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Abstract: This study examined whether changes in middle-aged children’s perceptions of their parents’ activities of daily living needs (ADL needs) were associated with changes in the mutuality of support in their relationship. A group of 366 middle-aged children in Waves 1 (2008) and 2 (2013) of the Family Exchanges Study self-reported providing and receiving tangible, emotional, and informational support to and from their n = 468 parents. Increased perceived parental ADL needs were associated with increased provision of tangible and informational support to parents but not with changes in support received. Increases in perceived parental ADL needs were associated with higher incongruence for all three support types (the child providing more support than they receive).

Objective:To examine the bidirectional associations between older adult spouses’ cognitive functioning and depressive symptoms over time and replicate previous findings from the United States (US) in Mexico.Design:Longitudinal, dyadic path analysis with the actor-partner interdependence model.Setting:Data were from the three most recent interview waves (2012, 2015, and 2018) of the Mexican Health and Aging Study (MHAS), a longitudinal national study of adults aged 50+ years in Mexico.Participants:Husbands and wives from 905 community-dwelling married couples (N = 1,810).Measurements:The MHAS cognitive battery measured cognitive function. Depressive symptoms were assessed using a modified nine-item Center for Epidemiologic Studies Depression Scale. Baseline covariates included age, education, number of children, limitation with any activity of daily living, limitation with any instrumental activity of daily living, and pain.Results:As hypothesized, there were significant within-individual associations in which one person’s own cognitive functioning and own depressive symptoms predicted their own follow-up cognitive functioning and depressive symptoms, respectively. In addition, a person’s own cognitive functioning predicted their own depressive symptoms, and a person’s own depressive symptoms predicted their own cognitive functioning over time. As hypothesized, there was a significant partner association such that one person’s depressive symptoms predicted more depressive symptoms in the partner.Conclusion:Findings from this study of older Mexican couples replicates findings from studies of older couples in the US, showing that depressive symptoms in one partner predict depressive symptoms in the other partner over time; however, there was no evidence for cognition–depression partner associations over time.

BACKGROUND: Commonly used thresholds for staging FEV1 have not been evaluated as standalone spirometric predictors of death in older persons. Specifically, the proportion of deaths attributed to a reduced FEV1, when staged by commonly used thresholds in L, percent of predicted (% pred), and Z scores, has not been previously reported. METHODS: In 4,232 white persons ≥ 65 y old, sampled from the Cardiovascular Health Study, FEV1 was stratified as stage 1 (FEV1 ≥ 2.00 L, ≥80% pred, and Z score ≥−1.64), stage 2 (FEV1 1.50–1.99 L, 50–79%pred, and Z score −2.55 to −1.63), and stage 3 (FEV1 RESULTS: FEV1 stage 2 and 3 in L, % pred, and Z scores yielded similar adjusted odds ratios of death: 1.40–1.51 for stage 2 and 2.35–2.66 for stage 3. Conversely, FEV1 stages 2 and 3 in L, % pred, and Z scores differed in prevalence: 12.8–28.6% for stage 2 and 6.4–17.5% for stage 3, and also differed in the adjusted average attributable fraction for death: 3.2–6.4% for stage 2 and 4.5–9.1% for stage 3. CONCLUSIONS: In older persons, the proportion of deaths attributed to a reduced FEV1 is best stratified by Z score staging thresholds because these yield a similar relative risk of death but a more age- and sex-appropriate prevalence of FEV1 stage.

Purpose: Transgender veterans are overrepresented in the Veterans Health Administration (VHA) compared with in the general population. Utilization of multiple different health care systems, or health care mobility, can affect care coordination and potentially affect outcomes, either positively or negatively. This study examines whether transgender veterans are more or less health care mobile than nontransgender veterans and compares the patterns of geographic mobility in these groups. Methods: Using an established cohort (n = 5,414,109), we identified 2890 transgender veterans from VHA electronic health records from 2000 to 2012. We compared transgender and nontransgender veterans on sociodemographic, clinical, and health care system-level measures and conducted conditional logistic regression models of mobility. Results: Transgender veterans were more likely to be younger, White, homeless, have depressive disorders, post-traumatic stress disorder (PTSD), and hepatitis C. Transgender veterans were more likely to have been health care mobile (9.9%) than nontransgender veterans (5.2%) (unadjusted odds ratio = 2.02, 95% confidence interval = 1.73–2.36). In a multivariable model, transgender status, being separated/divorced, receiving care in less-complex facilities, and diagnoses of depression, PTSD, or hepatitis C were associated with more mobility, whereas older age was associated with less mobility. For the top three health care systems utilized, a larger proportion of transgender veterans visited a second health care system in a different state (56.2%) than nontransgender veterans (37.5%). Conclusions: Transgender veterans were more likely to be health care mobile and more likely to travel out of state for health care services. They were also more likely to have complex chronic health conditions that require multidisciplinary care.

BackgroundMultimorbidity is common in adults aged 65 and older and is associated with health care utilization and mortality, but most methods ignore the interrelationship among concurrent outcome nor provide person-specific probabilities.MethodA longitudinal cohort of 5300 older Americans from the 2011–2015 rounds of the National Health and Aging Study was linked to Center for Medicare and Medicaid Services claims. Odds ratios for 15 chronic conditions adjusted for sociodemographic factors were estimated using a joint model of hospitalization, skilled nursing facility (SNF) admission, and mortality. Additionally, we estimated the person-specific probability of an outcome while currently at risk for other outcomes for different chronic disease combinations demonstrating the heterogeneity across persons with identical chronic conditions.ResultsDuring the 4-year follow-up period, 2867 (54.1%) individuals were hospitalized, 1029 (19.4%) were admitted to a SNF, and 1237 (23.3%) died. Chronic kidney disease, dementia, heart failure, and chronic obstructive pulmonary disease had significant increased odds for all 3 outcomes. By incorporating a person-specific random intercept, there was considerable range of person-specific probabilities for individuals with hypertension, diabetes, and depression with dementia, (hospitalization: 0.14–0.61; SNF admission: 0.04–0.28) and without dementia (hospitalization: 0.07–0.44; SNF admission: 0.02–0.15). Such heterogeneity was found among individuals with heart failure, ischemic heart disease, chronic kidney disease, hypertension, hyperlipidemia, and osteoarthritis with and without Medicare.ConclusionsThis approach of joint modeling of interrelated concurrent health care and mortality outcomes not only provides a cohort-level odds and probabilities but addresses the heterogeneity among otherwise similarly characterized persons identifying those with above-average probability of poor outcomes.

Introduction Electronic health care data offer an opportunity to improve clinical decision making through advanced statistical analyses of longitudinal observations. Objective To describe a Web application and SAS/STAT macro (SAS Institute Inc, Cary, NC) for computing joint models to estimate the typical and personalized risk of 2 concurrent binary outcomes. Methods Features of the Web application design include uploading longitudinal files formatted with constant or time-varying covariates, specification of 2 binary outcomes, specification of a propensity model for treatment, and joint and separate models of the outcomes. In addition we designed an SAS macro for conducting the analysis. Fitting of joint and separate statistical models was implemented using a model specified in the Web application, with subsequent processing by the SAS macro. To illustrate the fitting of models, a sample of older adults with comorbid hypertension and chronic obstructive pulmonary disease from the Medical Expenditure Panel Survey was created to examine the association between polypharmacy (use of ≥ 5 medication classes) and limitations in social activities and mobility. Results Relative to separate models, the joint models typically estimated attenuated associations between explanatory variables and the 2 outcomes with smaller standard errors. These joint models yielded estimates of personalized concurrent risk and typical concurrent risk. Discussion Clinical decision making based on electronic health data can be improved using joint modeling to generate an individual's probability of concurrent risk. Conclusion This user-friendly software performs the advanced statistical analyses needed to estimate typical and personalized concurrent risks.

Background In prior work involving older persons, the reported associations of spirometric impairments with cardiovascular outcomes may have been confounded by age-related changes in lung function. Hence, using more age-appropriate spirometric criteria from the Global Lung Function Initiative (GLI), we have evaluated the associations of spirometric impairments, specifically restrictive-pattern and airflow-obstruction, with cardiovascular death (CV-death) and hospitalization (CV-hospitalization). In these analyses, we also evaluated the competing outcome of noncardiovascular death (nonCV-death) and calculated measures of relative and absolute risk. Methods Our study sample was drawn from the Cardiovascular Health Study (CHS), including 4232 community-dwelling white persons aged ≥65 years. Multivariable regression models included the following baseline predictors: GLI-defined restrictive-pattern and airflow-obstruction, age, male gender, obesity, waist circumference, current smoker status, ≥10 pack-years of smoking, hypertension, dyslipidemia, diabetes, and cardiovascular and cerebrovascular disease. Outcomes included adjudicated CV-death, CV-hospitalization, and nonCV-death, ascertained over 10 years of follow-up. Measures of association included hazard ratios (HRs), rate ratios (RRs), and average attributable fraction (AAF), each with 95% confidence intervals. Results Restrictive-pattern and airflow-obstruction were associated with CV-death (adjusted HRs: 1.57 [1.18, 2.09] and 1.29 [1.04, 1.60]) and with nonCV-death (adjusted HRs: 2.10 [1.63, 2.69] and 1.79 [1.51, 2.12]), respectively. Airflow-obstruction, but not restrictive-pattern, was also associated with CV-hospitalization (adjusted RRs: 1.18 [1.02, 1.36] and 1.20 [0.96, 1.50], respectively). The adjusted AAFs of restrictive-pattern and airflow-obstruction were 1.68% (0.46, 3.06) and 2.35% (0.22, 4.72) for CV-death, and 3.44% (1.97, 5.08) and 7.77% (5.15, 10.60) for nonCV-death, respectively. Conclusion Assessment of GLI-defined spirometric impairments contributes to broad geriatric risk stratifications for both cardiovascular and non-cardiovascular outcomes.

Family and friend caregivers play a critical role in helping older adults live long and healthy lives. Using the construct of "care types" we examine whether caregivers providing more intense care experience higher burden and lower gain compared to caregivers providing less intense care. Data are from the 2015 and 2017 rounds of the National Study of Caregiving (N=2,146), a study of the caregivers of older adults enrolled in the National Health and Aging Trends Study. In a previous analysis, we derived five care types at baseline (2015), that varied in the number and type of care activities, care duration, and regularity of care provided. Caregivers reported whether caregiving was financially, emotionally, and physically difficult for them. Participants were also asked whether caregiving made them more confident, taught them to deal with difficult situations, brought them closer to the recipient, and gave them satisfaction that the recipient was well cared for. We estimated the association between care types derived at baseline and caregiver burden and gains at follow-up using logistic regression. Compared to caregivers in the least intense care type, those in the more intense care types were significantly more likely to report financial and physical burden, as well as increased ability to deal with difficult situations and increased satisfaction that their loved one was well cared for. These associations remained significant after adjusting for confounders. Care types can be used to predict burdens and gains experienced by caregivers and to effectively target caregiver support services and interventions.

Epidemiologic studies have linked dietary patterns to psychological health including depression, anxiety, and stress. However, no research has examined dyadic associations between dietary behavior and depressive symptoms in older married couples. In this study, one hundred and one couples 51 to 90 years of age who were married or in a marriage-like relationship and living together for at least 6 months were recruited. Participants completed questionnaires and self-reported their dietary behavior (i.e., the total number of meals, number of snacks, and number of fast-food meals eaten in a typical day and the number of meals they eat alone and eat sitting down). They also completed the 20-item Center for Epidemiologic Studies Depression Scale. Results of the Actor Partner Interdependence Models controlling for income, education, chronic conditions, and marital satisfaction, showed that for wives only, more meals eaten in a day were associated with lower depressive symptoms (actor effect). Additionally, more snacks eaten by the wife and more meals eaten alone by the wife were associated with higher depressive symptoms for the husband (partner effects). Findings suggest that wives’ dietary behavior is particularly important, not only for their own but also their husbands’ mental health in late-life marriage.

Background/Objectives: The benefit or harm of a single medication recommended for one specific condition can be difficult to determine in individuals with multiple chronic conditions and polypharmacy. There is limited information on the associations between guideline-recommended medications and physical function in older adults with multiple chronic conditions. The objective of this study was to estimate the beneficial or harmful associations between guideline-recommended medications and decline in physical function in older adults with multiple chronic conditions. Design: Prospective observational cohort. Setting: National. Participants: Community-dwelling adults aged 65 and older from the Medicare Current Beneficiary Survey study (N = 3,273). Participants with atrial fibrillation, coronary artery disease, depression, diabetes mellitus, or heart failure were included. Measurements: Self-reported decline in physical function; guideline-recommended medications; polypharmacy (taking

Carlos A Vaz Fragoso,1,2 Terrence E Murphy,1 George O Agogo,1 Heather G Allore,1,3 Gail J McAvay1 1Department of Medicine, Yale School of Medicine, New Haven, 2Veterans Affairs Clinical Epidemiology Research Center, West Haven, 3Department of Biostatistics, Yale School of Public Health, New Haven, CT, USA Background: Prior work suggests that asthma–COPD overlap syndrome (ACOS) has a greater health burden than asthma alone or COPD alone. In the current study, we have further evaluated the health burden of ACOS in a nationally representative sample of the US population, focusing on patient-reported outcomes and health care utilization and on comparisons with asthma alone and COPD alone. Patient-reported outcomes are especially meaningful, as these include functional activities that are highly valued by patients and are the basis for patient-centered care.Methods: Using data from the Medical Expenditure Panel Survey (MEPS), we evaluated patient-reported outcomes and health care utilization among participants who were aged 40–85 years and had self-reported, physician-diagnosed asthma or COPD. MEPS administered five rounds of interviews, at baseline and approximately every 6 months over 2.5 years. Patient-reported outcomes included activities of daily living (ADLs), mobility, social/recreational activities, disability days in bed, and health status (Short Form 12, Version 2). Health care utilization included outpatient and emergency department (ED) visits, and hospitalization.Results: Of 3,486 participants with asthma or COPD, 1,585 (45.4%) had asthma alone, 1,294 (37.1%) had COPD alone, and 607 (17.4%) had ACOS. Relative to asthma alone, ACOS was significantly associated with higher odds of prevalent disability in ADLs and limitations in mobility and social/recreational activities (adjusted odds ratios [adjORs]: 1.91–3.98), as well as with higher odds of incident limitations in mobility and social/recreational activities, disability days in bed, and respiratory-based outpatient and ED visits, and hospitalization (adjORs: 1.86–2.35). In addition, ACOS had significantly worse physical and mental health scores than asthma alone (P-values

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.

Purpose We define personalized concurrent risk (PCR) as the subject-specific probability of an index outcome within a defined interval of time, while currently at risk for a separate outcome, where the outcomes are not mutually exclusive and can be jointly modeled with a shared random intercept. We further define typical concurrent risk as the risk obtained by setting the random intercept to null. Methods Drawing data from the Medical Expenditure Panel Survey (cohorts 2008–2013), we jointly model limitations in social activity and mobility over two years among older community-dwelling persons with both hypertension and chronic obstructive pulmonary disease. The joint model uses inverse probability of treatment weighting based on each participant's baseline propensity of polypharmacy (≥5 classes of medication). Results Even among participants with the same covariates, older persons with multiple chronic conditions exhibit wide-ranging heterogeneity of the treatment effect from polypharmacy, a risk factor for negative health outcomes among older persons. The magnitude of the PCRs is dominated by the value of the subject-specific random effect. Conclusions Estimates of PCR and typical concurrent risk can be calculated from national or institutional data sets and may facilitate the practice of personalized care for older patients with multiple chronic conditions.

Timely escalation of care for patients experiencing clinical deterioration in the inpatient setting is challenging. Deterioration on a general floor has been associated with an increased risk of death, and the early period of deterioration may represent a time during which admission to the intensive care unit (ICU) improves survival. Previous studies examining the association between delay from onset of clinical deterioration to ICU transfer and mortality are few in number and were conducted more than 10 years ago.We aimed to evaluate the impact of delays in the escalation of care among clinically deteriorating patients in the current era of inpatient medicine.This was a retrospective cohort study that analyzed data from 793 patients transferred from non-intensive care unit (ICU) inpatient floors to the medical intensive care unit (MICU), from 2011 to 2013 at an urban, tertiary, academic medical center."Deterioration to door time (DTDT)" was defined as the time between onset of clinical deterioration (as evidenced by the presence of one or more vital sign indicators including respiratory rate, systolic blood pressure, and heart rate) and arrival in the MICU.In our sample, 64.6 % had delays in care escalation, defined as greater than 4 h based on previous studies. Mortality was significantly increased beginning at a DTDT of 12.1 h after adjusting for age, gender, and severity of illness.Delays in the escalation of care for clinically deteriorating hospitalized patients remain frequent in the current era of inpatient medicine, and are associated with increased in-hospital mortality. Development of performance measures for the care of clinically deteriorating inpatients remains essential, and timeliness of care escalation deserves further consideration.

Approximately 75% of adults over the age of 65 years are affected by two or more chronic medical conditions. We provide a conceptual justification for individualized absolute risk calculators for competing patient-centered outcomes (PCO) (i.e. outcomes deemed important by patients) and patient reported outcomes (PRO) (i.e. outcomes patients report instead of physiologic test results). The absolute risk of an outcome is the probability that a person receiving a given treatment will experience that outcome within a pre-defined interval of time, during which they are simultaneously at risk for other competing outcomes. This allows for determination of the likelihood of a given outcome with and without a treatment. We posit that there are heterogeneity of treatment effects among patients with multiple chronic conditions (MCC) largely depends on those coexisting conditions. We outline the development of an individualized absolute risk calculator for competing outcomes using propensity score methods that strengthen causal inference for specific treatments. Innovations include the key concept that any given outcome may or may not concur with any other outcome and that these competing outcomes do not necessarily preclude other outcomes. Patient characteristics and MCC will be the primary explanatory factors used in estimating the heterogeneity of treatment effects on PCO and PRO. This innovative method may have wide-spread application for determining individualized absolute risk calculations for competing outcomes. Knowing the probabilities of outcomes in absolute terms may help the burgeoning population of patients with MCC who face complex treatment decisions.

BACKGROUND. Reference equations from the Global Lung Function Initiative (GLI) are now available for both spirometry and diffusion. However, respiratory phenotypes defined by GLI-based measures of diffusion have not yet been evaluated in GLI-based normal-for-age spirometry or spirometric impairments. METHODS. We evaluated cross-sectional data from 2100 Caucasians, aged 40–85 years. GLI-based spirometric categories included normal-for-age and the impairments of restrictive-pattern and three-level severity of airflow-obstruction (mild, moderate, severe). GLI-based diffusion included diffusing capacity of the lung for carbon monoxide (D(LCO)) and measured components of alveolar volume (V(A)) and transfer coefficient (K(CO)): D(LCO)=[V(A)]x[K(CO)]. Using multivariable regression models, adjusted odds ratios (adjORs) for D(LCO), V(A), and K(CO)

Purpose Correlated healthcare utilization outcomes may be encoded as binary outcomes in epidemiologic studies. We demonstrate how to account for correlation between concurrent binary outcomes and confounding by person characteristics when estimating a treatment effect in observational studies. Methods We present a joint shared-parameter model, weighted by inverse probability of treatment weights (IPTW) to account for confounding. The model is evaluated in a simulation study that emulates the Medical Expenditure Panel Survey data and compared with a covariate-adjusted joint model and with separate outcome models (IPTW weighted and covariate adjusted). Results For the IPTW-weighted joint model, relative bias in the estimated treatment effect on outcome 1 ranged from −0.057 to −0.033 and outcome 2 from −0.077 to −0.043. For the covariate-adjusted joint model, relative bias ranged from −0.010 to −0.083 for outcome 1 and from −0.087 to −0.110 for outcome 2. The covariate-adjusted joint model estimated the effect more closely than the covariate-adjusted separate model. The IPTW-weighted joint model estimated the effect more closely for outcome 1. Conclusions The IPTW-weighted joint model handles correlation between binary outcomes, adjusts for confounding, and estimates the treatment effect accurately in observational studies. We illustrate the contribution of person-specific effects in estimating personalized risk.

BACKGROUND Forced expiratory volume in 1 second (FEV1) over time is commonly expressed in liters and percent predicted (%Pred), or alternatively in L/m(3) and Z-scores-which approach is more clinically meaningful has not been evaluated. Because it uniquely accounts for the effect of aging on FEV1 and spirometric performance, we hypothesized that the Z-score approach is more clinically meaningful, based on associations between cardiopulmonary predictors and FEV1 over time. METHODS Using linear mixed-effects models and data from the Baltimore Longitudinal Study on Aging, including 501 white participants aged 40-95 who had completed at least three longitudinal spirometric assessments, we evaluated the associations between cardiopulmonary predictors (obesity, smoking status, hypertension, chronic bronchitis, diabetes mellitus, and myocardial infarction) and FEV1 over time, in liters, %Pred, L/m(3), and Z-scores. RESULTS Mean baseline values for FEV1 were 3.240L, 96.4%Pred, 0.621L/m(3), and -0.239 as a Z-score (40.6th percentile). The annual decline in FEV1 was 0.040L, 0.234 %Pred, 0.007L/m(3), and 0.008 Z-score units. Baseline age was associated with FEV1 over time in liters and L/m(3) (p < .001), and included a time interaction for %Pred (p < .001), but was not associated with Z-scores (p = .933). The associations of cardiopulmonary predictors with FEV1 over time were all significant when using Z-scores (p < .05), but varied for other methods of expressing FEV1. CONCLUSION A Z-score approach is more clinically meaningful when evaluating FEV1 over time, as it accounted for the effect of aging and was more frequently associated with multiple cardiopulmonary predictors.

RationaleIn aging populations, the commonly used Global Initiative for Chronic Obstructive Lung Disease (GOLD) may misclassify normal spirometry as respiratory impairment (airflow obstruction and restrictive pattern), including the presumption of respiratory disease (chronic obstructive pulmonary disease [COPD]).ObjectivesTo evaluate the phenotype of normal spirometry as defined by a new approach from the Global Lung Initiative (GLI), overall and across GOLD spirometric categories.MethodsUsing data from COPDGene (n = 10,131; ages 45-81; smoking history, ≥10 pack-years), we evaluated spirometry and multiple phenotypes, including dyspnea severity (Modified Medical Research Council grade 0-4), health-related quality of life (St. George's Respiratory Questionnaire total score), 6-minute-walk distance, bronchodilator reversibility (FEV1 % change), computed tomography-measured percentage of lung with emphysema (% emphysema) and gas trapping (% gas trapping), and small airway dimensions (square root of the wall area for a standardized airway with an internal perimeter of 10 mm).Measurements and main resultsAmong 5,100 participants with GLI-defined normal spirometry, GOLD identified respiratory impairment in 1,146 (22.5%), including a restrictive pattern in 464 (9.1%), mild COPD in 380 (7.5%), moderate COPD in 302 (5.9%), and severe COPD in none. Overall, the phenotype of GLI-defined normal spirometry included normal adjusted mean values for dyspnea grade (0.8), St. George's Respiratory Questionnaire (15.9), 6-minute-walk distance (1,424 ft [434 m]), bronchodilator reversibility (2.7%), % emphysema (0.9%), % gas trapping (10.7%), and square root of the wall area for a standardized airway with an internal perimeter of 10 mm (3.65 mm); corresponding 95% confidence intervals were similarly normal. These phenotypes remained normal for GLI-defined normal spirometry across GOLD spirometric categories.ConclusionsGLI-defined normal spirometry, even when classified as respiratory impairment by GOLD, included adjusted mean values in the normal range for multiple phenotypes. These results suggest that among adults with GLI-defined normal spirometry, GOLD may misclassify normal phenotypes as having respiratory impairment.

Objectives To evaluate whether a novel definition of spirometric respiratory impairment from the Global Lung Initiative (GLI) is strongly associated with respiratory symptoms and, in turn, frequently establishes symptomatic respiratory disease. Design Cross-sectional. Setting Third National Health and Nutrition Examination Survey. Participants Community-dwelling individuals aged 40 to 80 (N = 7,115). Measurements GLI-defined spirometric respiratory impairment (airflow obstruction and restrictive pattern), dyspnea on exertion (DOE), chronic bronchitis (CB), and wheezing. Results Prevalence rates were 12.7% for airflow obstruction, 6.2% for restrictive pattern, 28.6% for DOE, 12.6% for CB, and 12.9% for wheezing. Airflow obstruction was associated with DOE (adjusted odds ratio (aOR) = 1.69, 95% confidence interval (CI) = 1.42–2.02), CB (aOR = 1.92, 95% CI = 1.62–2.29), and wheezing (aOR = 2.50, 95% CI = 2.08–3.00), and restrictive pattern was associated with DOE (aOR = 1.75, 95% CI = 1.36–2.25), CB (aOR = 1.39, 95% CI = 1.08–1.78), and wheezing (aOR = 1.53, 95% CI = 1.15–2.04). Nonetheless, among participants who had airflow obstruction and restrictive pattern, only a minority had DOE (38.6% and 45.5%), CB (23.3% and 15.9%), and wheezing (24.4% and 19.1%), yielding a positive predictive value (PPV) of only 53% for any respiratory symptom in the setting of any spirometric respiratory impairment. In addition, most participants who had DOE (73.0%), CB (67.8%), and wheezing (66.8%) did not have airflow obstruction or restrictive pattern, yielding a PPV of only 26% for any spirometric respiratory impairment in the setting of any respiratory symptom. The results differed only modestly when stratified according to age (40–64 vs 65–80). Conclusion GLI-defined spirometric respiratory impairment increased the likelihood of respiratory symptoms but was nonetheless a poor predictor of respiratory symptoms. Similarly, respiratory symptoms were poor predictors of GLI-defined spirometric respiratory impairment. Hence, a comprehensive assessment is needed when evaluating respiratory symptoms, even in the presence of spirometric respiratory impairment.

Terrence E Murphy,1 Gail J McAvay,1 Heather G Allore,1 Jason A Stamm,2 Paul F Simonelli2 1Department of Internal Medicine, Section of Geriatrics, Yale University School of Medicine, New Haven, CT, USA;2Department of Internal Medicine, Section of Thoracic Medicine, Geisinger Medical Center, Danville, PA, USA Background: Among persons with obstructive airway disease, the relative contributions of chronic obstructive pulmonary disease (COPD), asthma, and common comorbid conditions to health care utilization and patient-centered outcomes (PCOs) have not been previously reported.Methods: We followed a total of 3,486 persons aged ≥40 years with COPD, asthma, or both at baseline, from the Medical Expenditure Panel Survey (MEPS) cohorts enrolled annually from 2008 through 2012 for 1year. MEPS is a prospective observational study of US households recording self-reported COPD, asthma, and ten medical conditions: angina, arthritis, cancer, coronary heart disease, cognitive impairment, diabetes, hypertension, lung cancer, myocardial infarction, and stroke/transient ischemic attack. We studied the separate contributions of these conditions to health care utilization (all-cause and respiratory disease hospitalization, any emergency department [ED] visit, and six or more outpatient visits) and PCOs (seven or more days spent in bed due to illness, incident loss of mobility, and incident decline in self-perceivedhealth).Results: COPD made the largest contributions to all-cause and respiratory disease hospitalization and ED visits, while arthritis made the largest contribution to outpatient health care. Arthritis and COPD, respectively, made the greatest contributions to the PCOs.Conclusion: COPD made the largest and second largest contributions to health care utilization and PCOs among US adults with obstructive airway disease. The twelve medical conditions collectively accounted for between 52% and 61% of the health care utilization outcomes and between 53% and 68% of the PCOs. Cognitive impairment, diabetes, hypertension, and stroke also made significant contributions. Keywords: average attributable fraction, AAF, chronic obstructive pulmonary disease, COPD, patient-centered outcomes, health care utilization

Few treatment guidelines exist for multi-morbid patients. Individualized absolute risk calculators for competing patient-centred outcomes are a way to help with treatment decisions that account for patient preferences. The absolute risk of an outcome is the probability that a person receiving a given treatment will experience that outcome within a pre-defined time interval, during which they are simultaneously at risk for other competing outcomes. We developed an individualized absolute risk calculator for competing outcomes using doubly robust propensity scoring that strengthen causal inference for specific treatments. Heterogeneous treatment effects among multi-morbid patients largely depends on coexisting conditions and patient characteristics which are explanatory factors used in estimating the treatment effects. This innovative method has wide-spread application for determining individualized absolute risk calculations by presenting the probabilities of outcomes in absolute terms to help the increasing population of patients with multi-morbidity facing complex treatment decisions.

An increased resting heart rate (RHR) has long been associated with unhealthy life. Nevertheless, it remains uncertain whether time-varying measurements of RHR are predictive of mortality in older persons.The purpose of this study was to assess the relationship between repeated measurements of RHR and risk of death from all causes among older adults.We evaluated repeat measurements of resting heart rate among 5691 men and women (aged 65 years or older) enrolled in the Cardiovascular Health Study. RHR was measured annually for six consecutive years by validated electrocardiogram. All-cause mortality was confirmed by a study-wide Mortality Review Committee using reviews of obituaries, death certificates and hospital records, interviews with attending physicians, and next-of-kin.Of the study cohort, 974 (17.1%) participants died. Each 10 beat/min increment in RHR increased the risk of death by 33% (adjusted hazard ratio, 95% confidence interval (CI) = 1.33, 1.26-1.40). Similar results were observed (adjusted hazard ratio, 95% CI = 2.21, 1.88-2.59) when comparing the upper-most quartile of RHR (mean = 81 beats/min) with the lowest (mean = 53 beats/min). Compared with participants whose RHR was consistently ≤65 beats/min during the study period, the risk of death increased monotonically for each 10 beat/min (consistent) increment in RHR, with adjusted hazard ratios (95% CI) ranging from 1.30 (1.23-1.37) for 75 beats/min to 4.78 (3.49-6.52) for 125 beats/min.Elevations in the RHR over the course of six years are associated with an increased risk of all-cause mortality among older adults.

Background: Many older adults with hypertension receive multiple antihypertensives. It is unclear whether treatment with several antihypertensive classes results in greater cardiovascular benefits than fewer antihypertensive classes. Objectives: We investigated (a) the longitudinal associations between treatment with ≥ 3 versus 1-2 classes and death and major adverse cardiovascular events (MACE) and (b) whether these associations varied by the presence of mobility disability. Methods: We included 6,011 treated hypertensive adults ≥65 from the Medical Expenditure Panel Survey (MEPS), a nationally representative community sample. Times to MACE and death were compared between those receiving ≥3 versus 1-2 classes using multivariable proportional hazards regression. We used inverse probability of treatment weighting to account for indication and contraindication bias. Results: There were no significant differences in the risk of mortality (hazard ratio [HR] = 0.96, p = .769) or MACE (HR = 1.10, p = .574) between the exposure groups, and there were no significant exposure × mobility disability interactions. Discussion: We found no benefit of ≥3 versus 1-2 antihypertensive classes in reducing mortality and cardiovascular events in a representative cohort of older adults, raising concern about the added benefit of additional antihypertensives in the real world.

Objective Spirometric Z scores by lambda-mu-sigma (LMS) rigorously account for age-related changes in lung function. Recently, the Global Lung Function Initiative (GLI) expanded LMS spirometric Z scores to multiple ethnicities. Hence, in aging populations, the GLI provides an opportunity to rigorously evaluate ethnic differences in respiratory impairment, including airflow limitation and restrictive pattern. Methods Using data from the Third National Health and Nutrition Examination Survey, including participants aged 40–80, we evaluated ethnic differences in GLI-defined respiratory impairment, including prevalence and associations with mortality and respiratory symptoms. Results Among 3506 white Americans, 1860 African Americans and 1749 Mexican Americans, the prevalence of airflow limitation was 15.1% (13.9% to 16.4%), 12.4% (10.7% to 14.0%) and 8.2% (6.7% to 9.8%), and restrictive pattern was 5.6% (4.6% to 6.5%), 8.0% (6.9% to 9.0%) and 5.7% (4.5% to 6.9%), respectively. Airflow limitation was associated with mortality in white Americans, African Americans and Mexican Americans— adjusted HR (aHR) 1.66 (1.23 to 2.25), 1.60 (1.09 to 2.36) and 1.80 (1.17 to 2.76), respectively, but associated with respiratory symptoms only in white Americans—adjusted OR (aOR) 2.15 (1.70 to 2.73). Restrictive pattern was associated with mortality but only in white Americans and African Americans—aHR 2.56 (1.84 to 3.55) and 3.23 (2.06 to 5.05), and associated with respiratory symptoms but only in white Americans and Mexican Americans—aOR 2.16 (1.51 to 3.07) and 2.12 (1.45 to 3.08), respectively. Conclusions In an aging population, we found ethnic differences in GLI-defined respiratory impairment. In particular, African Americans had high rates of respiratory impairment that were associated with mortality but not respiratory symptoms.

Objectives This study sought to identify risk factors for the occurrence of all-cause hospital admissions among older persons after heart failure diagnosis, and to determine whether geriatric conditions would emerge as independent risk factors for admission when evaluated in the context of other relevant clinical data. Background Efforts to reduce costs in heart failure have focused on hospital utilization, yet few studies have examined how geriatric conditions affect the long-term risk for hospital admission after heart failure diagnosis. With the aging of the population with heart failure, geriatric conditions such as slow gait and muscle weakness are becoming increasingly common. Methods The study population included participants with a new diagnosis of heart failure in the Cardiovascular Health Study, a longitudinal study of community-living older persons. Data were collected through annual examinations and medical-record reviews. Geriatric conditions assessed were slow gait, muscle weakness (defined as weak grip), cognitive impairment, and depressive symptoms. Anderson-Gill regression modeling was used to determine the predictors of hospital admission after heart failure diagnosis. Results Of the 758 participants with a new diagnosis of heart failure, the mean rate of hospital admission was 7.9 per 10 person-years (95% CI: 7.4 to 8.4). Independent risk factors for hospital admission included diabetes mellitus (HR: 1.36; 95% CI: 1.13 to 1.64), New York Heart Association functional class III or IV (HR: 1.32; 95% CI: 1.11 to 1.57), chronic kidney disease (HR: 1.32; 95% CI: 1.14 to 1.53), slow gait (HR: 1.28; 95% CI: 1.06 to 1.55), depressed ejection fraction (HR: 1.25; 95% CI: 1.04 to 1.51), depression (HR: 1.23; 95% CI: 1.05 to 1.45), and muscle weakness (HR: 1.19; 95% CI: 1.00 to 1.42). Conclusions Geriatric conditions are important, and potentially modifiable, risk factors for hospital admission in heart failure that should be routinely assessed at the time of heart failure diagnosis.

Objectives. We decomposed the total effect of coexisting diseases on a timed occurrence of an adverse outcome into additive effects from individual diseases. Methods. In a cohort of older adults enrolled in the Precipitating Events Project in New Haven County, Connecticut, we assessed a longitudinal extension of the average attributable fraction method (LE-AAF) to estimate the additive and order-free contributions of multiple diseases to the timed occurrence of a health outcome, with right censoring, which may be useful when relationships among diseases are complex. We partitioned the contribution to death into additive LE-AAFs for multiple diseases. Results. The onset of heart failure and acute episodes of pneumonia during follow-up contributed the most to death, with the overall LE-AAFs equal to 13.0% and 12.1%, respectively. The contribution of preexisting diseases decreased over the years, with a trend of increasing contribution from new onset of diseases. Conclusions. LE-AAF can be useful for determining the additive and order-free contribution of individual time-varying diseases to a time-to-event outcome.

Background/Study Context: The objective of this study was to examine sequential and simultaneous approaches to multiple imputation of missing data in a longitudinal data set where losses due to death were common. Methods: Comparison of results from analyses and simulations of time to incident difficulty of activities of daily living (ADL) in the Cardiovascular Health Study when missing data were imputed simultaneously or sequentially. Results: Results differed with imputation methods. The largest proportional differences in 12 risk factor parameter estimates were heart failure by 106%, social support by 33%, and arthritis by 27%. Conclusion: Decedents’ final characteristics were influential on future imputations of those with missing values.

Background Among older persons, within the clinical context of respiratory symptoms and mobility, evidence suggests that improvements are warranted regarding the current approach for identifying respiratory impairment (ie, a reduction in pulmonary function). Methods Among 3583 white participants aged 65 to 80 years (Cardiovascular Health Study), we calculated the prevalence of respiratory impairment using the current spirometric standard from the Global Initiative for Obstructive Lung Disease (GOLD) and an alternative spirometric approach termed "lambda-mu-sigma" (LMS). Results for GOLD- and LMS-defined respiratory impairment were evaluated for their (cross-sectional) association with respiratory symptoms and gait speed, and for the 5-year cumulative incidence probability of mobility disability. Results The prevalence of respiratory impairment was 49.7% (1780/3583) when using the GOLD and 23.2% (831/3583) when using LMS. Differences in prevalence were most evident among participants who had no respiratory symptoms, with respiratory impairment classified more often by the GOLD (38.1% [326/855]) than LMS (12.3% [105/855]), as well as among participants who had normal gait speed, with respiratory impairment classified more often by the GOLD (46.4% [1003/2164]) than LMS (19.3% [417/2164]). Conversely, the 5-year cumulative incidence probability of mobility disability for respiratory impairment was higher for LMS than GOLD (0.313 and 0.249 for never-smokers, and 0.352 and 0.289 for ever-smokers, respectively), but was similar for normal spirometry by LMS or GOLD (0.193 and 0.185 for never-smokers, and 0.219 and 0.216 for ever-smokers, respectively). Conclusions Among older persons, the LMS approach (vs the GOLD approach) classifies respiratory impairment less frequently in those who are asymptomatic and is more strongly associated with mobility disability.

RationaleThe Global Lung Initiative (GLI) provides age-appropriate criteria for establishing spirometric impairment, including mild, moderate, and severe chronic obstructive pulmonary disease (COPD) and restrictive pattern, but its association with respiratory-related phenotypes has not been evaluated.ObjectivesTo evaluate respiratory-related phenotypes in GLI-defined spirometric impairment.MethodsIn COPDGene (N = 10,131 patients; age range, 45-81 yr; average smoking history, 44.3 pack-years), we evaluated spirometry, dyspnea (modified Medical Research Council grade, ≥2), poor respiratory health-related quality of life (St. George's Respiratory Questionnaire total score, ≥25), poor exercise performance (6-minute-walk distance, 12% and ≥200 ml), and computed tomography-diagnosed emphysema and gas trapping (>5% and >15% of lung, respectively).Measurements and main resultsGLI established normal spirometry in 5,100 patients (50.3%), mild COPD in 669 (6.6%), moderate COPD in 865 (8.5%), severe COPD in 2,522 (24.9%), and restrictive pattern in 975 (9.6%). Relative to normal spirometry, graded associations with respiratory-related phenotypes were found for mild, moderate, and severe COPD, with respective adjusted odds ratios (95% confidence intervals) as follows: dyspnea-1.31 (1.10-1.56), 2.20 (1.81-2.68), and 10.73 (8.04-14.33); poor respiratory health-related quality of life-1.49 (1.28-1.75), 2.69 (2.08-3.47), and 14.61 (10.09-21.17); poor exercise performance-1.11 (0.94-1.31), 1.58 (1.33-1.88), and 4.58 (3.42-6.12); bronchodilator reversibility-2.76 (2.24-3.40), 5.18 (4.29-6.27), and 6.21 (5.06-7.62); emphysema-4.86 (3.16-7.47), 6.41 (4.09-10.05), and 17.79 (10.79-29.32); and gas trapping-3.92 (3.12-4.93), 5.20 (3.82-7.07), and 16.28 (9.71-27.30). Restrictive pattern was also associated with multiple respiratory-related phenotypes at a level similar to moderate COPD, but it was otherwise not associated with emphysema (0.89 [0.60-1.32]) or gas trapping (1.15 [0.92-1.42]).ConclusionsGLI-defined spirometric impairment establishes clinically meaningful respiratory disease, as validated by graded associations with respiratory-related phenotypes.

Persons with multiple chronic conditions receive multiple guideline-recommended medications to improve outcomes such as mortality. Our objective was to estimate the longitudinal average attributable fraction for 3-year survival of medications for cardiovascular conditions in persons with multiple chronic conditions and to determine whether heterogeneity occurred by age.Medicare Current Beneficiary Survey participants (N = 8,578) with two or more chronic conditions, enrolled from 2005 to 2009 with follow-up through 2011, were analyzed. We calculated the longitudinal extension of the average attributable fraction for oral medications (beta blockers, renin-angiotensin system blockers, and thiazide diuretics) indicated for cardiovascular conditions (atrial fibrillation, coronary artery disease, heart failure, and hypertension), on survival adjusted for 18 participant characteristics. Models stratified by age (≤80 and80 years) were analyzed to determine heterogeneity of both cardiovascular conditions and medications.Heart failure had the greatest average attributable fraction (39%) for mortality. The fractional contributions of beta blockers, renin-angiotensin system blockers, and thiazides to improve survival were 10.4%, 9.3%, and 7.2% respectively. In age-stratified models, of these medications thiazides had a significant contribution to survival only for those aged 80 years or younger. The effects of the remaining medications were similar in both age strata.Most cardiovascular medications were attributed independently to survival. The two cardiovascular conditions contributing independently to death were heart failure and atrial fibrillation. The medication effects were similar by age except for thiazides that had a significant contribution to survival in persons younger than 80 years.

Objectives: To determine the extent to which the co-occurrence of chronic obstructive pulmonary disease (COPD) and cognitive impairment affect adverse health outcomes in older adults. Design: Multicenter longitudinal cohort study. Setting: California, Pennsylvania, Maryland, and North Carolina. Participants: Three thousand ninety-three community-dwelling adults aged 65 and older from the Cardiovascular Health Study. Four hundred thirty-one had chronic obstructive pulmonary disease (COPD) at study baseline. Measurements: Follow-up began at the second CHS visit and continued for 3 years. Spirometric criteria for airflow limitation served to establish COPD using the Lambda-Mu-Sigma method, which accounts for age-related changes in lung function. Cognitive impairment was evaluated using the modified Mini-Mental State Examination and claims data. Outcomes were respiratory-related and all-cause hospitalizations and death. Results: Participants with coexisting COPD and cognitive impairment had the highest rates of respiratory-related (adjusted hazard ratio (aHR) = 4.10, 95% confidence interval (CI) = 1.86�9.05) and all-cause hospitalizations (aHR = 1.34, 95% CI = 1.00�1.80) and death (aHR = 2.29, 95% CI = 1.18�4.45). In particular, individuals with both conditions had a 48% higher rate of all-cause hospitalizations (adjusted synergy index (aSI) = 1.48, 95% CI = 0.19�11.31) and a rate of death nearly three times as high (aSI = 2.74, 95% CI = 0.43�17.32) as the sum of risks for each respective outcome associated with having COPD or cognitive impairment alone. Nevertheless, tests for interaction were not statistically significant for the presence of synergism between the two conditions contributing to each of the outcomes. Therefore, it cannot be concluded that the combined effect of COPD and cognitive impairment is greater than additive. Conclusion: Coexisting COPD and cognitive impairment have an additive effect on respiratory-related and all-cause hospitalizations and death. Optimizing outcomes in older adults with COPD and cognitive impairment will require that how to improve concurrent management of both conditions be determined.

Objectives: To determine empirically the diseases contributing most commonly and strongly to death in older adults, accounting for coexisting diseases. Design: Longitudinal. Setting: United States. Participants: Twenty-two thousand eight hundred ninety Medicare Current Beneficiary Survey participants, a national representative sample of Medicare beneficiaries, enrolled during 2002 to 2006. Measurements: Information on chronic and acute diseases was ascertained from Medicare claims data. Diseases contributing to death during follow-up were identified empirically using regression models for all diseases with a frequency of 1% or greater and hazard ratio for death of greater than 1. The additive contributions of these diseases, adjusting for coexisting diseases, were calculated using a longitudinal extension of average attributable fraction; 95% confidence intervals were estimated from bootstrapping. Results: Fifteen diseases and acute events contributed significantly to death, together accounting for nearly 70% of death. Heart failure (20.0%), dementia (13.6%), chronic lower respiratory disease (12.4%), and pneumonia (5.3%) made the largest contributions to death. Cancer, including lung, colorectal, lymphoma, and head and neck, together contributed to 5.6% of death. Other diseases and events included acute kidney injury, stroke, septicemia, liver disease, myocardial infarction, and unintentional injuries. Conclusion: The use of methods that focus on determining a single underlying cause may lead to underestimation of the extent of the contribution of some diseases such as dementia and respiratory disease to death in older adults and overestimation of the contribution of other diseases. Current conceptualization of a single underlying cause may not account adequately for the contribution to death of coexisting diseases that older adults experience.

Calculating the longitudinal extension of the average attributable fraction (LE-AAF) for many risk factors (RFs) requires a two-stage computational process using only those combinations of RFs observed in the dataset. We first screen candidates RFs in a Cox Model, and assuming piecewise constant hazards, use pooled logistic regression to model the probability of death as a function of combinations of selected RFs. We average the iterative differencing of the attributable fractions calculated for all overlapping subsets of co-occurring RFs to obtain a LE-AAF for each RF that is additive and symmetrical. We illustrate by partitioning the additive proportions of death from 10 different groupings of acute and chronic diseases, on a national sample of older persons from the US (Medicare Beneficiary Survey) over a 4-year period and compare with results reported by the National Center for Healthcare Statistics. We conclude that careful screening of RFs with analysis restricted to extant combinations greatly reduces computational burden. LE-AAF accounted for a cumulative total of 66% of the deaths in our sample, compared with the 83% accounted for by the National Center for Healthcare Statistics.

The aim of the present study was to evaluate, among older persons, the association between respiratory impairment and hospitalisation for chronic obstructive pulmonary disease (COPD), based on spirometric Z-scores, i.e. the LMS (lambda, mu, sigma) method, and a competing risk approach. Using data on 3,563 white participants aged 65-80 yrs (from the Cardiovascular Health Study) we evaluated the association of LMS-defined respiratory impairment with the incident of COPD hospitalisation and the competing outcome of death without COPD hospitalisation, over a 5-yr period. Respiratory impairment included airflow limitation (mild, moderate or severe) and restrictive pattern. Over a 5-yr period, 276 (7.7%) participants had a COPD hospitalisation incident, whereas 296 (8.3%) died without COPD hospitalisation. The risk of COPD hospitalisation was elevated more than two-fold in LMS-defined mild and moderate airflow limitation and restrictive pattern (adjusted HR (95% CI): 2.25 (1.25-4.05), 2.54 (1.53- 4.22) and 2.65 (1.82-3.86), respectively), and more than eight-fold in LMS-defined severe airflow limitation (adjusted HR (95% CI) 8.33 (6.24-11.12)). Conversely, only LMS-defined restrictive-pattern was associated with the competing outcome of death without COPD hospitalisation (adjusted HR (95% CI) 1.68 (1.22-2.32)). In older white persons, LMS-defined respiratory impairment is strongly associated with an increased risk of COPD hospitalisation. These results support the LMS method as a basis for defining respiratory impairment in older persons.

Background Among older persons, the association between frailty and spirometry-confirmed respiratory impairment has not been evaluated yet. Methods By using data on white participants aged 65 to 80 years (Cardiovascular Health Study, N=3578), we evaluated cross-sectional and longitudinal associations between frailty and respiratory impairment, including their combined effect on mortality. Baseline assessments included frailty status (Fried phenotype: non-frail, pre-frail, and frail) and spirometry. Outcomes included development of frailty features (pre-frail or frail) at year 3 and respiratory impairment (airflow limitation or restrictive pattern) at year 4, and death (median follow-up, 13.2 years). Results At baseline, 48.3% of participants were pre-frail, 5.8% of participants were frail, 13.8% of participants had airflow limitation, and 9.3% of participants had restrictive pattern; 46.1% of participants subsequently died. At baseline, pre-frail and frail were cross-sectionally associated with airflow limitation (adjusted odds ratio [OR], 1.62; 95% confidence interval [CI], 1.29-2.04 and adjusted OR 1.88; 95% CI, 1.15-3.09) and restrictive pattern (adjusted OR, 1.80; 95% CI, 1.37-2.36 and adjusted OR, 3.05; 95% CI, 1.91-4.88), respectively. Longitudinally, participants with baseline frailty features had an increased likelihood of developing respiratory impairment (adjusted OR, 1.42; 95% CI, 1.11-1.82). Conversely, participants with baseline respiratory impairment had an increased likelihood of developing frailty features (adjusted OR, 1.58; 95% CI, 1.17-2.13). Mortality was highest among participants who were frail and had respiratory impairment (adjusted hazard ratio, 3.91; 95% CI, 2.93-5.22), compared with those who were non-frail and had no respiratory impairment. Conclusion Frailty and respiratory impairment are strongly associated with one another and substantially increase the risk of death when both are present. Establishing these associations may inform interventions designed to reverse or prevent the progression of either condition and to reduce adverse outcomes.

BACKGROUND: The lambda-mu-sigma (LMS) method calculates the lower limit of normal for spirometric values as the 5th percentile of the distribution of Z scores. Conceptually, LMS-derived Z scores account for normal age-related changes in pulmonary function, including variability and skewness in reference data. Evidence is limited, however, on whether the LMS method is valid for evaluating respiratory impairment in middle-aged persons. OBJECTIVE: To evaluate the association of LMS-defined respiratory impairment (airflow limitation and restrictive pattern) with mortality and respiratory symptoms. METHODS: We analyzed spirometric data from white participants ages 45–64 years in the Third National Health and Nutrition Examination Survey (NHANES III, n 1,569) and the Atherosclerosis Risk in Communities study (ARIC, n 8,163). RESULTS: LMS-defined airflow limitation was significantly associated with mortality (adjusted hazard ratios: NHANES III 1.90, 95% CI 1.32–2.72, ARIC 1.28, 95% CI 1.06–1.57), and respiratory symptoms (adjusted odds ratios: NHANES III 2.48, 95% CI 1.75–3.51, ARIC 2.27, 95% CI 1.98–2.62). LMS-defined restrictive-pattern was also significantly associated with mortality (adjusted hazard ratios: NHANES III 1.98, 95% CI 1.08–3.65, ARIC 1.38, 95% CI 1.03–1.85), and respiratory symptoms (adjusted odds ratios: NHANES III 2.34, 95% CI 1.44–3.80, ARIC 1.89, 95% CI 1.46–2.45). CONCLUSIONS: In white middle-age persons, LMS-defined airflow limitation and restrictive-pattern were significantly associated with mortality and respiratory symptoms. Consequently, an approach that reports spirometric values based on LMS-derived Z scores might provide an age-appropriate and clinically valid strategy for evaluating respiratory impairment. Key words: spirometry; airflow limitation; restrictive-pattern; mortality; respiratory symptoms. [Respir Care 2011;56(11):1771–1777. © 2011 Daedalus Enterprises]

OBJECTIVES: To determine the relative effect of five chronic conditions on four representative universal health outcomes. DESIGN: Cross-sectional. SETTING: Cardiovascular Health Study. PARTICIPANTS: Five thousand two hundred and ninety-eight community-living participants aged 65 and older. MEASUREMENTS: Multiple regression and Cox models were used to determine the effect of heart failure (HF), chronic obstructive pulmonary disease (COPD), osteoarthritis, depression, and cognitive impairment on self-rated health, 12 basic and instrumental activities of daily living (ADLs and IADLs), six-item symptom burden scale, and death. RESULTS: Each condition adversely affected self-rated health (P

OBJECTIVES: To determine the extent to which disease-related symptoms and impairments, which constitute measures of disease severity or targets of therapy, account for the associations between chronic diseases and universal health outcomes. DESIGN: Cross-sectional. SETTING: The Cardiovascular Health Study (CHS) and the Health, Aging and Body Composition Study (Health ABC). PARTICIPANTS: Five thousand six hundred fifty-four CHS members and 2,706 Health ABC members. MEASUREMENTS: Diseases included heart failure (HF), chronic obstructive pulmonary disease (COPD), osteoarthritis, and cognitive impairment. The universal health outcomes included self-rated health, basic and instrumental activities of daily living (ADLs and IADLs), and death. Disease-related symptoms and impairments included HF symptoms and ejection fraction (EF) for HF, Dyspnea Scale and forced expiratory volume in 1 second for COPD, joint pain for osteoarthritis, and executive function for cognitive impairment. RESULTS: The diseases were associated with the universal health outcomes (P

OBJECTIVES: To determine the relative importance of geriatric impairments (in muscle strength, physical capacity, cognition, vision, hearing, and psychological status) and chronic diseases in predicting subsequent functional disability in longitudinal analyses. DESIGN: Longitudinal data from the Cardiovascular Health Study were analyzed. Multivariable Cox hazards regression modeling was used to analyze associations between time-dependent predictors and onset of disability in activities of daily living (ADLs) and mobility. SETTING: Four communities across the United States (Sacramento County, CA; Washington County, MD; Forsyth County, NC; and Allegheny County, PA). PARTICIPANTS: Five thousand eight hundred eighty-eight elderly persons. MEASUREMENTS: Data were collected annually through in-person examinations. RESULTS: ADL disability developed in 15% of participants and mobility disability in 30%. A single multivariable model was developed that included demographics, marital status, body mass index, and number of impairments and diseases. The hazard ratios (HRs) of having one, two, and three or more geriatric impairments (vs none) for the outcome of ADL disability were 2.12 (95% confidence interval (CI)=1.63–2.75), 4.25 (95% CI=3.30–5.48), and 7.87 (95% CI=6.10–10.17), respectively, and for having one, two, and three or more chronic diseases were 1.75 (95% CI=1.41–2.19), 2.45 (95% CI=1.95–3.07), and 3.26 (95% CI=2.53–4.19), respectively. Similarly, the HRs of having one, two, and three or more impairments for the outcome of mobility disability were 1.48 (95% CI=1.27–1.73), 2.08 (95% CI=1.77–2.45), and 3.70 (95% CI=3.09–4.42), respectively, and for having one, two, and three or more diseases were 2.06 (95% CI=1.76–2.40), 2.80 (95% CI=2.36–3.31), and 4.20 (95% CI=3.44–5.14), respectively. CONCLUSION: Number of geriatric impairments was more strongly associated than number of chronic diseases with subsequent ADL disability and nearly as strongly associated with the subsequent mobility disability.

Rationale: The lambda-mu-sigma (LMS) method is a novel approach that defines the lower limit of normal (LLN) for the ratio of FEV1/FVC as the fifth percentile of the distribution of Z scores. The clinical validity of this threshold as a basis for establishing chronic obstructive pulmonary disease is unknown. Objective: To evaluate the association between the LMS method of determining the LLN for the FEV1/FVC, set at successively higher thresholds, and clinically meaningful outcomes. Methods: Using data from a nationally representative sample of 3,502 white Americans aged 40–80 years, we stratified the FEV1/FVC according to the LMS-LLN, with thresholds set at the 5th, 10th, 15th, 20th, and 25th percentiles (i.e., LMS-LLN5, LMS-LLN10, etc.). We then evaluated whether these thresholds were associated with an increased risk of death or prevalence of respiratory symptoms. Spirometry was not specifically completed after a bronchodilator. Measurements and Main Results: Relative to an FEV1/FVC greater than or equal to LMS-LLN25 (reference group), the risk of death and the odds of having respiratory symptoms were elevated only in participants who had an FEV1/FVC less than LMS-LLN5, with an adjusted hazard ratio of 1.68 (95% confidence interval, 1.34–2.12) and an adjusted odds ratio of 2.46 (95% confidence interval, 2.01–3.02), respectively, representing 13.8% of the cohort. Results were similar for persons aged 40–64 years and those aged 65–80 years. Conclusions: In white persons aged 40–80 years, an FEV1/FVC less than LMS-LLN5 identifies persons with an increased risk of death and prevalence of respiratory symptoms. These results support the use of the LMS-LLN5 threshold for establishing chronic obstructive pulmonary disease.

SummaryObjectiveTo develop a more age-appropriate spirometric definition of chronic obstructive pulmonary disease (COPD) among older persons.MethodsUsing data from the Third National Health and Nutrition Examination Survey (NHANES III), we developed a two-part spirometric definition of COPD in older persons, aged 65–80 years, that 1) determines a cut-point for the ratio of forced expiratory volume in 1s to forced vital capacity (FEV1/FVC) based on mortality risk; and 2) among persons below this critical FEV1/FVC threshold, determines cut-points for the FEV1, expressed as a standardized residual percentile (SR-tile) and based on the prevalence of respiratory symptoms and mortality risk. Measurements included spirometry, health questionnaires, and mortality (National Death Index).ResultsThere were 2480 older participants with a mean age of 71.7 years; 1372 (55.4%) had a smoking history, 1097 (44.2%) had respiratory symptoms and, over the course of 12-years, 868 (35.0%) had died. Among participants with an FEV1/FVC

OBJECTIVES: To determine the priority that older adults with coexisting hypertension and fall risk give to optimizing cardiovascular outcomes versus fall- and medication symptom-related outcomes. DESIGN: Interview. SETTING: Community. PARTICIPANTS: One hundred twenty-three cognitively intact persons aged 70 and older with hypertension and fall risk. MEASUREMENTS: Discrete choice task was used to elicit the relative importance placed on reducing the risk of three outcomes: cardiovascular events, serious fall injuries, and medication symptoms. Risk estimates with and without antihypertensive medications were obtained from the literature. Participants chose between 11 pairs of options that displayed lower risks for one or two outcomes and a higher risk for the other outcome(s), versus the reverse. Results were used to calculate relative importance scores for the three outcomes. These scores, which sum to 100, reflect the relative priority participants placed on the difference between the risk estimates of each outcome. RESULTS: Sixty-two participants (50.4%) placed greater importance on reducing risk of cardiovascular events than reducing risk of the combination of fall injuries and medication symptoms; 61 participants did the converse. A lower percentage of participants with chronic obstructive pulmonary disease (P=.02), unsteadiness (P=.02), functional dependency (P=.04), lower cognition (P=.02) and depressive symptoms (P=.03) prioritized cardiovascular outcomes over fall injuries and medication symptoms than did participants without these characteristics. CONCLUSION: Interindividual variability in the face of competing outcomes supports individualizing decision-making to individual priorities. In the current example, this may mean forgoing antihypertensive medications or compromising on blood pressure reduction for some individuals. Language: en

In patients with multiple health conditions, the treatment of one condition may worsen another one. Clinical decision-making should incorporate patients’ priorities when faced with these potentially competing health outcomes.1 The older adult with coexisting hypertension and fall risk represents a common clinical situation for which a method for eliciting patient priorities would be useful. Falls and hypertension are both major causes of disability. The 3-year incidence of all nonfatal cardiovascular events in older adults with hypertension is 16.2%,2 similar to the incidence of serious fall injury in elderly persons with fall risk.3,4 Treatment of hypertension in elderly patients decreases the risk of cardiovascular disease (CVD) outcomes.2,5–7 Although the relationship between antihypertensive medications and fall risk is complex and as yet inadequately studied, most studies adjusting for appropriate confounders have reported a greater risk of falls, fall injuries, or fall risk factors with antihypertensive medications. Conversely, the risk of falls may be decreased if medications are reduced.8 Cardiovascular medications, including antihypertensives, are the drugs most commonly implicated in medication-related symptoms and adverse effects.9 Furthermore, falling and fall risk factors such as postural unsteadiness, weakness, dizziness, and postural hypotension are among the most common adverse effects of medications, including antihypertensive medications.10,11 The co-occurrence of hypertension and fall risk, therefore, can serve as a model for studying health priorities in the face of potentially competing health conditions, although eliciting priorities raises concerns about well-known challenges, including reluctance to articulate feelings about outcomes not yet experienced, the tendency to select all outcomes as equally important, and change in priorities with time and changing health status.12,13 Limited health literacy, the effects of framing and ordering, and inadequate numeracy and communication skills of patients and clinicians further complicate efforts to elicit patient priorities and preferences reliably.14–16 If, as precepts of patient-centered care espouse, clinical decision-making is to incorporate patients’ priorities and individualize therapy to meet these priorities,1 then an approach must be found that addresses these challenges. Conjoint analysis,17 which elicits priorities by asking respondents to make explicit tradeoffs between competing outcomes, is one possible approach that has been applied in several health-related areas. Conjoint analysis has been used successfully in older individuals with visual deficits, limited education, and lack of computer experience.18–20 The aim of the present study was to describe the development and testing of a choice-based conjoint analysis task designed to elicit older individuals’ priorities in the face of competing CVD outcomes, medication-related symptoms, and fall injuries.

BACKGROUND. It is unclear how noncancer conditions affect the use or effectiveness of adjuvant therapy among older patients with colon cancer. METHODS. The authors conducted a cohort study of older patients with stage III colon cancer who were diagnosed from 1993 to 1999 in the Surveillance, Epidemiology, and End Results-Medicare database. The correlations between receipt of adjuvant chemotherapy and heart failure, diabetes, and chronic obstructive pulmonary disease (COPD) were assessed. Multivariable regression analysis was used to assess the risk of death and hospitalization as a function of treatment and comorbidity status. RESULTS. The study sample consisted of 5330 patients (median age, 76 years). The use of adjuvant therapy was related significantly to heart failure (36.2% vs 64.9% of patients with vs without heart failure, respectively; adjusted odds ratio [OR], 0.49; 95% confidence interval [95% CI], 0.40–0.60). More moderate correlations were observed for COPD (OR, 0.83; 95% CI, 0.70–0.99) and diabetes (OR, 0.81; 95% CI, 0.68–0.97). Among patients who had heart failure, the 5-year survival was significantly higher among those who received adjuvant chemotherapy (adjusted 5-year survival rate, 43%; 95% CI, 40–47%) than among those who did not receive adjuvant chemotherapy (30%; 95% CI, 27–34%). Among patients without heart failure, the 5-year survival estimates among treated and untreated patients were 54% (95% CI, 52–56%) and 41% (95% CI, 38–44%), respectively. The probability of all-cause, condition-specific, or toxicity-related hospitalization associated with adjuvant therapy was not altered by the presence of any of the 3 conditions. CONCLUSIONS. Although chronic conditions appeared to be a strong barrier to the receipt of adjuvant chemotherapy, adjuvant therapy appeared to provide a significant survival benefit to patients who had colon cancer with the conditions studied. Cancer 2007. © 2007 American Cancer Society.

OBJECTIVES: To determine whether specific subsets of symptoms from the Geriatric Depression Scale (GDS), assessed at hospital admission, were associated with the incidence of delirium. DESIGN: Secondary analysis of a prospective cohort study of patients from the Delirium Prevention Trial. SETTING: General medicine service at Yale New Haven Hospital, March 25, 1995, through March 18, 1998. PARTICIPANTS: Four hundred sixteen patients aged 70 and older who were at intermediate or high risk for delirium and were not taking antidepressants at hospital admission. MEASUREMENTS: Depressive symptoms were assessed GDS, and daily assessments of delirium were obtained using the Confusion Assessment Method. RESULTS: Of the 416 patients in the analysis sample, 36 (8.6%) developed delirium within the first 5 days of hospitalization. Patients who developed delirium reported 5.7 depressive symptoms on average, whereas patients without delirium reported an average of 4.2 symptoms. Using a Cox proportional hazards model, it was found that depressive symptoms assessing dysphoric mood and hopelessness were predictive of incident delirium, controlling for measures of physical and mental health. In contrast, symptoms of withdrawal, apathy, and vigor were not significantly associated with delirium. CONCLUSION: These findings suggest that assessing symptoms of dysphoric mood and hopelessness could help identify patients at risk for incident delirium. Future studies should evaluate whether nonpharmacological treatment for these symptoms reduces the risk of delirium.