Exploring the molecular pathways linking sleep phenotypes and POGZ-associated neurodevelopmental disorder.

Pogo transposable element-derived protein with ZNF domain (POGZ) gene encodes a chromatin regulator and rare variants on this gene have been associated with a broad spectrum of neurodevelopmental disorders, such as White-Sutton syndrome. Patient clinical manifestations frequently include developmental delay, autism spectrum disorder and obesity. Sleep disturbances are also commonly observed in these patients, yet the biological pathways which link sleep traits to the POGZ-associated syndrome remain unclear. We screened for sleep implications among individuals with causative POGZ variants previously described. Sleep disturbances were observed in 52% of patients, and being obese was not observed as a risk factor for sleep problems. Next, we identified genes associated with sleep-associated traits among the POGZ regulatory targets, aiming to uncover the molecular pathways that, when disrupted by POGZ loss of function, contribute to the aetiology of sleep phenotypes in these patients. The intersect between POGZ targets and sleep-related genes was used in a pathway enrichment analysis. Relevant pathways among these overlapping genes are involved in the regulation of circadian rhythm, tau protein binding, ATPase activator activity. This study may represent the beginning for novel functional investigations on shared molecular mechanisms between sleep disturbances and rare developmental syndromes related to POGZ and its regulatory targets.

Disentangling the complex landscape of sleep-wake disorders with data-driven phenotyping: A study of the Bernese center.

BACKGROUND AND PURPOSE: The diagnosis of sleep-wake disorders (SWDs) is challenging because of the existence of only few accurate biomarkers and the frequent coexistence of multiple SWDs and/or other comorbidities. The aim of this study was to assess in a large cohort of well-characterized SWD patients the potential of a data-driven approach for the identification of SWDs. METHODS: We included 6958 patients from the Bernese Sleep Registry and 300 variables/biomarkers including questionnaires, results of polysomnography/vigilance tests, and final clinical diagnoses. A pipeline, based on machine learning, was created to extract and cluster the clinical data. Our analysis was performed on three cohorts: patients with central disorders of hypersomnolence (CDHs), a full cohort of patients with SWDs, and a clean cohort without coexisting SWDs. RESULTS: A first analysis focused on the cohort of patients with CDHs and revealed four patient clusters: two clusters for narcolepsy type 1 (NT1) but not for narcolepsy type 2 or idiopathic hypersomnia. In the full cohort of SWDs, nine clusters were found: four contained patients with obstructive and central sleep apnea syndrome, one with NT1, and four with intermixed SWDs. In the cohort of patients without coexisting SWDs, an additional cluster of patients with chronic insomnia disorder was identified. CONCLUSIONS: This study confirms the existence of clear clusters of NT1 in CDHs, but mainly intermixed groups in the full spectrum of SWDs, with the exception of sleep apnea syndromes and NT1. New biomarkers are needed for better phenotyping and diagnosis of SWDs.

Optimizing the Time and Dose of Melatonin as a Sleep-Promoting Drug: A Systematic Review of Randomized Controlled Trials and Dose-Response Meta-Analysis.

Previous studies have reported inconsistent results about exogenous melatonin's sleep-promoting effects. A possible explanation relies on the heterogeneity in administration schedule and dose, which might be accountable for differences in treatment efficacy. In this paper, we undertook a systematic review and meta-analysis of double-blind, randomized controlled trials performed on patients with insomnia and healthy volunteers, evaluating the effect of melatonin administration on sleep-related parameters. The standardized mean difference between treatment and placebo groups in terms of sleep onset latency and total sleep time were used as outcomes. Dose-response and meta-regression models were estimated to explore how time of administration, dose, and other treatment-related parameters might affect exogenous melatonin's efficacy. We included 26 randomized controlled trials published between 1987 and 2020, for a total of 1689 observations. Dose-response meta-analysis showed that melatonin gradually reduces sleep onset latency and increases total sleep time, peaking at 4 mg/day. Meta-regression models showed that insomnia status (ß = 0.50, p < 0.001) and time between treatment administration and the sleep episode (ß = -0.16, p = 0.023) were significant predictors of sleep onset latency, while the time of day (ß = -0.086, p < 0.01) was the only significant predictor of total sleep time. Our results suggest that advancing the timing of administration (3 h before the desired bedtime) and increasing the administered dose (4 mg/day), as compared to the exogenous melatonin schedule most used in clinical practice (2 mg 30 min before the desired bedtime), might optimize the efficacy of exogenous melatonin in promoting sleep.

Promoting healthy sleep in 0-2-year-old infants: a study protocol for the development and mixed method evaluation of a sleep health program tailored to Dutch youth healthcare regions.

BACKGROUND: Sleep problems are common among infants and can have a serious impact on the health and wellbeing of both child and parents. To sustainably promote infant sleep on a population level, it is necessary to develop evidence-based programs that can be implemented on a large scale. The Youth Health Care setting, with its focus on prevention, child health promotion and services widely available for parents, can be a suitable setting to do so. Currently however, sleep health promotion in this setting seems to be suboptimal. To promote healthy infant sleep on a population level, programs need to be accessible and comprehensible for all parents, including parents with limited (health) literacy. Therefore, this study aims to develop, implement and evaluate a program called 'Sleep on number 1', that is tailored to Dutch Youth Health Care, to sustainably promote healthy sleep in 0-2-year-old infants. METHODS: The program was developed based on co-creation with parents and Youth Health Care professionals, evidence-based behaviour change theories and sleep health promotion methods. Program effectiveness is investigated with a quasi-experimental study design comparing the program group with the care as usual control group. Participants consist of parents of 0-2-year-old children. Primary outcome is infant sleep quality at the age of 10 weeks and 6, 9, 14 and 24 months, measured with a sleep diary. The primary data analysis focuses on night awakenings at 9 months. Secondary outcomes focus on parental behaviour regarding infant sleep, related behavioural determinants and parental satisfaction with Youth Health Care sleep advice. Program effectiveness is analysed using a linear mixed-model in case of data clustering, and an independent samples T-test or linear regression in case no substantial clustering effects are found. A mixed methods process evaluation is performed with parents and Youth Health Care professionals, assessing program reach, adoption, implementation, maintenance and working mechanisms. DISCUSSION: The 'Sleep on number 1' program is an evidence-based sleep health program for 0-2-year-old children, tailored to Dutch Youth Health Care. If effective, this program has the potential to improve infant sleep on a population level. TRIAL REGISTRATION: ISRCTN, ISRCTN27246394, registered on 10/03/2023. https://www.isrctn.com/ISRCTN27246394 .

Relationship between sleep disturbance and developmental status in preschool-aged children with developmental disorder.

BACKGROUND: Sleep has been known to affect childhood development. Sleep disturbance is likely more common in children with developmental delay (DD) than in typical development. There are few studies on the correlation between sleep disturbance and developmental features in children with DD. Therefore, this study aimed to evaluate the associations between the two in children with DD. METHODS: A total of 45 children (age range 27.0 ± 11.1) with DD were recruited and evaluated using the Sleep Disturbance Scale for Children (SDSC) and Bayley Scales of Infant and Toddler Development (BSID-III). The outcomes are expressed as means and standard deviations. The correlation between SDSC and BSID-III was assessed using Spearman's rank correlation test. Multiple regression analysis was performed to investigate the relationship between BSID-III domains and SDSC questionnaire subscales. Statistical significance was set at p < 0.05. RESULTS: Based on the correlation analysis and subsequent hierarchical regression analysis, cognition and socio-emotional domains of BSID-III were significantly associated with the DOES subscale of the SDSC questionnaire. In addition, the expressive language domain of the BSID-III was found to be associated with the DA subscale of the SDSC questionnaire. It seems that excessive daytime sleepiness might negatively affect emotional and behavioral problems and cognitive function. Also, arousal disorders seem to be related to memory consolidation process, which is thought to affect language expression. CONCLUSION: This study demonstrated that DA and DOES subscales of the SDSC questionnaire were correlated with developmental aspects in preschool-aged children with DD. Sleep problems in children with DD can negatively affect their development, thereby interfering with the effectiveness of rehabilitation. Identifying and properly managing the modifiable factors of sleep problems is also crucial as a part of comprehensive rehabilitation treatment. Therefore, we should pay more attention to sleep problems, even in preschool-aged children with DD.

Validity and Reliability of the Korean Version of Reduced Morningness-Eveningness Questionnaire: Results From a General Population-Based Sample.

BACKGROUND: Chronotype refers to individual variations in diurnal preferences that manifest as everyday behaviors, including sleep patterns. Traditionally, the Horne & Östberg Morningness-Eveningness Questionnaire (MEQ), which comprises of 19 items, has been the standard for determining chronotype. However, its length makes it cumbersome for widespread application. To address this issue, the reduced MEQ (rMEQ), a concise version containing only five items from the MEQ, was developed for a more practical approach to chronotype assessment. This study aimed to evaluate the validity and reliability of Korean version of rMEQ in a sample from the general Korean population. METHODS: The Korean version of the rMEQ comprises of items 1, 7, 10, 18, and 19 of the original MEQ. The validity of the rMEQ was assessed by correlating its scores with those of the MEQ and Munich Chronotype Questionnaire (MCTQ). Its reliability was determined by calculating internal consistency. RESULTS: A total of 3,030 individuals participated in the study, yielding an average rMEQ score of 14.0 ± 3.4. There was a substantial positive correlation between the rMEQ and MEQ scores (r = 0.859, P < 0.001). Furthermore, the rMEQ scores were significantly negatively correlated with the midpoint of sleep on free days corrected for sleep debt as measured by the MCTQ (r = -0.388, P < 0.001), indicating a robust association with chronotype. The internal consistency of rMEQ, measured using Cronbach's alpha, was 0.609. CONCLUSION: This study finds the Korean version of the rMEQ to be a valid and reliable instrument for assessing chronotype in the general population.

Exploring the causal effects of sleep characteristics on TMD-related pain: a two-sample Mendelian randomization study.

OBJECTIVES: The study was to explore the causal effects of sleep characteristics on temporomandibular disorder (TMD)-related pain using Mendelian randomization (MR) analysis. MATERIALS AND METHODS: Five sleep characteristics (short sleep, insomnia, chronotype, snoring, sleep apnea) were designated as exposure factors. Data were obtained from previous publicized genome-wide association studies and single nucleotide polymorphisms (SNPs) strongly associated with them were utilized as instrumental variables (IVs). TMD-related pain was designed as outcome variable and sourced from the FinnGens database. MR analysis was employed to explore the causal effects of the five sleep characteristics on TMD-related pain. The causal effect was analyzed using the inverse variance-weighted (IVW), weighted median, and MR-Egger methods. Subsequently, sensitivity analyses were conducted using Cochran's Q tests, funnel plots, leave-one-out analyses, and MR-Egger intercept tests. RESULTS: A causal effect of short sleep on TMD-related pain was revealed by IVW (OR: 1.60, 95% CI: 1.06-2.41, P = 0.026). No causal relationship was identified between other sleep characteristics (insomnia, chronotype, snoring, sleep apnea) and TMD-related pain. CONCLUSIONS: Our study suggests that short sleep may increase the risk of TMD-related pain, while there was no causal relationship between other sleep characteristics and TMD-related pain. Further studies are warranted to deepen and definitively clarify their relationship. CLINICAL RELEVANCE: These findings reveal that the short sleep may be a risk factor of TMD-related pain and highlight the potential therapeutical effect of extending sleep time on alleviating TMD-related pain.

Prevalence of Anxiety, Depression, and Sleep Disturbance Among Emergency Nurses in Oman.

INTRODUCTION: Anxiety, depression, and sleep disturbances among accident and emergency nurses not only harm their well-being but also affect patient care and organizational outcomes. This study examines anxiety, depression, and sleep prevalence and associations among accident and emergency nurses. METHODS: We conducted a cross-sectional correlational survey with 331 accident and emergency nurses in 12 Omani governmental hospitals. RESULTS: Results showed that 28.7% of accident and emergency nurses reported symptoms indicative of anxiety, with 13.6% experiencing symptoms of depression, 16.6% reporting mild sleep disturbances, and 1.5% experiencing moderate disturbance. Those with symptoms of anxiety (r = 0.183, P = .001) or depression (r = 0.152, P = .005) were more likely to experience sleep disturbances. Being single (t [170.7] = 2.5, P = .015), childless (t [169.7] = -2.807, P = .008), Omani (t [215] = 7.201, P < .001), younger (r = -0.375, P < .001) and having less clinical experience (t [329] = 4.6, P < .001) were associated with a higher anxiety score. For depression, being of Omani nationality (t [215] = 7.201, P < .001), having less than 10 years of experience (t [329] = 3.2, P = .002), and being of younger age (r = -0.285, P < .001) were associated with a higher score. DISCUSSION: Accident and emergency nurses commonly experience anxiety, depression, and sleep disturbances. Implementing interventions to promote their mental well-being or manage these issues is crucial. Organizational support is vital for ensuring their mental health, and individual-level interventions may also prove beneficial.

The Impact of SARS-CoV-2 Infection on Sleep, Daytime Sleepiness, and Depression-Longitudinal Cohort Study.

Background and Objectives: COVID-19 disease, caused by the SARS-CoV-2 virus, has presented significant challenges to global health, with acute and chronic implications for various aspects of well-being, including sleep and quality of life. This study aimed to investigate the impact of SARS-CoV-2 infection on sleep quality, daytime sleepiness, and quality of life in hospitalised and home-treated patients after three and six months. Materials and Methods: A longitudinal cohort study was conducted, enrolling hospitalised patients from a single clinical university hospital and home-treated participants through a survey spread through social networks. Individuals who had tested positive for the SARS-CoV-2 virus in the past three months and had a symptomatic course of the disease were included in the study. Participants with previously diagnosed sleep disorders were excluded from the study. Participants were evaluated using internationally validated self-evaluation scales, including the Epworth Sleepiness Scale (ESS), Pittsburgh Sleep Quality Index (PSQI), Patient Health Questionnaire-9 (PHQ-9) and Fatigue Severity Scale (FSS). Data were collected three and six months after laboratory-confirmed SARS-CoV-2 infection, with informed consent obtained from all participants. Statistical analysis was performed using the Wilcoxon signed rank test, Fisher-Freeman-Halton exact, Pearson Chi tests and Spearman correlation. Results were considered statistically significant with p value < 0.05. Results: In total, 66 participants with a mean age of 44.05 ± 21.61 years were enrolled in the study. Most patients (n = 36) were treated at home and 30 at hospital. Six months after SARS-CoV-2 infection, home-treated patients reported a higher prevalence of poor sleep quality (52.8%, n = 19, p = 0.015, PSQI) and hospitalised patients showed a lower prevalence of depressive symptoms (p < 0.001, PHQ-9) as 90% (n = 27) had minimal or no symptoms compared to 30.6% (n = 11) in a home-treated group. Conclusions: These findings mark the importance of the COVID-19 patients' management settings as people treated at home had worse sleep quality and more depressive symptoms six months after infection indicating worse life quality.

[Structured case conference for sleep disturbances in nursing home residents with cognitive impairment]. / Strukturierte Fallbesprechung bei Schlafproblemen von Pflegeheimbewohner_innen mit kognitiven Einschränkungen.

Structured case conference for sleep disturbances in nursing home residents with cognitive impairment Abstract: Background: Nursing home residents living with cognitive impairment often suffer from sleep disturbances. Pharmacological interventions are not recommended to be the first-choice therapy. In general, a wide variance of non-pharmacological interventions is available, but no clearly suitable intervention can currently be specified. Aim: The case report presents the procedure of a structured analysis to support the selection of non-pharmacological interventions to promote sleep. Methods: A structured case conference was held using a developed case management template to draw up an individual intervention plan. Results: Based on the description of the situation and the determination of causes, different interventions from six main topics were planned: "offering appropriate activations during daytime", "creating bedtime routines", "checking the sleep environment", "observation of potential physical and psychological causes", "reflection on night care routines", and "use of drug therapies only in exceptional cases". Conclusions: For a successful management of sleep disturbances in nursing home residents living with cognitive impairment, it is essential that the specific sleep-related symptoms and causes are assessed systematically and interprofessionally to be able to work towards an improvement with appropriate measures. In order to obtain adequate solutions, evidence-based expertise should be taken into consideration.

Chronobiology of Parkinson's disease: Past, present and future.

Parkinson's disease is a neurodegenerative disorder predominately affecting midbrain dopaminergic neurons that results in a broad range of motor and non-motor symptoms. Sleep complaints are among the most common non-motor symptoms, even in the prodromal period. Sleep alterations in Parkinson's disease patients may be associated with dysregulation of circadian rhythms, intrinsic 24-h cycles that control essential physiological functions, or with side effects from levodopa medication and physical and mental health challenges. The impact of circadian dysregulation on sleep disturbances in Parkinson's disease is not fully understood; as such, we review the systems, cellular and molecular mechanisms that may underlie circadian perturbations in Parkinson's disease. We also discuss the potential benefits of chronobiology-based personalized medicine in the management of Parkinson's disease both in terms of behavioural and pharmacological interventions. We propose that a fuller understanding of circadian clock function may shed important new light on the aetiology and symptomatology of the disease and may allow for improvements in the quality of life for the millions of people with Parkinson's disease.

Insomnia and workplace productivity loss among young working adults: a prospective observational study of clinical sleep disorders in a community cohort.

OBJECTIVE: To examine associations between three clinically significant sleep disorders (chronic insomnia, obstructive sleep apnoea, restless legs syndrome) and workplace productivity losses among young Australian adults. DESIGN, SETTING: Prospective, observational study; 22-year follow-up of participants in the longitudinal birth cohort Raine Study (Perth, Western Australia). PARTICIPANTS: Currently employed 22-year-old Raine Study participants who underwent in-laboratory sleep disorder screening for moderate to severe obstructive sleep apnoea (apnoea-hypopnea index of more than fifteen events/hour or obstructive sleep apnoea syndrome) and were assessed for insomnia and restless legs syndrome using validated measures. MAIN OUTCOME MEASURES: Total workplace productivity loss over twelve months, assessed with the World Health Organization Health and Work Performance Questionnaire. RESULTS: Of 1235 contactable 22-year-old Raine Study cohort members, 554 people (44.9%; 294 women [53%]) underwent overnight polysomnography, completed the baseline sleep questionnaire, and completed at least three quarterly workplace productivity assessments. One or more clinically significant sleep disorders were identified in 120 participants (21.7%); 90 participants had insomnia (17%), thirty clinically significant obstructive sleep apnoea (5.4%), and two restless legs syndrome (0.4%). Seventeen people (14% of those with sleep disorders) had previously been diagnosed with a sleep disturbance by a health professional, including fourteen with insomnia. Median total workplace productivity loss was greater for participants with sleep disorders (164 hours/year; interquartile range [IQR], 0-411 hours/year) than for those without sleep disorders (30 hours/year; IQR, 0-202 hours/year); total workplace productivity loss was 40% greater for participants with sleep disorders (adjusted incidence rate ratio, 1.40; bias-corrected and accelerated 95% confidence interval, 1.10-1.76). The estimated population total productivity loss (weighted for disorder prevalence) was 28 644 hours per 1000 young workers per year, primarily attributable to insomnia (28 730 hours/1000 workers/year). CONCLUSION: Insomnia is a risk factor for workplace productivity loss in young workers. Tailored interventions are needed to identify and manage sleep disorders, particularly as most of the sleep disorders detected in the Raine Study had not previously been diagnosed.

Per- and polyfluoroalkyl substances and sleep health in U.S. adults, NHANES 2005-2014.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are synthetic chemicals that induce oxidative inflammatory responses and disrupt the endocrine and central nervous systems, all of which can influence sleep. OBJECTIVE: To investigate the association between PFAS exposure and sleep health measures in U.S. adults. METHODS: We analyzed serum concentration data of four PFAS [perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonic acid (PFHxS), and perfluorononanoic acid (PFNA)] reported for 8913 adults in NHANES 2005-2014. Sleep outcomes, including trouble sleeping, having a diagnosis of sleep disorder, and recent daily sleep duration classified as insufficient or excessive sleep (<6 or >9 h/day) were examined. Weighted logistic regression was used to estimate the association between the sleep outcomes and each PFAS modeled continuously (log2) or in exposure tertiles. We applied quantile g-computation to estimate the effect of the four PFAS as a mixture on the sleep outcomes. We conducted a quantitative bias analysis to assess the potential influence of self-selection and uncontrolled confounding. RESULTS: We observed some inverse associations between serum PFAS and trouble sleeping or sleep disorder, which were more consistent for PFOS (e.g., per log2-PFOS (ng/ml) and trouble sleeping OR = 0.93, 95%CI: 0.89, 0.98; sleep disorder OR = 0.89, 95%CI: 0.83, 0.95). Per quartile increase of the PFAS mixture was inversely associated with trouble sleeping and sleep disorder. No consistent associations were found for sleep duration across analyses. Our bias analysis suggests that the finding on sleep disorder could be explained by a moderate level of self-selection and negative confounding effects. CONCLUSIONS: We found no evidence to suggest exposure to four legacy PFAS worsened self-reported sleep health among U.S. adults. While some inverse associations between specific PFAS and sleep disorder were observed, self-selection and uncontrolled confounding biases may play a role in these findings.

The association of sleep disturbances with burning mouth syndrome: An overlooked relationship-A qualitative systematic review.

OBJECTIVES: To review the relevant literature to assess whether patients with burning mouth syndrome (BMS) are more prone to have sleep disturbances than general population. METHODS: The literature search for relevant articles was from July 2020 to March 2021. A systematic search of PubMed, Embase, Google Scholar, Cochrane library, Dentistry & Oral Sciences Source, and Scopus was conducted to search for relevant studies. The quality of studies was assessed in accordance with the Joanna Briggs Institute's guidelines and using the software SUMARI-The System for the Unified Management, Assessment and Review of Information. Confidence in the findings was assessed using the GRADE-CERQual approach. RESULTS: A total of 1064 studies were initially identified from the search; six studies, two cross-sectional and four case-control, met the inclusion criteria and were selected for this systematic review. Sleep disturbances were a required outcome measured in selected studies evaluating symptoms of BMS. For studies that were included in the final analyses, BMS was found to relate to several dimensions of sleep including sleep disturbance and duration (n = 6), sleep affecting daytime function (n = 4), sleep quality (n = 6), sleep efficiency (n = 4), and ability to fall asleep (n = 4). Consistent evidence of moderate confidence found that BMS was associated with greater sleep disturbance, reduced sleep quality, increased time taken to fall asleep, reduced sleep efficiency, and poor daytime function, whereas evidence of low confidence was found regarding the association of BMS with reduced sleep duration. CONCLUSIONS: Although the presented studies could not establish a direct causal relationship between BMS and sleep disturbances, it supports the evidence that sleep disturbance is associated with symptoms of BMS. Management strategies to improve sleep may be considered in future research for managing BMS patients.

Association between insomnia disorder and mortality among patients who underwent craniotomy for brain tumor resection: a South Korean nationwide cohort study.

PURPOSE: To assess the prevalence and related factors of a newly developed insomnia disorder following craniotomy for brain tumor resection. Furthermore, we examined the association of pre- and postoperative insomnia with the 2-year mortality rate. METHODS: The South Korean national registration cohort database was used as the data source. This study includes all adult patients who underwent craniotomy for brain tumor resection from January 1, 2011, to December 31, 2017. G47.0 and F51.0 (International Statistical Classification of Diseases and Related Health Problems 10th Revision codes) were used to identify insomnia disorders. RESULTS: In total, 4,851 patients were included. Among them, 913 (18.8%) and 447 (9.2%) patients were assigned to the preoperative and postoperative insomnia groups, respectively. After modeling using multivariable logistic regression, older age (odds ratio (OR) 1.02, 95% confidence interval (CI) 1.01-1.03; P < 0.001), reoperation within 1 year (OR 2.12, 95% CI 1.47-3.06; P < 0.001), and newly acquired brain disability (OR 1.32, 95% CI 1.01-1.71; P = 0.043) were associated with an increased prevalence of newly developed postoperative insomnia disorder. After modeling using multivariable Cox regression, the preoperative and postoperative insomnia disorder groups showed a 1.17-fold (hazard ratio (HR) 1.17, 95% CI 1.02-1.34; P = 0.021) and a 1.85-fold (HR 1.85, 95% CI 1.59-2.15, P < 0.001) increased 2-year all-cause mortality risk compared to the control group, respectively. CONCLUSION: In South Korea, 9.2% of the patients with brain tumors were newly diagnosed with an insomnia disorder following craniotomy for brain tumor resection, which was associated with an increased risk of 2-year mortality.

Severity and determinants of psychosocial comorbidities in granulomatosis with polyangiitis and their impact on quality of life.

Depression, anxiety, sleep disturbances, and fatigue are inadequately addressed comorbidities in granulomatosis with polyangiitis (GPA). We determined the prevalence, severity, determinants, and the impact of these comorbidities on quality-of-life (QoL) in GPA. This observational study included adult GPA patients; patients with RA and lupus were included as comparators. Patient Health Questionnaire-9 for depression, Generalized Anxiety Disorder 7-item scale for anxiety, Epworth Sleepiness Scale for sleep disturbances, and Fatigue Severity Scale for fatigue were administered prospectively to estimate prevalence and severity. QoL and disability were estimated using PROMIS-HAQ, HAQ-health and HAQ-pain. Correlations among these parameters were assessed. Stepwise regression analyses were performed to identify determinants of depression, anxiety, excessive sleepiness, and fatigue. One hundred eighty-one patients-62 GPA [mean age 43 (13) years], 57 RA and 62 SLE- were included. The prevalence of depression (47%), excessive sleepiness (21%), and fatigue (39%) in GPA were comparable to RA and lupus; anxiety was less prevalent (29% versus 46% and 53%, p = 0.02). Severity was mostly mild-moderate. Younger age [OR = 0.93 (0.89-0.98)], higher BMI [OR = 1.2 (1.0-1.4)], and greater disease damage [OR = 2.0 (1.3-3.3)] independently predicted presence of depression. Higher BMI [OR = 1.3 (1.1-1.5)] and concomitant FMS [OR = 80.9 (5.1-1289.2)] were independently associated with excessive sleepiness. No association with disease activity, duration, or gender was seen. GPA patients with depression, anxiety, excessive sleepiness, and fatigue had worse PROMIS-HAQ, HAQ-pain, and HAQ-health. In conclusion, depression, anxiety, sleep disturbances, and fatigue are common in GPA. Although their severity is mostly mild-moderate, they impair QoL significantly. Potentially modifiable determinants that can form targets for future interventions have been identified.

Associations between changes in habitual sleep duration and lower self-rated health among COVID-19 survivors: findings from a survey across 16 countries/regions.

BACKGROUND: Self-rated health (SRH) is widely recognized as a clinically significant predictor of subsequent mortality risk. Although COVID-19 may impair SRH, this relationship has not been extensively examined. The present study aimed to examine the correlation between habitual sleep duration, changes in sleep duration after infection, and SRH in subjects who have experienced SARS-CoV-2 infection. METHODS: Participants from 16 countries participated in the International COVID Sleep Study-II (ICOSS-II) online survey in 2021. A total of 10,794 of these participants were included in the analysis, including 1,509 COVID-19 individuals (who reported that they had tested positive for COVID-19). SRH was evaluated using a 0-100 linear visual analog scale. Habitual sleep durations of < 6 h and > 9 h were defined as short and long habitual sleep duration, respectively. Changes in habitual sleep duration after infection of ≤ -2 h and ≥ 1 h were defined as decreased or increased, respectively. RESULTS: Participants with COVID-19 had lower SRH scores than non-infected participants, and those with more severe COVID-19 had a tendency towards even lower SRH scores. In a multivariate regression analysis of participants who had experienced COVID-19, both decreased and increased habitual sleep duration after infection were significantly associated with lower SRH after controlling for sleep quality (ß = -0.056 and -0.058, respectively, both p < 0.05); however, associations between current short or long habitual sleep duration and SRH were negligible. Multinomial logistic regression analysis showed that decreased habitual sleep duration was significantly related to increased fatigue (odds ratio [OR] = 1.824, p < 0.01), shortness of breath (OR = 1.725, p < 0.05), diarrhea/nausea/vomiting (OR = 2.636, p < 0.01), and hallucinations (OR = 5.091, p < 0.05), while increased habitual sleep duration was significantly related to increased fatigue (OR = 1.900, p < 0.01). CONCLUSIONS: Changes in habitual sleep duration following SARS-CoV-2 infection were associated with lower SRH. Decreased or increased habitual sleep duration might have a bidirectional relation with post-COVID-19 symptoms. Further research is needed to better understand the mechanisms underlying these relationships for in order to improve SRH in individuals with COVID-19.

Suicidal Ideation, Depression, and Insomnia in Parent Survivors of Suicide: Based on Korean Psychological Autopsy of Adolescent Suicides.

BACKGROUND: This study aims to evaluate suicidal ideation, depression, and insomnia among parent survivors of adolescents who died by suicide and their relevant risk factors using psychological autopsy results from South Korea. METHODS: The participants were 42 parent survivors (10 fathers and 32 mothers) of 35 adolescents who died by suicide. We used the Patient Health Questionnaire-9 and the Korean version of the Insomnia Severity Index to evaluate the mental health of the bereaved parents. We used the Korean Psychological Autopsy Checklist for Adolescents, the Korean Beck Depression Inventory, the Korean Version of the Barratt Impulsiveness Scale-II, and the Kiddie-Schedule for Affective Disorders and Schizophrenia-Present and Lifetime-Korean versions to evaluate the mental health of deceased adolescents before their deaths. RESULTS: The results showed that many parent survivors of suicide had developed clinically significant suicidal ideation, depression, and insomnia (75.6%, 73.2%, and 42.9%, respectively). Furthermore, the higher the incidence of traumatic events experienced by the deceased adolescents, the higher the severity of depression and insomnia experienced by surviving parents. CONCLUSION: We should pay attention that parent survivors of suicide can suffer mental disorders after their offspring's death. In future studies, long-term follow-up studies with larger samples need to generalize our findings and clarify the causal relationship.

Diagnostic accuracy of a portable device (Bruxoff®) to measure sleep bruxism.

BACKGROUND: Diagnosis of sleep bruxism (SB) challenges clinicians every day due to multiple forms of assessment tools available, including self-reported questionnaires, clinical examinations, portable devices and laboratory polysomnography (PSG). PSG has become the gold standard for evaluating SB, but it can be limited due to cost and restricted accessibility which often is characterised by long waiting times. Hence, there is a need for the development of a reliable method that can assess SB in a simple and portable manner, which would offer acceptable sensitivity and specificity to evaluate SB. OBJECTIVE: The objective of this study was to investigate reliability and validity of the Bruxoff® device for the diagnosis of SB compared to the PSG. METHODS: Forty-nine subjects underwent one night of polysomnographic study with simultaneous recording with the Bruxoff® device. Rhythmic masticatory muscle activity (RMMA) index was scored according to published criteria. Pearson correlation, Bland-Altman plot and receiver operating characteristic (ROC) curve outcomes were used to quantify the agreement between both methods. RESULTS: Receiver operating characteristic analysis showed an acceptable accuracy for the Bruxoff® with sensitivity of 83.3% and specificity of 72% when the cut-off was set at two events per hour. Pearson correlation analysis showed a nearly significant correlation between PSG and Bruxoff® for RMMA index (r = .282 p = .071) and for total SB episodes per night (r = .295 p = .058). Additionally, the Bland-Altman plot revealed a consistent and systematic difference in the measurement of events between devices. CONCLUSION: The Bruxoff® device appears to be a promising diagnostic method for clinical use, but further study is needed.

The Role of the Circadian Rhythm in Dyslipidaemia and Vascular Inflammation Leading to Atherosclerosis.

Cardiovascular diseases (CVD) are among the leading causes of death worldwide. Many lines of evidence suggest that the disturbances in circadian rhythm are responsible for the development of CVDs; however, circadian misalignment is not yet a treatable trait in clinical practice. The circadian rhythm is controlled by the central clock located in the suprachiasmatic nucleus and clock genes (molecular clock) located in all cells. Dyslipidaemia and vascular inflammation are two hallmarks of atherosclerosis and numerous experimental studies conclude that they are under direct influence by both central and molecular clocks. This review will summarise the results of experimental studies on lipid metabolism, vascular inflammation and circadian rhythm, and translate them into the pathophysiology of atherosclerosis and cardiovascular disease. We discuss the effect of time-respected administration of medications in cardiovascular medicine. We review the evidence on the effect of bright light and melatonin on cardiovascular health, lipid metabolism and vascular inflammation. Finally, we suggest an agenda for future research and recommend on clinical practice.