Multidimensional sleep health domains in older men and women: an actigraphy factor analysis.

The multidimensional sleep health framework emphasizes that sleep can be characterized across several domains, with implications for developing novel sleep treatments and improved prediction and health screening. However, empirical evidence regarding the domains and representative measures that exist in actigraphy-assessed sleep is lacking. We aimed to establish these domains and representative measures in older adults by examining the factor structure of 28 actigraphy-derived sleep measures from 2,841 older men from the Osteoporotic Fractures in Men Sleep Study and, separately, from 2,719 older women from the Study of Osteoporotic Fractures. Measures included means and standard deviations of actigraphy summary measures and estimates from extended cosine models of the raw actigraphy data. Exploratory factor analyses revealed the same five factors in both sexes: Timing (e.g. mean midpoint from sleep onset to wake-up), Efficiency (e.g. mean sleep efficiency), Duration (e.g. mean minutes from sleep onset to wake-up), Sleepiness/Wakefulness (e.g. mean minutes napping and amplitude of rhythm), and Regularity (e.g. standard deviation of the midpoint). Within each sex, confirmatory factor analyses confirmed the one-factor structure of each factor and the entire five-factor structure (Comparative Fit Index and Tucker-Lewis Index ≥ 0.95; Root Mean Square Error of Approximation 0.08-0.38). Correlation magnitudes among factors ranged from 0.01 to 0.34. These findings demonstrate the validity of conceptualizing actigraphy sleep as multidimensional, provide a framework for selecting sleep health domains and representative measures, and suggest targets for behavioral interventions. Similar analyses should be performed with additional measures of rhythmicity, other age ranges, and more racially/ethnically diverse samples.

International, evidence-based consensus treatment guidelines for idiopathic multicentric Castleman disease.

Castleman disease (CD) describes a group of heterogeneous hematologic disorders with characteristic histopathological features. CD can present with unicentric or multicentric (MCD) regions of lymph node enlargement. Some cases of MCD are caused by human herpesvirus-8 (HHV-8), whereas others are HHV-8-negative/idiopathic (iMCD). Treatment of iMCD is challenging, and outcomes can be poor because no uniform treatment guidelines exist, few systematic studies have been conducted, and no agreed upon response criteria have been described. The purpose of this paper is to establish consensus, evidence-based treatment guidelines based on the severity of iMCD to improve outcomes. An international Working Group of 42 experts from 10 countries was convened by the Castleman Disease Collaborative Network to establish consensus guidelines for the management of iMCD based on published literature, review of treatment effectiveness for 344 cases, and expert opinion. The anti-interleukin-6 monoclonal antibody siltuximab (or tocilizumab, if siltuximab is not available) with or without corticosteroids is the preferred first-line therapy for iMCD. In the most severe cases, adjuvant combination chemotherapy is recommended. Additional agents are recommended, tailored by disease severity, as second- and third-line therapies for treatment failures. Response criteria were formulated to facilitate the evaluation of treatment failure or success. These guidelines should help treating physicians to stratify patients based on disease severity in order to select the best available therapeutic option. An international registry for patients with CD (ACCELERATE, #NCT02817997) was established in October 2016 to collect patient outcomes to increase the evidence base for selection of therapies in the future.

Which Sleep Health Characteristics Predict All-Cause Mortality in Older Men? An Application of Flexible Multivariable Approaches.

Study Objectives: Sleep is multidimensional, with domains including duration, timing, continuity, regularity, rhythmicity, quality, and sleepiness/alertness. Individual sleep characteristics representing these domains are known to predict health outcomes. However, most studies consider sleep characteristics in isolation, resulting in an incomplete understanding of which sleep characteristics are the strongest predictors of health outcomes. We applied three multivariable approaches to robustly determine which sleep characteristics increase mortality risk in the osteoporotic fractures in men sleep study. Methods: In total, 2,887 men (mean 76.3 years) completed relevant assessments and were followed for up to 11 years. One actigraphy or self-reported sleep characteristic was selected to represent each of seven sleep domains. Multivariable Cox models, survival trees, and random survival forests were applied to determine which sleep characteristics increase mortality risk. Results: Rhythmicity (actigraphy pseudo-F statistic) and continuity (actigraphy minutes awake after sleep onset) were the most robust sleep predictors across models. In a multivariable Cox model, lower rhythmicity (hazard ratio, HR [95%CI] =1.12 [1.04, 1.22]) and lower continuity (1.16 [1.08, 1.24]) were the strongest sleep predictors. In the random survival forest, rhythmicity and continuity were the most important individual sleep characteristics (ranked as the sixth and eighth most important among 43 possible sleep and non-sleep predictors); moreover, the predictive importance of all sleep information considered simultaneously followed only age, cognition, and cardiovascular disease. Conclusions: Research within a multidimensional sleep health framework can jumpstart future research on causal pathways linking sleep and health, new interventions that target specific sleep health profiles, and improved sleep screening for adverse health outcomes.

Association between sleep duration and mortality is mediated by markers of inflammation and health in older adults: the Health, Aging and Body Composition Study.

STUDY OBJECTIVES: Inflammation may represent a common physiological pathway linking both short and long sleep duration to mortality. We evaluated inflammatory markers as mediators of the relationship between sleep duration and mortality in community-dwelling older adults. DESIGN: Prospective cohort with longitudinal follow-up for mortality outcomes. SETTING: Pittsburgh, Pennsylvania, and Memphis, Tennessee. PARTICIPANTS: Participants in the Health, Aging and Body Composition (Health ABC) Study (mean age 73.6 ± 2.9 years at baseline) were sampled and recruited from Medicare listings. MEASUREMENTS AND RESULTS: Baseline measures of subjective sleep duration, markers of inflammation (serum interleukin-6, tumor necrosis factor-α, and C-reactive protein) and health status were evaluated as predictors of all-cause mortality (average follow-up = 8.2 ± 2.3 years). Sleep duration was related to mortality, and age-, sex-, and race-adjusted hazard ratios (HR) were highest for those with the shortest (< 6 h HR: 1.30, CI: 1.05-1.61) and longest (> 8 h HR: 1.49, CI: 1.15-1.93) sleep durations. Adjustment for inflammatory markers and health status attenuated the HR for short (< 6 h) sleepers (HR = 1.06, 95% CI = 0.83-1.34). Age-, sex-, and race-adjusted HRs for the > 8-h sleeper group were less strongly attenuated by adjustment for inflammatory markers than by other health factors associated with poor sleep with adjusted HR = 1.23, 95% CI = 0.93-1.63. Inflammatory markers remained significantly associated with mortality. CONCLUSION: Inflammatory markers, lifestyle, and health status explained mortality risk associated with short sleep, while the mortality risk associated with long sleep was explained predominantly by lifestyle and health status.

Circadian rest-activity rhythms predict future increases in depressive symptoms among community-dwelling older men.

OBJECTIVE: Circadian rest-activity rhythms (CARs) have been cross-sectionally associated with depressive symptoms, although no longitudinal research has examined whether CARs are a risk factor for developing depressive symptoms. METHODS: We examined associations of CARs (measured with actigraphy over a mean of 4.8 days) with depressive symptoms (measured with the Geriatric Depression Scale) among 2,892 community-dwelling older men (mean age: 76.2 ± 5.5 years) from the MrOS Sleep Study who were without cognitive impairment. Among 2,124 men with minimal (0-2) symptoms at baseline, we assessed associations between CAR parameters and increases to mild (3-5) or clinically significant (≥6) symptoms after an average of 1.2 (±0.32) years. RESULTS: Cross-sectional associations between rhythm height parameters were independent of chronic diseases, lifestyle, sleep, and self-reported physical activity covariates. For example, men in the lowest mesor quartile had twice the adjusted odds (adjusted odds ratio [AOR]: 2.04, 95% confidence interval [CI]: 1.36-3.04, p = 0.0005) of having prevalent clinically significant symptoms (compared to minimal). Longitudinally, low CAR robustness (being in the lowest quartile of the pseudo-F statistic) was independently associated with increasing odds of developing symptoms (i.e., AOR for having clinically significant depressive symptoms at follow-up = 2.58, 95% CI: 1.11-5.99, p = 0.03). CONCLUSION: CAR disturbances are indicative of depressive symptomology. Low CAR robustness may independently contribute to the risk of worsening depression symptomology.