Centroid cluster analysis grouped hospitals by patterns of mortality rates across the eight EGS operations using z scores. Multinomial logistic regression compared hospital characteristics by cluster., Results: A total of 220 acute care hospitals were included. Three distinct clusters of hospitals were defined based on assessment of mortality for each operation type: high-performing hospitals (n = 66), average performing (n = 99), and low performing (n = 55). The mortality by individual operation type at the high-performing cluster was consistently at least 1.5 standard deviations better than the low-performing cluster (p < 0.001). Within-cluster variation was minimal at high-performing hospitals compared with wide variation at low-performing hospitals. A hospital's high performance in one EGS operation type predicted high performance on all EGS operation types., Conclusion: High-performing EGS hospitals attain excellence across all types of EGS operations, with minimal variability in mortality. Poor-performing hospitals are persistently below average, even for low-risk operations. These findings suggest that top-performing EGS hospitals are highly reliable, with systems of care in place to achieve consistently superior results. Further investigation and collaboration are needed to identify the factors associated with high performance., Level of Evidence: Prognostic, level III.

Objective: To determine whether burden of multiple chronic conditions (MCCs) influences the risk of receiving inappropriate vs appropriate device therapies., Design: Retrospective cohort study., Setting: Seven US healthcare delivery systems., Participants: Adults with left ventricular systolic dysfunction receiving an implantable cardioverter-defibrillator (ICD) for primary prevention., Measurements: Data on 24 comorbid conditions were captured from electronic health records and categorized into quartiles of comorbidity burden (0-3, 4-5, 6-7 and 8-16). Incidence of ICD therapies (shock and antitachycardia pacing [ATP] therapies), including appropriateness, was collected for 3 years after implantation. Outcomes included time to first ICD therapy, total ICD therapy burden, and risk of inappropriate vs appropriate ICD therapy., Results: Among 2235 patients (mean age = 69 ± 11 years, 75% men), the median number of comorbidities was 6 (interquartile range = 4-8), with 98% having at least two comorbidities. During a mean 2.2 years of follow-up, 18.3% of patients experienced at least one appropriate therapy and 9.9% experienced at least one inappropriate therapy. Higher comorbidity burden was associated with an increased risk of first inappropriate therapy (adjusted hazard ratio [HR] = 1.94 [95% confidence interval {CI} = 1.14-3.31] for 4-5 comorbidities; HR = 2.25 [95% CI = 1.25-4.05] for 6-7 comorbidities; and HR = 2.91 [95% CI = 1.54-5.50] for 8-16 comorbidities). Participants with 8-16 comorbidities had a higher total burden of ICD therapy (adjusted relative risk [RR] = 2.12 [95% CI = 1.43-3.16]), a higher burden of inappropriate therapy (RR = 3.39 [95% CI = 1.67-6.86]), and a higher risk of receiving inappropriate vs appropriate therapy (RR = 1.74 [95% CI = 1.07-2.82]). Comorbidity burden was not significantly associated with receipt of appropriate ICD therapies. Patterns were similar when separately examining shock or ATP therapies., Conclusions: In primary prevention ICD recipients, MCC burden was independently associated with an increased risk of inappropriate but not appropriate device therapies. Comorbidity burden should be considered when engaging patients in shared decision making about ICD implantation., (© 2019 The American Geriatrics Society.)

Background: As the geriatric population grows, the need for hospitals performing high quality emergency general surgery (EGS) on older patients will increase. Identifying clusters of high-performing geriatric emergency general surgery hospitals would substantiate the need for in-depth analyses of hospital-specific structures and practices that benefit older EGS patients. The objectives of this study were therefore to identify clusters of hospitals based on mortality performance for geriatric patients undergoing common EGS operations and to determine if hospital performance was similar for all operation types., Methods: Hospitals in the California State Inpatient Database were included if they performed a range of eight common EGS operations in patients 65 years or older, with a minimum requirement of three of each operation performed over 2 years. Multivariable beta regression models were created to define hospital-level risk-adjusted mortality. Centroid cluster analysis was used to identify groups of hospitals based on mortality and to determine if mortality-performance differed by operation., Results: One hundred seven hospitals were included, performing a total of 24,279 operations in older patients. Hospitals separated into three distinct clusters: high, average, and low performers. The high-performing hospitals had survival rates 1 to 2 standard deviations better than the low-performers (p < 0.001). For each cluster, high performance in any one EGS operation consistently translated into high performance across all EGS operations., Conclusion: Hospitals conducting EGS operations in the geriatric patient population cluster into three distinct groups based on their survival performance. High-performing hospitals significantly outperform the average and low performers across every operation. The high-performers achieve reliable, high-quality results regardless of operation type. Further qualitative research is needed to investigate the perioperative drivers of hospital performance in the geriatric EGS population., Level of Evidence: Study Type Prognostic, level III.

Background: An individual's rate of aging directly influences his/her susceptibility to morbidity and mortality. Thus, quantifying aging and disentangling how various factors coalesce to produce between-person differences in the rate of aging, have important implications for potential interventions. We recently developed and validated a novel multi-system-based aging measure, Phenotypic Age (PhenoAge), which has been shown to capture mortality and morbidity risk in the full US population and diverse subpopulations. The aim of this study was to evaluate associations between PhenoAge and a comprehensive set of factors, including genetic scores, childhood and adulthood circumstances, and health behaviors, to determine the relative contributions of these factors to variance in this aging measure., Methods and Findings: Based on data from 2,339 adults (aged 51+ years, mean age 69.4 years, 56% female, and 93.9% non-Hispanic white) from the US Health and Retirement Study, we calculated PhenoAge and evaluated the multivariable associations for a comprehensive set of factors using 2 innovative approaches-Shapley value decomposition (the Shapley approach hereafter) and hierarchical clustering. The Shapley approach revealed that together all 11 study domains (4 childhood and adulthood circumstances domains, 5 polygenic score [PGS] domains, and 1 behavior domain, and 1 demographic domain) accounted for 29.2% (bootstrap standard error = 0.003) of variance in PhenoAge after adjustment for chronological age. Behaviors exhibited the greatest contribution to PhenoAge (9.2%), closely followed by adulthood adversity, which was suggested to contribute 9.0% of the variance in PhenoAge. Collectively, the PGSs contributed 3.8% of the variance in PhenoAge (after accounting for chronological age). Next, using hierarchical clustering, we identified 6 distinct subpopulations based on the 4 childhood and adulthood circumstances domains. Two of these subpopulations stood out as disadvantaged, exhibiting significantly higher PhenoAges on average. Finally, we observed a significant gene-by-environment interaction between a previously validated PGS for coronary artery disease and the seemingly most disadvantaged subpopulation, suggesting a multiplicative effect of adverse life course circumstances coupled with genetic risk on phenotypic aging. The main limitations of this study were the retrospective nature of self-reported circumstances, leading to possible recall biases, and the unrepresentative racial/ethnic makeup of the population., Conclusions: In a sample of US older adults, genetic, behavioral, and socioenvironmental circumstances during childhood and adulthood account for about 30% of differences in phenotypic aging. Our results also suggest that the detrimental effects of disadvantaged life course circumstances for health and aging may be further exacerbated among persons with genetic predisposition to coronary artery disease. Finally, our finding that behaviors had the largest contribution to PhenoAge highlights a potential policy target. Nevertheless, further validation of these findings and identification of causal links are greatly needed., Competing Interests: The authors have declared that no competing interests exist.

Objectives: To evaluate the time course of "taking to bed" at the end of life and determine whether it differs according to age, sex, and condition leading to death., Design: Prospective longitudinal study., Setting: Greater New Haven, Connecticut., Participants: A total of 651 decedents from a cohort of 754 community-living persons, 70+ years of age., Measurements: During the last 2 years of life, the occurrence of bed rest and number of days in bed, two indicators of bed rest burden, were ascertained each month. Bed rest was defined as staying in bed for at least a half day due to an illness, injury, or other problem., Results: The occurrence of bed rest increased modestly from 12.4% at 24 months before death to 19.0% at 5 months before death, before increasing exponentially to 51.6% at 1 month before death. The median number of days in bed fluctuated within a narrow range of 3 to 7 from 24 months to 4 months before death, before increasing substantially to a high of 14 at 1 month before death. In the last 2 years of life, the burden of bed rest did not differ by age but was significantly greater in women than men. Among the conditions leading to death, the burden of bed rest was highest among persons dying from organ failure and cancer, lowest for sudden death, and intermediate for frailty, advanced dementia, and other conditions., Conclusion: The burden of bed rest at the end of life is greater in women than men, does not differ by age, and is highest among persons dying from organ failure and cancer. The steep increases observed in the last 3 to 5 months of life suggest that taking to bed may be an indicator that death is approaching and should prompt discussions about referral to hospice among older persons with serious illness., (© 2019 The American Geriatrics Society.)

Background: Within the growing geriatric population, there is an increasing need for emergency operations. Optimizing outcomes can require a structured system of surgical care based on key quality indicators. To investigate this, the current study sought to answer 2 questions. First, to what degree does hospital emergency operative volume impact mortality for geriatric patients undergoing emergency general surgery (EGS) operations? Second, at what procedure-specific hospital volume will geriatric patients undergoing an emergency operation achieve at or better than average mortality risk?, Study Design: Retrospective cohort study of geriatric patients (aged 65 years and older) who underwent 1 of 10 EGS operations identified from the California State Inpatient Database (2010 to 2011). β-Logistic generalized linear regression was used, with the hospital as the unit of analysis, to investigate the relationship between hospital operative volume and in-hospital riskv-adjusted mortality. Hospital operative volume thresholds to optimize probability of survival were defined., Results: There were 41,860 operations evaluated at 299 hospitals. For each operation, mortality decreased as hospital emergency operative volume increased (p < 0.001 for each operation); for every standardized increase in volume (meaning +1 natural logarithm of volume), the reduction in mortality ranged from 14% for colectomy to 61% for appendectomy. Hospital volume thresholds, which optimize to 95% probability of survival, varied by procedure, with a mean of 14 operations over 2 years. More than 50% of hospitals did not meet the threshold benchmarks, representing 22% of patients., Conclusions: Survival rates for geriatric patients were improved substantially when emergency operations were performed at hospitals with higher operative volumes. Consistent with all active Quality Programs of the American College of Surgeons, hospital operative volume appears to be an important metric of surgical quality for older patients undergoing emergency operations., (Copyright © 2019 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)

Compulsive alcohol drinking, where intake persists regardless of adverse consequences, plays a major role in the substantial costs of alcohol use disorder. However, the processes that promote aversion-resistant drinking remain poorly understood. Compulsion-like responding has been considered automatic and reflexive and also to involve higher motivation, since drinking persists despite adversity. Thus, we used lickometry, where microstructural behavioral changes can reflect altered motivation, to test whether conflict-resistant intake [quinine-alcohol (QuiA)] reflected greater automaticity or motivation relative to alcohol-only drinking (Alc). Front-loading during QuiA and Alc suggested incentive to drink in both. However, the relationship between total licking and intake was less variable during QuiA, as was lick volume, without changes in average responding. QuiA bout organization was also less variable, with fewer licks outside of bouts (stray licks) and fewer gaps within bouts. Interestingly, QuiA avoidance of stray licking continued into short bouts, with fewer short and more medium-length bouts, which was striking given their minor impact on intake. Instead, more effort at bout onset could allow short bouts to persist longer. Indeed, while QuiA licking was overall faster, QuiA bouts were especially fast at bout initiation. However, few QuiA changes individually predicted greater intake, perhaps suggesting an overarching strategy during aversion-resistant responding. Thus, our results indicate that aversion-resistant intake exhibited less variability, where increased automaticity could decrease need for awareness, and stronger bout initiation, which might prolong responding despite adversity. This may reflect a collective strategy, which we call Head Down and Push responding that facilitates conflict-resistant, compulsion-like intake., (© 2018 Society for the Study of Addiction.)

Background: Clinical trials of COPD pharmacotherapy typically involve aging populations with moderate-to-severe COPD, but the latter is often diagnosed by spirometric criteria that are not age-appropriate across the continuum of lung function. We have therefore re-evaluated the clinical effect of combination therapy (salmeterol plus fluticasone) in moderate-to-severe COPD, using more age-appropriate spirometric criteria from the Global Lung Function Initiative (GLI) and trial data from Towards a Revolution in COPD Health (TORCH)., Methods: Of the 6112 TORCH participants, 5688 (93.1%) had GLI-based moderate-to-severe COPD (mean age 64.8 years). The primary outcome was all-cause mortality and the primary comparison was combination therapy vs. placebo. Secondary outcomes included COPD and cardiovascular (CV) mortality and pneumonia. A modified intention-to-treat analysis evaluated differences in time-to-event over a three-year period, using Cox proportional hazards models with statistical significance at p < 0.010 (acknowledging repeated significance testing)., Results: Relative to placebo, combination therapy yielded a statistically non-significant reduction in all-cause mortality-adjusted hazard ratio [adjHR] 0.78 (95% confidence interval [CI]: 0.64, 0.95), p = 0.012. Relative to placebo, combination therapy also yielded statistically non-significant reductions in COPD and CV mortality-adjHR 0.75 (95% CI: 0.55, 1.02), p = 0.068 and adjHR 0.76 (95% CI: 0.53, 1.09), p = 0.135, respectively. In contrast, combination therapy yielded a statistically significant increased risk of pneumonia, relative to placebo-adjHR 1.80 (95% CI: 1.46, 2.21), p < 0.001., Conclusion: In GLI-based moderate-to-severe COPD, combination therapy yields a statistically significant increased risk of pneumonia but the reductions in mortality are not statistically significant, although could potentially be clinically meaningful., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Early readmissions among older adults hospitalized for acute myocardial infarction (AMI) are costly and difficult to predict. Aging-related functional impairments may inform risk prediction but are unavailable in most studies. Our objective was to, therefore, develop and validate an AMI readmission risk model for older patients who considered functional impairments and was suitable for use before hospital discharge., Methods and Results: SILVER-AMI (Comprehensive Evaluation of Risk in Older Adults with AMI) is a prospective cohort study of 3006 patients of age ≥75 years hospitalized with AMI at 94 US hospitals. Participants underwent in-hospital assessment of functional impairments including cognition, vision, hearing, and mobility. Other variables plausibly associated with readmissions were also collected. The outcome was all-cause readmission at 30 days. We used backward selection and Bayesian model averaging to derive (N=2004) a risk model that was subsequently validated (N=1002). Mean age was 81.5 years, 44.4% were women, and 10.5% were nonwhite. Within 30 days, 547 participants (18.2%) were readmitted. Readmitted participants were older, had more comorbidities, and had a higher prevalence of functional impairments, including activities of daily living disability (17.0% versus 13.0%; P=0.013) and impaired functional mobility (72.5% versus 53.6%; P<0.001). The final risk model included 8 variables: functional mobility, ejection fraction, chronic obstructive pulmonary disease, arrhythmia, acute kidney injury, first diastolic blood pressure, P2Y12 inhibitor use, and general health status. Functional mobility was the only functional impairment variable retained but was the strongest predictor. The model was well calibrated (Hosmer-Lemeshow P value >0.05) with moderate discrimination (C statistics: 0.65 derivation cohort and 0.63 validation cohort). Functional mobility significantly improved performance of the risk model (net reclassification improvement index =20%; P<0.001)., Conclusions: In our final risk model, functional mobility, previously not included in readmission risk models, was the strongest predictor of 30-day readmission among older adults after AMI. The modest discrimination indicates that much of the variability in readmission risk among this population remains unexplained by patient-level factors., Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01755052.

Background: This paper describes a protocol for determining the incidence of serious fall injuries for Strategies to Reduce Injuries and Develop Confidence in Elders (STRIDE), a large, multicenter pragmatic clinical trial with limited resources for event adjudication. We describe how administrative data (from participating health systems and Medicare claims) can be used to confirm participant-reported events, with more time- and resource-intensive full-text medical record data used only on an "as-needed" basis., Methods: STRIDE is a pragmatic cluster-randomized controlled trial involving 5451 participants age ≥ 70 and at increased risk for falls, served by 86 primary care practices in 10 US health systems. The STRIDE intervention involves a nurse falls care manager who assesses a participant's underlying risks for falls, suggests interventions using motivational interviewing, and then creates, implements and longitudinally follows up on an individualized care plan with the participant (and caregiver when appropriate), in partnership with the participant's primary care provider. STRIDE's primary outcome is serious fall injuries, defined as a fall resulting in: (1) medical attention billable according to Medicare guidelines with a) fracture (excluding isolated thoracic vertebral and/or lumbar vertebral fracture), b) joint dislocation, or c) cut requiring closure; OR (2) overnight hospitalization with a) head injury, b) sprain or strain, c) bruising or swelling, or d) other injury determined to be "serious" (i.e., burn, rhabdomyolysis, or internal injury). Two sources of data are required to confirm a serious fall injury. The primary data source is the participant's self-report of a fall leading to medical attention, identified during telephone interview every 4 months, with the confirmatory source being (1) administrative data capturing encounters at the participating health systems or Medicare claims and/or (2) the full text of medical records requested only as needed., Discussion: Adjudication is ongoing, with over 1000 potentially qualifying events adjudicated to date. Administrative data can be successfully used for adjudication, as part of a hybrid approach that retrieves full-text medical records only when needed. With the continued refinement and availability of administrative data sources, future studies may be able to use administrative data completely in lieu of medical record review to maximize the quality of adjudication with finite resources., Trial Registration: ClinicalTrials.gov (NCT02475850)., Competing Interests: Competing interestsThe authors declare that they have no competing interests.

Cerebrovascular alterations are a key feature of Alzheimer's disease (AD) pathogenesis. However, whether vascular damage contributes to synaptic dysfunction and how it synergizes with amyloid pathology to cause neuroinflammation and cognitive decline remain poorly understood. Here, we show that the blood protein fibrinogen induces spine elimination and promotes cognitive deficits mediated by CD11b-CD18 microglia activation. 3D molecular labeling in cleared mouse and human AD brains combined with repetitive in vivo two-photon imaging showed focal fibrinogen deposits associated with loss of dendritic spines independent of amyloid plaques. Fibrinogen-induced spine elimination was prevented by inhibiting reactive oxygen species (ROS) generation or genetic ablation of CD11b. Genetic elimination of the fibrinogen binding motif to CD11b reduced neuroinflammation, synaptic deficits, and cognitive decline in the 5XFAD mouse model of AD. Thus, fibrinogen-induced spine elimination and cognitive decline via CD11b link cerebrovascular damage with immune-mediated neurodegeneration and may have important implications in AD and related conditions., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Days spent at home has recently been identified as an important patient-centered outcome; yet, relatively little is known about time spent at home at the end of life among community-living older persons., Methods: The analytic sample included 457 decedents from an ongoing cohort study of 754 community-living persons, aged ≥70 years. Days spent at home were calculated as 180 days minus the number of days in a hospital, nursing home, or hospice facility. The condition leading to death was determined from death certificates and comprehensive assessments., Results: The median number of days at home was 159 (interquartile range 125-174). There were 138 (30.2%) decedents at home during the entire 6-month period, while 163 (35.7%) were at home for fewer than 150 days. Days at home did not differ significantly by age (P = .922), sex (P = .238), or race/ethnicity (P = .199), but did differ according to the condition leading to death (P = .001), with the lowest value observed for organ failure (150 [106.5-168.5]), highest values for sudden death (177 [172-179]) and cancer (167 [140-174]), and intermediate values for advanced dementia (164 [118-174]), frailty (160.5 [130-174]), and other conditions (153 [118-175])., Conclusions: Among community-living older persons, days spent at home in the last 6 months of life do not differ by age, sex, or race/ethnicity, but are significantly lower for persons dying from organ failure. Additional efforts may be warranted to optimize time spent at home at the end of life, especially among older persons dying from organ failure., (Copyright © 2018. Published by Elsevier Inc.)

Objectives: To address the competing risk of death in longitudinal studies of older persons, we demonstrate sensitivity analyses that evaluate robustness of associations between exposures and three outcome types: dichotomous, count, and time to event., Design: A secondary analysis of data from a prospective cohort study., Setting: Community-based data from the Precipitating Events Project in New Haven, CT., Participants: Persons 70 years and older who were initially community dwelling and without disability in the four basic activities of daily living (N = 754)., Measurements: Missing outcome values from decedents were multiply imputed under different scenarios. Three outcomes were examined: dichotomous fall-related hospitalization (FRH); a count (0-13) of total disability in each of the 6 months after discharge; and days to functional recovery among those whose disability worsened in the hospital. Each outcome had a different exposure: for dichotomous, indicators of being overweight or obese; for count, frailty from the Fried phenotype (0-5, where not frail = 0, prefrail = 1-2, and frail = 3-5); for days to recovery, vision impairment., Results: For FRH, being overweight or obese lost significance when decedents were kept in the risk pool without outcome events for over 10 years. For disability count and time to recovery, with follow-up of 6 months, exposures only lost significance under highly implausible clinical scenarios., Conclusion: This method facilitates evaluation of potential bias from the competing risk of death in longitudinal studies for nondeath outcomes that are not necessarily time to event. Results suggest that death introduces substantive bias when long-term follow-up results in cumulatively high levels of mortality. J Am Geriatr Soc 67:357-362, 2019., (© 2018 The American Geriatrics Society.)

Objectives: To evaluate the effect of hospitalizations on patterns of sedentary and physical activity time in mobility-limited older adults randomized to structured physical activity or health education., Design: Secondary analysis of investigator-blinded, parallel-group, randomized trial conducted at 8 U.S. centers between February 2010 and December 2013., Participants: Sedentary men and women aged 70 to 89 at baseline who wore a hip-fitted accelerometer 7 consecutive days at baseline and 6, 12, and 24 months after randomization (N=1,341)., Measurements: Participants were randomized to a physical activity (PA; n = 669) intervention that included aerobic, resistance, and flexibility training or to a health education (HE; n = 672) intervention that consisted of workshops on older adult health and light upper-extremity stretching. Accelerometer patterns were characterized as bouts of sedentary (<100 counts/min; ≥1, ≥10, ≥30, ≥60 minute lengths) and activity (≥100 counts/min; ≥1, ≥2, ≥5, ≥10 minute lengths) time. Each participant was categorized as having 0, 1 to 3, or 4 or more cumulative hospital days before each accelerometer assessment., Results: Hospitalization increased sedentary time similarly in both intervention groups (8 min/d for 1-3 cumulative hospital days and 16 min/d for ≥4 cumulative hospital days). Hospitalization was also associated with less physical activity time across all bouts of less than 10 minutes (≥1: -7 min/d for 1-3 cumulative hospital days, -16 min/d for ≥4 cumulative hospital days; ≥2: -5 min/d for 1-3 cumulative hospital days, -11 min/d for ≥4 cumulative hospital days; ≥5: -3 min/d for 1-3 cumulative hospital days, -4 min/d for ≥4 cumulative hospital days). There was no evidence of recovery to prehospitalization levels (time effect p >.41). PA participants had less sedentary time in bouts of less than 30 minutes than HE participants (-8 to -10 min/d) and more total activity (+3 to +6 min/d), although hospital-related changes were similar between the intervention groups (interaction effect p >.26)., Conclusion: Participating in a PA intervention before hospitalization had expected benefits, but participants remained susceptible to hospitalization's detrimental effects on their daily activity levels. There was no evidence of better activity recovery after hospitalization. J Am Geriatr Soc 67:261-268, 2019., (© 2018, Copyright the Authors Journal compilation © 2018, The American Geriatrics Society.)

Background: China has transitioned from being one of the fastest-growing populations to among the most rapidly aging countries worldwide. In particular, the population of oldest-old individuals, those aged 80+, is projected to quadruple by 2050. The oldest-old represent a uniquely important group-they have high demand for personal assistance and the highest healthcare costs of any age group. Understanding trends in disability and longevity among the oldest-old-that is, whether successive generations are living longer and with less disability-is of great importance for policy and planning purposes., Methods: We utilized data from successive birth cohorts (n = 20,520) of the Chinese oldest-old born 10 years apart (the earlier cohort was interviewed in 1998 and the later cohort in 2008). Disability was defined as needing personal assistance in performing one or more of five essential activities (bathing, transferring, dressing, eating, and toileting) or being incontinent. Participants were followed for age-specific disability transitions and mortality (in 2000 and 2002 for the earlier cohort and 2011 and 2014 for the later cohort), which were then used to generate microsimulation-based multistate life tables to estimate partial life expectancy (LE) and disability-free LE (DFLE), stratified by sex and age groups (octogenarians, nonagenarians, and centenarians). We additionally explored sociodemographic heterogeneity in LE and DFLE by urban/rural residence and educational attainment., Results: More recently born Chinese octogenarians (born 1919-1928) had a longer partial LE between ages 80 and 89 than octogenarians born 1909-1918, and octogenarian women experienced an increase in partial DFLE of 0.32 years (P = 0.004) across the two birth cohorts. Although no increases in partial LE were observed among nonagenarians or centenarians, partial DFLE increased across birth cohorts, with a gain of 0.41 years (P < 0.001) among nonagenarians and 0.07 years (P = 0.050) among centenarians. Subgroup analyses revealed that gains in partial LE and DFLE primarily occurred among the urban resident population., Conclusions: Successive generations of China's oldest-old are living with less disability as a whole, and LE is expanding among octogenarians. However, we found a widening urban-rural disparity in longevity and disability, highlighting the need to improve policies to alleviate health inequality throughout the population.

Background: To characterize functional trajectories in the year before and after a new cancer diagnosis among older adults and to identify risk factors for worsening disability post-diagnosis., Methods: We identified 170 participants 70+ years with monthly assessments of thirteen basic, instrumental, and mobility activities and with a new cancer diagnosis from 1998 to 2014. A group-based trajectory model identified distinct functional trajectories based on a total disability score during the twelve months pre- and post-diagnosis. We evaluated associations between potential risk factors at the time of cancer diagnosis and worsening disability post-diagnosis, explored functional transitions from pre- to post-diagnosis and identified participants whose functional trajectories worsened., Results: Three pre-diagnosis functional trajectories were identified among 170 participants (mean age at diagnosis: 83 years (range: 73-105 years): mild, moderate, and severe disability. Three post-diagnosis functional trajectories were identified among 158 non-decedents: mild, moderate, and severe disability. Most participants (93.9%) with severe disability pre-diagnosis had severe disability post-diagnosis. Risk factors independently associated with worsening disability post-diagnosis included moderate or severe disability pre-diagnosis (adjusted risk ratio, aRR: moderate: 2.96; 95%CI: 2.11-4.16; severe: 5.11; 95%CI: 3.07-8.52) vs. mild (reference), poor physical capability (aRR: 1.57; 95%CI: 1.07-2.30), and incurable stage (aRR:1.99; 95%CI: 1.41-2.80). 40% of participants with a mild or moderate disability trajectory pre-diagnosis transitioned to a worse functional trajectory post-diagnosis., Conclusion: Older adults followed distinct functional trajectories in the twelve months before and after cancer diagnosis. Functional trajectory pre-diagnosis, poor physical capability, and incurable stage were independent risk factors for worsening disability post-diagnosis., (Copyright © 2018. Published by Elsevier Ltd.)

Objectives: To evaluate the relationship between number of falls and risk of injury after a specific fall., Design: Prospective cohort study., Setting: Greater New Haven, Connecticut., Participants: Probability sample of 1,103 community-living persons aged 72 and older., Measurements: Falls and fall-related injuries were ascertained monthly for 3 years using a fall calendar and follow-up telephone interviews., Results: Of 606 participants with a fall, 164 (27.0%) had at least 1 fall with a serious injury, and 455 (75.1%) had at least 1 fall with any injury; mean number of falls was 2.6±2.3 (range 1-18), of falls with serious injury was 0.3±0.6 (range 0-4), and of falls with any injury was 1.4±1.4 (range 0-9). On a per-participant basis, risk of serious injury and any injury increased progressively as the number of falls increased (P < .001). On a per-fall basis, risk of serious injury and any injury increased from 1 to 2 falls but then decreased from 2 to 3 or 4 falls and from 3 or 4 to 5 or more falls, although these differences were not statistically significant. The results were consistent for women and men and for analyses that evaluated the proportion of falls with injuries., Conclusion: In community-living older persons, risk of injury from a specific fall did not differ as the number of falls increased. Falls appear to operate independently in terms of conferring risk of injury in the setting of multiple falls. J Am Geriatr Soc 67:119-123, 2019., (© 2018, Copyright the Authors Journal compilation © 2018, The American Geriatrics Society.)