A Novel Metric for Developing Easy-to-Use and Accurate Clinical Prediction Models: The Time-cost Information Criterion.

BACKGROUND: Guidelines recommend that clinicians use clinical prediction models to estimate future risk to guide decisions. For example, predicted fracture risk is a major factor in the decision to initiate bisphosphonate medications. However, current methods for developing prediction models often lead to models that are accurate but difficult to use in clinical settings. OBJECTIVE: The objective of this study was to develop and test whether a new metric that explicitly balances model accuracy with clinical usability leads to accurate, easier-to-use prediction models. METHODS: We propose a new metric called the Time-cost Information Criterion (TCIC) that will penalize potential predictor variables that take a long time to obtain in clinical settings. To demonstrate how the TCIC can be used to develop models that are easier-to-use in clinical settings, we use data from the 2000 wave of the Health and Retirement Study (n=6311) to develop and compare time to mortality prediction models using a traditional metric (Bayesian Information Criterion or BIC) and the TCIC. RESULTS: We found that the TCIC models utilized predictors that could be obtained more quickly than BIC models while achieving similar discrimination. For example, the TCIC identified a 7-predictor model with a total time-cost of 44 seconds, while the BIC identified a 7-predictor model with a time-cost of 119 seconds. The Harrell C-statistic of the TCIC and BIC 7-predictor models did not differ (0.7065 vs. 0.7088, P=0.11). CONCLUSION: Accounting for the time-costs of potential predictor variables through the use of the TCIC led to the development of an easier-to-use mortality prediction model with similar discrimination.

Association of Coronary Artery Bypass Grafting vs Percutaneous Coronary Intervention With Memory Decline in Older Adults Undergoing Coronary Revascularization.

Importance: It is uncertain whether coronary artery bypass grafting (CABG) is associated with cognitive decline in older adults compared with a nonsurgical method of coronary revascularization (percutaneous coronary intervention [PCI]). Objective: To compare the change in the rate of memory decline after CABG vs PCI. Design, Setting, and Participants: Retrospective cohort study of community-dwelling participants in the Health and Retirement Study, who underwent CABG or PCI between 1998 and 2015 at age 65 years or older. Data were modeled for up to 5 years preceding and 10 years following revascularization or until death, drop out, or the 2016-2017 interview wave. The date of final follow-up was November 2017. Exposures: CABG (including on and off pump) or PCI, ascertained from Medicare fee-for-service billing records. Main Outcomes and Measures: The primary outcome was a summary measure of cognitive test scores and proxy cognition reports that were performed biennially in the Health and Retirement Study, referred to as memory score, normalized as a z score (ie, mean of 0, SD of 1 in a reference population of adults aged ≥72 years). Memory score was analyzed using multivariable linear mixed-effects models, with a prespecified subgroup analysis of on-pump and off-pump CABG. The minimum clinically important difference was a change of 1 SD of the population-level rate of memory decline (0.048 memory units/y). Results: Of 1680 participants (mean age at procedure, 75 years; 41% female), 665 underwent CABG (168 off pump) and 1015 underwent PCI. In the PCI group, the mean rate of memory decline was 0.064 memory units/y (95% CI, 0.052 to 0.078) before the procedure and 0.060 memory units/y (95% CI, 0.048 to 0.071) after the procedure (within-group change, 0.004 memory units/y [95% CI, -0.010 to 0.018]). In the CABG group, the mean rate of memory decline was 0.049 memory units/y (95% CI, 0.033 to 0.065) before the procedure and 0.059 memory units/y (95% CI, 0.047 to 0.072) after the procedure (within-group change, -0.011 memory units/y [95% CI, -0.029 to 0.008]). The between-group difference-in-differences estimate for memory decline for PCI vs CABG was 0.015 memory units/y (95% CI, -0.008 to 0.038; P = .21). There was statistically significant increase in the rate of memory decline after off-pump CABG compared with after PCI (difference-in-differences: mean increase in the rate of decline of 0.046 memory units/y [95% CI, 0.008 to 0.084] after off-pump CABG), but not after on-pump CABG compared with PCI (difference-in-differences: mean slowing of decline of 0.003 memory units/y [95% CI, -0.024 to 0.031] after on-pump CABG). Conclusions and Relevance: Among older adults undergoing coronary revascularization with CABG or PCI, the type of revascularization procedure was not significantly associated with differences in the change of rate of memory decline.

Functional Impairment and Decline in Middle Age: A Cohort Study.

BACKGROUND: Difficulties with daily functioning are common in middle-aged adults. However, little is known about the epidemiology or clinical course of these problems, including the extent to which they share common features with functional impairment in older adults. OBJECTIVE: To determine the epidemiology and clinical course of functional impairment and decline in middle age. DESIGN: Cohort study. SETTING: The Health and Retirement Study. PARTICIPANTS: 6874 community-dwelling adults aged 50 to 56 years who did not have functional impairment at enrollment. MEASUREMENTS: Impairment in activities of daily living (ADLs), defined as self-reported difficulty performing 1 or more ADLs, assessed every 2 years for a maximum follow-up of 20 years, and impairment in instrumental ADLs (IADLs), defined similarly. Data were analyzed by using multistate models that estimate probabilities of different outcomes. RESULTS: Impairment in ADLs developed in 22% of participants aged 50 to 64 years, in whom further functional transitions were common. Two years after the initial impairment, 4% (95% CI, 3% to 5%) of participants had died, 9% (CI, 8% to 11%) had further ADL decline, 50% (CI, 48% to 52%) had persistent impairment, and 37% (CI, 35% to 39%) had recovered independence. In the 10 years after the initial impairment, 16% (CI, 14% to 18%) had 1 or more episodes of functional decline and 28% (CI, 26% to 30%) recovered from their initial impairment and remained independent throughout this period. The pattern of findings was similar for IADLs. LIMITATION: Functional status was self-reported. CONCLUSION: Functional impairment and decline are common in middle age, as are transitions from impairment to independence and back again. Because functional decline in older adults has similar features, current interventions used for prevention in older adults may hold promise for those in middle age. PRIMARY FUNDING SOURCE: National Institute on Aging and National Center for Advancing Translational Sciences through the University of California, San Francisco, Clinical and Translational Sciences Institute.

Incidence of Traumatic Brain Injury in a Longitudinal Cohort of Older Adults.

Importance: Traumatic brain injury (TBI) occurs at the highest rate in older adulthood and increases risk for cognitive impairment and dementia. Objectives: To update existing TBI surveillance data to capture nonhospital settings and to explore how social determinants of health (SDOH) are associated with TBI incidence among older adults. Design, Setting, and Participants: This nationally representative longitudinal cohort study assessed participants for 18 years, from August 2000 through December 2018, using data from the Health and Retirement Study (HRS) and linked Medicare claims dates. Analyses were completed August 9 through December 12, 2022. Participants were 65 years of age or older in the HRS with survey data linked to Medicare without a TBI prior to HRS enrollment. They were community dwelling at enrollment but were retained in HRS if they were later institutionalized. Exposures: Baseline demographic, cognitive, medical, and SDOH information from HRS. Main Outcomes and Measures: Incident TBI was defined using inpatient and outpatient International Classification of Diseases, Ninth or Tenth Revision, diagnosis codes received the same day or within 1 day as the emergency department (ED) visit code and the computed tomography (CT) or magnetic resonance imaging (MRI) code, after baseline HRS interview. A cohort with TBI codes but no ED visit or CT or MRI scan was derived to capture diagnoses in nonhospital settings. Descriptive statistics and bivariate associations of TBI with demographic and SDOH characteristics used sample weights. Fine-Gray regression models estimated associations between covariates and TBI, with death as a competing risk. Imputation considering outcome and complex survey design was performed by race and ethnicity, sex, education level, and Area Deprivation Index percentiles 1, 50, and 100. Other exposure variables were fixed at their weighted means. Results: Among 9239 eligible respondents, 5258 (57.7%) were female and 1210 (9.1%) were Black, 574 (4.7%) were Hispanic, and 7297 (84.4%) were White. Mean (SD) baseline age was 75.2 (8.0) years. During follow-up (18 years), 797 (8.9%) of respondents received an incident TBI diagnosis with an ED visit and a CT code within 1 day, 964 (10.2%) received an incident TBI diagnosis and an ED code, and 1148 (12.9%) received a TBI code with or without an ED visit and CT scan code. Compared with respondents without incident TBI, respondents with TBI were more likely to be female (absolute difference, 7.0 [95% CI, 3.3-10.8]; P < .001) and White (absolute difference, 5.1 [95% CI, 2.8-7.4]; P < .001), have normal cognition (vs cognitive impairment or dementia; absolute difference, 6.1 [95% CI, 2.8-9.3]; P = .001), higher education (absolute difference, 3.8 [95% CI, 0.9-6.7]; P < .001), and wealth (absolute difference, 6.5 [95% CI, 2.3-10.7]; P = .01), and be without baseline lung disease (absolute difference, 5.1 [95% CI, 3.0-7.2]; P < .001) or functional impairment (absolute difference, 3.3 [95% CI, 0.4-6.1]; P = .03). In adjusted multivariate models, lower education (subdistribution hazard ratio [SHR], 0.73 [95% CI, 0.57-0.94]; P = .01), Black race (SHR, 0.61 [95% CI, 0.46-0.80]; P < .001), area deprivation index national rank (SHR 1.00 [95% CI 0.99-1.00]; P = .009), and male sex (SHR, 0.73 [95% CI, 0.56-0.94]; P = .02) were associated with membership in the group without TBI. Sensitivity analyses using a broader definition of TBI yielded similar results. Conclusions and Relevance: In this longitudinal cohort study of older adults, almost 13% experienced incident TBI during the 18-year study period. For older adults who seek care for TBI, race and ethnicity, sex, and SDOH factors may be associated with incidence of TBI, seeking medical attention for TBI in older adulthood, or both.

Delirium risk profiles in a population-based study of United States older adults undergoing common noncardiac surgeries.

BACKGROUND: Older adults often require surgical care and are at elevated risk of delirium. We explored delirium risk profiles across the population of U.S. older adults who underwent one of 10 common noncardiac surgeries. METHODS: We analyzed Health and Retirement Study (HRS) participants linked with Medicare billing data who underwent the following 10 noncardiac surgeries from 2000 to 2018 at age 65 or more: total knee arthroplasty (TKA), total hip arthroplasty (THA), spine surgery, cholecystectomy, colorectal surgery, hernia repair (ventral, umbilical, or incisional), endarterectomy, prostatectomy, transurethral resection of the prostate (TURP), and hysterectomy. Demographic and health covariates were obtained from the HRS dataset. Latent cognitive ability was calculated from cognitive testing, proxy reports, and demographics at the preoperative HRS interview. We compared standardized differences for delirium risk factors across the 10 surgeries and qualitatively clustered them into phenotypical subgroups. RESULTS: We analyzed 7424 older adults (mean age 76 ± 6 years, 45% male). Endarterectomy patients presented with the highest burden of nearly all health and cognitive factors, implying higher delirium risk (e.g., stroke, 22%; depressive symptoms, 30%; high school or less education, 73%; frailty, 42%; lowest latent cognitive ability). A second "general surgery" phenotype, including cholecystectomy, colorectal, and hernia surgery patients, experienced more frailty (29%-32%) and depressive symptoms (24%-26%), with moderate comorbidity burden. A third "pain" phenotype, which included TKA, THA, and spine surgery patients, commonly reported moderate or severe pain (47%-53%) and impairment in activities of daily living (ADL, 23%-30%), but fewer comorbid medical conditions. The remaining surgery types (hysterectomy, prostatectomy, TURP) were not phenotypically grouped and generally had lower risk features for delirium. CONCLUSION: In an epidemiological cohort of US older adults, we identified clinically meaningful heterogeneity in delirium risk profiles across different surgical types, which may have implications for delirium risk stratification and delirium prevention or treatment.

The Neighborhood Environment and Handgrip Strength: Longitudinal Findings from the Health and Retirement Study.

BACKGROUND: Muscle strength, as measured by handgrip strength (HGS), is associated with physical function and mortality. Yet, the environmental context that influences muscle strength is poorly understood. We evaluated built and social neighborhood characteristics and their association with muscle strength over time. METHODS: Using data from the Health and Retirement Study (2006-2018), linear mixed models assessed how 11 built and social neighborhood variables were associated with baseline levels and changes in HGS over time. RESULTS: Among the 20,045 respondents (mean age = 63 years, SD = 9.7) with up to 4 HGS measures, 8,455 were men and 11,590 were women. Among men, residing in a neighborhood with a 10% increment higher score on neighborhood disadvantage was associated with ~1 kg lower HGS at baseline (B = -0.96 kg, 95% CI = -1.39, -0.53). Similarly, each 1-point increment on the physical disorder scale was associated with a -0.39 kg lower (95% CI = -0.65, -0.12) baseline HGS value. Among women, each 10% increment in neighborhood disadvantage was associated with a 0.29 kg lower HGS at baseline (B = -0.29 kg for each 10% increment, 95% CI = -0.46, -0.13). Each 1-unit increment in the number of neighborhood gyms at baseline was associated with a 0.50 kg lower HGS (B = -0.50, 95% CI = -0.76, -0.23). Each 1-point increment in physical disorder was associated with a -0.12 kg lower (95% CI = -0.24, -0.00) baseline HGS value. None of the neighborhood features were associated with HGS rate of change. CONCLUSIONS: Findings suggest that residing in neighborhoods with greater disadvantage and physical disorder may pose challenges for HGS among middle aged adults as they enter into older adulthood.

Long-term cognitive outcome after elective hip or knee total joint arthroplasty: A population-based observational study.

BACKGROUND: One year after elective hip or knee total joint arthroplasty (TJA), >30% of older adults meet criteria for postoperative neurocognitive disorder. However, this is not contextualized with long-term cognitive outcomes in comparable surgical and nonsurgical controls. We analyzed population-based data to compare long-term cognitive outcomes in older adults after TJA, other surgeries, and with and without arthritis pain. METHODS: This was a retrospective observational analysis of United States older adults in the Health and Retirement Study (HRS) who underwent elective TJA, or elective surgery without expected functional benefits (e.g., cholecystectomy; inguinal herniorrhaphy), between 1998 and 2018 at aged 65 or older. TJA recipients were also age- and sex-matched to nonsurgical controls who reported moderate-severe arthritic pain or denied pain, so that comparison groups included surgical and nonsurgical (pain-suffering and pain-free) controls. We modeled biennially-assessed memory performance, a measure of direct and proxy cognitive assessments, before and after surgery, normalized to the rate of memory decline ("cognitive aging") in controls to express effect size estimates as excess, or fewer, months of memory decline. We used linear mixed effects models adjusted for preoperative health and demographic factors, including frailty, flexibly capturing time before/after surgery (knots at -4, 0, 8 years; discontinuity at surgery). RESULTS: There were 1947 TJA recipients (average age 74; 63% women; 1358 knee, 589 hip) and 1631 surgical controls (average age 76; 38% women). Memory decline 3 years after TJA was similar to surgical controls (5.2 [95% confidence interval, CI -1.2 to 11.5] months less memory decline in the TJA group, p = 0.11) and nonsurgical controls. At 5 years, TJA recipients experienced 5.0 [95% CI -0.9 to 10.9] months less memory decline than arthritic pain nonsurgical controls. CONCLUSION: There is no systematic accelerated memory decline at 3 years after TJA compared with surgical or nonsurgical controls.

Geriatric conditions and healthcare utilization among older adults living in subsidized housing.

BACKGROUND: Nearly 2.9 million older Americans with lower incomes live in subsidized housing. While regional and single-site studies show that this group has higher rates of healthcare utilization compared to older adults in the general community, little is known about healthcare utilization nationally nor associated risk factors. METHODS: We conducted a retrospective cohort study of Medicare beneficiaries aged ≥65 enrolled in the National Health and Aging Trends Study in 2011, linked to Medicare claims data, including individuals living in subsidized housing and the general community. Participants were followed annually through 2020. Outcomes were hospitalization, short-term skilled nursing facility (SNF) utilization, long-term care utilization, and death. Fine-Gray competing risks regression analysis was used to assess the association of subsidized housing residence with hospitalization and nursing facility utilization, and Cox proportional hazards regression analysis was used to assess the association with death. RESULTS: Among 6294 participants (3600 women, 2694 men; mean age, 75.5 years [SD, 7.0]), 295 lived in subsidized housing at baseline and 5999 in the general community. Compared to older adults in the general community, those in subsidized housing had a higher adjusted subdistribution hazard ratio [sHR] of hospitalization (sHR 1.21; 95% CI, 1.03-1.43), short-term SNF utilization (sHR 1.49; 95% CI, 1.15-1.92), and long-term care utilization (sHR 2.72; 95% CI, 1.67-4.43), but similar hazard of death (HR, 0.86; 95% CI, 0.69-1.08). Individuals with functional impairment had a higher adjusted subdistribution hazard of hospitalization and short-term SNF utilization and individuals with dementia and functional impairment had a higher hazard of long-term care utilization. CONCLUSIONS: Older adults living in subsidized housing have higher hazards of hospitalization and nursing facility utilization compared to those in the general community. Housing-based interventions to optimize aging in place and mitigate risk of nursing facility utilization should consider risk factors including functional impairment and dementia.

Preoperative Factors Predict Memory Decline After Coronary Artery Bypass Grafting or Percutaneous Coronary Intervention in an Epidemiological Cohort of Older Adults.

Background Durable memory decline may occur in older adults after surgical (coronary artery bypass grafting [CABG]) or nonsurgical (percutaneous coronary intervention) coronary revascularization. However, it is unknown whether individual memory risk can be predicted. We reanalyzed an epidemiological cohort of older adults to predict memory decline at ≈1 year after revascularization. Methods and Results We studied Health and Retirement Study participants who underwent CABG or percutaneous coronary intervention at age ≥65 years between 1998 and 2015 and participated in ≥1 biennial postprocedure assessment. Using a memory score based on direct and proxy cognitive tests, we identified participants whose actual postprocedure memory score was 1-2 ("mild") or >2 ("major") SDs below expected postprocedure performance. We modeled probability of memory decline using logistic regression on preoperatively known factors and evaluated model discrimination and calibration. A total of 1390 participants (551 CABG, 839 percutaneous coronary intervention) underwent CABG/percutaneous coronary intervention at 75±6 years old; 40% were women. The cohort was 83% non-Hispanic White, 8.4% non-Hispanic Black, 6.4% Hispanic ethnicity, and 1.7% from other groups masked by the HRS (Health and Retirement Study) to preserve participant confidentiality. At a median of 1.1 (interquartile range, 0.6-1.6) years after procedure, 267 (19%) had mild memory decline and 88 (6.3%) had major memory decline. Factors predicting memory decline included older age, frailty, and off-pump CABG; obesity was protective. The optimism-corrected area under the receiver operator characteristic curve was 0.73 (95% CI, 0.71-0.77). A cutoff of 50% probability of memory decline identified 14% of the cohort as high risk, and was 94% specific and 30% sensitive for late memory decline. Conclusions Preoperative factors can be used to predict late memory decline after coronary revascularization in an epidemiological cohort with high specificity.

Around the EQUATOR with Clin-STAR: Prediction modeling opportunities and challenges in aging research.

The 2015 Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis (TRIPOD) Statement was published to improve reporting transparency for prediction modeling studies. The objective of this review is to highlight methodologic challenges that aging-focused researchers will encounter when designing and reporting studies involving prediction models for older adults and provide guidance for addressing these challenges. In following the 22-item TRIPOD checklist, researchers must consider the representativeness of cohorts used (e.g., whether older adults with frailty, cognitive impairment, and social isolation were included), strategies for incorporating common geriatric predictors (e.g., age, comorbidities, functional status, and frailty), methods for handling missing data and competing risk of death, and assessment of model performance heterogeneity across important subgroups (e.g., age, sex, race, and ethnicity). We provide guidance to help aging-focused researchers develop, validate, and report models that can inform and improve patient care, which we label "TRIPOD-65."

A comprehensive prognostic tool for older adults: Predicting death, ADL disability, and walking disability simultaneously.

BACKGROUND: Many clinical and financial decisions for older adults depend on the future risk of disability and mortality. Prognostic tools for long-term disability risk in a general population are lacking. We aimed to create a comprehensive prognostic tool that predicts the risk of mortality, of activities of daily living (ADL) disability, and walking disability simultaneously using the same set of variables. METHODS: We conducted a longitudinal analysis of the nationally-representative Health and Retirement Study (HRS). We included community-dwelling adults aged ≥70 years who completed a core interview in the 2000 wave of HRS, with follow-up through 2018. We evaluated 40 predictors encompassing demographics, diseases, physical functioning, and instrumental ADLs. We applied novel methods to optimize three models simultaneously while prioritizing variables that take less time to ascertain during backward stepwise elimination. The death prediction model used Cox regression and both the models for walking disability and for ADL disability used Fine and Gray competing-risk regression. We examined calibration plots and generated optimism-corrected statistics of discrimination using bootstrapping. To simulate unavailable patient data, we also evaluated models excluding one or two variables from the final model. RESULTS: In 6646 HRS participants, 2662 developed walking disability, 3570 developed ADL disability, and 5689 died during a median follow-up of 9.5 years. The final prognostic tool had 16 variables. The optimism-corrected integrated area under the curve (iAUC) was 0.799 for mortality, 0.685 for walking disability, and 0.703 for ADL disability. At each percentile of predicted mortality risk, there was a substantial spread in the predicted risks of walking disability and ADL disability. Discrimination and calibration remained good even when missing one or two predictors from the model. This model is now available on ePrognosis (https://eprognosis.ucsf.edu/alexlee.php) CONCLUSIONS: Given the variability in disability risk for people with similar mortality risks, using individualized risks of disabilities may inform clinical and financial decisions for older adults.

Changes in the Hierarchy of Functional Impairment From Middle Age to Older Age.

BACKGROUND: Understanding the hierarchy of functional impairment in older adults has helped illuminate mechanisms of impairment and inform interventions, but little is known about whether hierarchies vary by age. We compared the pattern of new-onset impairments in activities of daily living (ADLs) and instrumental ADLs (IADLs) from middle age through older age. METHODS: We conducted a cohort study using nationally representative data from 32 486 individuals enrolled in the Health and Retirement Study. The outcomes were new-onset impairment in each ADL and IADL, defined as self-reported difficulty performing each task, assessed yearly for 9 years. We used multistate models and competing risks survival analysis to estimate the cumulative incidence of impairment in each task by age group (ages 50-64, 65-74, 75-84, and 85 or older). RESULTS: The pattern of incident ADL impairments differed by age group. Among individuals ages 50-64 and 65-74 who were independent at baseline, over 9 years' follow-up, difficulties dressing and transferring were the most common impairments to develop. In individuals ages 75-84 and 85 or older who were independent at baseline, difficulties bathing, dressing, and walking were most common. For IADLs, the pattern of impairments was similar across age groups; difficulty shopping was most common followed by difficulty managing money and preparing meals. Complementary analyses demonstrated a similar pattern. CONCLUSIONS: These findings suggest that the hierarchy of ADL impairment differs by age. These findings have implications for the development of age-specific interventions to prevent or delay functional impairment.

Changes in functional status associated with radiation for prostate cancer in older veterans.

BACKGROUND: Although older men value maintaining independence and avoiding functional decline, little is known about their functional trajectories with receipt of prostate radiation. METHODS: We performed a retrospective cohort study including veterans age 65+ with localized prostate cancer who resided in a VA nursing facility while receiving prostate radiation from 2005 to 2015. We evaluated the change in Minimum Data Set (MDS) activities of daily living (ADL) score during 6 months from the start of treatment. Because prior studies have shown Charlson Comorbidity Index (CCI) to be a strong predictor of treatment-related toxicity, analysis included interaction with CCI. RESULTS: We identified 487 patients with median age 73 (range 65-94). For the average patient in our cohort, the predicted MDS-ADL score worsened from 2.9 (95% CI 2.4-3.6) at the start of radiation to 3.8 (95% CI 3.1-4.8) at 3 months and then 4.5 (95% CI 3.5-5.7) at month 6. Patients with greater comorbidity (CCI ≥ 4) had worse functional outcomes in months 0-3 compared to patients with less comorbidity (CCI 0-3). MDS-ADL score worsened by 1.9 in the CCI ≥4 patients compared to 0.3 in the CCI 0-3 group During months 3-6, patients in both Charlson groups experienced similar worsening of MDS-ADL score. CONCLUSIONS: In a vulnerable population of older patients with localized prostate cancer, radiation was associated with a decline in functional independence. Patients with higher comorbidity experienced more severe functional decline within the first 3 months of radiation therapy. In all comorbidity levels, functional status had not returned to baseline by 6 months.

A Novel Method for Identifying a Parsimonious and Accurate Predictive Model for Multiple Clinical Outcomes.

BACKGROUND AND OBJECTIVE: Most methods for developing clinical prognostic models focus on identifying parsimonious and accurate models to predict a single outcome; however, patients and providers often want to predict multiple outcomes simultaneously. As an example, for older adults one is often interested in predicting nursing home admission as well as mortality. We propose and evaluate a novel predictor-selection computing method for multiple outcomes and provide the code for its implementation. METHODS: Our proposed algorithm selected the best subset of common predictors based on the minimum average normalized Bayesian Information Criterion (BIC) across outcomes: the Best Average BIC (baBIC) method. We compared the predictive accuracy (Harrell's C-statistic) and parsimony (number of predictors) of the model obtained using the baBIC method with: 1) a subset of common predictors obtained from the union of optimal models for each outcome (Union method), 2) a subset obtained from the intersection of optimal models for each outcome (Intersection method), and 3) a model with no variable selection (Full method). We used a case-study data from the Health and Retirement Study (HRS) to demonstrate our method and conducted a simulation study to investigate performance. RESULTS: In the case-study data and simulations, the average Harrell's C-statistics across outcomes of the models obtained with the baBIC and Union methods were comparable. Despite the similar discrimination, the baBIC method produced more parsimonious models than the Union method. In contrast, the models selected with the Intersection method were the most parsimonious, but with worst predictive accuracy, and the opposite was true in the Full method. In the simulations, the baBIC method performed well by identifying many of the predictors selected in the baBIC model of the case-study data most of the time and excluding those not selected in the majority of the simulations. CONCLUSIONS: Our method identified a common subset of variables to predict multiple clinical outcomes with superior balance between parsimony and predictive accuracy to current methods.

Defining intraspecific conservation units in the endemic Cuban Rock Iguanas (Cyclura nubila nubila).

Defining conservation units is an important step in species management and requires interpretation of the genetic diversity and ecological function of the taxon being considered. We used the endemic Cuban Rock Iguanas (Cyclura nubila nubila) as a model to highlight this challenge and examined patterns of its intraspecific genetic diversity across Cuba. We evaluated nuclear (microsatellite loci) and mitochondrial diversity across eight populations from the island and its off-shore cays, and applied the population genetics results for assignment of Management Unit (MU) status and Evolutionary Significant Units (ESUs) based on phylogeographic and time of divergence information. We identified at least six distinct Cuban Rock Iguana MUs, encompassing demographically isolated and genetically differentiated populations across Cuba, most with low effective population size, declining populations, and with high risk of inbreeding and genetic drift. Hence, each MU should be considered of urgent conservation priority. Given the key ecological seed dispersal role of C. n. nubila, the disappearance of any MU could trigger the loss of local ecological functional diversity and major negative impacts on their ecosystems. Two divergent ESUs were also identified, exhibiting an historical east-west geographic separation on Cuba. Based on a Caribbean phylogeographic assessment, our findings strengthen the conclusion that all geographically and evolutionarily differentiated Cyclura species and subspecies across the archipelago warrant ESU distinction.

Association of Functional Impairment in Middle Age With Hospitalization, Nursing Home Admission, and Death.

Importance: Difficulty performing daily activities such as bathing and dressing ("functional impairment") affects nearly 15% of middle-aged adults. Older adults who develop such difficulties, often because of frailty and other age-related conditions, are at increased risk of acute care use, nursing home admission, and death. However, it is unknown if functional impairments that develop among middle-aged people, which may have different antecedents, have similar prognostic significance. Objective: To determine whether middle-aged individuals who develop functional impairment are at increased risk for hospitalization, nursing home admission, and death. Design, Setting, and Participants: This matched cohort study analyzed longitudinal data from the Health and Retirement Study, a nationally representative prospective cohort study of US adults. The study population included 5540 adults aged 50 to 56 years who did not have functional impairment at study entry in 1992, 1998, or 2004. Participants were followed biennially through 2014. Individuals who developed functional impairment between 50 and 64 years were matched by age, sex, and survey wave with individuals without impairment as of that age and survey wave. Statistical analysis was conducted from March 15, 2017, to December 11, 2018. Exposures: Impairment in activities of daily living (ADLs), defined as self-reported difficulty performing 1 or more ADLs, and impairment in instrumental ADLs (IADLs), defined similarly. Main Outcomes and Measures: The 3 primary outcomes were time from the first episode of functional impairment (or matched survey wave, in controls) to hospitalization, nursing home admission, and death. Follow-up assessments occurred every 2 years until 2014. Competing risks survival analysis was used to assess the association of functional impairment with hospitalization and nursing home admission and Cox proportional hazards regression analysis was used to assess the association with death. Results: Of the 5540 study participants (2739 women and 2801 men; median age, 53.7 years [interquartile range, 52.3-55.2 years]), 1097 (19.8%) developed ADL impairment between 50 and 64 years, and 857 (15.5%) developed IADL impairment. Individuals with ADL impairment had an increased risk of each adverse outcome compared with those without impairment, including hospitalization (subhazard ratio, 1.97; 95% CI, 1.77-2.19), nursing home admission (subhazard ratio, 2.62; 95% CI, 1.99-3.45), and death (hazard ratio, 2.06; 95% CI, 1.74-2.45). After multivariable adjustment, the risks of hospitalization (subhazard ratio, 1.54; 95% CI, 1.36-1.75) and nursing home admission (subhazard ratio, 1.73; 95% CI, 1.24-2.43) remained significantly higher among individuals with ADL impairment, but the risk of death was not statistically significant (hazard ratio, 1.06; 95% CI, 0.85-1.32). Individuals with IADL impairment had an increased risk of all 3 outcomes in adjusted and unadjusted analyses. Conclusions and Relevance: Similar to older adults, middle-aged adults who develop functional impairment appear to be at increased risk for adverse outcomes. Even among relatively young people, functional impairment has important clinical implications.

Cognitive Change After Cardiac Surgery Versus Cardiac Catheterization: A Population-Based Study.

BACKGROUND: Despite concern that cardiac surgery may adversely affect cognition, little evidence is available from population-based studies using presurgery data. With the use of the Health and Retirement Study, we compared memory change after participant-reported cardiac catheterization or cardiac surgery. METHODS: Participants were community-dwelling adults aged 65 years and older who self-reported cardiac catheterization or "heart surgery" at any biennial Health and Retirement Study interview between 2000 and 2014. Participants may have undergone the index procedure any time in the preceding 2 years. We modeled preprocedure to postprocedure change in composite memory score, derived from objective memory testing, using linear mixed effects models. We modeled postprocedure subjective memory decline with logistic regression. To quantify clinical relevance, we used the predicted memory change to estimate impact on ability to manage medications and finances independently. RESULTS: Of 3,105 participants, 1,921 (62%) underwent catheterization and 1,184 (38%) underwent operation. In adjusted analyses, surgery participants had little difference in preprocedure to postprocedure memory change compared with participants undergoing cardiac catheterization (-0.021 memory units; 95% confidence interval: -0.046 to 0.005 memory units, p = 0.12). If the relationship were causal, the point estimate for memory decline would confer an absolute 0.26% or 0.19% decrease in ability to manage finances or medications, respectively, corresponding to 4.6 additional months of cognitive aging. Cardiac surgery was not associated with subjective memory decline (adjusted odds ratio 0.93, 95% confidence interval: 0.74 to 1.18). CONCLUSIONS: In this large, population-based cohort, memory declines after heart surgery and cardiac catheterization were similar. These findings suggest intermediate-term population-level adverse cognitive effects of cardiac surgery, if any, are likely subtle.

'Til Death Do Us Part: End-of-Life Experiences of Married Couples in a Nationally Representative Survey.

OBJECTIVES: To determine whether end-of-life (EOL) experiences in the first spouse in a marriage are associated with EOL experiences in the other spouse. DESIGN: Nationally representative, longitudinal survey. SETTING: Health and Retirement Study, Waves 1992-2012 linked to Medicare claims PARTICIPANTS: Community-dwelling older adults who died (N=4,558), representing 2,279 married heterosexual couples. MEASUREMENTS: We examined 3 EOL experiences: enrollment in hospice for >3 days before death, lack of advance care planning (ACP) before death, and intensive care unit (ICU) use during the last 30 days of life. We used multiple logistic regression to determine whether the EOL experience of the first spouse was a significant predictor of the EOL experience of the second spouse after adjusting for demographic characteristics, socioeconomic status, health status, and time between the first and second spouses' deaths. RESULTS: First spouses who died were on average 80 years old, and 62% were male; second spouses were on average 85 years old, and 62% were female. After adjustment, second spouses were more likely to use hospice if the first spouse used hospice (odds ratio (OR)=1.68, 95% confidence interval (CI)=1.29-2.20). Second spouses were less likely to have ACP when the first spouse did not have ACP (OR=2.91, 95% CI=2.02-4.21). Hospice and ACP associations were stronger when deaths were closer in time to one another (p-value for interaction < .05). Second spouses were more likely to use ICU services if the first spouse did (OR=1.80, 95% CI=1.27-2.55). CONCLUSIONS: The EOL experiences of older spouses are strongly associated, which may be relevant when framing ACP discussions. J Am Geriatr Soc 66:2360-2366, 2018.

Triglyceride Synthesis by DGAT1 Protects Adipocytes from Lipid-Induced ER Stress during Lipolysis.

Triglyceride (TG) storage in adipose tissue provides the major reservoir for metabolic energy in mammals. During lipolysis, fatty acids (FAs) are hydrolyzed from adipocyte TG stores and transported to other tissues for fuel. For unclear reasons, a large portion of hydrolyzed FAs in adipocytes is re-esterified to TGs in a "futile," ATP-consuming, energy dissipating cycle. Here we show that FA re-esterification during adipocyte lipolysis is mediated by DGAT1, an ER-localized DGAT enzyme. Surprisingly, this re-esterification cycle does not preserve TG mass but instead functions to protect the ER from lipotoxic stress and related consequences, such as adipose tissue inflammation. Our data reveal an important role for DGAT activity and TG synthesis generally in averting ER stress and lipotoxicity, with specifically DGAT1 performing this function during stimulated lipolysis in adipocytes.

Wealth-Associated Disparities in Death and Disability in the United States and England.

Importance: Low income has been associated with poor health outcomes. Owing to retirement, wealth may be a better marker of financial resources among older adults. Objective: To determine the association of wealth with mortality and disability among older adults in the United States and England. Design, Setting, and Participants: The US Health and Retirement Study (HRS) and English Longitudinal Study of Aging (ELSA) are nationally representative cohorts of community-dwelling older adults. We examined 12 173 participants enrolled in HRS and 7599 enrolled in ELSA in 2002. Analyses were stratified by age (54-64 years vs 66-76 years) because many safety-net programs commence around age 65 years. Participants were followed until 2012 for mortality and disability. Exposures: Wealth quintile, based on total net worth in 2002. Main Outcomes and Measures: Mortality and disability, defined as difficulty performing an activity of daily living. Results: A total of 6233 US respondents and 4325 English respondents aged 54 to 64 years (younger cohort) and 5940 US respondents and 3274 English respondents aged 66 to 76 years (older cohort) were analyzed for the mortality outcome. Slightly over half of respondents were women (HRS: 6570, 54%; ELSA: 3974, 52%). A higher proportion of respondents from HRS were nonwhite compared with ELSA in both the younger (14% vs 3%) and the older (13% vs 3%) age cohorts. We found increased risk of death and disability as wealth decreased. In the United States, participants aged 54 to 64 years in the lowest wealth quintile (Q1) (≤$39 000) had a 17% mortality risk and 48% disability risk over 10 years, whereas in the highest wealth quintile (Q5) (>$560 000) participants had a 5% mortality risk and 15% disability risk (mortality hazard ratio [HR], 3.3; 95% CI, 2.0-5.6; P < .001; disability subhazard ratio [sHR], 4.0; 95% CI, 2.9-5.6; P < .001). In England, participants aged 54 to 64 years in Q1 (≤£34,000) had a 16% mortality risk and 42% disability risk over 10 years, whereas Q5 participants (>£310,550) had a 4% mortality risk and 17% disability risk (mortality HR, 4.4; 95% CI, 2.7-7.0; P < .001; disability sHR, 3.0; 95% CI, 2.1-4.2; P < .001). In 66- to 76-year-old participants, the absolute risks of mortality and disability were higher, but risk gradients across wealth quintiles were similar. When adjusted for sex, age, race, income, and education, HR for mortality and sHR for disability were attenuated but remained statistically significant. Conclusions and Relevance: Low wealth was associated with death and disability in both the United States and England. This relationship was apparent from age 54 years and continued into later life. Access to health care may not attenuate wealth-associated disparities in older adults.