Identifying predictors of resilience to stressors in single-arm studies of pre-post change.

Many older adults experience a major stressor at some point in their lives. The ability to recover well after a major stressor is known as resilience. An important goal of geriatric research is to identify factors that influence resilience to stressors. Studies of resilience in older adults are typically conducted with a single-arm where everyone experiences the stressor. The simplistic approach of regressing change versus baseline yields biased estimates due to mathematical coupling and regression to the mean (RTM). We develop a method to correct the bias. We extend the method to include covariates. Our approach considers a counterfactual control group and involves sensitivity analyses to evaluate different settings of control group parameters. Only minimal distributional assumptions are required. Simulation studies demonstrate the validity of the method. We illustrate the method using a large, registry of older adults (N  =7239) who underwent total knee replacement (TKR). We demonstrate how external data can be utilized to constrain the sensitivity analysis. Naive analyses implicated several treatment effect modifiers including baseline function, age, body-mass index (BMI), gender, number of comorbidities, income, and race. Corrected analysis revealed that baseline (pre-stressor) function was not strongly linked to recovery after TKR and among the covariates, only age and number of comorbidities were consistently and negatively associated with post-stressor recovery in all functional domains. Correction of mathematical coupling and RTM is necessary for drawing valid inferences regarding the effect of covariates and baseline status on pre-post change. Our method provides a simple estimator to this end.

Domains of Frailty Predict Loss of Independence in Older Adults After Noncardiac Surgery.

IMPORTANCE: Preoperative frailty has been consistently associated with death, severe complications, and loss of independence (LOI) after surgery. LOI is an important patient-centered outcome, but it is unclear which domains of frailty are most strongly associated with LOI. Such information would be important to target individual geriatric domains for optimization. OBJECTIVE: To assess whether impairment in individual domains of the Edmonton Frail Scale (EFS) can predict LOI in older adults after noncardiac surgery. DESIGN: Retrospective Cohort Study. SETTING: One Academic Hospital. PARTICIPANTS: Patients aged 65 or older who were living independently and evaluated with the EFS during a preoperative visit to the Center for Preoperative Optimization at the Johns Hopkins Hospital between June 2018 and January 2020. MAIN OUTCOME: LOI defined as discharge to increased level of care outside of the home with new mobility deficit or functional dependence. New mobility deficit and functional dependence were extracted from chart review of the standardized occupational therapy and physical therapy assessment performed before discharge. RESULTS: A total of 3497 patients were analyzed. Age (mean±SD) was 73.4±6.2 years, and 1579 (45.2%) were female. The median total EFS score was 3 (range 0-16), and 725/3497 (27%) were considered frail (EFS≥6). The frequencies of impairment in each EFS domain were functional performance (33.5% moderately impaired, 11% severely impaired), history of hospital readmission (42%), poor self-described health status (37%), and abnormal cognition (17.1% moderately impaired, 13.8% severely impaired). Overall, 235/3497 (6.7%) patients experienced LOI. Total EFS score was associated with LOI (odds ratio: 1.37, 95% CI, 1.30-1.45, P <0.001) in a model adjusted for age, sex, body mass index, American Society of Anesthesiologists rating, congestive heart failure, valvular heart disease, hypertension diagnosis, chronic lung disease, diabetes, renal failure, liver disease, weight loss, anemia, and depression. Using a nested log likelihood approach, the domains of functional performance, functional dependence, social support, health status, and urinary incontinence improved the base multivariable model. In cross-validation, total EFS improved the prediction of LOI with the final model achieving an area under the curve of 0.840. Functional performance was the single domain that most improved outcome prediction, but together with functional dependence, social support, and urinary incontinence, the model resulted in an area under the curve of 0.838. CONCLUSION AND RELEVANCE: Among domains measured by the EFS before a wide range of noncardiac surgeries in older adults, functional performance, functional dependence, social support, and urinary incontinence were independently associated with and improved the prediction of LOI. Clinical initiatives to mitigate LOI may consider screening with the EFS and targeting abnormalities within these domains.

Sinus inflammation and chronic rhinosinusitis are associated with a diagnosis of new onset asthma in the following year.

BACKGROUND: Chronic rhinosinusitis (CRS) and asthma commonly co-occur. No studies have leveraged large samples needed to formally address whether preexisting CRS is associated with new onset asthma over time. METHODS: We evaluated whether prevalent CRS [identified in two ways: validated text algorithm applied to sinus computerized tomography (CT) scan or two diagnoses] was associated with new onset adult asthma in the following year. We used electronic health record data from Geisinger from 2008 to 2019. For each year we removed persons with any evidence of asthma through the end of the year, then identified those with new diagnosis of asthma in the following year. Complementary log-log regression was used to adjust for confounding variables (e.g., sociodemographic, contact with the health system, comorbidities), and hazard ratios (HRs) and 95% confidence intervals (CI) were calculated. RESULTS: A total of 35,441 persons were diagnosed with new onset asthma and were compared to 890,956 persons who did not develop asthma. Persons with new onset asthma tended to be female (69.6%) and younger (mean [SD] age 45.9 [17.0] years). Both CRS definitions were associated (HR, 95% CI) with new onset asthma, with 2.21 (1.93, 2.54) and 1.48 (1.38, 1.59) for CRS based on sinus CT scan and two diagnoses, respectively. New onset asthma was uncommonly observed in persons with a history of sinus surgery. CONCLUSION: Prevalent CRS identified with two complementary approaches was associated with a diagnosis of new onset asthma in the following year. The findings may have clinical implications for the prevention of asthma.

Caregiving-Related Work Productivity Loss Among Employed Family and Other Unpaid Caregivers of Older Adults.

OBJECTIVES: Although nearly half of all family and unpaid caregivers to older adults work, little is known about short-term work impacts of caregiving using measures encompassing both missed work time and reduced productivity while physically at work. We quantify the prevalence, costs, and correlates of caregiving-related work productivity loss. METHODS: We used the 2015 National Study of Caregiving and National Health and Aging Trends Study to estimate caregiving-related work absences (absenteeism) and reduced productivity while at work (presenteeism). We calculated costs of lost productivity using hours lost, compensation, and a wage multiplier, accounting for the additional cost of replacing employee time. We examined correlates of caregiving-related absenteeism and presenteeism separately, using multivariable logistic regression models, adjusting for caregiver sociodemographic characteristics, occupation and hours worked, role overload, older adult health, use of respite care, support groups, flexible workplace schedules, help from family or friends, and caregiver training. RESULTS: Nearly 1 in 4 (23.3%) of the estimated 8.8 million employed family caregivers reported either absenteeism or presenteeism over a 1-month period owing to caregiving. Among those affected, caregiving reduced work productivity by one-third on average-or an estimated $5600 per employee when annualized across all employed caregivers-primarily because of reduced performance while present at work. Productivity loss was higher among caregivers of older adults with significant care needs and varied according to sociodemographic characteristics and caregiver supports. CONCLUSIONS: Findings emphasize the potential economic value of targeted policy intervention to support working caregivers.

Substitution of self-reported measures for objectively assessed grip strength and slow walk in the Physical Frailty Phenotype: ramifications for validity.

BACKGROUND: Frailty assessment promises to identify older adults at risk for adverse consequences following stressors and target interventions to improve health outcomes. The Physical Frailty Phenotype (PFP) is a widely-studied, well validated assessment but incorporates performance-based slow walk and grip strength criteria that challenge its use in some clinical settings. Variants replacing performance-based elements with self-reported proxies have been proposed. Our study evaluated whether commonly available disability self-reports could be substituted for the performance-based criteria in the PFP while still identifying as "frail" the same subpopulations of individuals. METHODS: Parallel analyses were conducted in 3393 female and 2495 male Cardiovascular Health Study, Round 2 participants assessed in 1989-90. Candidate self-reported proxies for the phenotype's "slowness" and "weakness" criteria were evaluated for comparable prevalence and agreement by mode of measurement. For best-performing candidates: Frailty status (3 + positive criteria out of 5) was compared for prevalence and agreement between the PFP and mostly self-reported versions. Personal characteristics were compared between those adjudicated as frail by (a) only a self-reported version; (b) only the PFP; (c) both, using bivariable analyses and multinomial logistic regression. RESULTS: Self-reported difficulty walking ½ mile was selected as a proxy for the phenotype's slowness criterion. Two self-reported weakness proxies were examined: difficulty transferring from a bed or chair or gripping with hands, and difficulty as just defined or in lifting a 10-pound bag. Prevalences matched to within 4% between self-reported and performance-based criteria in the whole sample, but in all cases the self-reported prevalence for women exceeded that for men by 11% or more. Cross-modal agreement was moderate, with by-criterion and frailty-wide Kappa statistics of 0.55-0.60 in all cases. Frail subgroups (a), (b), (c) were independently discriminated (p < 0.05) by race, BMI, and depression in women; by age in men; and by self-reported health for both. CONCLUSIONS: Commonly used self-reported disability items cannot be assumed to stand in for performance-based criteria in the PFP. We found subpopulations identified as frail by resultant phenotypes versus the original phenotype to systematically differ. Work to develop self-reported proxies that more closely replicate their objective phenotypic counterparts than standard disability self-reports is needed.

Clinical trial participation predicts improved survival in older adults receiving allogeneic blood and marrow transplant.

BACKGROUND: Older adults represent a large oncologic demographic and are under-represented within oncology research despite constituting nearly two-thirds of the oncologic population in the United States. Because many social factors influence research participation, those who enroll in research do not reflect the oncology population at large, introducing bias and creating issue with external validity of studies. The same factors that influence study enrollment may also impact cancer outcomes, meaning that those who enroll in studies may already have an improved chance of cancer survival, further skewing results of these studies. This study evaluates characteristics that influence study enrollment in older adults and explore to what degree these factors may influence survival after allogeneic blood or marrow transplantation. METHODS: This retrospective comparison study evaluates 63 adults aged 60 and above undergoing allogenic transplantation at one institution. Patients who elected and declined enrollment in a non-therapeutic observational study were evaluated. Demographic and clinical characteristics between groups were compared and assessed as predictors of transplant survival, including decision to enroll in the study. RESULTS: Participants who chose to enroll in the parent study were not different with regard to gender, race/ethnicity, age, insurance type, donor age, and neighborhood income/poverty level compared to patients who were invited to participate but declined enrollment. The research participant group had higher proportion assessed as being fully active (23.8% vs. 12.7%, p = 0.034) and lower mean comorbidity scores (1.0 vs 2.47, p = 0.008). Enrollment in an observational study independently predicted transplant survival (HR = 0.316, 95% CI 0.12-0.82, p = 0.017). When controlling for relevant confounders of disease severity, comorbidities, and transplant age, enrolling in the parent study was associated with a lower hazards of death following transplant (HR = 0.302, 95% CI 0.10-0.87, p = 0.027). CONCLUSIONS: Despite being demographically comparable, persons who enrolled in one non-therapeutic transplant study had significantly improved survivorship than those who did not participate in observational research. These findings suggest that there are unidentified factors that influence study involvement that may also impact disease survivorship, over-estimating outcomes from these studies. Results from prospective observational studies should be interpreted with the consideration that study participants have an improved chance of survival at baseline.

Resilient Adaptation Strategies: Unveiling Older Adults' Coping Dynamics Amidst the COVID-19 Pandemic.

Older adults, who are particularly vulnerable to coronavirus disease 2019 (COVID-19), exhibit less stress and greater well-being than their younger peers. However, there have been no in-depth explorations of adaptive coping strategies among this population, nor has the role of frailty status been addressed. The current study examined stress and coping in 30 U.S. older adults (mean age = 81 years, range = 68 to 95 years) amidst the COVID-19 pandemic, uncovering themes of: (1) Pandemic Stresses: stresses experienced during the pandemic centered around social isolation and concern for others' well-being; (2) Resilience: older adults proved highly adaptable, with lifetime experience as a stress buffer; and (3) Silver Linings: older adults reported positive by-products, such as reconnecting with and a renewed appreciation for life and nature. Motivation for change and change itself centered around creating value and meaning in the present, especially around social isolation. Findings challenge existing ageist stereotypes, give insight into interventional design, and highlight the importance of ensuring infrastructural and societal support. [Journal of Gerontological Nursing, 49(12), 32-39.].

The association of unconventional natural gas development with diagnosis and treatment of internalizing disorders among adolescents in Pennsylvania using electronic health records.

BACKGROUND: Unconventional natural gas development (UNGD) introduces physical and psychosocial hazards into communities, which could contribute to psychosocial stress in adolescents and an increased risk of internalizing disorders, common and impactful health outcomes. OBJECTIVES: To evaluate associations between a 180-day composite UNGD activity metric and new onset of internalizing disorders, overall and separately for anxiety and depressive disorders, and effect modification by sex. METHODS: We used a nested case-control design from 2008 to 2016 in 38 Pennsylvania counties using electronic health records from adolescent Geisinger subjects. Cases were defined by at least two diagnoses or medication orders indicating new onset of an internalizing disorder, and controls frequency-matched 4:1 on age, sex, and year. To evaluate associations, we used generalized estimating equations, with logit link, robust standard errors, and an exchangeable correlation structure within community. RESULTS: We identified 7,974 adolescents (65.9% female, mean age 15.0 years) with new onset internalizing disorders. There were no associations when we used data from the entire study period. When restricted to years with higher UNGD activity (2010-2016), comparing the highest to lowest quartile, UNGD activity was associated (odds ratio [95% confidence level]) with new onset internalizing disorders (1.15 [1.06, 1.25]). Associations were slightly stronger for depressive disorders. Associations were only present in females (p = 0.009). DISCUSSION: This is the first epidemiologic study of UNGD in relation to adolescent mental health, an important health outcome in a potentially susceptible group to the environmental and community impacts of UNGD. UNGD activity was associated with new onset internalizing disorders in females in this large sample in an area of active UNGD.

New horizons in evidence-based care for older people: individual participant data meta-analysis.

Evidence-based decisions on clinical and cost-effectiveness of interventions are ideally informed by meta-analyses of intervention trial data. However, when undertaken, such meta-analyses in ageing research have typically been conducted using standard methods whereby summary (aggregate) data are extracted from published trial reports. Although meta-analysis of aggregate data can provide useful insights into the average effect of interventions within a selected trial population, it has limitations regarding robust conclusions on which subgroups of people stand to gain the greatest benefit from an intervention or are at risk of experiencing harm. Future evidence synthesis using individual participant data from ageing research trials for meta-analysis could transform understanding of the effectiveness of interventions for older people, supporting evidence-based and sustainable commissioning. A major advantage of individual participant data meta-analysis (IPDMA) is that it enables examination of characteristics that predict treatment effects, such as frailty, disability, cognitive impairment, ethnicity, gender and other wider determinants of health. Key challenges of IPDMA relate to the complexity and resources needed for obtaining, managing and preparing datasets, requiring a meticulous approach involving experienced researchers, frequently with expertise in designing and analysing clinical trials. In anticipation of future IPDMA work in ageing research, we are establishing an international Ageing Research Trialists collective, to bring together trialists with a common focus on transforming care for older people as a shared ambition across nations.

Agreement between standard and self-reported assessments of physical frailty syndrome and its components in a registry of community-dwelling older adults.

BACKGROUND: The ability to identify frail older adults using a self-reported version of the physical frailty phenotype (PFP) that has been validated with the standard PFP could facilitate physical frailty detection in clinical settings. METHODS: We collected data from volunteers (N = 182), ages 65 years and older, in an aging research registry in Baltimore, Maryland. Measurements included: standard PFP (walking speed, grip strength, weight loss, activity, exhaustion); and self-reported questions about walking and handgrip strength. We compared objectively-measured gait speed and grip strength to self-reported questions using Cohen's Kappa and diagnostic accuracy tests. We used these measures to compare the standard PFP with self-reported versions of the PFP, focusing on a dichotomized identification of frail versus pre- or non-frail participants. RESULTS: Self-reported slowness had fair-to-moderate agreement (Kappa(k) = 0.34-0.56) with measured slowness; self-reported and objective weakness had slight-to-borderline-fair agreement (k = 0.10-0.21). Combining three self-reported slowness questions had highest sensitivity (81%) and negative predictive value (NPV; 91%). For weakness, three questions combined had highest sensitivity (72%), while all combinations had comparable NPV. Follow-up questions on level of difficulty led to minimal changes in agreement and decreased sensitivity. Substituting subjective for objective measures in our PFP model dichotomized by frail versus non/pre-frail, we found substantial (k = 0.76-0.78) agreement between standard and self-reported PFPs. We found highest sensitivity (86.4%) and NPV (98.7%) when comparing the dichotomized standard PFP to a self-reported version combining all slowness and weakness questions. Substitutions in a three-level model (frail, vs pre-frail, vs. non-frail) resulted in fair-to-moderate agreement (k = 0.33-0.50) with the standard PFP. CONCLUSIONS: Our results show potential utility as well as challenges of using certain self-reported questions in a modified frailty phenotype. A self-reported PFP with high agreement to the standard phenotype could be a valuable frailty screening assessment in clinical settings.

Development of Severe COVID-19 Adaptive Risk Predictor (SCARP), a Calculator to Predict Severe Disease or Death in Hospitalized Patients With COVID-19.

BACKGROUND: Predicting the clinical trajectory of individual patients hospitalized with coronavirus disease 2019 (COVID-19) is challenging but necessary to inform clinical care. The majority of COVID-19 prognostic tools use only data present upon admission and do not incorporate changes occurring after admission. OBJECTIVE: To develop the Severe COVID-19 Adaptive Risk Predictor (SCARP) (https://rsconnect.biostat.jhsph.edu/covid_trajectory/), a novel tool that can provide dynamic risk predictions for progression from moderate disease to severe illness or death in patients with COVID-19 at any time within the first 14 days of their hospitalization. DESIGN: Retrospective observational cohort study. SETTINGS: Five hospitals in Maryland and Washington, D.C. PATIENTS: Patients who were hospitalized between 5 March and 4 December 2020 with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) confirmed by nucleic acid test and symptomatic disease. MEASUREMENTS: A clinical registry for patients hospitalized with COVID-19 was the primary data source; data included demographic characteristics, admission source, comorbid conditions, time-varying vital signs, laboratory measurements, and clinical severity. Random forest for survival, longitudinal, and multivariate (RF-SLAM) data analysis was applied to predict the 1-day and 7-day risks for progression to severe disease or death for any given day during the first 14 days of hospitalization. RESULTS: Among 3163 patients admitted with moderate COVID-19, 228 (7%) became severely ill or died in the next 24 hours; an additional 355 (11%) became severely ill or died in the next 7 days. The area under the receiver-operating characteristic curve (AUC) for 1-day risk predictions for progression to severe disease or death was 0.89 (95% CI, 0.88 to 0.90) and 0.89 (CI, 0.87 to 0.91) during the first and second weeks of hospitalization, respectively. The AUC for 7-day risk predictions for progression to severe disease or death was 0.83 (CI, 0.83 to 0.84) and 0.87 (CI, 0.86 to 0.89) during the first and second weeks of hospitalization, respectively. LIMITATION: The SCARP tool was developed by using data from a single health system. CONCLUSION: Using the predictive power of RF-SLAM and longitudinal data from more than 3000 patients hospitalized with COVID-19, an interactive tool was developed that rapidly and accurately provides the probability of an individual patient's progression to severe illness or death on the basis of readily available clinical information. PRIMARY FUNDING SOURCE: Hopkins inHealth and COVID-19 Administrative Supplement for the HHS Region 3 Treatment Center from the Office of the Assistant Secretary for Preparedness and Response.

Patient Trajectories Among Persons Hospitalized for COVID-19 : A Cohort Study.

BACKGROUND: Risk factors for progression of coronavirus disease 2019 (COVID-19) to severe disease or death are underexplored in U.S. cohorts. OBJECTIVE: To determine the factors on hospital admission that are predictive of severe disease or death from COVID-19. DESIGN: Retrospective cohort analysis. SETTING: Five hospitals in the Maryland and Washington, DC, area. PATIENTS: 832 consecutive COVID-19 admissions from 4 March to 24 April 2020, with follow-up through 27 June 2020. MEASUREMENTS: Patient trajectories and outcomes, categorized by using the World Health Organization COVID-19 disease severity scale. Primary outcomes were death and a composite of severe disease or death. RESULTS: Median patient age was 64 years (range, 1 to 108 years); 47% were women, 40% were Black, 16% were Latinx, and 21% were nursing home residents. Among all patients, 131 (16%) died and 694 (83%) were discharged (523 [63%] had mild to moderate disease and 171 [20%] had severe disease). Of deaths, 66 (50%) were nursing home residents. Of 787 patients admitted with mild to moderate disease, 302 (38%) progressed to severe disease or death: 181 (60%) by day 2 and 238 (79%) by day 4. Patients had markedly different probabilities of disease progression on the basis of age, nursing home residence, comorbid conditions, obesity, respiratory symptoms, respiratory rate, fever, absolute lymphocyte count, hypoalbuminemia, troponin level, and C-reactive protein level and the interactions among these factors. Using only factors present on admission, a model to predict in-hospital disease progression had an area under the curve of 0.85, 0.79, and 0.79 at days 2, 4, and 7, respectively. LIMITATION: The study was done in a single health care system. CONCLUSION: A combination of demographic and clinical variables is strongly associated with severe COVID-19 disease or death and their early onset. The COVID-19 Inpatient Risk Calculator (CIRC), using factors present on admission, can inform clinical and resource allocation decisions. PRIMARY FUNDING SOURCE: Hopkins inHealth and COVID-19 Administrative Supplement for the HHS Region 3 Treatment Center from the Office of the Assistant Secretary for Preparedness and Response.

Urban-Rural Differences in Health Care Utilization and COVID-19 Outcomes in Patients With Type 2 Diabetes.

INTRODUCTION: Two studies in Pennsylvania aimed to determine whether community type and community socioeconomic deprivation (CSD) 1) modified associations between type 2 diabetes (hereinafter, diabetes) and COVID-19 hospitalization outcomes, and 2) influenced health care utilization among individuals with diabetes during the COVID-19 pandemic. METHODS: The hospitalization study evaluated a retrospective cohort of patients hospitalized with COVID-19 through 2020 for COVID-19 outcomes: death, intensive care unit (ICU) admission, mechanical ventilation, elevated D-dimer, and elevated troponin level. We used adjusted logistic regression models, adding interaction terms to evaluate effect modification by community type (township, borough, or city census tract) and CSD. The utilization study included patients with diabetes and a clinical encounter between 2017 and 2020. Autoregressive integrated moving average time-series models evaluated changes in weekly rates of emergency department and outpatient visits, hemoglobin A1c (HbA1c) laboratory tests, and antihyperglycemic medication orders from 2018 to 2020. RESULTS: In the hospitalization study, of 2,751 patients hospitalized for COVID-19, 1,020 had diabetes, which was associated with ICU admission and elevated troponin. Associations did not differ by community type or CSD. In the utilization study, among 93,401 patients with diabetes, utilization measures decreased in March 2020. Utilization increased in July, and then began to stabilize or decline through the end of 2020. Changes in HbA1c tests and medication order trends during the pandemic differed by community type and CSD. CONCLUSION: Diabetes was associated with selected outcomes among individuals hospitalized for COVID-19, but these did not differ by community features. Utilization trajectories among individuals with diabetes during the pandemic were influenced by community type and CSD and could be used to identify individuals at risk of gaps in diabetes care.

Frailty and cardiovascular outcomes in the National Health and Aging Trends Study.

AIMS: Physical frailty is a commonly encountered geriatric syndrome among older adults without coronary heart disease (CHD). The impact of frailty on the incidence of long-term cardiovascular outcomes is not known.We aimed to evaluate the long-term association of frailty, measured by the Fried frailty phenotype, with all-cause-mortality and MACE among older adults without a history of CHD at baseline in the National Health and Aging Trends Study. METHODS AND RESULTS: We used the National Health and Aging Trends Study, a prospective cohort study linked to a Medicare sample. Participants with a prior history of CHD were excluded. Frailty was measured during the baseline visit using the Fried physical frailty phenotype. Cardiovascular outcomes were assessed during a 6-year follow-up.Of the 4656 study participants, 3259 (70%) had no history of CHD 1 year prior to their baseline visit. Compared to those without frailty, subjects with frailty were older (mean age 82.1 vs. 75.1 years, P < 0.001), more likely to be female (68.3% vs. 54.9%, P < 0.001), and belong to an ethnic minority. The prevalence of hypertension, falls, disability, anxiety/depression, and multimorbidity was much higher in the frail and pre-frail than the non-frail participants. In a Cox time-to-event multivariable model and during 6-year follow-up, the incidences of death and of each individual cardiovascular outcomes were all significantly higher in the frail than in the non-frail patients including major adverse cardiovascular event (MACE) [hazard ratio (HR) 1.77, 95% confidence interval (CI) 1.53, 2.06], death (HR 2.70, 95% CI 2.16, 3.38), acute myocardial infarction (HR 1.95, 95% CI 1.31, 2.90), stroke (HR 1.71, 95% CI 1.34, 2.17), peripheral vascular disease (HR 1.80, 95% CI 1.44, 2.27), and coronary artery disease (HR 1.35, 95% CI 1.11, 1.65). CONCLUSION: In patients without CHD, frailty is a risk factor for the development of MACEs. Efforts to identify frailty in patients without CHD and interventions to limit or reverse frailty status are needed and, if successful, may limit subsequent adverse cardiovascular events.

Evidence from two cohorts for the frailty syndrome as an emergent state of parallel dysregulation in multiple physiological systems.

Frailty is a clinical syndrome often present in older adults and characterized by a heightened vulnerability to stressors. The biological antecedents and etiology of frailty are unclear despite decades of research: frailty is associated with dysregulation in a wide range of physiological systems, but no specific cause has been identified. Here, we test predictions stemming from the hypothesis that there is no specific cause: that frailty is an emergent property arising from the complex systems dynamics of the broad loss of organismal homeostasis. Specifically, we use dysregulation of six physiological systems using the Mahalanobis distance approach in two cohorts of older adults to test the breadth, diffuseness, and nonlinearity of associations between frailty and system-specific dysregulation. We find clear support for the breadth of associations between frailty and physiological dysregulation: positive associations of all systems with frailty in at least some analyses. We find partial support for diffuseness: the number of systems or total amount of dysregulation is more important than the identity of the systems dysregulated, but results only partially replicate across cohorts. We find partial support for nonlinearity: trends are exponential but not always significantly so, and power is limited for groups with very high levels of dysregulation. Overall, results are consistent with-but not definitive proof of-frailty as an emergent property of complex systems dynamics. Substantial work remains to understand how frailty relates to underlying physiological dynamics across systems.

Frailty-a risk factor of global and domain-specific cognitive decline among a nationally representative sample of community-dwelling older adult U.S. Medicare beneficiaries.

OBJECTIVES: frail older adults may be more vulnerable to stressors, resulting in steeper declines in cognitive function. Whether the frailty-cognition link differs by cognitive domain remains unclear; however, it could lend insight into underlying mechanisms. METHODS: we tested whether domain-specific cognitive trajectories (clock-drawing test, (CDT), immediate and delayed recall, orientation to date, time, president and vice-president naming) measured annually (2011-2016) differ by baseline frailty (physical frailty phenotype) in the National Health and Aging Trends Study (n = 7,439), a nationally representative sample of older adult U.S. Medicare beneficiaries, using mixed effects models to describe repeated measures of each cognitive outcome. To determine if the association between frailty and subsequent cognitive change differed by education, we tested for interaction using the Wald test. RESULTS: we observed steeper declines for frail compared to non-frail participants in each domain-specific outcome, except for immediate recall. Largest differences in slope were observed for CDT (difference = -0.12 (standard deviations) SD/year, 95%CI: -0.15, -0.08). By 2016, mean CDT scores for frail participants were 1.8 SD below the mean (95%CI: -1.99, -1.67); for non-frail participants, scores were 0.8 SD below the mean (95%CI: -0.89, -0.69). Associations differed by education for global cognitive function (Pinteraction < 0.001) and for each domain-specific outcome: CDT (Pinteraction < 0.001), orientation (Pinteraction < 0.001), immediate (Pinteraction < 0.001) and delayed (Pinteraction < 0.001) word recalls. CONCLUSION: frailty is associated with lower levels and steeper declines in cognitive function, with strongest associations for executive function. These findings suggest that aetiologies are multifactorial, though primarily vascular related; further research into its association with dementia sub-types and related pathologies is critical.

A Note on Proposed Estimation Procedures for Claims-Based Frailty Indexes.

Two groups (Segal et al. Med Care. 2017;55(7):716-722; Segal et al. Am J Epidemiol. 2017;186(6):745-747; and Kim et al. J Gerontol A Biol Sci Med Sci. 2018;73(7):980-987) recently proposed methods for modeling frailty in studies where a reference standard frailty measure is not directly observed, but Medicare claims data are available. The groups use competing frailty measures, but the premise is similar: In a validation data set, model the frailty measure versus claims variables; in the primary data set, impute frailty status from claims variables, and conduct inference with those imputed values in place of the unobserved frailty measure. Potential use cases include risk prediction, confounding control, and prevalence estimation. In this commentary, we describe validity issues underlying these approaches, focusing mainly on risk prediction. Our main concern is that these approaches do not permit valid estimation of associations between the reference standard frailty measure (i.e., "frailty") and health outcomes. We argue that Segal's approach is akin to multiple imputation but with the outcome variable omitted from the imputation model, while Kim's is akin to regression calibration but with many variables improperly treated as surrogates. We discuss alternatives for risk prediction, including a secondary approach previously considered by Kim et al., and briefly comment on other use cases.

Sarcopenia and health-related quality of life in older adults after transcatheter aortic valve replacement.

BACKGROUND: Skeletal muscle wasting, or sarcopenia, affects a significant proportion of patients undergoing transcatheter aortic valve replacement (TAVR). However, its influence on post-TAVR recovery and 1-year health-related quality of life (HR-QOL) remains unknown. We examined the relationship between skeletal muscle index (SMI), post-TAVR length of hospital stay (LOS), and 1-year QOL. METHODS: The study sample consisted of 300 consecutive patients undergoing TAVR from 2012 to 2018 who had pre-TAVR computed tomographic scans suitable for analysis of body composition. Skeletal muscle mass was quantified as cm2 of skeletal mass per m2 of body surface area from the cross-sectional computed tomographic image at the third lumbar vertebra. Sarcopenia was defined using established sex-specific cutoffs (women: SMI < 39 cm2/m2; men: < 55 cm2/m2). Multivariable linear regression analysis was used to determine the relationship between SMI, LOS, and HR-QOL using the Kansas City Cardiomyopathy Questionnaire. RESULTS: Sarcopenia was present in most (59%) patients and associated with older age (82 vs 76 years; P < .001) and lower body mass index (27 vs 33 kg/m2; P < .001). There were no other differences in baseline clinical or echocardiographic characteristics among the 4 quartiles of SMI. SMI was positively correlated with LOS and 1-year QOL. After adjusting for age, gender, race, and body mass index, SMI remained a significant predictor of both LOS (P = .01) and 1-year QOL (P = .012). For every 10 cm2/m2 higher SMI, there was an 8-point increase in Kansas City Cardiomyopathy Questionnaire score, a difference that is clinically meaningful. CONCLUSIONS: Sarcopenia is prevalent in TAVR patients. Higher SMI is associated with shorter LOS and better 1-year HR-QOL. To achieve optimal TAVR benefits, further study into how body composition influences post-TAVR recovery and durable improvement in QOL is warranted.

Radiologic sinus inflammation and symptoms of chronic rhinosinusitis in a population-based sample.

BACKGROUND: Chronic rhinosinusitis (CRS) epidemiology has been largely studied using symptom-based case definitions, without assessment of objective sinus findings. OBJECTIVE: To describe radiologic sinus opacification and the prevalence of CRS, defined by the co-occurrence of symptoms and sinus opacification, in a general population-based sample. METHODS: We collected questionnaires and sinus CT scans from 646 participants selected from a source population of 200 769 primary care patients. Symptom status (CRSS ) was based on guideline criteria, and objective radiologic inflammation (CRSO ) was based on the Lund-Mackay (L-M) score using multiple L-M thresholds for positivity. Participants with symptoms and radiologic inflammation were classified as CRSS+O . We performed negative binomial regression to assess factors associated with L-M score and logistic regression to evaluate factors associated with CRSS+O . Using weighted analysis, we calculated estimates for the source population. RESULTS: The proportion of women with L-M scores ≥ 3, 4, or 6 (CRSO ) was 11.1%, 9.9%, and 5.7%, respectively, and 16.1%, 14.6%, and 8.7% among men. The respective proportion with CRSS+O was 1.7%, 1.6%, and 0.45% among women and 8.8%, 7.5%, and 3.6% among men. Men had higher odds of CRSS+O compared to women. A greater proportion of men (vs women) had any opacification in the frontal, anterior ethmoid, and sphenoid sinuses. CONCLUSION: In a general population-based sample in Pennsylvania, sinus opacification was more common among men than in women and opacification occurred in different locations by sex. Male sex, migraine headache, and prior sinus surgery were associated with higher odds of CRSS+O .

Longitudinal partially ordered data analysis for preclinical sarcopenia.

Sarcopenia is a geriatric syndrome characterized by significant loss of muscle mass. Based on a commonly used definition of the condition that involves three measurements, different subclinical and clinical states of sarcopenia are formed. These states constitute a partially ordered set (poset). This article focuses on the analysis of longitudinal poset in the context of sarcopenia. We propose an extension of the generalized linear mixed model and a recoding scheme for poset analysis such that two submodels-one for ordered categories and one for nominal categories-that include common random effects can be jointly estimated. The new poset model postulates random effects conceptualized as latent variables that represent an underlying construct of interest, that is, susceptibility to sarcopenia over time. We demonstrate how information can be gleaned from nominal sarcopenic states for strengthening statistical inference on a person's susceptibility to sarcopenia.