Publications by authors named "Charles A Czeisler"

217 Publications

Resolving delayed sleep-wake phase disorder with a pandemic: two case reports.

J Clin Sleep Med 2021 Jul 13. Epub 2021 Jul 13.

Division of Sleep and Circadian Disorders, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts.

Two patients with delayed sleep-wake phase disorder (DSWPD) demonstrated improvement in sleep quality and duration, reduction in symptoms and elimination of the need for hypnotic or stimulant medications after changing their sleep schedules in response to the coronavirus disease 2019 (COVID-19) pandemic lockdown work schedule changes. These cases highlight the impact of work schedules on patient health and raise questions about approaches to workplace schedule requirements post pandemic.
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http://dx.doi.org/10.5664/jcsm.9526DOI Listing
July 2021

Resolving delayed sleep-wake phase disorder with a pandemic: two case reports.

J Clin Sleep Med 2021 Jul 13. Epub 2021 Jul 13.

Division of Sleep and Circadian Disorders, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts.

Two patients with delayed sleep-wake phase disorder (DSWPD) demonstrated improvement in sleep quality and duration, reduction in symptoms and elimination of the need for hypnotic or stimulant medications after changing their sleep schedules in response to the coronavirus disease 2019 (COVID-19) pandemic lockdown work schedule changes. These cases highlight the impact of work schedules on patient health and raise questions about approaches to workplace schedule requirements post pandemic.
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http://dx.doi.org/10.5664/jcsm.9526DOI Listing
July 2021

Associations between changes in daily behaviors and self-reported feelings of depression and anxiety about the COVID-19 pandemic among older adults.

J Gerontol B Psychol Sci Soc Sci 2021 Jun 22. Epub 2021 Jun 22.

Division of Sleep and Circadian Disorders, Brigham & Women's Hospital, Boston, Massachusetts, United States.

Objectives: Due to the significant mortality and morbidity consequences of the coronavirus 2019 (COVID-19) pandemic among older adults, these individuals were urged to avoid going out in public and socializing with others, among other major disruptions to daily life. While these significant and often unavoidable disruptions have been shown to bear consequences for mental health, less attention has been devoted to behavioral changes, such as changes to sleeping or eating due to the COVID-19 pandemic, and their implications for emotional well-being.

Methods: We utilized data from a nationally representative survey of Medicare beneficiaries (aged ≥65 years), which was administered between June and October 2020 (n=3,122). We examine the relationship between self-reported changes to daily behaviors (e.g., sleep, drinking alcohol, and exercise) and emotional impacts of COVID-19 (i.e., feelings of depression and anxiety about the COVID-19 pandemic) using stepwise hierarchical multivariable Poisson regression.

Results: We found that worse sleep quality, sleeping more or less, watching more television, and walking less, were associated with more feelings of depression and anxiety about COVID-19.

Discussion: Previous research has shown a connection between the significant and often unavoidable disruptions to daily life due to the COVID-19 pandemic (e.g., sheltering-in-place) and adverse mental health symptoms. Less attention has been paid to potentially modifiable behaviors, such as sleep and exercise. Our findings highlight the behavioral changes associated with adverse emotional impacts among older adults during the COVID-19 pandemic. Future research may evaluate whether behavioral interventions may aim to attenuate the impact of pandemics on daily, modifiable behaviors to buffer against adverse emotional impacts.
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http://dx.doi.org/10.1093/geronb/gbab110DOI Listing
June 2021

Mental Health Among Parents of Children Aged <18 Years and Unpaid Caregivers of Adults During the COVID-19 Pandemic - United States, December 2020 and February-⁠March 2021.

MMWR Morb Mortal Wkly Rep 2021 Jun 18;70(24):879-887. Epub 2021 Jun 18.

Early during the COVID-19 pandemic, nearly two thirds of unpaid caregivers of adults reported adverse mental or behavioral health symptoms, compared with approximately one third of noncaregivers (1). In addition, 27% of parents of children aged <18 years reported that their mental health had worsened during the pandemic (2). To examine mental health during the COVID-19 pandemic among U.S. adults on the basis of their classification as having a parenting role (i.e., unpaid persons caring for children and adolescents aged <18 years, referred to as children in this report) or being an unpaid caregiver of adults (i.e., persons caring for adults aged ≥18 years), CDC analyzed data from cross-sectional surveys that were administered during December 2020 and February-March 2021 for The COVID-19 Outbreak Public Evaluation (COPE) Initiative. Respondents were categorized as parents only, caregivers of adults only, parents-caregivers (persons in both roles), or nonparents/noncaregivers (persons in neither role). Adjusted odds ratios (aORs) for any adverse mental health symptoms, particularly suicidal ideation, were higher among all respondents who were parents, caregivers of adults, or both compared with respondents who were nonparents/noncaregivers and were highest among persons in both roles (parents-caregivers) (any adverse mental health symptoms: aOR = 5.1, 95% confidence interval [CI] = 4.1-6.2; serious suicidal ideation: aOR = 8.2, 95% CI = 6.5-10.4). These findings highlight that parents and caregivers, especially those balancing roles both as parents and caregivers, experienced higher levels of adverse mental health symptoms during the COVID-19 pandemic than adults without these responsibilities. Caregivers who had someone to rely on for support had lower odds of experiencing any adverse mental health symptoms. Additional measures are needed to improve mental health among parents, caregivers, and parents-caregivers.
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http://dx.doi.org/10.15585/mmwr.mm7024a3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8220951PMC
June 2021

Endogenous circadian regulation and phase resetting of clinical metabolic biomarkers.

J Pineal Res 2021 Jun 12:e12752. Epub 2021 Jun 12.

Division of Sleep and Circadian Disorders, Departments of Medicine and Neurology, Brigham and Women's Hospital, Boston, MA, USA.

Shiftwork and circadian disruption are associated with adverse metabolic effects. Therefore, we examined whether clinical biomarkers of metabolic health are under endogenous circadian regulation using a 40 hours constant routine protocol (CR; constant environmental and behavioral conditions) and evaluated the impact of typical daily conditions with periodic sleep and meals (baseline; 8 hours sleep at night, four meals during a 16 hour wake episode) on the phase and amplitude of these rhythms. Additionally, we tested whether these circadian rhythms are reset during simulated shiftwork. Under CR (n = 16 males, mean age ± SD = 23.4 ± 2.3 years), we found endogenous circadian rhythms in cholesterol, HDL and LDL, albumin and total protein, and VLDL and triglyceride. The rhythms were masked under baseline conditions except for cholesterol, which had near-identical phases under both conditions. Resetting of the cholesterol rhythm and Dim Light Melatonin Onset (DLMO) was then tested in a study of simulated shiftwork (n = 25, 14 females, 36.3 ± 8.9 years) across four protocols; two with abrupt 8 hour delay shifts and exposure to either blue-enriched or standard white light; and either an abrupt or gradual 8 hour advance (1.6 hours/day over 5 days) both with exposure to blue-enriched white light. In the delay protocols, the cholesterol rhythm shifted later by -3.7 hours and -4.2 hours, respectively, compared to -6.6 hours and -4.7 hours, for DLMO. There was a significant advance in cholesterol in the abrupt (+5.1 hours) but not the gradual (+2.1 hours) protocol, compared to +3.1 hours and +2.8 hours in DLMO, respectively. Exploratory group analysis comparing the phases of all metabolic biomarkers under both studies showed evidence of phase shifts due to simulated shiftwork. These results show that clinical biomarkers of metabolic health are under endogenous circadian regulation but that the expression of these rhythms is substantially influenced by environmental factors. These rhythms can also be reset, which has implications for understanding how both behavioral changes and circadian shifts due to shiftwork may disrupt metabolic function.
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http://dx.doi.org/10.1111/jpi.12752DOI Listing
June 2021

Sleep difficulties, incident dementia and all-cause mortality among older adults across 8 years: Findings from the National Health and Aging Trends Study.

J Sleep Res 2021 Jun 2:e13395. Epub 2021 Jun 2.

Division of Sleep and Circadian Disorders, Brigham and Women's Hospital, Boston, MA, USA.

Sleep difficulties have been implicated in the development and progression of dementia and in all-cause mortality. This study examines the relationship between sleep difficulties, incident dementia and all-cause mortality over 8 years of follow-up among a nationally representative sample of older (≥65 years) adults in the United States. We used data collected from the National Health and Aging Trends Study (NHATS) from 2011 to 2018, a prospective cohort study of Medicare beneficiaries. At baseline, the NHATS sample comprised 6,376 older adults who were representative of 32 million older adults. Respondents reported routine difficulty initiating sleep or difficulty falling back asleep "most nights" or "every night" in each study year. In each year, dementia was determined by either self-reported diagnosis or performance on immediate and delayed recall word and clock drawing tests, whereas all-cause mortality was determined by proxy. We conducted Cox proportional hazards modelling, adjusting for age, sex, marital status and chronic conditions. In models predicting all-cause mortality, we also controlled for dementia. Among respondents at baseline, 19% were 65-75 years of age, 71% identified as non-Hispanic white and 59% were female. Difficulty initiating sleep (hazard ratio [HR], 1.49; 95% confidence interval [CI],1.25-1.77), difficulty falling back asleep (HR, = 1.39; 95% CI,1.14-1.70) and concurrent sleep difficulties (HR, 1.58; 95% CI, 1.25-1.99) were associated with greater risk of dementia. Difficulty initiating sleep (HR, 1.44; 95% CI,1.20-1.72), difficulty falling back asleep (HR, 1.56; 95% CI,1.29-1.89), and concurrent sleep difficulties (HR, 1.80; 95% CI, 1.44-2.24) were associated with greater risk of all-cause mortality. Our findings demonstrate that reported difficulties are prospectively associated with an increased risk of dementia and all-cause mortality among older people.
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http://dx.doi.org/10.1111/jsr.13395DOI Listing
June 2021

A classification approach to estimating human circadian phase under circadian alignment from actigraphy and photometry data.

J Pineal Res 2021 Aug 20;71(1):e12745. Epub 2021 Jun 20.

Division of Sleep Medicine, Harvard Medical School, Boston, MA, USA.

The time of dim light melatonin onset (DLMO) is the gold standard for circadian phase assessment in humans, but collection of samples for DLMO is time and resource-intensive. Numerous studies have attempted to estimate circadian phase from actigraphy data, but most of these studies have involved individuals on controlled and stable sleep-wake schedules, with mean errors reported between 0.5 and 1 hour. We found that such algorithms are less successful in estimating DLMO in a population of college students with more irregular schedules: Mean errors in estimating the time of DLMO are approximately 1.5-1.6 hours. We reframed the problem as a classification problem and estimated whether an individual's current phase was before or after DLMO. Using a neural network, we found high classification accuracy of about 90%, which decreased the mean error in DLMO estimation-identifying the time at which the switch in classification occurs-to approximately 1.3 hours. To test whether this classification approach was valid when activity and circadian rhythms are decoupled, we applied the same neural network to data from inpatient forced desynchrony studies in which participants are scheduled to sleep and wake at all circadian phases (rather than their habitual schedules). In participants on forced desynchrony protocols, overall classification accuracy dropped to 55%-65% with a range of 20%-80% for a given day; this accuracy was highly dependent upon the phase angle (ie, time) between DLMO and sleep onset, with the highest accuracy at phase angles associated with nighttime sleep. Circadian patterns in activity, therefore, should be included when developing and testing actigraphy-based approaches to circadian phase estimation. Our novel algorithm may be a promising approach for estimating the onset of melatonin in some conditions and could be generalized to other hormones.
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http://dx.doi.org/10.1111/jpi.12745DOI Listing
August 2021

Uncovering survivorship bias in longitudinal mental health surveys during the COVID-19 pandemic.

Epidemiol Psychiatr Sci 2021 May 26;30:e45. Epub 2021 May 26.

Turner Institute for Brain and Mental Health and School of Psychological Sciences, Monash University, Melbourne, Victoria, Australia.

Aims: Markedly elevated adverse mental health symptoms were widely observed early in the coronavirus disease-2019 (COVID-19) pandemic. Unlike the U.S., where cross-sectional data indicate anxiety and depression symptoms have remained elevated, such symptoms reportedly declined in the U.K., according to analysis of repeated measures from a large-scale longitudinal study. However, nearly 40% of U.K. respondents (those who did not complete multiple follow-up surveys) were excluded from analysis, suggesting that survivorship bias might partially explain this discrepancy. We therefore sought to assess survivorship bias among participants in our longitudinal survey study as part of The COVID-19 Outbreak Public Evaluation (COPE) Initiative.

Methods: Survivorship bias was assessed in 4039 U.S. respondents who completed surveys including the assessment of mental health as part of The COPE Initiative in April 2020 and were invited to complete follow-up surveys. Participants completed validated screening instruments for symptoms of anxiety, depression and insomnia. Survivorship bias was assessed for (1) demographic differences in follow-up survey participation, (2) differences in initial adverse mental health symptom prevalence adjusted for demographic factors and (3) differences in follow-up survey participation based on mental health experiences adjusted for demographic factors.

Results: Adjusting for demographics, individuals who completed only one or two out of four surveys had significantly higher prevalence of anxiety and depression symptoms in April 2020 (e.g. one-survey v. four-survey, anxiety symptoms, adjusted prevalence ratio [aPR]: 1.30, 95% confidence interval [CI]: 1.08-1.55, p = 0.0045; depression symptoms, aPR: 1.43, 95% CI: 1.17-1.75, p = 0.00052). Moreover, individuals who experienced incident anxiety or depression symptoms had significantly higher adjusted odds of not completing follow-up surveys (adjusted odds ratio [aOR]: 1.68, 95% CI: 1.22-2.31, p = 0.0015, aOR: 1.56, 95% CI: 1.15-2.12, p = 0.0046, respectively).

Conclusions: Our findings reveal significant survivorship bias among longitudinal survey respondents, indicating that restricting analytic samples to only respondents who provide repeated assessments in longitudinal survey studies could lead to overly optimistic interpretations of mental health trends over time. Cross-sectional or planned missing data designs may provide more accurate estimates of population-level adverse mental health symptom prevalence than longitudinal surveys.
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http://dx.doi.org/10.1017/S204579602100038XDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8207539PMC
May 2021

Exploratory assessment of pineal gland volume, composition, and urinary 6-sulfatoxymelatonin levels on prostate cancer risk.

Prostate 2021 Jun 16;81(8):487-496. Epub 2021 Apr 16.

Department of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, Ohio, USA.

Introduction: Melatonin levels are partially driven by the parenchyma volume of the pineal gland. Low urinary levels of 6-sulfatoxymelatonin have been associated with increased risk of advanced prostate cancer, but the relationship between pineal gland volume and composition and prostate cancer risk has not been examined.

Materials And Methods: We utilized data from 864 men from the AGES-Reykjavik Study with complete pineal gland volumes and urinary 6-sulfatoxymelatonin measurements. Pineal parenchyma, calcification, and cyst volumes were calculated from brain magnetic resonance imaging. Levels of 6-sulfatoxymelatonin were assayed from prediagnostic urine samples. We calculated Pearson correlation coefficients between parenchyma volume and urinary 6-sulfatoxymelatonin levels. We used Cox proportional hazards regression to calculate multivariable hazard ratios (HRs) and 95% confidence intervals (95% CIs) comparing prostate cancer risk across parenchyma volume tertiles and across categories factoring in parenchyma volume, gland composition, and urinary 6-sulfatoxymelatonin level.

Results: Parenchyma volume was moderately correlated with urinary 6-sulfatoxymelatonin level (r = .24; p < .01). There was no statistically significant association between parenchyma volume tertile and prostate cancer risk. Men with high parenchyma volume, pineal cysts and calcifications, and low urinary 6-sulfatoxymelatonin levels had almost twice the risk of total prostate cancer as men with low parenchyma volume, no pineal calcifications or cysts, and low urinary 6-sulfatoxymelatonin levels (HR: 1.98; 95% CI: 1.02, 3.84; p: .04).

Conclusions: Although parenchyma volume is not associated with prostate cancer risk, pineal gland composition and other circadian dynamics may influence risk for prostate cancer. Additional studies are needed to examine the interplay of pineal gland volume, composition, and melatonin levels on prostate cancer risk.
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http://dx.doi.org/10.1002/pros.24130DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8194005PMC
June 2021

Adverse impact of polyphasic sleep patterns in humans: Report of the National Sleep Foundation sleep timing and variability consensus panel.

Sleep Health 2021 Jun 29;7(3):293-302. Epub 2021 Mar 29.

Division of Sleep and Circadian Disorders, Departments of Medicine and Neurology, Brigham and Women's Hospital, Boston, Massachusetts, USA; Division of Sleep Medicine, Harvard Medical School, Boston, Massachusetts, USA. Electronic address:

Polyphasic sleep is the practice of distributing multiple short sleep episodes across the 24-hour day rather than having one major and possibly a minor ("nap") sleep episode each day. While the prevalence of polyphasic sleep is unknown, anecdotal reports suggest attempts to follow this practice are common, particularly among young adults. Polyphasic-sleep advocates claim to thrive on as little as 2 hours of total sleep per day. However, significant concerns have been raised that polyphasic sleep schedules can result in health and safety consequences. We reviewed the literature to identify the impact of polyphasic sleep schedules (excluding nap or siesta schedules) on health, safety, and performance outcomes. Of 40,672 potentially relevant publications, with 2,023 selected for full-text review, 22 relevant papers were retained. We found no evidence supporting benefits from following polyphasic sleep schedules. Based on the current evidence, the consensus opinion is that polyphasic sleep schedules, and the sleep deficiency inherent in those schedules, are associated with a variety of adverse physical health, mental health, and performance outcomes. Striving to adopt a schedule that significantly reduces the amount of sleep per 24 hours and/or fragments sleep into multiple episodes throughout the 24-hour day is not recommended.
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http://dx.doi.org/10.1016/j.sleh.2021.02.009DOI Listing
June 2021

Efficacy of intermittent exposure to bright light for treating maladaptation to night work on a counterclockwise shift work rotation.

Scand J Work Environ Health 2021 Jul 28;47(5):356-366. Epub 2021 Mar 28.

Division of Sleep and Circadian Disorders, 221 Longwood Avenue, Boston, MA 02115, USA.

Objectives: Rotating shift work is associated with adverse outcomes due to circadian misalignment, sleep curtailment, work-family conflicts, and other factors. We tested a bright light countermeasure to enhance circadian adaptation on a counterclockwise rotation schedule.

Methods: Twenty-nine adults (aged 20-40 years; 15 women) participated in a 4-week laboratory simulation with weekly counterclockwise transitions from day, to night, to evening, to day shifts. Each week consisted of five 8-hour workdays including psychomotor vigilance tests, two days off, designated 8-hour sleep episodes every day, and an assessment of circadian melatonin secretion. Participants were randomized to a treatment group (N=14), receiving intermittent bright light during work designed to facilitate circadian adaptation, or a control group (N=15) working in indoor light. Adaptation was measured by how much of the melatonin secretion episode overlapped with scheduled sleep timing.

Results: On the last night shift, there was a greater overlap between melatonin secretion and scheduled sleep time in the treatment group [mean 4.90, standard deviation (SD) 2.8 hours] compared to the control group (2.62, SD 2.8 hours; P=0.002), with night shift adaptation strongly influenced by baseline melatonin timing (r=-0.71, P=0.01). While the control group exhibited cognitive deficits on the last night shift, the treatment group's cognitive deficits on the last night and evening shifts were minimized.

Conclusions: In this laboratory setting, intermittent bright light during work hours enhanced adaptation to night work and subsequent readaptation to evening and day work. Light regimens scheduled to shift circadian timing should be tested in actual shift workers on counterclockwise schedules as a workplace intervention.
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http://dx.doi.org/10.5271/sjweh.3953DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8259707PMC
July 2021

Tempering optimism from repeated longitudinal mental health surveys.

Lancet Psychiatry 2021 04;8(4):274-275

Turner Institute for Brain and Mental Health, Monash University, Melbourne, VIC 3800, Australia; Institute for Breathing and Sleep, Austin Health, Melbourne, VIC, Australia; Division of Medicine, University of Melbourne, Melbourne, VIC, Australia.

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http://dx.doi.org/10.1016/S2215-0366(21)00045-6DOI Listing
April 2021

Early public adherence with and support for stay-at-home COVID-19 mitigation strategies despite adverse life impact: a transnational cross-sectional survey study in the United States and Australia.

BMC Public Health 2021 03 15;21(1):503. Epub 2021 Mar 15.

Turner Institute for Brain and Mental Health, Monash University, Melbourne, VIC, 3800, Australia.

Background: Governments worldwide recommended unprecedented measures to contain the coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). As pressure mounted to scale back measures, understanding public priorities was critical. We assessed initial public adherence with and support for stay-at-home orders in nations and cities with different SARS-CoV-2 infection and COVID-19 death rates.

Methods: Cross-sectional surveys were administered to representative samples of adults aged ≥18 years from regions with different SARS-CoV-2 prevalences from April 2-8, 2020. Regions included two nations [the United States (US-high prevalence) and Australia (AU-low prevalence)] and two US cities [New York City (NY-high prevalence) and Los Angeles (LA-low prevalence)]. Regional SARS-CoV-2 and COVID-19 prevalence (cumulative SARS-CoV-2 infections, COVID-19 deaths) as of April 8, 2020: US (363,321, 10,845), AU (5956, 45), NY (81,803, 4571), LA (7530, 198). Of 8718 eligible potential respondents, 5573 (response rate, 63.9%) completed surveys. Median age was 47 years (range, 18-89); 3039 (54.5%) were female.

Results: Of 5573 total respondents, 4560 (81.8%) reported adherence with recommended quarantine or stay-at-home policies (range of samples, 75.5-88.2%). Additionally, 29.1% of respondents screened positive for anxiety or depression symptoms (range of samples, 28.6-32.0%), with higher prevalences among those of younger age, female gender, and those in quarantine or staying at home most of the time versus those who did not report these behaviours. Despite elevated prevalences of adverse mental health symptoms and significant life disruptions, 5022 respondents (90.1%) supported government-imposed stay-at-home orders (range of samples, 88.9-93.1%). Of these, 90.8% believed orders should last at least three more weeks or until public health or government officials recommended, with support spanning the political spectrum.

Conclusions: Public adherence with COVID-19 mitigation policies was highly prevalent, in both highly-affected (US, NY) and minimally-affected regions (AU, LA). Despite disruption of respondents' lives, the vast majority supported continuation of extended stay-at-home orders. Despite common support, these two countries diverged in stringent mitigation implementation, which may have contributed to subsequent outcomes. These results reveal the importance of surveillance of public support for and adherence with such policies during the COVID-19 pandemic and for future infectious disease outbreaks.
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http://dx.doi.org/10.1186/s12889-021-10410-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7957462PMC
March 2021

Spectral sensitivity of circadian phase resetting, melatonin suppression and acute alerting effects of intermittent light exposure.

Biochem Pharmacol 2021 Mar 10:114504. Epub 2021 Mar 10.

Division of Sleep and Circadian Disorders, Departments of Medicine and Neurology, Brigham and Women's Hospital, Boston, MA, USA; Division of Sleep Medicine, Harvard Medical School, Boston, MA, USA.

Intermittent light (IML) pulses are more efficient per minute of exposure than continuous exposure in resetting the phase of the human circadian pacemaker. We assessed the spectral sensitivity in phase resetting, melatonin suppression and alertness induced by IML pulses. Twelve healthy young adults (6 females; mean age ± SD = 25.4 ± 3.6 years) were exposed to six monochromatic light pulses (2.8 × 10 photons/cm/s) over a 6.5 h window during the biological night. Six participants (3F) received 6 × 15-minute 460 nm (blue) pulses and six participants received 6 × 2-minute 555 nm (green) light pulses. Results were compared to historical data in 16 individuals who received continuous 460 nm (n = 8) or 555 nm (n = 8) light exposure using an identical protocol. As expected, long duration continuous 460 nm light exposure induced the largest total phase delay shifts, but intermittent 555 nm light induced the largest phase delay shifts per minute of the photic stimulus. Melatonin suppression was significantly higher under continuous light exposure compared to intermittent exposure patterns, and for 460 nm versus 555 nm exposure (under both light patterns). These data extend prior work showing a non-linear relationship between light exposure duration and phase resetting responses and illustrate the potential role of light wavelength, and therefore photoreceptor recruitment, in mediating these responses.
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http://dx.doi.org/10.1016/j.bcp.2021.114504DOI Listing
March 2021

Extended Work Shifts and Neurobehavioral Performance in Resident-Physicians.

Pediatrics 2021 03 22;147(3). Epub 2021 Feb 22.

Division of Sleep and Circadian Disorders, Departments of Medicine and Neurology, Brigham and Women's Hospital, Boston, Massachusetts.

Objectives: Extended-duration work rosters (EDWRs) with shifts of 24+ hours impair performance compared with rapid cycling work rosters (RCWRs) that limit shifts to 16 hours in postgraduate year (PGY) 1 resident-physicians. We examined the impact of a RCWR on PGY 2 and PGY 3 resident-physicians.

Methods: Data from 294 resident-physicians were analyzed from a multicenter clinical trial of 6 US PICUs. Resident-physicians worked 4-week EDWRs with shifts of 24+ hours every third or fourth shift, or an RCWR in which most shifts were ≤16 consecutive hours. Participants completed a daily sleep and work log and the 10-minute Psychomotor Vigilance Task and Karolinska Sleepiness Scale 2 to 5 times per shift approximately once per week as operational demands allowed.

Results: Overall, the mean (± SE) number of attentional failures was significantly higher ( =.01) on the EDWR (6.8 ± 1.0) compared with RCWR (2.9 ± 0.7). Reaction time and subjective alertness were also significantly higher, by ∼18% and ∼9%, respectively (both <.0001). These differences were sustained across the 4-week rotation. Moreover, attentional failures were associated with resident-physician-related serious medical errors (SMEs) ( =.04). Although a higher rate of SMEs was observed under the RCWR, after adjusting for workload, RCWR had a protective effect on the rate of SMEs (rate ratio 0.48 [95% confidence interval: 0.30-0.77]).

Conclusions: Performance impairment due to EDWR is improved by limiting shift duration. These data and their correlation with SME rates highlight the impairment of neurobehavioral performance due to extended-duration shifts and have important implications for patient safety.
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http://dx.doi.org/10.1542/peds.2020-009936DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7919117PMC
March 2021

Correction: Estimated Sleep Duration Before and During the COVID-19 Pandemic in Major Metropolitan Areas on Different Continents: Observational Study of Smartphone App Data.

J Med Internet Res 2021 Feb 22;23(2):e28057. Epub 2021 Feb 22.

Division of Sleep and Circadian Disorders, Departments of Medicine and Neurology, Brigham and Women's Hospital, Boston, MA, United States.

[This corrects the article DOI: 10.2196/20546.].
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http://dx.doi.org/10.2196/28057DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7901679PMC
February 2021

Correction: Estimated Sleep Duration Before and During the COVID-19 Pandemic in Major Metropolitan Areas on Different Continents: Observational Study of Smartphone App Data.

J Med Internet Res 2021 Feb 22;23(2):e28057. Epub 2021 Feb 22.

Division of Sleep and Circadian Disorders, Departments of Medicine and Neurology, Brigham and Women's Hospital, Boston, MA, United States.

[This corrects the article DOI: 10.2196/20546.].
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http://dx.doi.org/10.2196/28057DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7901679PMC
February 2021

Examining sleep deficiency and disturbance and their risk for incident dementia and all-cause mortality in older adults across 5 years in the United States.

Aging (Albany NY) 2021 02 11;13(3):3254-3268. Epub 2021 Feb 11.

Division of Sleep and Circadian Disorders, Departments of Medicine and Neurology, Brigham and Women's Hospital, Boston, MA 02115, USA.

Background: Sleep disturbance and deficiency are common among older adults and have been linked with dementia and all-cause mortality. Using nationally representative data, we examine the relationship between sleep disturbance and deficiency and their risk for incident dementia and all-cause mortality among older adults.

Methods: The National Health and Aging Trends Study (NHATS) is a nationally-representative longitudinal study of Medicare beneficiaries in the US age 65 and older. Surveys that assessed sleep disturbance and duration were administered at baseline. We examined the relationship between sleep disturbance and deficiency and incident dementia and all-cause mortality over the following 5 years using Cox proportional hazards modeling, controlling for confounders.

Results: Among the sample (n = 2,812), very short sleep duration (≤5 hours: HR = 2.04, 95% CI: 1.26 - 3.33) and sleep latency (>30 minutes: HR = 1.45, 95% CI: 1.03 - 2.03) were associated with incident dementia in adjusted Cox models. Difficulty maintaining alertness ("Some Days": HR = 1.49, 95% CI: 1.13 - 1.94 and "Most/Every Day": HR = 1.65, 95% CI: 1.17 - 2.32), napping ("Some days": HR = 1.38, 95% CI: 1.03 - 1.85; "Most/Every Day": HR = 1.73, 95% CI: 1.29 - 2.32), sleep quality ("Poor/Very Poor": HR = 1.75, 95% CI: 1.17 - 2.61), and very short sleep duration (≤5 hours: HR = 2.38, 95% CI: 1.44 - 3.92) were associated with all-cause mortality in adjusted Cox models.

Conclusions: Addressing sleep disturbance and deficiency may have a positive impact on risk for incident dementia and all-cause mortality among older adults.
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http://dx.doi.org/10.18632/aging.202591DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7906211PMC
February 2021

Robust stability of melatonin circadian phase, sleep metrics, and chronotype across months in young adults living in real-world settings.

J Pineal Res 2021 Apr 16;70(3):e12720. Epub 2021 Feb 16.

Division of Sleep and Circadian Disorders, Departments of Medicine and Neurology, Brigham and Women's Hospital, Boston, MA, USA.

Appropriate synchronization of the timing of behaviors with the circadian clock and adequate sleep are both important for almost every physiological process. The timing of the circadian clock relative to social (ie, local) clock time and the timing of sleep can vary greatly among individuals. Whether the timing of these processes is stable within an individual is not well-understood. We examined the stability of circadian-controlled melatonin timing, sleep timing, and their interaction across ~ 100 days in 15 students at a single university. At three time points ~ 35-days apart, circadian timing was determined from the dim-light melatonin onset (DLMO). Sleep behaviors (timing and duration) and chronotype (ie, mid-sleep time on free days corrected for sleep loss on school/work days) were determined via actigraphy and analyzed in ~ 1-month bins. Melatonin timing was stable, with an almost perfect relationship strength as determined via intraclass correlation coefficients ([ICC]=0.85); average DLMO timing across all participants only changed from the first month by 21 minutes in month 2 and 5 minutes in month 3. Sleep behaviors also demonstrated high stability, with ICC relationship strengths ranging from substantial to almost perfect (ICCs = 0.65-0.85). Average DLMO was significantly associated with average chronotype (r  = 0.53, P <.01), with chronotype displaying substantial stability across months (ICC = 0.61). These findings of a robust stability in melatonin timing and sleep behaviors in young adults living in real-world settings holds promise for a better understanding of the reliability of previous cross-sectional reports and for the future individualized strategies to combat circadian-associated disease and impaired safety (ie, "chronomedicine").
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http://dx.doi.org/10.1111/jpi.12720DOI Listing
April 2021

Estimated Sleep Duration Before and During the COVID-19 Pandemic in Major Metropolitan Areas on Different Continents: Observational Study of Smartphone App Data.

J Med Internet Res 2021 02 2;23(2):e20546. Epub 2021 Feb 2.

Division of Sleep and Circadian Disorders, Departments of Medicine and Neurology, Brigham and Women's Hospital, Boston, MA, United States.

Background: Amid the COVID-19 pandemic, public health policies to curb the spread of SARS-CoV-2 and its associated disease, COVID-19, have resulted in significant alterations to daily routines (eg, work-from-home policies) that may have enabled longer sleep duration among the general population.

Objective: We aimed to examine changes in estimated sleep duration in 5 major metropolitan areas before and after the start of the COVID-19 pandemic.

Methods: We conducted a prospective observational study using estimated sleep duration data obtained from a smartphone app. The data were obtained from regular users of the smartphone app before and after the World Health Organization declared COVID-19 a pandemic in March 2020. We compared within-subject estimated sleep duration before and during the COVID-19 pandemic using generalized linear mixed models.

Results: Among the 2,871,037 observations, 957,022 (33.3%) were from users in London; 549,151 (19.1%) were from users in Los Angeles; 846,527 (29.5%) were from users in New York City; 251,113 (8.7%) were from users in Seoul; and 267,224 (9.3%) were from users in Stockholm. The average age of the users in the sample was 35 years (SE 11 years). Prior to the COVID-19 pandemic, people residing in Seoul had the shortest estimated sleep duration (mean 6 hours 28 minutes, SE 11.6 minutes) and those residing in Stockholm had the longest estimated sleep duration (mean 7 hours 34 minutes, SE 9.9 minutes). The onset of the COVID-19 pandemic was associated with a 13.7 minute increase in estimated sleep duration when comparing March 2019 and March 2020 (95% CI 13.1-14.3, P<.001) and an increase of 22.3 minutes when comparing April 2019 and April 2020 (95% CI 21.5-23.1, P<.001).

Conclusions: The average estimated sleep duration increased sharply in the months after the onset of the COVID-19 pandemic. This finding suggests that the implementation of COVID-19 mitigation strategies has provided people worldwide with increased opportunities to sleep, which may enhance the response of the immune system to viral pathogens.
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http://dx.doi.org/10.2196/20546DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7857389PMC
February 2021

Stability of the timing of food intake at daily and monthly timescales in young adults.

Sci Rep 2020 11 30;10(1):20849. Epub 2020 Nov 30.

Division of Sleep and Circadian Disorders, Departments of Medicine and Neurology, Brigham and Women's Hospital, 221 Longwood Ave, Boston, MA, 02115, USA.

Cross-sectional observations have shown that the timing of eating may be important for health-related outcomes. Here we examined the stability of eating timing, using both clock hour and relative circadian time, across one semester (n = 14) at daily and monthly time-scales. At three time points ~ 1 month apart, circadian phase was determined during an overnight in-laboratory visit and eating was photographically recorded for one week to assess timing and composition. Day-to-day stability was measured using the Composite Phase Deviation (deviation from a perfectly regular pattern) and intraclass correlation coefficients (ICC) were used to determine individual stability across months (weekly average compared across months). Day-to-day clock timing of caloric events had poor stability within individuals (~ 3-h variation; ICC = 0.12-0.34). The timing of eating was stable across months (~ 1-h variation, ICCs ranging from 0.54-0.63), but less stable across months when measured relative to circadian timing (ICC = 0.33-0.41). Our findings suggest that though day-to-day variability in the timing of eating has poor stability, the timing of eating measured for a week is stable across months within individuals. This indicates two relevant timescales: a monthly timescale with more stability in eating timing than a daily timescale. Thus, a single day's food documentation may not represent habitual (longer timescale) patterns.
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http://dx.doi.org/10.1038/s41598-020-77851-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7705740PMC
November 2020

Sleep medication use and incident dementia in a nationally representative sample of older adults in the US.

Sleep Med 2021 03 11;79:183-189. Epub 2020 Nov 11.

Division of Sleep and Circadian Disorders, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA; Division of Sleep Medicine, Harvard Medical School, Boston, MA, USA.

Background: Sleep difficulties are common among older adults, and clinical management of sleep difficulties commonly includes sleep medication (pharmacological and non-pharmacological). Our research examines sleep medication use and incident dementia over 8 years using nationally representative data from older adults ages 65 years and older in the United States.

Methods: We used data collected from the National Health and Aging Trends Study (NHATS), a nationally-representative longitudinal study of Medicare beneficiaries. Routine sleep medication use (pharmacological and non-pharmacological) was defined as use "most nights" or "every night." Participants were screened for dementia with validated instruments that assessed memory, orientation, and executive function. We conduct prospective analyses to examine the relationship between routine sleep medication use and incident dementia using Cox proportional hazards modeling and estimated survival curves. Analyses controlled for age, sex, marital status, education, and chronic conditions.

Results: Among respondents at baseline (n = 6373), most participants (21%) were age 70-74 years of age. Participants were 59% female and the sample comprised non-Hispanic White (71%). At baseline, 15% of our study sample reported using sleep medication routinely, which is representative of 4.6 million older adults in the US. Covariate adjusted proportional hazard models revealed that routinely using sleep medication was associated with incident dementia (HR = 1.30, 95%CI: 1.10 to 1.53, p < 0.01).

Conclusions: Our study observed, in a nationally representative study of older adults in the US across 8 years of data that 15% of older adults report routinely using sleep medication, yet routine use of sleeping medication was associated with incident dementia across the follow-up interval. Future research may examine behavioral approaches to improving sleep among older adults.
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http://dx.doi.org/10.1016/j.sleep.2020.11.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7925354PMC
March 2021

Employee Sleep Enhancement and Fatigue Reduction Programs: Analysis of the 2017 CDC Workplace Health in America Poll.

Am J Health Promot 2021 05 11;35(4):503-513. Epub 2020 Nov 11.

Department of Psychiatry, 12216University of Arizona College of Medicine, Tucson, AZ, USA.

Background: Poor sleep health, including sleep deficiency and sleep disturbance, is common among employed adults in the U.S. and is associated with undesirable workplace outcomes. Adoption of workplace health promotion programs (WHPPs) is increasing, yet few programs aim to reduce fatigue or improve sleep among employees.

Objective: We analyzed data from the nationally representative 2017 Centers for Disease Control Workplace Health in America poll to identify the prevalence of sleep enhancement or fatigue reduction WHPPs and the characteristics of employers that offer these programs.

Method: A stratified random sample of nationally-representative worksites with ≥10 employees was generated. It comprised 2,843 worksites. Worksite representatives reported workplace characteristics, health promotion activities, and the likelihood of offering WHPPs relating to sleep enhancement or fatigue reduction. Logistic regression analyses were utilized to identify characteristics associated with offering a sleep enhancement or fatigue reduction WHPP, controlling for WHPP budget and size of the company, and contingent on worksites having a comprehensive workplace health plan.

Results: Less than 1 in 10 worksites (10%) reported offering a sleep enhancement or fatigue reduction WHPP. Worksites most likely to offer a sleep-focused WHPP were those in retail, wholesale, or technology industries (OR = 2.71, 95%CI: 1.08-6.8) vs. those in the finance, information, technology industries; those with a large WHPP budget (>$500,000, OR = 6.85, 95%CI: 2.1-22.35) vs. those with no budget; and those that had visible support of WHPP initiatives from senior leadership (OR = 4.74, 95%CI: 1.91-11.75) vs. those without such support.

Conclusions: Our results highlight how few worksites reported offering sleep-focused programs for their employees. Those worksites that did feature such programs, were commonly well-resourced and had senior leadership support for WHPP initiatives in general. Future research should consider working directly with leaders to expand the implementation of employee sleep enhancement and fatigue reduction WHPPs.
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http://dx.doi.org/10.1177/0890117120969091DOI Listing
May 2021

Association of Sleep Disorders With Physician Burnout.

JAMA Netw Open 2020 10 1;3(10):e2023256. Epub 2020 Oct 1.

Sleep Matters Initiative, Division of Sleep and Circadian Disorders, Departments of Medicine and Neurology, Brigham and Women's Hospital, Boston, Massachusetts.

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http://dx.doi.org/10.1001/jamanetworkopen.2020.23256DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7599440PMC
October 2020

Psychological Screening for Exceptional Environments: Laboratory Circadian Rhythm and Sleep Research.

Clocks Sleep 2020 Jun 15;2(2):13. Epub 2020 Apr 15.

Division of Sleep and Circadian Disorders, Departments of Medicine and Neurology, Brigham and Women's Hospital, Boston, MA 02115, USA; (S.A.A.); (B.L.B.); (J.H.L.); (C.A.C.).

Selecting participants who constitute a representative sample while protecting them from potential adverse outcomes is a concern for clinical researchers. Our research group conducts deep phenotyping studies of the circadian timing system and sleep-wake regulation in long (up to 3 months) laboratory experiments, similar in many ways to "exceptional environment" conditions. Here, we describe the psychological screening process we have used for more than 30 years. We outline our "Select In" and "Select Out" measures within three major categories: psychological, psychophysiological, and psychosocial factors. We describe the screening process, inclusion-exclusion criteria on standard questionnaires, and clinical interview questions. We also describe how we manage the exclusion process during screening, ensure continued psychological health during the laboratory study, and manage study terminations. We present data from one recent study, outlining the number of individuals excluded at each stage of the process and present subjective mood data from the included individuals, showing the trajectory of mood across the five-week laboratory study and the end-of-study debriefing, during which the participants rated their comfort with various aspects of the study and their willingness to return for a future study. While designed for our inpatient research studies, elements of these procedures may also be useful for selecting individuals for other exceptional environments.
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http://dx.doi.org/10.3390/clockssleep2020013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7445832PMC
June 2020

Exposure to Short Wavelength-Enriched White Light and Exercise Improves Alertness and Performance in Operational NASA Flight Controllers Working Overnight Shifts.

J Occup Environ Med 2021 02;63(2):111-118

Division of Sleep and Circadian Disorders, Departments of Medicine and Neurology, Brigham and Women's Hospital, Boston, Massachusetts (Dr Barger, Sullivan, Dr Lockley, Dr Czeisler); Division of Sleep Medicine, Harvard Medical School, Boston, Massachusetts (Dr Barger, Dr Lockley, Dr Czeisler).

Objective: We evaluated the efficacy of a combined short-wavelength-enriched white light and exercise fatigue countermeasure during breaks for flight controllers working overnight shifts.

Methods: Twenty NASA flight controllers were studied for two blocks of nightshifts in ISS mission control, randomized to either the control or countermeasure condition. The countermeasure constituted passive exposure to blue-enriched polychromatic lighting for three 20-minute intervals, which included 10 minutes of exercise and occurred before and twice during their shifts. Alertness, performance, and mood were evaluated.

Results: Flight controllers reported being significantly more alert (P < 0.0001) and happy (P = 0.003) and had faster reaction times (10% slowest responses; P < 0.05) during the countermeasure condition compared to control.

Conclusions: The combined light and exercise countermeasure improved alertness, performance, and mood in shift workers overnight. Further research is necessary to determine their relative contribution.
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http://dx.doi.org/10.1097/JOM.0000000000002054DOI Listing
February 2021

Demographic Characteristics, Experiences, and Beliefs Associated with Hand Hygiene Among Adults During the COVID-19 Pandemic - United States, June 24-30, 2020.

MMWR Morb Mortal Wkly Rep 2020 Oct 16;69(41):1485-1491. Epub 2020 Oct 16.

Frequent hand hygiene, including handwashing with soap and water or using a hand sanitizer containing ≥60% alcohol when soap and water are not readily available, is one of several critical prevention measures recommended to reduce the spread of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19).* Previous studies identified demographic factors associated with handwashing among U.S. adults during the COVID-19 pandemic (1,2); however, demographic factors associated with hand sanitizing and experiences and beliefs associated with hand hygiene have not been well characterized. To evaluate these factors, an Internet-based survey was conducted among U.S. adults aged ≥18 years during June 24-30, 2020. Overall, 85.2% of respondents reported always or often engaging in hand hygiene following contact with high-touch public surfaces such as shopping carts, gas pumps, and automatic teller machines (ATMs). Respondents who were male (versus female) and of younger age reported lower handwashing and hand sanitizing rates, as did respondents who reported lower concern about their own infection with SARS-CoV-2 and respondents without personal experience with COVID-19. Focused health promotion efforts to increase hand hygiene adherence should include increasing visibility and accessibility of handwashing and hand sanitizing materials in public settings, along with targeted communication to males and younger adults with focused messages that address COVID-19 risk perception.
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http://dx.doi.org/10.15585/mmwr.mm6941a3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7561087PMC
October 2020

Time-of-day and Meal Size Effects on Clinical Lipid Markers.

J Clin Endocrinol Metab 2021 Mar;106(3):e1373-e1379

Division of Sleep and Circadian Disorders, Departments of Medicine and Neurology, Brigham and Women's Hospital, Boston, Massachusetts.

Context: Dyslipidemia and cardiovascular disease are common in shift workers and eating at night may contribute to this pathophysiology.

Objective: To examine the effects of eating at different times of day on lipid profiles.

Design: Two 24-hour baseline days with 8 hours of sleep, 3 meals (breakfast, lunch, dinner) and a snack, followed by a 40-hour constant routine (CR) with hourly isocaloric meals.

Setting: Intensive Physiological Monitoring Unit, Brigham and Women's Hospital.

Participants: Twenty-one healthy adults [23.4 ± 2.7 years, 5F].

Intervention: Forty-hour CR.

Main Outcome Measures: A standard clinical lipid panel, consisting of total cholesterol, triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C), was assayed in blood samples collected 4-hourly across ~4 days.

Results: When participants ate at night, levels of TG were similar to eating during the day, however, these levels at night were reached with consuming approximately half the calories. Additionally, 24-hour levels of TG were 10% higher when meals were consumed hourly across 24 hours compared to consuming a typical 3-meal schedule while awake during the day and sleeping at night. The endogenous circadian rhythms of TG, which peaked at night, were shifted earlier by ~10 hours under baseline conditions, whereas the rhythms in total cholesterol, HDL-C, and LDL-C remained unchanged and peaked in the afternoon.

Conclusions: The time-of-day dependency on postprandial lipid metabolism, which leads to hypersensitivity in TG responses when eating at night, may underlie the dyslipidemia and elevated cardiovascular disease risk observed in shift workers.
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http://dx.doi.org/10.1210/clinem/dgaa739DOI Listing
March 2021

Patient Safety and Resident Schedules without 24-Hour Shifts. Reply.

N Engl J Med 2020 09;383(13):1288

Brigham and Women's Hospital, Boston, MA

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http://dx.doi.org/10.1056/NEJMc2025843DOI Listing
September 2020
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