The Role of Estradiol in Modifying Circadian Rhythms, Sleep Regularity and Risk for Depression During the Pubertal Transition

Background: The pubertal transition (PT) is characterized by dramatic reproductive hormone fluctuations, a developmental circadian delay, and significant changes in sleep and wake patterns. The PT also marks an abrupt divergence between the sexes in risk for depression and sleep disorders that remains elevated for females across the reproductive lifespan, implicating ovarian hormones (i.e., estradiol (E2)) as a common pathway of risk. Notably, inconsistent schedules during the COVID-19 pandemic have contributed to greater sleep irregularity (especially for adolescents), which is associated with affective impairment and inferior clinical outcomes. The objective of this research is to characterize the pathophysiological impact of E2 on sleep disturbances, endocrine rhythm dysregulation and depressive symptoms in peripubertal females. Method(s): 44 peripubertal females (ages 11-14, within 1-year post-menarche) provided daily hormone (E1G-urinary metabolite of E2) and mood assessments for one menstrual cycle and completed an 8-day sleep assessment (actigraphy, daily sleep diaries), with cortisol and melatonin circadian measurement (over four days) starting at day 7 of the following menstrual cycle. Minute-to-minute consistency in sleep/wake state over 24-hrs was calculated to index sleep regularity (SRI). Result(s): A multiple regression model predicted depressive symptoms (CES-DC) from follicular menstrual cycle phase E1G-AUC, sleep regularity index (SRI), cortisol and melatonin AUCs (F(4,18) = 3.833, p=.020, R2=.46). E1G, cortisol-AUC (p<.05) and SRI (marginally, p=.08) contributed to the prediction. Conclusion(s): Results suggest that greater sleep irregularity, greater follicular estradiol and blunted cortisol may contribute to increased depressive symptoms in peripubertal females, providing mechanistic insight into the estradiol-related sleep and affect disruptions experienced during the pubertal transition. Funding Source: K01MH121575;Foundation of Hope for Research and Treatment of Mental Illness (NC) Keywords: Puberty, Sleep Disturbances, Estradiol, Circadian Rhythms, Depressive SymptomsCopyright © 2023

The evolving landscape of pulmonary arterial hypertension clinical trials

Although it is a rare disease, the number of available therapeutic options for treating pulmonary arterial hypertension has increased since the late 1990s, with multiple drugs developed that are shown to be effective in phase 3 randomised controlled trials. Despite considerable advancements in pulmonary arterial hypertension treatment, prognosis remains poor. Existing therapies target pulmonary endothelial dysfunction with vasodilation and anti-proliferative effects. Novel therapies that target proliferative vascular remodelling and affect important outcomes are urgently needed. There is need for additional innovations in clinical trial design so that all emerging candidate therapies can be rigorously studied. Pulmonary arterial hypertension trial design has shifted from short-term submaximal exercise capacity as a primary endpoint, to larger clinical event-driven trial outcomes. Event-driven pulmonary arterial hypertension trials could face feasibility and efficiency issues in the future because increasing sample sizes and longer follow-up durations are needed, which would be problematic in such a rare disease. Enrichment strategies, innovative and alternative trial designs, and novel trial endpoints are potential solutions that could improve the efficiency of future pulmonary arterial hypertension trials while maintaining robustness and clinically meaningful evidence.Copyright © 2022 Elsevier Ltd

CNS Summit 2022

The proceedings contain 66 papers. The topics discussed include: AI-driven COVID-19 mRNA vaccine degradation prediction;evidence-based clinical trial feasibility and protocol design using artificial intelligence;reducing sample sizes by up to 30% in clinical trials for mood disorders via enhanced primary endpoint reliability using audio-visual multimodal machine learning;the development of an automated EEG-based machine learning pipeline for the detection of Alzheimer's disease: a proof of concept for novel clinical trial biomarkers;tools for rapid development of EEG-based pharmacodynamic biomarkers;TWINRCT: novel ai-based solution to reduce sample size of control arms;circadian rhythm-related endpoints derived from actigraphy: validation of SOMNO-ART;and reliability of real world digital end-points of functional neurophysiology.

Predictors of objectively-measured sedentary time during the COVID-19 pandemic among breast cancer survivors participating in a diet and physical activity intervention

Purpose of the study: The purpose of this study was to investigate the predictors of objectively-measured sedentary time (ST) among breast cancer (BC) survivors who were 60 days post-treatment and were initiating participation in an intervention to improve diet and physical activity (PA) during the early phase of the COVID-19 pandemic. Methods: Cook and Move for Your Life (CMFYL) was a pilot and feasibility study of stage 0-III BC survivors testing the effects of a remotely-delivered and remotely-assessed nutrition and PA intervention. Women were ≥60 days post-treatment (current endocrine therapy allowed), consumed <5 servings of fruits/vegetables per day and/or engaged in <150 minutes/week of moderate to vigorous physical activity (MVPA). Hip-worn Actigraph GT3X accelerometers measured ST for 7 consecutive days at baseline. ST was defined as minutes/day (continuous) based on the Troiano cutpoint (<100 counts/minute), during awake (6am-11pm) wear time, and non-wear was identified using the Choi algorithm on the vector magnitude counts/minute. Multivariable linear regression models adjusting for wear time (average minutes/day) and minutes of MVPA/day were used to examine whether the following factors were predictors of ST at baseline: self-reported demographics, psychosocial factors (assessed via PROMIS Physical Function and PROMIS Anxiety forms), diet quality (Healthy Eating Index 2015 score), caloric intake (calories/day), and fruit and vegetable intake (servings/day). Results: Among the 84 women included in this analysis who had actigraphy measurements at baseline, the average ST/day was 684±79 minutes. On average, women were 58±10 years in age and most self-identified as non-Hispanic white (87%). The average time since diagnosis at time of enrollment was 4.5 years and 59% of women were receiving endocrine therapy at baseline. Adjusted models show that participants with a college degree had 24.7 (95%CI 2.0, 47.4) more minutes of ST than those with less than a college degree, and for every 1-point increase in PROMIS Physical Function scores participants had 2.5 (95%CI -4.9, -0.2) fewer minutes of ST. Conclusion: In a sample of BC survivors enrolled in a diet and PA intervention, higher level of education and poorer physical function were associated with higher ST during the early phase of the COVID-19 pandemic. These findings provide preliminary insight into factors associated with ST. Future work will investigate how these factors influence change in ST after participation in the CMFYL intervention.

Examination of prospective sleep across the menstrual cycle

Introduction: Women are twice as likely to develop insomnia across their lifetime compared with men. This may be explained, in part, by changes in hormones and menstrual cycle phase in reproductive-aged women. Intra- and inter-variability of menstrual cycle timing can make it difficult to accurately measure sleep quality and quantity in sleep research studies. This study aimed to examine the role of menstrual cycle phase in daily self-report and actigraphy-assessed sleep across two consecutive menstrual cycles. Materials and Methods: Fifty-one women (43% Caucasian) between the ages of 18 and 35 (m age = 23.67, SD = 4.68) completed continuous sleep monitoring via actigraphy and daily sleep diaries over two menstrual cycles (m days = 51.29). Cycles were identified via first date of menstrual bleeding and midcycle urinary ovulation testing and were coded into four phases: perimenstrual, mid-follicular, periovulatory, and mid-luteal. The perimenstrual phase was defined as the 3 days prior to and the first 3 days of menstrual bleeding. Within- and between-person relationships between menstrual phase and sleep parameters were estimated using multistep hierarchical linear modeling. Subjective and objective measures yielded the following sleep variables: Total Wake Time (TWTsub and TWTobj), Sleep Efficiency (SEsub and SEobj), and subjective sleepiness. Pandemic-related stress and daily US and region-specific COVID-19 case counts were included as covariates in adjusted models. Results: The sample had a mean a cycle length of 28.61 days (SD = 2.69). Regarding actigraphy data, menstrual phase predicted TWTobj and SEobj. Women spent 4-7 fewer minutes awake during the mid-follicular (m = 61.54, SE = 3.37) and mid-luteal phases (m = 63.11, SE = 3.29), compared to the perimenstrual phase (m = 67.54, SE = 3.37;p <.001). Sleep efficiency was higher in the mid-luteal phase (m = 82.50, SE = 0.79) compared to the perimenstrual phase (m = 80.71, SE = 0.82, p =.006). Subjective ratings indicated that during the perimenstrual phase women spent 8-16 minutes longer awake (m = 52.23, SE = 5.01, p <.001) and experienced reduced sleep efficiency of between 1-3 percentage points (m = 89.70, SE = 0.10, p <.001) compared to all other phases. Women also reported increased morning sleepiness in the perimenstrual (m = 4.71, SE = 0.21) compared to the periovulatory phase (m = 4.34, SE = 0.22, p =.02). Random coefficients models for objective and subjective sleep variables were nonsignificant, indicating that these relationships did not vary significantly between participants. Conclusions: To our knowledge, this is one of the first studies to examine subjective and objective sleep prospectively across two consecutive menstrual cycles. Disturbed sleep was highest in the perimenstrual phase. Future studies should measure menstrual cycle phase when investigating sleep in reproductive age women.

Impact of sleep duration on the response to vaccination: A meta-analysis

Introduction: The SARS-COV-2 pandemic has resulted in over than 5 millions confirmed deaths. Although vaccination is a major strategy to control this pandemic, to date, only 54% of the world population has received at least one dose of a COVID-19 vaccine. Booster inoculations are increasingly recommended. Thus, the vaccination effort may need to continue for several years before the epidemic can be considered as contained. Although antibody response is just one facet of the adaptive immune system’s response to vaccination, it is considered to be a clinically significant biomarker of protection. The role of insufficient sleep duration in individual differences in antibody responses to vaccination against influenza or hepatitis has been examined in a number of studies, with somewhat mixed results. In order to summarize and clarify these findings, we have used a meta-analytical approach to determine whether the current body of evidence suggests that optimizing sleep duration may be an easily modifiable behavior that could increase the efficacy of anti-viral vaccination. Materials and Methods: The PubMed database was searched with the combination “sleep*” and “vaccin*” keywords. Studies were selected if they met the following criteria: (1) were performed on healthy human adults;(2) assessed vaccine efficacy by antibody titers or protection status;(3) performed subjective (survey items, questionnaire, sleep diary, interview) and/or objective (actigraphy, polysomnography) measures of sleep duration;(4) were laboratory-conducted studies of manipulation of sleep duration over 1 or more nights;(5) were cohort studies;(6) were peer reviewed original research papers. Since the number of available studies was small, we have engaged in a collaborative effort with the authors of all publications to obtain the information needed to optimize the estimation of the pooled effect size (ES) and the 95% confidence intervals: log transformed data when non parametric testing was used;calculation of separate ES for men and women;analyses corrected for age and overweight/obesity status whenever appropriate;sleep data no more than one week apart from inoculation. Number of participants, mean, beta or odd ratio and their respective dispersion were collected. The ES was interpreted as small when ≤0.20, moderate when >0.50 - ≤ 0.80 or large when >0.80. Results: No relationship was observed between self-reported short sleep and vaccine efficacy (n=504;overall ES=0.16 [-0.12, 0.44]). In contrast, when studies that used objective measures of sleep were examined, a robust adverse impact of short sleep on vaccine efficacy was detected (n=282;overall ES=0.96 [0.15, 1.78]). The pooled ES for experimental studies (n=111) was 0.84 [0.20, 1.49] and 1.08 [0.10, 2.06] for prospective studies (n=171). The meta-analysis did not find significant differences in ES between women and men. Conclusions: When assessed objectively, short sleep duration was associated with a clinically relevant decrease in efficacy of anti-viral vaccination. These findings suggest that achieving adequate amount of sleep during the time window surrounding the time of inoculation may increase the efficacy of vaccines against diverse strains of viruses, possibly including strains of SARS-CoV-2. Acknowledgements: Collectively, the authors acknowledge the support of their respective institutions in these challenging times.

Digital Cognitive Behavioural Therapy for Insomnia (dCBT-I) and emotion regulation as early intervention for employees in the workplace

Insomnia is a serious public health concern and has been linked to impaired work productivity. Studies show a link between poor sleep and aspects of occupational functioning such as absenteeism, reduced productivity and low work satisfaction. One in every three workers in the UK are affected by sleep problems costing the economy around £36 billion/year due to loss of productivity in the workplace. This results in around 200,000 working days lost every year, and it is estimated that the cost to industry will rise steadily to £44 billion by 2030 if nothing is done about it. Few studies have evaluated the effectiveness of CBT-I in workplaces, and have found improvements in severity of insomnia and quality of sleep, and slight improvements in productivity and presenteeism, but not in absenteeism. While most interventions for insomnia are focused on the treatment of those above clinical thresholds, there is crucial need for early intervention/prevention of insomnia. This has been further exacerbated during the Covid-19 pandemic due to isolation, financial insecurities, loss of loved ones and fear of infection, causing extensive sleep problems as well as stress, anxiety and depressive symptoms. This study will examine the efficacy of a new hybrid dCBT-I for mild to severe insomnia and symptoms of depression and anxiety delivered to employees in the workplace. This trial tests the efficacy of implementing a hybrid dCBT-I + emotion regulation (ER) in the workplace in a mixed methods evaluation with a two-arm randomised waitlist control (WLC) design. The dCBT-I+ER intervention is 8-weeks long and delivered via self-guided online platform and four videoconferencing therapy sessions. Primary outcomes are the Insomnia Severity Index, the Patient Health Questionnaire and the Generalised Anxiety Disorder. Secondary outcomes are job productivity, job satisfaction, well-being, quality of life, self-reported (sleep diary data) and objective (actigraphy) sleep parameters. We recruited 163 workers with sleep and emotion regulation problems ranging from subclinical to clinical levels not engaged in treatment at the time of the trial. Due to the study design, analyses for the primary hypotheses will be done when the last enrolled participant provides post-intervention follow-up (1-month) outcome measures. We hypothesise that participants randomly allocated to dCBT-I+ER will demonstrate significantly greater improvements on the primary outcomes compared to WLCs post-intervention. They will also demonstrate significantly greater improvements on objective (actigraphy) and self-reported (sleep diary) sleep parameters. Exploratory analyses will also indicate the impact of the dCBT-I+ER on work productivity, job satisfaction, wellbeing, and quality of life. Evaluation of an early intervention for workers with mild to severe symptoms of insomnia and emotion regulation difficulties will contribute to the understanding of benefits of early interventions in the workplace, and its impact on mental health and productivity. The mixed methods evaluation will provide insight into the application of intervention and help us understand people’s experiences of the intervention and what helped or hindered its use. This pilot study forms the basis of what could become a larger nationwide service delivery programme of mental health interventions for insomnia in the workplace.

Sleep disturbances in craniopharyngioma: a challenging diagnosis

Introduction: The hypothalamus plays a crucial role in regulating vital functions and circadian rhythms. Both the tumor involving the hypothalamic area and its treatment can lead to hypothalamic dysfunction, resulting in disturbances in sleep-wake patterns, sleep fragmentation, and increased daytime sleepiness. We describe two patients with craniopharyngioma who came to our attention due to the occurrence of episodes characterized by psychomotor slowing and afinalistic limb movements, temporal and spatial disorientation, psychomotor agitation, and oneiric stupor like episodes diagnosed as severe sleep disturbances. Case reports: Patient 1 is a 19-year-old male diagnosed with surgically treated craniopharyngioma. Subsequently, episodes of psychomotor slowing, afinalistic movements of the upper limbs diagnosed as seizures in another neurological center appeared;antiepileptic treatment was started without improvement. At the first examination in our center, excessive daytime sleepiness (EDS), fragmented nighttime sleep, episodes characterized by bimanual automatic gestures occurring during drowsy state, hypnagogic hallucinations, and sudden loss of muscle tone while awake were recognized. Actigraphy demonstrated irregular bedtimes, frequent nocturnal activity, and inappropriate daytime rest episodes. The Epworth Sleepiness Scale (ESS) showed subjective EDS (ESS=19). At PSG, hypersomnolence, severe sleep-related breathing disorder (SRBD), and no interictal and ictal seizure abnormalities were found. A BiPAP NIV was started, and antiepileptic therapy was discontinued. In the following months, PSG revealed marked improvement in SRBD and 1 SOREMP, and the MSLT a mean SOL of 6 min and 10 sec and 3 SOREMPs. These data allowed the diagnosis of secondary narcolepsy, and treatment with pitolisant was initiated with clinical improvement and reduced daytime sleepiness (ESS=9). Patient 2 is a 12-year-old male, surgically treated for craniopharyngioma at the age of 4 years, who developed episodes of myoclonic jerks, temporal and spatial disorientation, and psychomotor agitation during the lockdown period for COVID-19 emergency. Surmising paroxysmal epileptic episodes, the patient was hospitalized. The anamnestic data collection revealed a sleep-wake rhythm dysregulation, fragmented nighttime sleep, EDS, oneiric stupor-like episodes during which the patient performed simple automatic gestures mimicking daily-life activity, and severe impairment of alertness. The Long-term video-EEG, including polygraphic measurements, showed destruction of the wake-NREM sleep-REM sleep boundaries, episodes of undetermined state of vigilance, and concurrence of elements typical of different sleep stages. Moreover, a severe SRBD (AHI 19/h) has been observed. The MRI showed a volumetric increase in the post-surgical interpeduncular fossa and right paramedian cysts. Therefore, a multifactorial therapeutic plan including sleep hygiene and slow-release melatonin was started with improvement in nighttime sleep, but EDS persisted. Surgical treatment of cyst fenestration improved sleep-wake rhythm and behavior;BiPAP NIV was initiated with very poor adherence. Discussion: We aim to focus on sleep disorders as a possible complication of tumors involving the hypothalamic region. Our cases highlight that the clinical manifestation of these dysfunctions can be challenging to diagnose and can lead to misdiagnosis and inappropriate treatment that can harm patients' health and the quality of life of patients and their families. Conclusion: These findings support the need to incorporate comprehensive sleep assessment in survivors from childhood brain tumors involving the suprasellar/hypothalamic region.

The role of BDNF Val66Met polymorphism in circadian rhythm variation and attention in adolescents

Introduction: Adolescents' cognitive performance is impacted by factors such as sleep habits, chronotypes and also genetic characteristics. The periods of human sleep and wakefulness are controlled by homeostatic and circadian factors, which the combination generates variations in the preferences for hours of activity and rest, called chronotypes. Chronotypic classification impacts cognitive skills such as logic and problem solving. In adolescence, there is a greater tendency to evening chronotype. The neural factor called BDNF, Brain- Derived Neurotrophic Factor, showed a significant role in cognitive performance variations as in different sleep patterns. The human BDNF gene has a frequent polymorphism called Val66Met, related to several cognitive functions and different patterns of sleep and circadian rhythm. Objective: Evaluate the association of BDNF Val66Met polymorphism with circadian patterns and cognitive performance on tests of attention, in high school students. Methods: High school students, aged between 15 and 17 years old were included in the study, whose cognitive attention skills were investigated by the Psychological Battery for Assessment of Attention. Their BDNF genotypes were determined by analyzing self-collected oral cell samples, which were amplified by real-time PCR using fluorescent probes. Chronotypic characteristics were evaluated by completing two morningness and eveningness scales. Because of the pandemic of COVID-19, a questionnaire about the presence of symptoms, in the previous days of the tests, was included. At present, volunteers are being evaluated through actigraphy. Results: Eighty-five adolescents were evaluated in that study. The average attention score of students who study in the afternoon was lower than individuals who study in the morning. The average score attention for the female gender was significantly lower than that obtained for the male gender. The students who reported symptoms of COVID- 19 had a significantly lower attention score. Lastly, there was no correlation between the chronotype defined by the scales, the performance in the attention test, or even the BDNF genotype of the participants. Conclusion: The central findings obtained, in the first phase of the study, complement the understanding of the associations between the parameters of cognition, chronobiology and genetic aspects. In the next phase, the use of actigraphy will make it possible to deepen these analyzes and conclusions.

Sleep behavior of shift workers who maintained external work activities during the period of social restriction of COVID-19

Introduction: Sleep contributes to the proper functioning of the body and the immune system. During the COVID-19 pandemic, isolation was a strategy to contain the spread of the virus and altered daily routine and sleep. Some studies have shown improved sleep in some populations, while others have reported worsening, especially in health shift worker groups. Objective: To compare the sleep behavior of shift workers at a mining company, who remained active before and during the isolation period of the COVID-19 pandemic. Methods: The sample consisted of 15 workers (14 men and 1 woman) of a mining company in the State of Minas Gerais, aged 38.9 ± 3.5 years. All worked 6 hours a day in a fast-rotating shift (4x1) for 10.2±3.8 years on average. To assess sleep behavior, the actigraphy method was used, which assesses sleep onset latency (SOL), wake after sleep onset (WASO), total sleep time (TTS) all in minutes and sleep efficiency (ES) in percentage values. The assessments were carried out in October and November 2019 for the pre-pandemic moment and November and December 2020 for the postpandemic moment. For comparison between moments, the paired t-test was used, considering the value of p ≤ 0.05. Results: Clinically, sleep behavior in this group of shift workers did not change. Only SOL (3.4±1.7 vs. 1.9±0.9) showed a statistical difference (t(14)=4.399, p=0.001), while WASO (t(14)=0.916;p=0.375) with means 18.1±8.5 vs. 16.9±6.4, TTS (t(14)=-1.258;p=0.229) 422.5±36.9 vs. 437.2±68.9 and ES (t(14)=-0.934, p=0.366) 92.8±2.8 vs. 93.3±2.9 before and after the pandemic, respectively, showed no difference. Conclusion: The maintenance of external work, in the mining company, even with social restrictions in the workplace and outside it, contributed to the maintenance of the routine and sleep behavior. However, the workers in this study did not face increased workload, anxiety and greater risk of contagion associated with the work environment as health workers. Our results indicate that the improvement or worsening of sleep before and after the pandemic should be related to the group and culture that will be evaluated. The authors thank the support given by Pró-Reitoria De Pesquisa (PRPq) and PPG em Ciências do Esporte UFMG, Instituto Tecnológico VALE (ITV), CEPE (Centro De Estudos em Psicobiologia e Exerćcio), CEMSA (Centro Multidisciplinar De Sonolência e Acidentes), CNPq, FAPEMIG, CAPES e FEPE-UFMG.

INTERACTION OF SLEEP AND EMOTION ACROSS THE MENSTRUAL CYCLE

Introduction: Women experience increased risk for sleep and affective disorders compared to men, attributed in part to monthly oscillations in sex hormones. Emotional functioning worsens during the perimenstrual phase. There is increasing evidence that sleep continuity also decreases during this phase. Thus, this study examined the interactive effects of sleep and menstrual phase on emotion across two menstrual cycles in healthy women. Methods: Participants (N=51, 43% Caucasian) aged 18-35 (m=23.67) completed actigraphy and daily sleep/emotion diaries over two menstrual cycles (m days=51.29). Cycles were identified via date of menses and urinary ovulation detection, and coded into four phases: perimenstrual, mid-follicular, periovulatory, and mid-luteal. The perimenstrual phase was defined the 3 days prior to and the 3 days following menses onset. Variables included diary and actigraphic total wake time (TWT), daily ratings of positive (happy, calm, enthusiastic) and negative (angry, afraid, sad) affect using a 9-point scale. Relationships between phase, sleep, and emotion were estimated using multistep hierarchical linear modeling. Pandemic-related stress and daily US and region-specific COVID-19 case counts were included as covariates in adjusted models. Results: Mean menstrual cycle length was 28.61±2.69 days. Menstrual phase was first entered into models as predictors for sleep and emotion variables independently. The perimenstrual phase positively predicted anger (p<.001) but no other emotions. Additionally, the perimenstrual phase predicted higher rates of TWT, such that diary-reported TWT was 8-16 minutes longer during the perimenstrual (m=67.54, SE=3.37) compared to other phases (p<.001). Actigraphic TWT was also increased by 4-7 minutes (m=61.54, SE=3.37) in the perimenstrual phase (p<.001). A second model included the interaction term, TWT∗phase to the original model. Positive emotions were .05- .10 points lower (ps=.006-.02) when TWT was greater in the perimenstrual phase. Conclusion: Menstruating women experienced greater rates of anger and sleep disruption during the perimenstrual phase compared to other phases. When poor sleep occurred during the perimenstrual phase, however, women reported reduced positive emotions. Sleep disruptions, particularly occurring during the perimenstrual phase, may be an important intervention target for women at risk for affective disorders. Future studies should be mindful to assess menstrual phases when assessing sleep and circadian rhythm.

IDENTIFICATION OF SLEEP FACTORS RELATED TO BLOOD PRESSURE IN EMERGENCY MEDICINE HEALTHCARE WORKERS

Introduction: Emergency Department (ED) healthcare workers (HCWs) may be at elevated risk for the development of cardiovascular disease (CVD), due in part to sleep and/or circadian disturbances. This study aimed to evaluate the relationship of sleep factors with blood pressure, a primary marker of CVD risk, in ED HCWs. Methods: Participants were HCWs (physicians, nurses, advanced practice providers, technicians, etc.) from 4 EDs in New York City who completed study procedures between November 2020-October 2021. Participants completed a 2-week data burst, which included sleep/activity (Fitbit Inspire) and home blood pressure monitoring (Omron 5 Series BP7250;preceding and following their main daily sleep episode). Linear regression models, adjusted for age, gender, and race/ethnicity, were conducted predicting blood pressure from sleep factors. Results: The sample included n=74 ED HCWs (mean [SD] age=38.4 [8.7] years). Most were female (62.2%) and non-Hispanic/ Latino White (55.6%). Mean systolic blood pressure (SBP) and diastolic blood pressure (DBP) were 116.1 (12.5) mmHg and 75.1 (7.6) mmHg, respectively. Actigraphy-derived sleep factor means for the data burst period were: a) Total sleep time (TST): 6.8 (1.0) hours;b) Sleep efficiency (SE): 94.5 (2.2)%;c) Percentage of main sleep episodes throughout the burst with TST <6 hours: 25.9 (20.8)%;d) Sleep start time: 24:06 (01:24);and e) Within-subject inter-daily bedtime variability (i.e., SD of sleep start times): 2.4 (1.8) hours. Higher TST was associated with lower SBP (B [SE] =-0.50 [0.30] mmHg/10 min, p=.04) and DBP (B [SE] =-0.50 [0.20] mmHg/10 min, p=.01). Greater SE was associated with lower SBP (B [SE] =-1.23 [0.55], mmHg/%, p=.03) and DBP (B [SE] =-1.05 [0.39], mmHg/%, p=.01). A higher proportion of nights with TST <6 hours was associated with higher DBP (B [SE] =1.4 [0.40], mmHg/10%, p<0.01) but not SBP. Sleep start time and bedtime variability were not associated with BP. Conclusion: These findings provide support for the relationship between sleep and blood pressure. Of note, data were collected during the COVID-19 pandemic, which may impact observed relationships. Because this is a cross-sectional analysis, the causal direction of the association may be (at least partially) reversed. Further research should examine psychological and work-related factors in ED HCWs that may modify these relationships, e.g., stress/anxiety, burnout, and job strain, and include assessments of the circadian system.

THE ASSOCIATION BETWEEN SLEEP HEALTH AND WORK- AND HEALTH-RELATED QUALITY OF LIFE IN DESK WORKERS AND DIFFERENCES IN ASSOCIATIONS PRE- AND POST-COVID-19 EMERGENCE

Introduction: COVID-19 resulted in many office workers switching to remote work. Emerging studies report working from home has negatively affected sleep health (SH) and psychological well-being. Our aim was to evaluate the relationship between SH and healthand work-related quality of life and explore whether these associations differed pre- and post-COVID-19 emergence. Methods: Baseline data from 125 adults enrolled pre- (n=59) and post-COVID-19 emergence (n=66) in a clinical trial with desk jobs were included in this analysis (86.4% White;49.6% female;43.9±10.7 y). Health-related quality of life (HRQoL) was assessed using the SF-36 questionnaire, which addresses eight health concepts (physical, social, and role functioning;mental health;health perceptions;energy or fatigue;pain;general health) and yields 2 summary scales (mental component summary, physical component summary). Workplace productivity and worker health was measured using the Health and Work Questionnaire (HWQ). Six SH dimensions were assessed using questionnaires (satisfaction, alertness) and 7 nights of actigraphy (regularity, timing, efficiency, duration). Each dimension was categorized as good or poor;a composite score was created based on the sum of good SH dimensions. Multiple linear regression models were adjusted for gender and age and stratified by enrollment pre- or post-COVID-19 emergence. Data are presented as standardized coefficients (β) and p-values (p). Results: Compared to participants enrolled prior to COVID-19, those enrolled post-COVID-19 had worse SF-36 emotional, social, and general health and greater HWQ-assessed impatience (all p<0.05);however, SH did not differ between those enrolled pre- and post-COVID. Prior to COVID-19, greater SH was associated with higher SF-36 physical component scores (β=.389, p=.003);however, no association was observed post-COVID (β=.137, p=.271). In contrast, no association was observed pre-COVID between SH and SF-36 mental component scores (β=.181, p=.160), but greater SH was associated with greater mental component scores post- COVID (β =.308, p=.004). Furthermore, better SH was associated with lower stress post-COVID (β =-.423, p<.001). Conclusion: SH was associated with HRQoL and workplace and worker health, though these associations sometimes differed between pre- and post-COVID emergence. Research should explore whether promoting SH in employees impacts their personal and workplace-related quality of life.

Neurophysiology of sleep in workers' health and safety during Covid19 pandemic

Introduction: Sleep problems appear to have been common and associated with higher levels of psychological distress. Sleep quality, however, has been mainly assessed by the use of self-reported measures, thus limiting clinical usefulness. We review the literature about the sleep quality of workers supported by objective neurophysiological tools, during the COVID-19 pandemic. Materials and Methods: We conducted a systematic search of the PubMed database through October 27, 2021, including terms Covid-19, sleep, workers, neurophysiology, polysomnography and actigraphy. Results: A total of 13 studies were included. Out of these, only two studies evaluated sleep problems in workers (Healthcare professionals) with objective neurophysiological tools such as actigraphic evaluation. About 35% of healthcare workers were suffering from sleep disturbances having a sleep efficiency value less than 90% and high PSQI scores with a significant negative correlation between SE and PSQI and a trend of a negative association between SE and age. No other job categories were evaluated. Conclusions: During the lockdown, increases in sleep problems are associated with sense of time and are more pronounced in individuals with higher levels of depression, anxiety, and stress. People who isolated at home (smart-working) reported significantly earlier sleep onset and wake-up times than actigraphy-defined, tending to overestimate their specific sleep times. It is of utmost relevance to assess sleep by objective measures to set appropriate preventive strategies treating sleep problems, thus also obtaining reduced psychological distress.