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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-LLN(5), 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. [ABSTRACT FROM AUTHOR]

Rationale: Delirium is a frequent occurrence in older intensive care unit (ICU) patients, but the importance of the duration of delirium in contributing to adverse long-term outcomes is unclear.Objectives: To examine the association of the number of days of ICU delirium with mortality in an older patient population.Methods: We performed a prospective cohort study in a 14-bed ICU in an urban acute care hospital. The patient population comprised 304 consecutive admissions 60 years of age and older.Measurements and Main Results: The main outcome was 1-year mortality after ICU admission. Patients were assessed daily for delirium with the Confusion Assessment Method for the ICU and a validated chart review method. The median duration of ICU delirium was 3 days (range, 1-46 d). During the follow-up period, 153 (50%) patients died. After adjusting for relevant covariates, including age, severity of illness, comorbid conditions, psychoactive medication use, and baseline cognitive and functional status, the number of days of ICU delirium was significantly associated with time to death within 1 year post-ICU admission (hazard ratio, 1.10; 95% confidence interval, 1.02-1.18).Conclusions: Number of days of ICU delirium was associated with higher 1-year mortality after adjustment for relevant covariates in an older ICU population. Investigations should be undertaken to reduce the number of days of ICU delirium and to study the impact of this reduction on important health outcomes, including mortality and functional and cognitive status. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To evaluate the association between sleep-- wake disturbances and frailty. DESIGN: Cross-sectional. SETTING: New Haven, Connecticut. PARTICIPANTS: Three hundred seventy-four community- living persons aged 78 and older. MEASUREMENTS: Frailty was based on the Fried phenotype, and sleep--wake disturbances were defined as daytime drowsiness, based on an Epworth Sleepiness Scale (ESS) score of 10 or greater, and as subthreshold and clinical insomnia, based on Insomnia Severity Index (ISI) scores of 8 to 14 and greater than 14, respectively. RESULTS: Mean age was 84.3; 87 (23.8%) participants were drowsy, 122 (32.8%) had subthreshold insomnia, 38 (10.2%) had clinical insomnia, and 154 (41.2%) were frail. There was a significant association between drowsiness and frailty, with unadjusted and adjusted odds ratios (ORs) of 3.79 (95% confidence interval (CI)=2.29--6.29) and 3.67 (95% CI=2.03--6.61), respectively. In contrast, clinical insomnia was significantly associated with frailty in the unadjusted analysis (OR=2.77, 95% CI=1.36--5.67) but not the adjusted analysis (OR=1.93, 95%CI=0.81--4.61)), and subthreshold insomnia was not associated with frailty in the unadjusted or adjusted analysis. CONCLUSION: In older persons, sleep--wake disturbances that present with daytime drowsiness, but not insomnia, are independently associated with frailty. Because drowsiness is potentially remediable, future studies should determine whether there is a temporal relationship between drowsiness and frailty, with the ultimate goal of informing interventions to reverse or prevent the progression of frailty. [ABSTRACT FROM AUTHOR]

Objective: A quantitative framework to assess harms and benefits of candidate medications in the context of drugs that a patient is already taking is proposed. Method: Probabilities of harms and benefits of a given medication are averaged to yield a utility value. The utility values of all medications under consideration are combined as a geometric mean to yield an overall measure of favorability. The grouping of medications yielding the highest favorability value is chosen. Results: Five examples of choosing between widely used candidate medications demonstrate the feasibility of the proposed framework. Discussion: The framework proposed provides a simple method for considering the trade-offs involved in prescribing multiple medications. It can be adapted to include additional parameters representing severity of condition, prioritization of outcomes, patient preferences, dosages, and medication interactions. Inconsistent reporting in the medical literature of data about benefits and harms of medications, dosages, and interactions constitutes its primary limitation. [ABSTRACT FROM AUTHOR]

Objective: The authors recommend confidence intervals as measures of precision for reliability coefficients, regression modeling as supplements for such omnibus reliability statistics, and unreliability detection as a goal of reliability testing distinct from reliability inference. Methods: Illustrative reliability analyses are conducted on measures selected from a study of clinical features associated with urinary tract infection in older nursing home residents. Results: Standard methods for reliability testing (e.g., kappa coefficients) are often inappropriate for small samples, and exact methods or descriptive reliability statistics are viable alternatives. Discussion: Supplementation of omnibus statistics by loglinear regression modeling is especially appropriate for aging research because it facilitates tests of marginal homogeneity and comparisons of reliability results for relatively young and old subgroups. Latent class regression analysis is useful for older samples because multifactorial health conditions are often measured in multiple ways and assessment of their reliability can be integrated, granting certain assumptions, with validity assessment. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The study investigated whether any of four measures of religiousness predicted longer survival for 145 African-American and 177 White women diagnosed with breast cancer in Connecticut between January 1987 and March 1989. METHOD: Multivariate Cox proportional hazards models included a religious predictor and sociodemographic, biomedical, treatment, behavioral, and medical care covariables. RESULTS: The no denomination group had a hazard ratio (HR) of 4.39 (95% Confidence Interval (CI) = 1.42, 13.64). Other measures of religiousness did not yield statistically significant results but showed a consistent pattern of nonreligiousness being more strongly and negatively related to breast cancer survival in African Americans than in Whites. CONCLUSIONS: Exploratory models confirmed that lack of religiousness was associated in this sample with poor breast cancer survival among African American women. [ABSTRACT FROM AUTHOR]

OBJECTIVES: This study examines whether attendance at religious services has an inverse association with cognitive dysfunction in an elderly cohort in whom it has already been shown that religious attendance has an inverse association with physical disability and that social engagement has an inverse association with cognitive decline. METHODS: The study population is a racially and religiously diverse sample of 2,812 community-dwelling men and women from New Haven, Connecticut; it was representative of New Haven in 1982, but not of the United States then or now. The primary study hypothesis proposes that attendance at religious services as measured in 1982 contributes to the prediction of lower levels of cognitive dysfunction in 1985 and 1988. A multivariate logistic regression analysis controlling for seven sociodemographic, four behavioral, and seven biomedical covariables is conducted. RESULTS: Study results show an inverse association between religious attendance in 1982 and cognitive dysfunction in 1985 (odds ratio = 0.64; 95% confidence interval = 0.49, 0.85). Religious attendance as measured in 1982 no longer contributes to the prediction of cognitive dysfunction in 1988. DISCUSSION: The short-term nature of the effect is partially explained by differential mortality. Persons with infrequent religious service attendance and with high levels of cognitive dysfunction in 1982 were more likely to die in the period from 1985 to 1988. [ABSTRACT FROM AUTHOR]

Background Meditation health benefits have been difficult to document, as many efficacy studies are marred by lack of statistical power secondary to small sample size and/or threats to validity from high attrition. To date, no published studies have examined barriers to meditation that are likely responsible for low enrollment and high attrition. Objective To develop an instrument to capture barriers to meditation use, namely, the Determinants of Meditation Practice Inventory (DMPI). Design A five-step, mixed-methods approach was used, including literature review, qualitative interviews, content validation, reliability testing, and construct validation. Participants/Setting Four distinct participant groups contributed. Four meditation teachers participated in qualitative interviews. Five expert panelists conducted the content validation. Ten nonmeditators participated in the pilot test. For reliability testing and construct validation, 150 cancer family caregivers participated. Outcome Measures Big Five Inventory (BFI) and Caregiver Reactions Assessment (CRA) were used to test convergent construct validity. Results The three content domains are perceptions and misconceptions, pragmatic concerns, and sociocultural beliefs. Initially, 53 items were generated. Three reviews by the expert panel concluded with a 22-item survey. After pilot testing, a 17-item survey was created. Data from 150 caregivers showed Cronbach's coefficient alpha of 0.87. The intraclass correlation for baseline and retest was 0.86 (confidence interval 0.82-0.90). BFI and CRA were significantly and positively correlated with DMPI. Conclusion Preliminary results indicate the DMPI is psychometrically sound. By identifying barriers to meditation, the DMPI will enable researchers to address the needs and concerns of the target population when designing recruitment and intervention procedures, potentially maximizing recruitment, minimizing attrition, and optimizing interpretation of results. [ABSTRACT FROM AUTHOR]

Background: Commonly used thresholds for staging FEV 1 have not been evaluated as standalone spirometric predictors of death in older persons. Specifically, the proportion of deaths attributed to a reduced FEV 1 , 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, FEV 1 was stratified as stage 1 (FEV 1 ≥ 2.00 L, ≥80% pred, and Z score ≥-1.64), stage 2 (FEV 1 1.50-1.99 L, 50-79%pred, and Z score -2.55 to -1.63), and stage 3 (FEV 1 < 1.50 L, < 50% pred, and Z score < -2.55). Notably, a Z score threshold of -1.64 defines normal-for-age lung function as the lower limit of normal (ie, 5th percentile of distribution), and accounts for differences in age, sex, height, and ethnicity. Next, adjusted odds ratios and average attributable fractions for 10-y all-cause mortality were calculated, comparing FEV 1 stages 2 and 3 against stage 1, expressed in L, % pred, and Z scores. The average attributable fraction estimates the proportion of deaths attributed to a predictor by combining the prevalence of the predictor with the relative risk of death conferred by that predictor., Results: FEV 1 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, FEV 1 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 FEV 1 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 FEV 1 stage., (Copyright © 2020 by Daedalus Enterprises.)

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

Objective: Little is known about the cardiovascular effects of mutual emotional spousal support given for health concerns. We examined the hypotheses that: (a) mutual support (both spouses giving and receiving support) compared to one-sided or no support, would decrease blood pressure and heart rate in both spouses during a recovery period; and (b) wives would benefit more from mutual support than would husbands. A second aim was to examine gender differences in cardiovascular reactivity, distress, and closeness in response to receiving support regardless of mutuality., Method: In 98 married couples (Age 50+), spouses discussed health concerns and were assigned randomly to one of four conditions: neither spouse received support (n = 26), only the wife received support from the husband (n = 22), only the husband received support from the wife (n = 23), or both received support (n = 27). Systolic and diastolic blood pressure and heart rate were measured during baseline, the discussions, and recovery. Distress, closeness, and support were self-reported. Support quality was observationally coded., Results: Mutual support did not affect cardiovascular reactivity. When husbands received support from wives, husbands' blood pressure and distress decreased, and both partners' closeness increased. When wives received support, husbands and wives felt closer, but both partners' heart rate remained elevated and wives felt more distressed., Conclusions: Receiving support individually may be more important than receiving support mutually for older adult spouses coping with their health concerns. Also, support interventions for couples coping with health conditions should take into account that husbands receive greater benefits from spousal support than wives. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Background and Objectives: To assess whether medically supportive care partners modify the associations of symptomatic chronic conditions with the number of functional disabilities in a cohort of multimorbid older adults with cognitive impairment., Research Design and Methods: The research design is a prospective study of a nationally representative cohort of Medicare beneficiaries. National Health and Aging Trends Study (NHATS) data were linked with Medicare claims for years 2011-2015. Participants were aged 65 or older and had cognitive impairment with at least 2 chronic conditions ( N = 1,003). Annual in-person interviews obtained sociodemographic information at baseline and time-varying variables for caregiving, hospitalization, and 6 activities of daily living (ADL); these variables were merged with Center for Medicare and Medicaid Services data to ascertain 16 time-varying chronic conditions. A care partner was defined as a person who sat with their care recipient during doctor visits in the past year and/or who helped them with prescribed medications in the last month. Chronic condition associations and their potential effect modifications by care partner status were assessed using weighted generalized estimating equations accounting for the complex survey design of the longitudinal analytical sample., Results: Chronic kidney disease, depression, and heart failure were associated with an increased number of functional disabilities. Among these, only the association of chronic kidney disease with the number of functional disabilities (interaction p value = .001) was weakened by the presence of a care partner., Discussion and Implications: The presence of care partners showed limited modification of the associations of symptomatic chronic conditions with functional disability.

Background: Polypharmacy and potentially inappropriate medications (PIMs) are increasingly common and associated with adverse health effects. However, post-graduate education in polypharmacy and complex medication management for older adults remain limited., Objective: The Initiative to Minimize Pharmaceutical Risk in Older Veterans (IMPROVE) polypharmacy clinic was created to provide a platform for teaching internal medicine (IM) and nurse practitioner (NP) residents about outpatient medication management and deprescribing for older adults. We aimed to assess residents' knowledge of polypharmacy and perceptions of this interprofessional education intervention., Design: A prospective cohort study with an internal comparison group., Participants: IM residents and NP residents; Veterans ≥ 65 years and taking ≥ 10 medications., Intervention: IMPROVE consists of a pre-clinic conference, shared medical appointment, individual appointment, and interprofessional precepting model., Main Measures: We assessed residents' performance on a pre-post knowledge test, residents' qualitative assessment of the educational impact of IMPROVE, and the number and type of medications discontinued or decreased., Key Results: The IMPROVE intervention group (n = 18) had a significantly greater improvement in test scores than the control group (n = 18) (14% ± 15% versus - 1.3% ± 16%) over a period of 6 months (Wilcoxon rank sum, p = 0.019). In focus groups, residents (n = 17) reported perceived improvements in knowledge and skills, noting that the experience changed their practice in other clinical settings. In addition, residents valued the unique interprofessional experience. Veterans (n = 71) had a median of 15 medications (IQR 12-19), and a median of 2 medications (IQR 1-3) was discontinued. Vitamins, supplements, and cardiovascular medications were the most commonly discontinued medications, and cardiovascular medications were the most commonly decreased in dose or frequency., Conclusions: Overall, IMPROVE is an effective model of post-graduate primary care training in complex medication management and deprescribing that improves residents' knowledge and skills, and is perceived by residents to influence their practice outside the program.

Objective. To develop a brief instrument for academic pharmacists or physicians to use in assessing postgraduate residents' knowledge of polypharmacy. Methods. Five clinicians used a modified Delphi process to create a 26-item multiple-choice test to assess knowledge of polypharmacy in geriatric primary care. The test was distributed to 74 participants: 37 internal medicine (MD) residents, six nurse practitioner (NP) residents, nine primary care attendings, 12 pharmacists and pharmacy residents, and 10 geriatrics attendings and fellows. Construct validity was assessed using factor analysis and item response theory. Overall group differences were examined using a Kruskal-Wallis test, and between group differences were assessed using the Wilcoxon rank sum test. Results. The response rate for the survey was 89%. Factor analysis resulted in a one factor solution. Item response theory modeling yielded a 12-item and six-item test. For the 12-item test, the mean scores of geriatricians and pharmacists (88%) were higher than those of MD and NP residents (58%) and primary care attendings (61%). No differences were found between MD and NP residents and primary care attendings. Findings for the six-item test were similar. Conclusion. Both the 12-item and six-item versions of this polypharmacy test showed acceptable internal consistency and known groups validity and could be used in other academic settings. The similar scores between MD and NP residents and primary care attendings, which were significantly lower than scores for pharmacists and geriatricians, support the need for increased educational interventions.

Both aging and HIV infection are associated with an enhanced pro-inflammatory environment that contributes to impaired immune responses and is mediated in part by innate immune pattern-recognition receptors. MINCLE is a C-type lectin receptor that recognizes trehalose-6,6'-dimycolate or "cord factor," the most abundant glycolipid in Mycobacterium tuberculosis. Here, we evaluated MINCLE function in monocytes in a cohort of HIV-infected and uninfected young (21-35 years) and older adults (≥60 years) via stimulation of peripheral blood mononuclear cells with trehalose-6,6-dibehenate, a synthetic analog of trehalose-6,6'-dimycolate and measurement of cytokine production (interleukin [IL]-10, IL-12, IL-6, tumor necrosis factor-α) by multicolor flow cytometry. Our studies show an age- and HIV-associated increase in cytokine multifunctionality of monocytes both at the population and single cell level that was dominated by IL-12, IL-10, and IL-6. These findings provide insight into the host response to M. tuberculosis and possible sources for the pro-inflammatory environment seen in aging and HIV infection., (© The Author(s) 2018. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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

Rationale: Psychiatric conditions are often falsely considered inherent to aging. We examined whether negative age stereotypes, which older individuals tend to assimilate from the environment across their lifespan, contributed to an increased risk of developing four psychiatric conditions, and, if so, whether this risk was reduced through active coping., Method: The sample consisted of participants aged 55 years and older, free of the psychiatric conditions at baseline, drawn from the National Health and Resilience in Veterans Study, a nationally representative sample. New cases of posttraumatic stress disorder, suicidal ideation, generalized anxiety disorder, and major depressive disorder were assessed during three waves spanning a four-year period., Results: As predicted, participants holding more-negative age stereotypes were more likely to develop the psychiatric conditions, and their engagement in active coping reduced the risk of their developing these conditions., Conclusion: Our findings suggest that prevention and treatment efforts designed to reduce psychiatric conditions in later life may benefit from bolstering active coping as well as positive age stereotypes., (Copyright © 2019. Published by Elsevier Ltd.)

Introduction: Older minority individuals are less likely to receive adequate health care than their white counterparts. This study investigates whether perceived racism is associated with delayed/forgone care among minority older adults, and whether poor doctor communication mediates this relationship., Methods: Study cohort consisted of minority participants, aged ≥65 years, in the 2015 California Health Interview Survey (N=1,756). Authors obtained data in November 2017, and statistical analyses were performed from February to April 2018. Multivariable logistic regression analyses were conducted with relevant covariates, including insurance coverage, years living in the U.S., and language. A mediation analysis was also performed., Results: Among minority older individuals, perceived racism was significantly associated with delayed/forgone care (AOR=3.92, 95% CI=1.38, 11.15, p=0.010). Poor doctor communication significantly and partially mediated the relationship (AOR=3.64, 95% CI=1.30, 10.21, p=0.014), accounting for 9.9% of the total effect., Conclusions: Perceived racism may contribute to health disparities for older minority individuals in part through doctors communicating messages that discourage adequate utilization of health care. Future research should explore culturally sensitive communication skills that reduce this barrier to receiving adequate health care., (Copyright © 2018 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.)

Objectives: To examine factors associated with caregiver burden from a multifactorial perspective by examining caregiver and care recipient characteristics and a full range of caregiving tasks., Design: Nationally representative surveys of community-dwelling older adults and their family caregivers residing in the United States., Setting: 2011 National Health and Aging Trends Study and National Study of Caregiving., Participants: Community-dwelling older adults and their family caregivers., Measurements: Caregiver burden, comprising emotional, physical, and financial difficulties associated with caregiving., Results: An estimated 14.9 million caregivers assisted 7.6 million care recipients. More than half of caregivers reported burden related to caregiving. In a multivariable regression model, caregivers who assisted with more activities of daily living and instrumental activities of daily living, health management tasks, and health system logistics were more likely to experience burden, as were female caregivers, adult child caregivers, caregivers in poor health, caregivers with anxiety symptoms, and those using respite care. Dementia was the only care recipient characteristic associated with burden., Conclusion: Caregiver characteristics and provision of caregiving tasks determine caregiver burden more than care recipient characteristics. Absence of an association between type of a care recipient's chronic conditions and burden, except for dementia, suggests that the tasks that caregivers who assist older adults with a variety of health conditions undertake shape the experience of caregiving. J Am Geriatr Soc 67:277-283, 2019., (© 2018, Copyright the Author Journal compilation © 2018, The American Geriatrics Society.)

Purpose: Critically ill patients experience significant sleep disruption. In this study of ICU patients with delirium, we evaluated associations between the loss of stage N2 features (K-complexes, sleep spindles), grade of encephalopathy based on electroencephalography (EEG), and intensive care unit (ICU) outcomes. We hypothesized that loss of stage N2 features is associated with more severe grades of encephalopathy and worse ICU outcomes including death., Materials and Methods: This was an observational cohort study of 93 medical ICU patients without primary acute brain injury who underwent continuous EEG. Type and severity of critical illness, sedative-hypnotic use, length of stay, modified Rankin Scale at hospital discharge, and death during hospitalization were abstracted from the medical record. EEG was evaluated for grade of encephalopathy and sleep features., Results: Patients without K-complexes or without sleep spindles had more severe encephalopathy and higher odds of death. The odds ratio for patients without K-complexes was 18.8 (p = .046). The odds ratio for patients without sleep spindles was 6.3 (p = .036)., Conclusions: Loss of stage N2 features is common and associated with more severe encephalopathy and higher odds of death. The absence of either Stage N2 feature, K complexes or sleep spindles, may have important prognostic value., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: To examine the bidirectional associations between older adult spouses' cognitive functioning and depressive symptoms over time., Design: Longitudinal, dyadic path analysis with the actor-partner interdependence model., Setting: Data were from visit 5 (1992/1993), visit 8 (1995/1996), and visit 11 (1998/1999) of the Cardiovascular Health Study, a multisite, longitudinal, observational study of risk factors for cardiovascular disease in adults 65 years or older. Demographic information was from the 1989/1990 original and 1992/1993 African American cohort baseline visits., Participants: Husbands and wives from 1,028 community-dwelling married couples (N = 2,065)., Measurements: Cognitive functioning was measured with the Modified Mini-Mental State Exam. Depressive symptoms were measured using the 10-item Center for Epidemiologic Studies Depression Scale. Age, education, and disability (activities of daily living and instrumental activities of daily living) were included as covariates., Results: Cross-partner associations (partner effects) revealed that one spouse's greater depressive symptoms predicted the other spouse's lower cognitive functioning, but a spouse's lower cognitive functioning did not predict the other spouse's greater depressive symptoms over time. Within-individual associations (actor effects) revealed that an individual's lower cognitive functioning predicted the individual's greater depressive symptoms over time, but greater depressive symptoms did not predict lower cognitive functioning over time. Effects did not differ for husbands and wives., Conclusion: Having a spouse who is depressed may increase one's risk of cognitive decline as well as one's risk of depression. Interventions for preventing cognitive decline and depression among older adults may be enhanced by considering the marital context., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

This study evaluated the effect of the alpha-2A-adrenoceptor agonist guanfacine on prefrontally mediated cognitive functions, as well as quality of life and global function in healthy older participants. One hundred twenty-three participants aged 75 years and older were randomly assigned to guanfacine 0.5 mg, 0.1 mg, or placebo daily for 12 weeks. The primary outcome measure was the change in z-score for 6 prefrontal executive function tasks over 12 weeks (PEF6). Neither dose of guanfacine improved PEF6 z-score relative to placebo. The rate of mean change (95% confidence interval) in PEF6 z-score over 12 weeks was 0.270 (0.159, 0.380) for placebo, compared with 0.121 (0.011, 0.232) for guanfacine 0.1 mg (p = 0.06, compared to placebo) and 0.213 (0.101, 0.324) for 0.5 mg (p = 0.47). Neither dose of guanfacine improved the quality of life or global function relative to placebo. Among common adverse events, only dry mouth was significantly more frequent on guanfacine compared to placebo. Guanfacine failed to ameliorate prefrontal cognitive function in older individuals, who were cognitively normal for age., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: To explore patient and caregiver experiences, preferences, and attitudes toward the provision and receipt of caregiving assistance with medical tasks., Design: Qualitative study consisting of in-depth interviews with 20 patient-caregiver dyads., Setting: Community and academic-affiliated primary care clinics., Participants: Individuals aged 65 or older with 2 or more health conditions and their family caregivers (n=20 patient-caregiver dyads)., Measurements: Open-ended questions were asked about the tasks that the patient and caregiver performed to manage the patient's health conditions; questions were designed to elicit participant reactions and attitudes toward the help they provided or received. Transcripts were analyzed using the constant comparative method., Results: Participant preferences and attitudes toward the receipt and provision of disease management tasks were highly personal. Participant responses clustered into 2 caregiving typologies: supportive caregiving relationships and conflicted caregiving relationships. Supportive relationships were characterized by patient-caregiver agreement about caregiver level of involvement, agreement about one another's competency to perform disease-related tasks, mutual understanding, collaborative decision-making and disease management, and use of family and formal caregiving. Conflicted relationships were characterized by disagreement about caregiver level of involvement, disagreement about one another's competency to perform disease management tasks, underappreciation of one another's experiences, disagreement over decision-making and disease management, and use of formal caregiving., Conclusions: The views that patient-caregiver dyads expressed in this study illustrate the varied preferences and attitudes toward caregiving assistance with multiple health conditions. These findings support a dyadic approach to evaluating and addressing patient and caregiver needs and attitudes toward provision of assistance., (© 2018, Copyright the Author Journal compilation © 2018, The American Geriatrics Society.)

Objective: To evaluate the epidemiology of insomnia, including demographic and clinical correlates, in older adults., Design: Cross-sectional., Setting: Community., Participants: Yale Precipitating Events Project participants (N=379; mean age 84.3; 67.8% female; 11.9% African American)., Measurements: Insomnia Severity Index (ISI), with scores of 8 and higher indicating insomnia, which was further stratified according to ISI score as mild (8-14), moderate (15-21), or severe (22-28). Baseline characteristics included age, sex, race, education, smoking, obesity, medical conditions, depressive symptoms (Center for Epidemiologic Studies Depression score ≥16), cognitive impairment (Mini-Mental State Examination score <24), restless legs syndrome (RLS), self-reported sleep-disordered breathing (SDB), medications, and daytime sleepiness (Epworth Sleepiness Scale (ESS), range 0-24)., Results: Insomnia was established in 163 (43.0%) participants (average ISI score 12.3 (mild)). For the entire sample, average baseline characteristics were as follows: 30.1% did not complete high school, 5% were current smokers, 19.2% were obese, 28.2% had cardiovascular disease, 19.3% had chronic lung disease, 27.2% had depressive symptoms, 16.1% had cognitive impairment, 36.8% had RLS, and 3.4% had self-reported SDB; mean number of medications was 9.2, and mean ESS was 6.4. In multivariable regression models, only depressive symptoms (adjusted odds ratio (aOR)=8.34, 95% confidence interval (CI)=4.49, 15.47) and RLS (aOR=2.49, 95% CI=1.48, 4.21) were significantly associated with insomnia., Conclusion: In a sample of older adults with high medical burden and polypharmacy, insomnia was highly prevalent but unexpectedly mild and associated only with depressive symptoms and RLS. The discordance of high prevalence but mild severity of insomnia in the oldest adults highlights the need for diagnostic confirmation with objective measures of sleep disturbances, whereas the strong associations with depressive symptoms and RLS inform priorities in managing insomnia., (© 2018, Copyright the Authors Journal compilation © 2018, The American Geriatrics Society.)

Objectives: To examine patterns and perceived benefits of seven major complementary health approaches (CHA) among older adults in the United States., Methods: Data from the 2012 National Health Interview Survey (NHIS), which represents non-institutionalized adults aged 65 or older (n = 7,116 unweighted), were used. We elicited seven most common CHA used in older adults, which are acupuncture, herbal therapies, chiropractic, massage, meditation, Tai Chi, and yoga. Survey participants were asked to self-report perceived benefits (eg, maintaining health and stress reduction) in their CHA used. We estimated prevalence and perceived benefits of CHA use. We also investigated socio-demographic and clinical factors associated with the use of any of these seven CHA., Results: Overall, 29.2% of older adults used any of seven CHA in the past year. Most commonly used CHA included herbal therapies (18.1%), chiropractic (8.4%), and massage (5.7%). More than 60% of older CHA users reported that CHA were important for maintaining health and well-being. Other perceived benefits included improving overall health and feeling better (52.3%), giving a better sense of control over health (27.4%), and making it easier to cope with health problems (24.7%). Older adults with higher education and income levels, ≥2 chronic conditions, and functional limitations had greater odds of using CHA (p < .01, respectively)., Conclusion: A substantial number of older CHA users reported CHA-related benefits. CHA may play a crucial role in improving health status among older adults. At the population level, further research on the effects of CHA use on bio-psycho-social outcomes is needed to promote healthy aging in older adults.

Objective: To ascertain perspectives of multiple stakeholders on contributors to inappropriate care for older adults with multiple chronic conditions., Method: Perspectives of 36 purposively sampled patients, clinicians, health systems, and payers were elicited. Data analysis followed a constant comparative method., Results: Structural factors triggering burden and fragmentation include disease-based quality metrics and need to interact with multiple clinicians. The key cultural barrier identified is the assumption that "physicians know best." Inappropriate decision making may result from inattention to trade-offs and adherence to multiple disease guidelines. Stakeholders recommended changes in culture, structure, and decision making. Care options and quality metrics should reflect a focus on patients' priorities. Clinician-patient partnerships should reflect patients knowing their health goals and clinicians knowing how to achieve them. Access to specialty expertise should not require visits., Discussion: Stakeholders' recommendations suggest health care redesigns that incorporate patients' health priorities into care decisions and realign relationships across patients and clinicians.

Suspected urinary tract infection is a common indication for antimicrobial therapy in long-term care residents. We sought to characterize antimicrobial susceptibilities among urine isolates collected from women long-term care residents enrolled in a clinical trial across 21 long-term care facilities in Connecticut, United States of America between August 2012 and October 2015. Among 967 urine cultures collected from 175 women long-term care residents with and without suspected urinary tract infection, we identified 456 bacterial isolates. Escherichia coli (55.3%), Klebsiella (13.8%) and Enterococcus (8.3%) species were the predominant organisms identified. Among all 456 urine isolates, 68.1% were ciprofloxacin-susceptible, 77.2% were trimethoprim/sulfamethoxazole-susceptible, 86.3% were cefazolin-susceptible, and 72.6% were nitrofurantoin-susceptible. Among 252 Escherichia coli urine isolates, 60.2% were ciprofloxacin-susceptible, 73.7% were trimethoprim/ sulfamethoxazole-susceptible, 84.5% were cefazolin-susceptible, and 86.5% were nitrofurantoin-susceptible. These findings suggest that trimethoprim/sulfamethoxazole may be favorable empiric therapy while the urinary isolate is unknown, and nitrofurantoin may be optimal therapy for uncomplicated urinary tract infection due to Escherichia coli in women long-term care residents.

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., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Clinical trials of pharmacotherapy in chronic obstructive pulmonary disease (COPD) often include older persons with moderate-to-severe airflow-obstruction, as defined by the Global Initiative for chronic Obstructive Lung Disease (GOLD). In this context, spirometric airflow-obstruction establishes COPD. Because GOLD misidentifies COPD and its severity in older persons, we set out to apply more age-appropriate spirometric criteria from the Global Lung function Initiative (GLI) in a prior clinical trial of COPD pharmacotherapy, specifically the Towards a Revolution in COPD Health (TORCH) trial - N = 6,112, mean age 65 years. In the TORCH trial, which enrolled GOLD-defined moderate COPD (26.2%, n = 1,200) and GOLD-defined severe COPD (73.8%, n = 4,511), the GLI reclassification yielded a higher frequency of severe COPD (89.6%, n = 5,474), the inclusion of restrictive-pattern (6.9%, n = 420) and, in turn, a very low frequency of moderate COPD (3.5%, n = 212). These GLI reclassification results suggest that GOLD-based enrollment criteria for the TORCH trial may have assembled a cohort that was: 1) less likely to respond to COPD pharmacotherapy, given the greater representation of severe COPD, very minor representation of moderate COPD, and inclusion of a non-obstructive spirometric impairment (restrictive-pattern); and 2) more likely to have medication-related adverse events, given the inappropriate use of COPD pharmacotherapy in misidentified COPD (restrictive-pattern). We therefore propose that future clinical trials of COPD pharmacotherapy should consider GLI criteria for defining COPD, including a greater representation of GLI-defined moderate COPD.

Background: Empirical data regarding the frequency of infection during fever episodes among women in long-term care facilities are lacking., Methods: We conducted a case-series analysis of women long-term care residents enrolled in a randomized trial evaluating cranberry capsules to reduce bacteriuria plus pyuria across twenty-one long-term care facilities in CT, USA. Fever episodes identified during adverse event surveillance were assessed using established guidelines for older adults. Among fever episodes, infections were classified using standardized infection surveillance definitions in long-term care residents., Results: We identified 123 fever episodes among 80 women long-term care residents. Median age was 88 years (range, 65-101), and 81% (N=65) had dementia. Among 123 fever episodes, 79 (64%) met criteria for 86 total infections (lower respiratory tract, N=43; pneumonia, N=27; gastroenteritis, N=9; urinary tract, N=7)., Conclusion: Data from this study suggest that approximately two-thirds of fever episodes involve infection among women in long-term care facilities. These data may guide provider assessments of fever in older adult women in long-term care facilities., Competing Interests: All authors report no conflicts of interest related to this work.

Models of preclinical Alzheimer's disease (AD) propose that cerebral amyloidosis leads to neurodegeneration and subsequent cognitive decline. This study investigated whether APOE genotype is related to β-amyloid (Aβ) burden in brain regions preferentially affected by AD and whether Aβ burden is associated with gray-matter (GM) fraction (as a marker of neurodegeneration) and episodic memory performance in cognitively normal middle-aged individuals at varying genetic risk for AD. Three groups of cognitively normal participants aged 50-65 years with a first-degree family history of AD (APOE genotype ε4ε4 [n = 15], ε3ε4 [n = 15], and ε3ε3 [n = 15]) underwent [ 11 C]PiB positron emission tomography scans to quantify cortical Aβ, brain magnetic resonance imaging, and neuropsychological testing. APOE ε4ε4 participants demonstrated significantly higher cortical Aβ burden than APOE ε3ε3 (p < 0.001). Furthermore, cortical Aβ burden was inversely associated with cortical GM fraction (p = 0.017) but not episodic memory performance. In cognitively normal, middle-aged individuals, Aβ burden is significantly associated with GM fraction but not episodic memory performance. These findings are consistent with models of preclinical AD in which neurodegeneration occurs before manifest cognitive decline., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Background/aims: Clinical trials of older adults are increasingly common, but risks of serious adverse events (SAE) may vary. We describe the incidence of SAE in two randomized trials, one community-based and one nursing home-based., Methods: We performed a secondary data analysis from two randomized clinical trials at one academic health center and 21 nursing homes involving 200 sedentary community dwellers aged 70-89 years and 185 female nursing home residents aged 65 years or older. Interventions included structured physical activity to reduce mobility disability in the Lifestyle Interventions and Independence for Elders (LIFE) study and oral cranberry capsules to reduce bacteriuria plus pyuria in nursing home residents (CRANNY) trial. We measured SAE incidence per 100 person-years and incidence of protocol-related unanticipated SAE per 100 person-years in LIFE and CRANNY trials., Results: Mean age and proportion of patients with dementia in LIFE and CRANNY trials were 79.3 years and 86.4 years and 0% and 78%, respectively. There were 179 total SAE in LIFE including 8 (4%) deaths, and 116 total SAE in CRANNY including 33 (28%) deaths. SAE incidence was 33.7 (95% CI 27.2, 41.8) events per 100 person-years in LIFE and 69.4 (95% CI 49.1, 98.1) events per 100 person-years in CRANNY. No protocol-related unanticipated SAE occurred in either trial., Conclusions: The frequency and severity of SAE vary in older adults. While SAE are common in nursing home residents, protocol-related, unanticipated SAE are rare in nursing home residents and community dwellers. This finding can inform trial monitoring protocols., Trial Registration: ClinicalTrials.gov identifiers: NCT01072500 and NCT01691430.

Background: Spirometric Z-scores from the Global Lung Initiative (GLI) rigorously account for age-related changes in lung function and are thus age-appropriate when establishing spirometric impairments, including a restrictive pattern and air-flow obstruction. However, GLI-defined spirometric impairments have not yet been evaluated regarding associations with static lung volumes (total lung capacity [TLC], functional residual capacity [FRC], and residual volume [RV]) and gas exchange (diffusing capacity)., Methods: We performed a retrospective review of pulmonary function tests in subjects ≥40 y old (mean age 64.6 y), including pre-bronchodilator measures for: spirometry ( n = 2,586), static lung volumes by helium dilution with inspiratory capacity maneuver ( n = 2,586), and hemoglobin-adjusted single-breath diffusing capacity ( n = 2,508). Using multivariable linear regression, adjusted least-squares means (adj LS Means) were calculated for TLC, FRC, RV, and hemoglobin-adjusted single-breath diffusing capacity. The adj LS Means were expressed with and without height-cubed standardization and stratified by GLI-defined spirometry, including normal ( n = 1,251), restrictive pattern ( n = 663), and air-flow obstruction (mild, [ n = 128]; moderate, [ n = 150]; and severe, [ n = 394])., Results: Relative to normal spirometry, restrictive-pattern had lower adj LS Means for TLC, FRC, RV, and hemoglobin-adjusted single-breath diffusing capacity ( P ≤ .001). Conversely, relative to normal spirometry, mild, moderate, and severe air-flow obstruction had higher adj LS Means for FRC and RV ( P < .001). However, only mild and moderate air-flow obstruction had higher adj LS Means for TLC ( P < .001), while only moderate and severe air-flow obstruction had higher adj LS Means for RV/TLC ( P < .001) and lower adj LS Means for hemoglobin-adjusted single-breath diffusing capacity ( P < .001). Notably, TLC (calculated as FRC + inspiratory capacity) was not increased in severe air-flow obstruction ( P ≥ .11) because inspiratory capacity decreased with increasing air-flow obstruction ( P < .001), thus opposing the increased FRC ( P < .001). Finally, P values were similar whether adj LS Means were height-cubed standardized., Conclusions: A GLI-defined spirometric restrictive pattern is strongly associated with a restrictive ventilatory defect (decreased TLC, FRC, and RV), while GLI-defined spirometric air-flow obstruction is strongly associated with hyperinflation (increased FRC) and air trapping (increased RV and RV/TLC). Both spirometric impairments were strongly associated with impaired gas exchange (decreased hemoglobin-adjusted single-breath diffusing capacity)., Competing Interests: The authors have disclosed no conflicts of interest., (Copyright © 2017 by Daedalus Enterprises.)

Objectives: To estimate the number of caregivers providing assistance to community-dwelling older persons with and without dementia and with or without substantial disability; to describe the characteristics of caregivers and care recipients in these groups; to characterize the health-related tasks that caregivers provide; and to estimate associations between the numbers of tasks and caregiver burden., Design: Nationally representative surveys of caregivers and older adults in the United States., Setting: 2011 National Health and Aging Trends Study and National Study of Caregiving., Participants: Community-dwelling older adults and their family caregivers, who were selected on the basis of having assisted with mobility, self-care, household activities, transportation, or medical tasks., Measurements: Caregiver burden (emotional, physical, financial difficulties) and restrictions on social participation., Results: Although much larger proportions of older adults with dementia and disability (98.4%, n = 1.0 million) and dementia but not disability (95.5%, n = 1.3 million) received caregiving assistance, the largest absolute number of individuals receiving assistance were older adults without dementia or disability (4.0 million). Within each caregiver group, caregivers provided assistance with at least one task across domains of activity of daily living and instrumental activity of daily living-related assistance (>98%), health systems logistics (>70%), and health management (>50%). There was a significant linear association between number of tasks provided and risk of burden in virtually all caregiver groups and domains of assistance., Conclusion: Caregivers of care recipients without dementia or disability accounted for the largest absolute number of helpers. These caregivers, similar to caregivers of care recipients with dementia or disability, delivered a broad spectrum of health-related tasks and experienced caregiver burden and restrictions on social participation. Findings support the need for interventions that address the needs of caregivers who have not typically been defined as high risk., (© 2017, Copyright the Authors Journal compilation © 2017, The American Geriatrics Society.)

In several ways, randomized controlled trials represent a high standard of rigor in clinical biomedical research. Randomized controlled trials fail, however, to yield knowledge applicable to specific individuals. This article presents a methodological rationale for a mixed methods approach to n-of-1 clinical studies that attends to the preferences and concerns of individuals while attaining high standards of qualitative and quantitative rigor. An illustrative research design involving a hypothetical music therapy intervention for a quality of life outcome is examined in some detail and a concluding argument is made that the proposed mixed methods approach is especially appropriate for early-stage research interventions intended to generate explanatory hypotheses., Competing Interests: Declaration of Conflicting Interests The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Importance: Bacteriuria plus pyuria is highly prevalent among older women living in nursing homes. Cranberry capsules are an understudied, nonantimicrobial prevention strategy used in this population., Objective: To test the effect of 2 oral cranberry capsules once a day on presence of bacteriuria plus pyuria among women residing in nursing homes., Design, Setting, and Participants: Double-blind, randomized, placebo-controlled efficacy trial with stratification by nursing home and involving 185 English-speaking women aged 65 years or older, with or without bacteriuria plus pyuria at baseline, residing in 21 nursing homes located within 50 miles (80 km) of New Haven, Connecticut (August 24, 2012-October 26, 2015)., Interventions: Two oral cranberry capsules, each capsule containing 36 mg of the active ingredient proanthocyanidin (ie, 72 mg total, equivalent to 20 ounces of cranberry juice) vs placebo administered once a day in 92 treatment and 93 control group participants., Main Outcomes and Measures: Presence of bacteriuria (ie, at least 105 colony-forming units [CFUs] per milliliter of 1 or 2 microorganisms in urine culture) plus pyuria (ie, any number of white blood cells on urinalysis) assessed every 2 months over the 1-year study surveillance; any positive finding was considered to meet the primary outcome. Secondary outcomes were symptomatic urinary tract infection (UTI), all-cause death, all-cause hospitalization, all multidrug antibiotic-resistant organisms, antibiotics administered for suspected UTI, and total antimicrobial administration., Results: Of the 185 randomized study participants (mean age, 86.4 years [SD, 8.2], 90.3% white, 31.4% with bacteriuria plus pyuria at baseline), 147 completed the study. Overall adherence was 80.1%. Unadjusted results showed the presence of bacteriuria plus pyuria in 25.5% (95% CI, 18.6%-33.9%) of the treatment group and in 29.5% (95% CI, 22.2%-37.9%) of the control group. The adjusted generalized estimating equations model that accounted for missing data and covariates showed no significant difference in the presence of bacteriuria plus pyuria between the treatment group vs the control group (29.1% vs 29.0%; OR, 1.01; 95% CI, 0.61-1.66; P = .98). There were no significant differences in number of symptomatic UTIs (10 episodes in the treatment group vs 12 in the control group), rates of death (17 vs 16 deaths; 20.4 vs 19.1 deaths/100 person-years; rate ratio [RR], 1.07; 95% CI, 0.54-2.12), hospitalization (33 vs 50 admissions; 39.7 vs 59.6 hospitalizations/100 person-years; RR, 0.67; 95% CI, 0.32-1.40), bacteriuria associated with multidrug-resistant gram-negative bacilli (9 vs 24 episodes; 10.8 vs 28.6 episodes/100 person-years; RR, 0.38; 95% CI, 0.10-1.46), antibiotics administered for suspected UTIs (692 vs 909 antibiotic days; 8.3 vs 10.8 antibiotic days/person-year; RR, 0.77; 95% CI, 0.44-1.33), or total antimicrobial utilization (1415 vs 1883 antimicrobial days; 17.0 vs 22.4 antimicrobial days/person-year; RR, 0.76; 95% CI, 0.46-1.25)., Conclusions and Relevance: Among older women residing in nursing homes, administration of cranberry capsules vs placebo resulted in no significant difference in presence of bacteriuria plus pyuria over 1 year., Trial Registration: clinicaltrials.gov Identifier: NCT01691430.

Objectives: To evaluate the associations between a broad array of cardiorespiratory and noncardiorespiratory impairments and dyspnea in older persons., Design: Cross-sectional., Setting: Cardiovascular Health Study., Participants: Community-dwelling persons (N = 4,413; mean age 72.6, 57.1% female, 4.5% African American, 27.2% 1 )), maximal inspiratory pressure (respiratory muscle strength), echocardiography, ankle-brachial index, blood pressure, whole-body muscle mass (bioelectrical impedance), single chair stand (lower extremity function), grip strength, serum hemoglobin and creatinine, Center for Epidemiologic Studies Depression Scale (CES-D), Mini-Mental State Examination, medication use, and body mass index (BMI)., Results: In a multivariable logistic regression model, impairments that had strong associations with moderate to severe dyspnea were FEV 1 less than the lower limit of normal (adjusted odds ratio (aOR) = 2.88, 95% confidence interval (CI) = 2.37-3.49), left ventricular ejection fraction less than 45% (aOR = 2.12, 95% CI = 1.43, 3.16), unable to perform a single chair stand (aOR = 2.10, 95% CI = 1.61-2.73), depressive symptoms (CES-D score ≥16; aOR = 2.02, 95% CI = 1.26-3.23), and obesity (BMI ≥30; aOR = 2.07, 95% CI = 1.67-2.55). Impairments with modest but still statistically significant associations with moderate to severe dyspnea included respiratory muscle weakness, diastolic cardiac dysfunction, grip weakness, anxiety symptoms, and use of cardiovascular and psychoactive medications (aORs = 1.31-1.71)., Conclusion: In community-dwelling older persons, several cardiorespiratory and noncardiorespiratory impairments were significantly associated with moderate to severe dyspnea, akin to a multifactorial geriatric health condition., (© 2016, Copyright the Authors Journal compilation © 2016, The American Geriatrics Society.)

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., (© The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Rationale: The 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., Objectives: To evaluate respiratory-related phenotypes in GLI-defined spirometric impairment., Methods: In 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, <391 m), bronchodilator reversibility (FEV1 change, >12% and ≥200 ml), and computed tomography-diagnosed emphysema and gas trapping (>5% and >15% of lung, respectively)., Measurements and Main Results: GLI 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])., Conclusions: GLI-defined spirometric impairment establishes clinically meaningful respiratory disease, as validated by graded associations with respiratory-related phenotypes.

Background.  Sepsis is a major cause of morbidity and mortality among older adults. The main goals of this study were to assess the association of sepsis at intensive care unit (ICU) admission with mortality and to identify predictors associated with increased mortality in older adults. Methods.  We conducted a prospective cohort study of 309 participants ≥60 years admitted to an ICU. Sepsis was defined as 2 of 4 systemic inflammatory response syndrome criteria plus a documented infection within 2 calendar days before or after admission. The main outcome measure was time to death within 1 year of ICU admission. Sepsis was evaluated as a predictor for mortality in a Cox proportional hazards model. Results.  Of 309 participants, 196 (63%) met the definition of sepsis. Among those admitted with and without sepsis, 75 (38%) vs 20 (18%) died within 1 month of ICU admission (P < .001) and 117 (60%) vs 48 (42%) died within 1 year (P < .001). When adjusting for baseline characteristics, sepsis had a significant impact on mortality (hazard ratio [HR] = 1.80; 95% confidence interval [CI], 1.28-2.52; P < .001); however, after adjusting for baseline characteristics and process covariates (antimicrobials and vasopressor use within 48 hours of admission), the impact of sepsis on mortality became nonsignificant (HR = 1.26; 95% CI, .87-1.84; P = .22). Conclusions.  The diagnosis of sepsis in older adults upon ICU admission was associated with an increase in mortality compared with those admitted without sepsis. After controlling for early use of antimicrobials and vasopressors for treatment, the association of sepsis with mortality was reduced.

Longitudinal research on older persons in the medical intensive care unit (MICU) is often complicated by the time-dependent confounding of concurrently administered interventions such as medications and intubation. Such temporal confounding can bias the respective longitudinal associations between concurrently administered treatments and a longitudinal outcome such as delirium. Although marginal structural models address time-dependent confounding, their application is non-trivial and preferably justified by empirical evidence. Using data from a longitudinal study of older persons in the MICU, we constructed a plausibility score from 0 - 10 where higher values indicate higher plausibility of time-dependent confounding of the association between a time-varying explanatory variable and an outcome. Based on longitudinal plots, measures of correlation, and longitudinal regression, the plausibility scores were compared to the differences in estimates obtained with non-weighted and marginal structural models of next day delirium. The plausibility scores of the three possible pairings of daily doses of fentanyl, haloperidol, and intubation indicated the following: low plausibility for haloperidol and intubation, moderate plausibility for fentanyl and haloperidol, and high plausibility for fentanyl and intubation. Comparing multivariable models of next day delirium with and without adjustment for time-dependent confounding, only intubation's association changed substantively. In our observational study of older persons in the MICU, the plausibility scores were generally reflective of the observed differences between coefficients estimated from non-weighted and marginal structural models.

Rationale: In 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])., Objectives: To evaluate the phenotype of normal spirometry as defined by a new approach from the Global Lung Initiative (GLI), overall and across GOLD spirometric categories., Methods: Using 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 Results: Among 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., Conclusions: GLI-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 age-related differences in sleep-wake symptoms., Design: Cross-sectional., Setting: Technologist-attended, laboratory-based polysomnography (PSG)., Participants: Community-dwelling adults aged 20 to 89 (N = 201): 52 aged 18 to 39, 72 aged 40 to 59, and 77 aged 60 and older., Measurements: Medical burden (Charlson Comorbidity Index, medications, health status), PSG-defined sleep disorders (sleep-disordered breathing (SDB), sleep-associated hypoxemia, periodic limb movements in sleep (PLMS)), sleep-wake symptoms (Epworth Sleepiness Scale (ESS), Insomnia Severity Index (ISI), fatigue (Facit-F Scale))., Results: Medical burden increased significantly with age (Charlson Comorbidity Index and number of medications, P < .001; health status, P = .005). Severity of sleep disorders also increased significantly with age (SDB and hypoxemia, P < .001; PLMS, P = .008). Conversely, sleep-wake symptoms decreased with age (daytime drowsiness (ESS ≥ 10), P = .02; insomnia (ISI ≥ 8), P = .04; fatigue, P < .001). In adjusted models, a 1-year increase in age was significantly associated with a 4% decrease in the odds of having daytime drowsiness (odds ratio (OR) = 0.96, 95% confidence interval (CI) = 0.93-0.98). Similarly, but only in those with mild SDB, a 1-year increase in age was significantly associated with a 5% decrease in the odds of having insomnia (OR = 0.95, 95% CI = 0.92-0.99)., Conclusion: Older age was characterized by less-severe sleep-wake symptoms (daytime drowsiness, insomnia, fatigue), despite an age-related increase in disease severity (medical burden, sleep disorders). Because the increase in disease severity included well-established risk factors for having sleep-wake symptoms, the age-related decrease in sleep-wake symptoms may reflect a decrease in symptom awareness., (© 2015, Copyright the Authors Journal compilation © 2015, The American Geriatrics Society.)

Objectives: To evaluate the association between performance on a single chair stand and moderate to severe exertional dyspnea., Design: Cross-sectional., Setting: Cardiovascular Health Study., Participants: Community-dwelling individuals aged 65 and older (N = 4,413; mean age 72.6; female, n = 2,518 (57.1%); nonwhite, n = 199 (4.5%); obese, n = 788 (17.9%); history of smoking, n = 2,410 (54.6%))., Measurements: Performance on single chair stand (poor (unable to rise without arm use) vs normal (able to rise without arm use)), moderate to severe exertional dyspnea (American Thoracic Society grade ≥2), age, sex, ethnicity, obesity, smoking, frailty status (Fried-defined nonfrail, prefrail, frail), high cardiopulmonary risk (composite of cardiopulmonary diseases and diabetes mellitus), spirometric impairment, arthritis, depression, stroke, and kidney disease., Results: Poor performance on the single chair stand was established in 369 (8.4%) and moderate to severe exertional dyspnea in 773 (17.5%). Prefrail status was established in 2,210 (50.1%), frail status in 360 (8.2%), arthritis in 2,241 (51.4%), high cardiopulmonary risk in 2,469 (55.9%), spirometric impairment in 1,076 (24.4%), kidney disease in 111 (2.5%), depression in 107 (2.4%), and stroke in 93 (2.1%). In multivariable regression models, poor performance on the single chair stand was associated with moderate to severe exertional dyspnea (unadjusted odds ratio (OR) = 3.48, 95% confidence interval (CI) = 2.78-4.36; adjusted OR = 1.85, 95% CI = 1.41-2.41)., Conclusion: Poor performance on a single chair stand was associated with an adjusted 85% greater likelihood of moderate to severe exertional dyspnea than normal performance. These results suggest that reduced proximal muscle function of the lower extremities is associated with moderate to severe exertional dyspnea, even after adjusting for multiple confounders., Competing Interests: The authors report no conflicts of interest., (© 2015, Copyright the Authors Journal compilation © 2015, The American Geriatrics Society.)

Background: assessment of baseline functional status of older patients during and after intensive care unit (ICU) admission is often hampered by challenges related to the critical illness such as cognitive dysfunction, neuropsychological morbidity and pain. To explore the reliability of assessments by carefully chosen proxies, we designed a discriminating selection of proxies and evaluated agreement between patient and proxy responses by assessing activities of daily living (ADLs) at 1 month post-ICU discharge., Methods: patients ≥60 years old admitted to the medical ICU were enrolled in a prospective parent cohort studying delirium. Proxies were carefully screened at ICU admission to choose the best available respondent. Follow-up interviews, including instruments for ADLs, were conducted 1 month after ICU discharge. We examined 179 paired patient-proxy follow-up interviews. Kappa statistics assessed inter-observer agreement, and McNemar's exact test assessed response differences., Results: patients averaged 73.3 ± 8.1 years old with 29% having evidence of cognitive impairment. Proxies were most commonly spouses (38%) or children (39%). Overall, there was substantial (κ ≥ 0.6) to excellent agreement (κ ≥ 0.8) between patients and proxies on assessment of all but one basic and one instrumental ADL., Conclusion: proxies carefully chosen at ICU admission show high levels of inter-observer agreement with older patients when assessing current functional status at 1 month post-ICU discharge. This motivates further study of proxy assessments that could be used earlier in critical illness to assess premorbid functional status., (© The Author 2014. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: Pneumonia remains an important public health problem among elderly nursing home residents. This clinical trial sought to determine if a multicomponent intervention protocol, including manual tooth/gum brushing plus 0.12% chlorhexidine oral rinse, twice per day, plus upright positioning during feeding, could reduce the incidence of radiographically documented pneumonia among nursing home residents, compared with usual care., Methods: This cluster-randomized clinical trial was conducted in 36 nursing homes in Connecticut. Eligible residents >65 years with at least 1 of 2 modifiable risk factors for pneumonia (ie, impaired oral hygiene, swallowing difficulty) were enrolled. Nursing homes were randomized to the multicomponent intervention protocol or usual care. Participants were followed for up to 2.5 years for development of the primary outcome, a radiographically documented pneumonia, and secondary outcome, a lower respiratory tract infection (LRTI) without radiographic documentation., Results: A total of 834 participants were enrolled: 434 to intervention and 400 to usual care. The trial was terminated for futility. The number of participants in the intervention vs control arms with first pneumonia was 119 (27.4%) vs 94 (23.5%), respectively, and with first LRTI, 125 (28.8%) vs 100 (25.0%), respectively. In a multivariable Cox regression model, the hazard ratio in the intervention vs control arms, respectively, was 1.12 (95% confidence interval [CI], .84-1.50; P = .44) for first pneumonia and 1.07 (95% CI, .79-1.46, P = .65) for first LRTI., Conclusions: The multicomponent intervention protocol did not significantly reduce the incidence of first radiographically confirmed pneumonia or LRTI compared with usual care in nursing home residents., Clinical Trials Registration: NCT00975780., (© The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)