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Circadian alignment of rest-activity rhythms is an essential biological process that may be vulnerable to misalignment in critically ill patients. We evaluated circadian rest-activity rhythms in critically ill patients and their association with baseline (e.g. age) and clinical (e.g. mechanical ventilation status) variables, along with intensive care unit light-dark cycles. Using wrist actigraphy, we collected 48-hr activity and light exposure data from critically ill patients in a tertiary care medical intensive care unit. We evaluated circadian rest-activity rhythms using COSINOR and non-parametric circadian rhythm analysis models, and stratified these data across baseline and clinical variables. We used linear regression to evaluate the association of circadian rest-activity and light-dark exposure rhythms. In COSINOR and non-parametric circadian rhythm analysis analyses, the 34 medical intensive care unit patients completing 48-hr actigraphy recordings exhibited mean MESOR (mean activity levels of a fitted curve) and amplitudes of 0.50 ± 0.32 and 0.20 ± 0.19 movements per 30-s epoch, with high interdaily variability. Patients who were older, mechanically ventilated, sedated, restrained and with higher organ failure scores tended to exhibit greater circadian rest-activity misalignment, with three of 34 (9%) patients exhibiting no circadian rhythmicity. Circadian light-dark exposure misalignment was observed as well and was associated with rest-activity misalignment (p = 0.03). Critically ill patients in our MICU experienced profound circadian rest-activity misalignment, with mostly weak or absent rhythms, along with circadian light-dark exposure misalignment. Potentially modifiable factors contributing to rest-activity misalignment (i.e. mechanical ventilation, restraints, low daytime light levels) highlight possible targets for future improvement efforts.

STUDY PURPOSE:The integration of methods to assess daytime physical activity (PA) and sedentary behavior (SB) and nighttime sleep would allow the evaluation of 24-hour daily activity using a single device. Accelerometer devices used to assess daytime PA have not been substantially validated to evaluate sleep. The objective of this study was to use polysomnography (PSG) to validate a commonly used PA accelerometer worn on both wrists and the hip. METHODS:Seventeen participants (50-75years) completed a single-night in-home PSG recording while concurrently wearing 3 PA accelerometers. Accelerometer devices were worn on each wrist and the hip. Total sleep time (TST), sleep efficiency (SE), and wake after sleep onset (WASO) were compared for each device against PSG. Correlation coefficients estimated measurement agreement. Paired t tests and Bland-Altman plots assessed measurement differences. RESULTS:Between PSG and devices, mean TST ranged from 361.6 to 403.2minutes. Mean SE estimates ranged from 86.9% to 96.9%. Mean WASO estimates ranged from 12 to 51.2minutes. For TST, SE, and WASO hip estimates differed significantly from PSG estimates (paired t tests, TST: P=.03, SE: P

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Physiological and cellular functions operate in a 24-hour cyclical pattern orchestrated by an endogenous process known as the circadian rhythm. Circadian rhythms represent intrinsic oscillations of biological functions that allow for adaptation to cyclic environmental changes. Key clock genes that affect the persistence and periodicity of circadian rhythms include BMAL1/CLOCK, Period 1, Period 2, and Cryptochrome. Remarkable progress has been made in our understanding of circadian rhythms and their role in common medical conditions. A critical review of the literature supports the association between circadian misalignment and adverse health consequences in sepsis, obstructive lung disease, obstructive sleep apnea, and malignancy. Circadian misalignment plays an important role in these disease processes and can affect disease severity, treatment response, and survivorship. Normal inflammatory response to acute infections, airway resistance, upper airway collapsibility, and mitosis regulation follows a robust circadian pattern. Disruption of normal circadian rhythm at the molecular level affects severity of inflammation in sepsis, contributes to inflammatory responses in obstructive lung diseases, affects apnea length in obstructive sleep apnea, and increases risk for cancer. Chronotherapy is an underused practice of delivering therapy at optimal times to maximize efficacy and minimize toxicity. This approach has been shown to be advantageous in asthma and cancer management. In asthma, appropriate timing of medication administration improves treatment effectiveness. Properly timed chemotherapy may reduce treatment toxicities and maximize efficacy. Future research should focus on circadian rhythm disorders, role of circadian rhythm in other diseases, and modalities to restore and prevent circadian disruption.

ObjectiveSleep duration is associated with obesity and cardiometabolic disease. It is unclear, though, how these relationship differs across age groups.MethodsData from 2007 to 2008 National Health and Nutrition Examination Survey (NHANES) were used, including respondents aged 16+ with complete data (N = 5,607). Sleep duration and age were evaluated by self-report, and body mass index (BMI) was assessed objectively. Sleep duration was evaluated continuously and categorically [very short (≤4 h), short (5-6 h), and long (≥9 h) versus average (7-8 h)]. Age was also evaluated continuously and categorically [adolescent (16-17 years), young adult (18-29 years), early middle age (30-49 years), late middle age (50-64 years), and older adult (≥65 years)].ResultsThere was a significant interaction with age for both continuous (Pinteraction  = 0.014) and categorical (Pinteraction  = 0.035) sleep duration. A pseudo-linear relationship was seen among the youngest respondents, with the highest BMI associated with the shortest sleepers and the lowest BMI associated with the longest sleepers. This relationship became U-shaped in middle-age, and less of a relationship was seen among the oldest respondents.ConclusionsThese findings may provide insights for clinical recommendations and could help to guide mechanistic research regarding the sleep-obesity relationship.

A workshop was held at the National Institute for Diabetes and Digestive and Kidney Diseases with a focus on the impact of sleep and circadian disruption on energy balance and diabetes. The workshop identified a number of key principles for research in this area and a number of specific opportunities. Studies in this area would be facilitated by active collaboration between investigators in sleep/circadian research and investigators in metabolism/diabetes. There is a need to translate the elegant findings from basic research into improving the metabolic health of the American public. There is also a need for investigators studying the impact of sleep/circadian disruption in humans to move beyond measurements of insulin and glucose and conduct more in-depth phenotyping. There is also a need for the assessments of sleep and circadian rhythms as well as assessments for sleep-disordered breathing to be incorporated into all ongoing cohort studies related to diabetes risk. Studies in humans need to complement the elegant short-term laboratory-based human studies of simulated short sleep and shift work etc. with studies in subjects in the general population with these disorders. It is conceivable that chronic adaptations occur, and if so, the mechanisms by which they occur needs to be identified and understood. Particular areas of opportunity that are ready for translation are studies to address whether CPAP treatment of patients with pre-diabetes and obstructive sleep apnea (OSA) prevents or delays the onset of diabetes and whether temporal restricted feeding has the same impact on obesity rates in humans as it does in mice.

The American Academy of Sleep Medicine and Sleep Research Society recently released a Consensus Statement regarding the recommended amount of sleep to promote optimal health in adults. This paper describes the methodology, background literature, voting process, and voting results for the consensus statement. In addition, we address important assumptions and challenges encountered during the consensus process. Finally, we outline future directions that will advance our understanding of sleep need and place sleep duration in the broader context of sleep health.

Sleep disordered breathing (SDB) is highly prevalent among patients with cardiovascular disease (CVD), and the relationship between SDB and CVD may be bidirectional. However, SDB remains underdiagnosed and undertreated. One of the major barriers identified by cardiologists is lack of satisfaction with SDB therapy. This situation could be the result of the discordance between treatment and the pathophysiological characteristics of SDB. This condition is caused by multiple pathophysiological mechanisms, which could be classified into upper airway anatomic compromise, pharyngeal dilator muscle dysfunction, and ventilatory control instability. However, the effective treatment of SDB remains limited, and positive airway pressure therapy is still the mainstay of the treatment. Therefore, we review the pathophysiological characteristics of SDB in this article, and we propose to provide individualized treatment of SDB based on the underlying mechanism. This approach requires further study but could potentially improve adherence and success of therapy.

BackgroundObesity and short sleep duration are significant public health issues. Current evidence suggests that these conditions are associated with cardiovascular disease, metabolic syndrome, inflammation, and premature mortality. Increased interest in the potential link between obesity and short sleep duration, and its health consequences, has been driven by the apparent parallel increase in the prevalence of both conditions in recent decades, their overlapping association with cardiometabolic outcomes, and the potential causal connection between the two health issues. The SLUMBRx (Short Sleep Undermines Cardiometabolic Health) study seeks to contribute to the development of a comprehensive adiposity-sleep model while laying the groundwork for a future research program that will be designed to prevent and treat adiposity- and sleep-related cardiometabolic disease risk factors. ObjectiveThis SLUMBRx study aims to address 4 topics pertinent to the adiposity-sleep hypothesis: the relationship between adiposity and sleep duration; sex-based differences in the relationship between adiposity and sleep duration; the influence of adiposity indices and sleep duration on cardiometabolic outcomes; and the role of socioecological factors as effect modifiers in the relationship between adiposity indices, sleep, and cardiometabolic outcomes. MethodsSLUMBRx will employ a large-scale survey (n=1000), recruiting 159 participants (53 normal weight, 53 overweight, and 53 obese) to be assessed in 2 phases. ResultsSLUMBRx was funded by the National Institutes of Health, Heart, Lung, and Blood Institute through a K01 grant award mechanism (1K01HL145128-01A1) on July 23, 2019. Institutional Review Board (IRB) approval for the research project was sought and obtained on July 10, 2019. Phase 1 of SLUMBRx, the laboratory-based component of the study, will gather objective adiposity indices (air displacement plethysmography and anthropometrics) and cardiometabolic data (blood pressure, pulse wave velocity and pulse wave analysis, and a blood-based biomarker). Phase 2 of SLUMBRx, a 1-week, home-based component of the study, will gather sleep-related data (home sleep testing or sleep apnea, actigraphy, and sleep diaries). During phase 2, detailed demographic and socioecological data will be collected to contextualize hypothesized adiposity and sleep-associated cardiometabolic disease risk factors. Collection and analyses of these data will yield information necessary to customize future observational and intervention research. ConclusionsPrecise implementation of the SLUMBRx protocol promises to provide objective and empirical data on the interaction between body composition and sleep duration. The hypotheses that will be tested by SLUMBRx are important for understanding the pathogenesis of cardiometabolic disease and for developing future public health interventions to prevent its conception and treat its consequences. International Registered Report Identifier (IRRID)PRR1-10.2196/27139

Bright light in the blue-green range, administered in the early morning hours (prior to waking) may be particularly effective in shifting circadian rhythms and may increase gonadotropin production. Accordingly, we tested the feasibility and utility of a mask that emits bright blue/green light (compared to a similar mask that emitted a dim red light) towards the end of sleep in a randomized, placebo-controlled pilot study. The study included a 3-day baseline period, immediately followed by a 12-day intervention period. Subjects were 30 healthy young men with minimal-mild depression. The bright light masks were well-tolerated and demonstrated adequate safety and feasibility. Following the intervention, those who wore the bright light mask demonstrated altered sleep timing suggestive of an earlier sleep period, and excreted a slight increase in follicle-stimulating hormone. Overall, light masks may prove useful in future studies of bright light therapy.