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Resilience is the cornerstone to mental health, and entails multiple biological and psychological mechanistic processes. However, the interplay of the psychobiological processes in shaping resilience is unclear. Here we report the results of testing whether an acute cortisol response and positive affectivity traits moderate the relationship between participants’ five-year major life stress and current psychological symptoms. The participants comprised 147 individuals (93 females and 54 males, age = 24–45 years) without clinical diagnosis. Acute stress was induced using the Trier Social Stress Task. We found that both the cortisol response to anticipatory acute stress and positive affectivity moderated the stress–symptom relationship. Specifically, a positive relationship between life stress and current symptoms was only observed at low, but not high, levels of cortisol response and positive affectivity. Moreover, the moderating effect of cortisol response was only observed at a low level of trait positive affectivity. These results unravel how the biological and emotional processes of the stress response interact to shape resilience to major life stress.

Circadian dysregulation has long been thought to be a key component in the pathophysiology of bipolar disorder (BD). However, it remains unclear whether this dysregulation constitutes a risk factor, manifestation, or consequence of BD. This study aimed to compare dim light melatonin secretion patterns between unaffected offspring of parents with BD (OBD) and offspring of control parents (OCP).This case-control study included unaffected OBD (mean age 14.0 years; male 50.0 %) and age- and sex-matched OCP (mean age 13.0 years; male: 43.5 %). Seventeen saliva samples were collected in dim light conditions. Dim light melatonin onset (DLMO), phase angles, and area under the curve (AUC) were calculated.185 saliva samples from 12 OBD (n = 12) and 741 from OCP (n = 46) were collected. Unaffected OBD had a significant lower nocturnal melatonin level (14.8 ± 4.6 vs. 20.3 ± 11.7 pg/mL) and a smaller melatonin AUC within two hours after DLMO (35.5 ± 11.3 vs. 44.6 ± 18.1 pg/mL) but a significant larger phase angle between DLMO and sleep onset (2.2 ± 1.0 vs. 1.4 ± 1.2 h) than OCP. There was no significant between-group difference in DLMO. The graphic illustrations showed a considerably flattened melatonin secretion in unaffected OBD.The main limitations include lack of 24-h dim melatonin secretion measurement, large age range of participants, and small sample size.These findings suggest that unaffected OBD already presented with circadian rhythm dysregulations. Future investigations are needed to clarify the role of abnormal melatonin secretion in the onset of BD.

The current study aimed to examine the association of insomnia symptoms with daytime behavior and cognitive functioning in children with attention-deficit/hyperactivity disorder (ADHD).Thirty-six children with ADHD and insomnia symptoms, 27 children with ADHD without insomnia symptoms, and 21 age-matched healthy controls were recruited in this study (age range: 6-12 years, 70% male). They were assessed by parent-report questionnaires on insomnia symptoms (Children's Sleep Habits Questionnaire) and ADHD symptoms (Strengths and Weaknesses of ADHD Symptoms and Normal Behavior Scale [SWAN]), and completed a battery of cognitive tests including the Continuous Performance Test (CPT) for sustained attention, Letter-digit test for processing speed, Digit Span forward test andChildren with ADHD and insomnia symptoms had the highest scores on SWAN total and inattention and hyperactivity subscales, followed by children with ADHD without insomnia and healthy controls (allInsomnia symptoms are associated with more severe ADHD symptoms and cognitive impairments in children with ADHD, especially deficits in sustained attention and processing speed. Future longitudinal studies are needed to explore the long-term impacts of insomnia symptoms and the effects of sleep-focused intervention on cognitive functioning in children with ADHD.Li X, Shea KSC, Chiu WV, et al. The associations of insomnia symptoms with daytime behavior and cognitive functioning in children with attention-deficit/hyperactivity disorder.

Insufficient sleep contributes negatively to child developmental processes and neurocognitive abilities, which argues the need for implementing interventions to promote sleep health in children. In this study, we evaluated the effectiveness of a multimodal and multilevel school-based sleep education program in primary school children using a cluster randomized controlled design. Twelve schools were randomly assigned to either the sleep education or nonactive control groups. The sleep education group included a town hall seminar, small class teaching, leaflets, brochures, and a painting competition for children. Parents and teachers were invited to participate in a one-off sleep health workshop. Parental/caregiver-reported questionnaires were collected at baseline and 1-month follow-up. A total of 3769 children were included in the final analysis. There were no significant improvements observed in the sleep-wake patterns, daytime functioning, and insomnia symptoms between the two groups at follow-up, whereas the intervention group had significantly improved parental sleep knowledge than the controls (paternal: adjusted mean difference: 0.95 [95% confidence interval (CI): 0.18 to 1.71]; maternal: adjusted mean difference: 0.87 [95% CI: 0.17 to 1.57]). In addition, children receiving the intervention had a lower persistence rate of excessive beverage intake (adjusted odds ratio: 0.49 [95% CI: 0.33 to 0.73]), and experienced greater reductions in conduct problems (adjusted mean difference: 0.12 [95% CI: 0.01 to 0.24]) compared with the controls at 1-month of follow-up. Moreover, a marginally significant reduction for emotional problems in the intervention group was also observed (adjusted mean difference: 0.16 [95% CI: −0.00 to 0.32]). These findings demonstrated that school-based sleep education was effective in enhancing parental sleep knowledge and improving behavioral outcomes in children, but not sufficient in altering the children’s sleep-wake patterns and sleep problems.

The microbiota-gut-brain axis has been suggested to play an important role in Parkinson’s disease (PD). Here we performed a cross-sectional study to profile gut microbiota across early PD, REM sleep behavior disorder (RBD), first-degree relatives of RBD (RBD-FDR), and healthy controls, which could reflect the gut-brain staging model of PD. We show gut microbiota compositions are significantly altered in early PD and RBD compared with control and RBD-FDR. Depletion of butyrate-producing bacteria and enrichment of pro-inflammatory Collinsella have already emerged in RBD and RBD-FDR after controlling potential confounders including antidepressants, osmotic laxatives, and bowel movement frequency. Random forest modelling identifies 12 microbial markers that are effective to distinguish RBD from control. These findings suggest that PD-like gut dysbiosis occurs at the prodromal stages of PD when RBD develops and starts to emerge in the younger RBD-FDR subjects. The study will have etiological and diagnostic implications.

Background Both sleep duration and efficiency are essential for health outcomes. However, few studies have considered the effects of both sleep duration and efficiency on predicting the risks of mortality. This study investigated the independent and joint associations of accelerometer-measured sleep duration and efficiency with all-cause and cause-specific mortality. Methods The UK Biobank is a cohort study of over 500 000 individuals recruited between 2006 and 2010. This study included participants wearing wrist accelerometers for 7 consecutive days between February 2013 and December 2015. Mortality was ascertained by the national death registries. Results 90 398 participants (age, 62.4 [7.8] years, 43.5% male) were included, 2 685 deaths were reported within a median follow-up duration of 6.4 years. Both accelerometer-measured short (adjusted hazard ratios [HR], 1.27; 95%CI, 1.11 to 1.45) and long sleep duration (adjusted HR, 1.16; 95%CI, 1.06 to 1.28) was positively associated with the risks of all-cause mortality. Lower sleep efficiency was associated with an increased risk of all-cause and cause-specific mortality. Significant interaction existed between accelerometer-measured sleep duration and efficiency for the risk of all-cause mortality (Pinteraction = 0.001), participants with long sleep duration and lower sleep efficiency had a double mortality risk compared with those with higher sleep efficiency and normal sleep duration (adjusted HR = 2.11; 95%CI, 1.44 to 3.09). Conclusions Accelerometer-measured short/long sleep duration and lower sleep efficiency were associated with increased risks of mortality. Sleep efficiency modified the effects of long sleep duration on survival.

Background and ObjectivesIndividuals with a history of recurrent dream-enactment behaviors, but with subthreshold REM sleep without atonia levels for REM sleep behavior disorder (RBD) diagnosis, are currently classified to have prodromal RBD (pRBD). However, the REM sleep–elevated EMG diagnostic cutoff, progression trajectory, and long-term neurodegenerative outcome of pRBD are not well understood. This study aimed to delineate the evolution of REM sleep EMG levels, determine the EMG cutoff score for diagnosing pRBD, and examine the risk for neurodegenerative diseases of pRBD.MethodsThis retrospective longitudinal case-control study recruited patients with pRBD and age-matched, sex-matched, and follow-up duration–matched controls who were free of neurodegenerative disease at baseline in the Sleep Assessment Unit, the Chinese University of Hong Kong from 1997 to 2018. Patients and controls underwent clinical and video-polysomnography (PSG) assessments at baseline and follow-up(s). REM sleep EMG activity level on mentalis and anterior tibialis (AT) muscles on video-PSG at each visit was scored. The diagnosis of neurodegenerative diseases was confirmed by a neurologist.ResultsA total of 44 patients (age 67.4 ± 8.2 years, 6 females) and 44 controls were recruited. The combined REM sleep EMG level on mentalis and AT muscles of patients with pRBD significantly increased during 8.2 ± 3.3 years of follow-up (from 19.3% ± 9.7% to 47.3% ± 27.4% with estimated annual increase of 3.9%), yielding 29 patients with pRBD (66%) meeting the full-blown RBD diagnostic criteria. Baseline REM sleep mentalis and AT muscles EMG activity of patients who developed full-blown RBD could favorably differentiate pRBD from controls (6.3% for mentalis “any” and 9.1% for combination of mentalis any and bilateral AT muscles phasic EMG with an area under the curve of 0.88 [0.78–0.98] and 0.97 [0.92–1.00], respectively). Patients with pRBD had a higher risk for neurodegenerative diseases (9 developed Parkinson disease and 3 developed dementia with Lewy bodies) when compared with controls (5 developed Alzheimer disease, adjusted hazard ratio = 2.95, 95% CI = 1.02–8.54).DiscussionpRBD has a predictive progression in both pathophysiology and neurodegenerative outcome. This finding has significant implications to the nosological status of pRBD, the current REM sleep-related EMG diagnostic criteria, spectrum concept of RBD, and future neuroprotective intervention.Classification of EvidenceThis study provides Class III evidence that EMG activity during REM sleep predicts the development of pRBD.

The purpose of the study was to compare the efficacy of group-based therapy (GT) and email-delivered self-help (ESH) cognitive behavioral therapy for insomnia (CBT-I) with the wait-list (WL) control group in youths.The study involved an assessor-blind, parallel group randomized controlled trial in youths meeting the diagnostic criteria for insomnia disorder. Participants were randomized to one of the three groups (8-week GT, 8-week ESH, or WL). Participants in all three groups were assessed at baseline and after treatment (week 9 for the WL group). The two treatment groups were additionally assessed at one month and six months after the intervention. Treatment effects were examined using linear mixed models.A total of 135 youths (mean age: 20.0 ± 2.5 years, female: 67.4%) were recruited. After treatment, both active treatment groups showed significant improvements in insomnia symptoms (GT vs. WL: Cohen's d = -1.03, ESH vs. WL: d = -.63), less presleep arousal (d = -.52 to -1.47), less sleep-related dysfunctional belief (d = -.88 to -1.78), better sleep hygiene practice (d = -.79 to -.84), and improved daytime functioning (d = -.56 to -.96) compared with the WL group. In addition, GT outperformed ESH in improving maladaptive sleep-related beliefs and mood symptoms at post-treatment and 6-month follow-up. A reduction of suicidality with moderate effect size favoring GT emerged at 6-month follow-up.Our findings suggested that both group-based and email-delivered CBT-I were effective in treating youth insomnia, but group-based CBT-I showed superior effects on reducing maladaptive beliefs and mood symptoms.

Aims To investigate the joint association of accelerometer-measured physical activity (PA) and sleep duration with mortality risk. Methods and results A 7-day accelerometer recording was performed on 92 221 participants (age 62.4 ± 7.8 years; 56.4% women) from the UK Biobank between February 2013 and December 2015. We divided sleep duration into three groups (short, normal, and long), total volume of PA into three levels according to tertiles (high, intermediate, low), and moderate-to-vigorous PA (MVPA) into two groups based on the World Health Organization guidelines. The mortality outcomes were prospectively collected through the death registry. Over a median follow-up of 7.0 years, 3080 adults died, of which 1074 died from cardiovascular disease (CVD) and 1871 from cancer. The associations of PA and sleep duration with mortality risk were all in a curvilinear dose–response pattern (Pnonlinearity Conclusion MVPA meeting recommendations or a higher volume of PA at any intensity potentially diminished the adverse effects on all-cause and cause-specific mortality associated with short and long sleep duration.

Background: The COVID-19 pandemic and related restriction measures have affected our daily life, sleep, and circadian rhythms worldwide. Their effects on hypersomnolence and fatigue remain unclear. Methods: The International COVID-19 Sleep Study questionnaire which included items on hypersomnolence such as excessive daytime sleepiness (EDS), and excessive quantity of sleep (EQS), as well as sociodemographic factors, sleep patterns, psychological symptoms, and quality of life was distributed in 15 countries across the world from May to September in 2020. Results: Altogether responses from 18,785 survey participants (65% women, median age 39 years) were available for analysis. Only 2.8% reported having had COVID-19. Compared to before the pandemic, the prevalence of EDS, EQS, and fatigue increased from 17.9% to 25.5%, 1.6%–4.9%, and 19.4%–28.3% amid the pandemic, respectively. In univariate logistic regression models, reports of having a COVID-19 were associated with EQS (OR 5.3; 95%-CI 3.6–8.0), EDS (2.6; 2.0–3.4), and fatigue (2.8; 2.1–3.6). In adjusted multivariate logistic regression, sleep duration shorter than desired (3.9; 3.2–4.7), depressive symptoms (3.1; 2.7–3.5), use of hypnotics (2.3; 1.9–2.8), and having reported COVID-19 (1.9; 1.3–2.6) remained strong predictors of EDS. Similar associations emerged for fatigue. In the multivariate model, depressive symptoms (4.1; 3.6–4.6) and reports of having COVID-19 (2.0; 1.4–2.8) remained associated with EQS. Conclusions: A large increase in EDS, EQS, and fatigue occurred due to the COVID-19 pandemic, and especially in self-reported cases of COVID-19. These findings warrant a thorough understanding of their pathophysiology to target prevention and treatment strategies for long COVID condition. publishedVersion

There is a growing interest in the role of timing of daily behaviors in improving health. However, little is known about the optimal timing of physical activity to maximize health benefits. We perform a cohort study of 92,139 UK Biobank participants with valid accelerometer data and all-cause and cause-specific mortality outcomes, comprising over 7 years of median follow-up (638,825 person-years). Moderate-to-vigorous intensity physical activity (MVPA) at any time of day is associated with lower risks for all-cause, cardiovascular disease, and cancer mortality. In addition, compared with morning group (>50% of daily MVPA during 05:00-11:00), midday-afternoon (11:00-17:00) and mixed MVPA timing groups, but not evening group (17:00-24:00), have lower risks of all-cause and cardiovascular disease mortality. These protective associations are more pronounced among the elderly, males, less physically active participants, or those with preexisting cardiovascular diseases. Here, we show that MVPA timing may have the potential to improve public health.

BACKGROUND: The health effects of rest-activity rhythm are of major interest to public health, but its associations with health outcomes remain elusive. We aimed to examine the associations between accelerometer-measured rest-activity rhythm amplitude and health risks among the general UK population. METHODS: We did a prospective cohort analysis of UK Biobank participants aged 43-79 years with valid wrist-worn accelerometer data. Low rest-activity rhythm amplitude was defined as the first quintile of relative amplitude; all other quintiles were classified as high rest-activity rhythm amplitude. Outcomes of interest were defined using International Classification of Diseases 10th Revision codes and consisted of incident cancer and cardiovascular, infectious, respiratory, and digestive diseases, and all-cause and disease-specific (cardiovascular, cancer, and respiratory) mortality. Participants with a current diagnosis of any outcome of interest were excluded. We assessed the associations between decreased rest-activity rhythm amplitude and outcomes using Cox proportional hazards models. FINDINGS: Between June 1, 2013, and Dec 23, 2015, 103 682 participants with available raw accelerometer data were enrolled. 92 614 participants (52 219 [56·4%] women and 40 395 [42·6%] men) with a median age of 64 years (IQR 56-69) were recruited. Median follow-up was 6·4 years (IQR 5·8-6·9). Decreased rest-activity rhythm amplitude was significantly associated with increased incidence of cardiovascular diseases (adjusted hazard ratio 1·11 [95% CI 1·05-1·16]), cancer (1·08 [1·01-1·16]), infectious diseases (1·31 [1·22-1·41]), respiratory diseases (1·26 [1·19-1·34]), and digestive diseases (1·08 [1·03-1·14]), as well as all-cause mortality (1·54 [1·40-1·70]) and disease-specific mortality (1·73 [1·34-2·22] for cardiovascular diseases, 1·32 [1·13-1·55] for cancer, and 1·62 [1·25-2·09] for respiratory diseases). Most of these associations were not modified by age older than 65 years or sex. Among 16 accelerometer-measured rest-activity parameters, low rest-activity rhythm amplitude had the strongest or second- strongest associations with nine health outcomes. INTERPRETATION: Our results suggest that low rest-activity rhythm amplitude might contribute to major health outcomes and provide further evidence to promote risk-modifying strategies associated with rest-activity rhythm to improve health and longevity.

Introduction Despite the efficacy of cognitive behavioural therapy for insomnia (CBT-I) for treating youth insomnia, there remain individual differences in treatment outcomes. Previous studies found that demographic (e.g., age) and clinical features (e.g., depression, anxiety) could potentially affect treatment responses in adults but there has been limited research conducted in youth. This study aimed to identify potential predictors of treatment response and remission of insomnia following CBT-I in a sample of adolescents with insomnia and eveningness. Methods The sample consisted of 57 adolescents with insomnia with eveningness (Age: 20.21 ± 1.95, 15-24, female: 56.14%) who had completed a 6-session group-based cognitive behavioural therapy (CBT-I) with (n = 27) or without bright light therapy (n=30). Assessments were conducted at baseline and one-week post-intervention. Insomnia Severity Index (ISI) was used to measure self-reported insomnia symptoms. Treatment response was defined as a reduction in ISI score ≥ 6 after treatment, and remission was defined as an ISI score < 9 at post-treatment. Backward stepwise logistic regression was conducted to explore baseline demographic and clinical factors (e.g., comorbid depression or anxiety, suicidality) that might contribute to treatment response and remission of insomnia. Results About 64.9% and 68.4% of the participants achieved treatment response and remission of insomnia, respectively. There was no significant difference in response (60.0% vs. 73.4%) and remission (63.3% vs. 74.1%) rates between participants with and without adjunctive light therapy. Treatment response was significantly predicted by lower suicidality (p Conclusion CBT-I is more effective in adolescents with less eveningness, elevated insomnia symptoms, and less suicidality. Future research should explore whether addressing these factors in the delivery of CBT-I could improve treatment outcomes in youths with insomnia. Support (if any) This work was funded by General Research Fund (Ref. 17608918), Research Grants Council, University Grants Committee, Hong Kong SAR, China.

ObjectiveTo investigate the prevalence and clinical correlates of video polysomnography (vPSG)-confirmed rapid eye movement sleep behaviour disorder (RBD) in patients with major depressive disorder (MDD).MethodsThis is a clinic-based two-phase epidemiological study. In phase 1, patients with MDD were screened by a validated questionnaire, RBD Questionnaire-Hong Kong (RBDQ-HK). In phase 2, a subsample of both the screen-positive (RBDQ-HK >20) and screen–negative patients with MDD underwent further clinical and sleep assessment (vPSG) to confirm the diagnosis of RBD (MDD+RBD). Poststratification weighting method was used to estimate the prevalence of MDD+RBD. The total likelihood ratio and the probability of prodromal Parkinson’s disease (PD) were calculated from prodromal markers and risk factors, as per the Movement Disorder Society research criteria.ResultsA total of 455 patients with MDD were screened (median age (IQR)=52.66 (15.35) years, 77.58% woman, 43.74% positive). Eighty-one patients underwent vPSG and 12 of them were confirmed MDD+RBD. The prevalence of MDD+RBD was estimated to be 8.77% (95% CI: 4.33% to 16.93%), with possibly male predominance. MDD+RBD were associated with colour vision and olfaction deficit and a higher probability for prodromal PD.ConclusionsAlmost 9% of patients with MDD in the psychiatric outpatient clinic has vPSG-confirmed RBD. Comorbid MDD+RBD may represent a subtype of MDD with underlying α-synucleinopathy neurodegeneration. Systematic screening of RBD symptoms and necessity of vPSG confirmation should be highlighted for capturing this MDD subtype with a view to enhance personalised treatment and future neuroprotection to prevent neurodegeneration.

Eveningness and insomnia are highly comorbid and closely related to psychopathology in adolescents. We aimed to prospectively investigate the trajectories and associations of eveningness and insomnia with daytime functioning, depression and suicidal risk in adolescents.A 3-year longitudinal study was conducted among 414 Chinese adolescents. The associations of eveningness and insomnia with daytime functioning, depression and suicidal ideation were analyzed using logistic regressions.The prevalence rates of eveningness were similar at baseline and follow-up (19.3% vs 22.5%; p = 0.27), while the prevalence of insomnia increased at follow-up (29.2% vs 40.8%; p0.001). Among those eveningness adolescents (n=80) at baseline, 46.2% remained as stable evening-type at follow-up, and among those insomnia adolescents (n=121) at baseline, 64.5% had persistent insomnia at follow-up. Logistic regressions showed that stable, incident, and resolved eveningness were associated with excessive daytime sleepiness (EDS) at follow-up, while only persistent and incident insomnia increased the risk of EDS. Persistent and incident insomnia, as well as stable eveningness were independently associated with depression at follow-up. Persistent and incident insomnia, but not eveningness, were associated with suicidal ideation.The outcome assessments were based on self-reported questionnaires and the sample size is modest.Persistent eveningness and insomnia are significantly associated with greater risks of EDS and depression in adolescents, while both persistent and incident insomnia, but not eveningness, increased the risk of suicidal ideation. These findings underscore the importance of addressing sleep and circadian factors in the management of adolescent mood and daytime functioning.

Study ObjectivesThis study aimed to examine the craniofacial phenotype of Chinese prepubertal children with and without obstructive sleep apnea (OSA) using a quantitative photographic analysis technique and to develop a prediction model for OSA diagnosis based on the photogrammetric data. Potential ethnic differences in the association between OSA and photogrammetric data between Chinese and Caucasian children were also examined.MethodsThis was a cross-sectional study. Chinese children aged 5–12 years old, suspected to have OSA were recruited from our sleep clinic. Frontal and side photos were taken for craniofacial phenotyping by photogrammetry. Polysomnography was performed and participants were divided into three groups: non-OSA (obstructive apnea hypopnea index (OAHI) < 1/h), mild OSA (OAHI between 1/h and 5/h), and moderate-to-severe (MS) OSA (OAHI ≥ 5/h). Prediction models were built from 70% of training data using logistic regression and evaluated on the remaining 30% of test data for receiver operating characteristic (ROC) curve construction.ResultsThis study included 90 participants (mean age: 8.2 ± 1.6 years, 67 males). Non-OSA, mild OSA, and MS OSA groups included 32, 31, and 27 participants, respectively. There were significant trends for an increasing maxillary-mandibular relationship angle (p = .002) and a decreasing anterior mandibular height to whole face length ratio (p < .001) with increasing OSA severity. A prediction model built with clinical measurements and the two photogrammetric features yielded an area under the ROC curve (AUC) of 0.81 (95% C.I.: 0.64–0.96).ConclusionsCraniofacial features obtained by photogrammetry are significantly different between OSA groups in prepubertal children. Increased maxillary-mandibular relationship angle is an OSA feature found in both Asian and Caucasian children.

Hoi Man Yuen,1 Andy CY Lai,1 Eric KH Liu,2 Ming Chung Lee,2 Winnie CW Chu,2 Joey WY Chan,3 Ngan Yin Chan,3 Yun Kwok Wing,3 Albert M Li,1,4,5 Kate C Chan,1,4,5 Chun Ting Au1,4,5 1Department of Pediatrics, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong SAR, People’s Republic of China; 2Department of Imaging and Interventional Radiology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong SAR, People’s Republic of China; 3Li Chiu Kong Family Sleep Assessment Unit, Department of Psychiatry, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong SAR, People’s Republic of China; 4Laboratory for Pediatric Respiratory Research, Li Ka Shing Institute of Health Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, People’s Republic of China; 5Hong Kong Hub of Pediatric Excellence, The Chinese University of Hong Kong, Hong Kong SAR, People’s Republic of ChinaCorrespondence: Kate C Chan; Chun Ting Au, Department of Pediatrics, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong SAR, People’s Republic of China, Tel +852 35053515 ; +852 35052917, Fax +852 26360020, Email katechan@cuhk.edu.hk; junau@cuhk.edu.hkBackground: Lateral parapharyngeal wall (LPW) thickness is a potentially useful anatomical marker of childhood obstructive sleep apnea (OSA). Measuring LPW thickness by ultrasonography (USG) is technically feasible but its use in children has not been validated. Therefore, this study aimed to assess the intra- and inter-operator reliability of the sonographic measurements of LPW thickness in children and to assess its validity against magnetic resonance imaging (MRI) measurements.Methods: Prepubertal children aged 6– 11 years suspected to suffer from OSA were recruited. Repeated measurements of LPW thickness by USG were conducted to evaluate the intra- and inter-operator reliability, examined by intraclass correlation coefficient (ICC). LPW thickness was measured as the distance between the internal carotid artery and the echogenic surface of the pharynx in an oblique coronal plane by USG. LPW thickness was measured by MRI at the retropalatal level. The agreement between the LPW thickness measured by USG and MRI was assessed by ICC and Bland-Altman plot.Results: Thirty-four children (mean age: 8.66 ± 1.61, 26 male) were recruited. The intra- and inter-operator reliability of the LPW thickness by USG was good (ICC = 0.84 and 0.82, respectively). The agreement between the USG-measured and MRI-measured LPW thickness was moderate (ICC = 0.72). he Bland-Altman plot demonstrated a mean difference of 0.061 cm and a 95% limit of agreement from 0.91 to 1.12 cm.Conclusion: In this study, we demonstrated that ultrasonography is a valid and reliable method to assess LPW thickness in children. This study was supported by the Direct Grant for Research from the Research Committee of the Chinese University of Hong Kong (Project no. 2020.073).Keywords: pediatric, ultrasound, MRI, obstructive sleep apnea

Recurrent dream-enactment behaviours (DEB) and rapid eye movement (REM) sleep without atonia (RSWA) are two diagnostic hallmarks of REM sleep behaviour disorder (RBD), a specific prodrome of α-synucleinopathy. Whilst isolated RSWA (without DEB) was suggested as a prodrome of RBD, the implication of 'isolated' recurrent DEB remains under-investigated. In this cross-sectional study, we sought to investigate neurodegenerative markers amongst the first-degree relatives (FDRs, aged40 years) of patients with RBD who underwent clinical assessment for DEB, neurodegenerative markers, and video-polysomnography assessment. Isolated recurrent DEB was defined as: (i) three or more episodes of DEB, (ii) had a DEB episode in the past 1 year, and (iii) subthreshold RSWA. We identified 29 FDRs (mean [SD] age 53.4 [8.3] years, 55.2% male) with isolated recurrent DEB and 98 age and sex-matched FDRs as controls. Isolated DEB was associated with nightmare (27.6% versus 11.2%, p = 0.02), and the DEB group had a higher rate of current smoking (27.6% versus 3.1%, p = 0.006), type 2 diabetes mellitus (24.1% versus 10.2%, p = 0.003), anxiety disorder (24.1% versus 11.2%, p = 0.02), and constipation (hard lump of stool, 31.0% versus 7.1%, p 0.001) than the control group. The present findings revealed that family relatives of patients with RBD with isolated recurrent DEB have increased risk of RBD and neurodegenerative features, which adds to the emerging data that isolated DEB is a prodromal feature of RBD and α-synucleinopathy neurodegeneration.

In response to the all-round development of primary school children, this study aimed to evaluate the effectiveness of a blended intervention program on children's health-related outcomes of aerobic fitness, motor skills, inhibition and daytime sleepiness in classroom settings. Three experimental conditions include: (1) the “Stand + Move” group combining sit-stand desks and physical activity (PA) recess, (2) “Move” group with PA recess only, and (3) Control group (CG; normal class schedule). A total of 64 primary school children (37.5% girls and 62.5% boys, M [SD] = 9.6 [0.61], BMI mean = 17.0 ± 3.0) participated in all assessments, including aerobic fitness, motor skills, inhibitory control, and daytime sleepiness. The baseline data collection starts from January 2019, with the intervention lasting for 13 weeks and followed by post-intervention and follow up tests conducted in July and October 2019. There was a significant interaction effect on aerobic fitness [F(2,76) = 10.62, p < 0.001, η2 = 0.22] after the intervention period, whereas no significant interaction was observed for other variables. Significant main effects were observed in aerobic fitness (pre – post: −11.75 and −7.22) for both experimental groups, with the blended group showing greater improvements immediately post the test, while motor skills only showed a significant increase at the three-month follow-up, with the greatest increase in the blended group (pre-follow-up: −2.50). For inhibition control and daytime sleepiness, better improvements were shown for the experimental groups than for the control group. The blended designed intervention, by incorporating multiple components as an innovative strategy to reconstruct children's traditional classroom environment in Hong Kong, has demonstrated improved physical and psychological development of school children.Clinical trial registrationChiCTR, ChiCTR2000035038. Registered 29 July 2020 – Retrospectively registered. http://www.chictr.org.cn/hvshowproject.aspx?id=46038.

BACKGROUND Long COVID induces a substantial global burden of disease. The pathogenesis, complications, and epidemiological and clinical characteristics of patients with COVID-19 in the acute phase have been evaluated, while few studies have characterized the epidemiology, symptomatology, and risk factors of long COVID symptoms. Its characteristics among patients with COVID-19 in the general population remain unaddressed. OBJECTIVE We examined the prevalence of long COVID symptoms, its symptom patterns, and its risk factors in 4 major Chinese cities in order to fill the knowledge gap. METHODS We performed a population-based, multicenter survey using a representative sampling strategy via the Qualtrics platform in Beijing, Shanghai, Guangzhou, and Hong Kong in June 2022. We included 2712 community-dwelling patients with COVID-19 and measured the prevalence of long COVID symptoms defined by the World Health Organization (WHO), and their risk factors. The primary outcomes were the symptoms of long COVID, with various levels of impact. A descriptive analysis of the prevalence and distribution of long COVID symptoms according to disease severity was conducted. A sensitivity analysis of increasing the number of long COVID symptoms was also conducted. Univariate and multivariate regression analyses were performed to examine the risk factors of severe long COVID symptoms, including age, gender, marital status, current occupation, educational level, living status, smoking habits, monthly household income, self-perceived health status, the presence of chronic diseases, the use of chronic medication, COVID-19 vaccination status, and the severity of COVID-19. RESULTS The response rate was 63.6% (n=2712). The prevalence of long COVID, moderate or severe long COVID, and severe long COVID was 90.4% (n=2452), 62.4% (n=1692), and 31.0% (n=841), respectively. Fatigue (n=914, 33.7%), cough (n=865, 31.9%), sore throat (n=841, 31.0%), difficulty in concentrating (n=828, 30.5%), feeling of anxiety (n=817, 30.2%), myalgia (n=811, 29.9%), and arthralgia (n=811, 29.9%) were the most common severe long COVID symptoms. From multivariate regression analysis, female gender (adjusted odds ratio [aOR]=1.49, 95% CI 1.13-1.95); engagement in transportation, logistics, or the discipline workforce (aOR=2.52, 95% CI 1.58-4.03); living with domestic workers (aOR=2.37, 95% CI 1.39-4.03); smoking (aOR=1.55, 95% CI 1.17-2.05); poor or very poor self-perceived health status (aOR=15.4, 95% CI 7.88-30.00); ≥3 chronic diseases (aOR=2.71, 95% CI 1.54-4.79); chronic medication use (aOR=4.38, 95% CI 1.66-11.53); and critical severity of COVID-19 (aOR=1.52, 95% CI 1.07-2.15) were associated with severe long COVID. Prior vaccination with ≥2 doses of COVID-19 vaccines was a protective factor (aOR=0.35-0.22, 95% CI 0.08-0.90). CONCLUSIONS We examined the prevalence of long COVID symptoms in 4 Chinese cities according to the severity of COVID-19. We also evaluated the pattern of long COVID symptoms and their risk factors. These findings may inform early identification of patients with COVID-19 at risk of long COVID and planning of rehabilitative services.

Brigitte Holzinger,1,2 Franziska Nierwetberg,1 Frances Chung,3 Courtney J Bolstad,4 Bjørn Bjorvatn,5 Ngan Yin Chan,6 Yves Dauvilliers,7 Colin A Espie,8 Fang Han,9 Yuichi Inoue,10 Damien Leger,11 Tainá Macêdo,12 Kentaro Matsui,13,14 Ilona Merikanto,15,16 Charles M Morin,17 Sérgio A Mota-Rolim,18 Markku Partinen,19 Giuseppe Plazzi,20,21 Thomas Penzel,22 Mariusz Sieminski,23 Yun Kwok Wing,6 Serena Scarpelli,24 Michael R Nadorff,4,25 Luigi De Gennaro24,26 1Institute for Consciousness and Dream Research, Vienna, Austria; 2Medical University Vienna, Postgraduate Master ULG Sleep Coaching, Vienna, Austria; 3Department of Anesthesiology and Pain Medicine, University Health Network, University of Toronto, Toronto, ON, Canada; 4Mississippi State University, Mississippi State, MS, USA; 5Department of Global Public Health and Primary Care, University of Bergen and Norwegian Competence Center for Sleep Disorders, Haukeland University Hospital, Bergen, Norway; 6Li Chiu Kong Family Sleep Assessment Unit, Department of Psychiatry, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong, Special Administrative Region, People’s Republic of China; 7Sleep-Wake Disorders Unit, Department of Neurology, Gui-de-Chauliac Hospital, CHU Montpellier, INM, Univ Montpellier, INSERM, Montpellier, France; 8Sir Jules Thorn Sleep & Circadian Neuroscience Institute (SCNi), University of Oxford, Oxford, UK; 9Department of Pulmonary and Critical Care Medicine, Peking University People’s Hospital, Beijing, People’s Republic of China; 10Tokyo Medical University, Tokyo, Japan; 11Université de Paris, APHP, Hôtel-Dieu, Centre du Sommeil et de la Vigilance, Paris, France; 12Department of Psychology, Federal University of Rio Grande do Norte, Natal, Brazil; 13Department of Laboratory Medicine, National Center Hospital, National Center of Neurology and Psychiatry, Kodaira, Japan; 14Department of Psychiatry, Tokyo Women’s Medical University, Tokyo, Japan; 15SleepWell Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland; 16Department of Public Health and Welfare, Finnish Institute for Health and Welfare, Helsinki, Finland; 17École de Psychologie, Centre d’étude des troubles du sommeil, Centre de recherche CERVO/Brain Research Center, Université Laval, Québec, QC, Canada; 18Brain Institute, Physiology and Behavior Department, and Onofre Lopes University Hospital - Federal University of Rio Grande do Norte, Natal, Brazil; 19Helsinki Sleep Clinic, Terveystalo Healthcare, and Department of Neurosciences, Clinicum, University of Helsinki, Helsinki, Finland; 20IRCCS, Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy; 21Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy; 22Sleep Medicine Center, Charité Universitätsmedizin Berlin, Berlin, Germany; 23Department of Emergency Medicine, Medical University of Gdansk, Gdansk, Poland; 24Department of Psychology, Sapienza University of Rome, Rome, Italy; 25Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, TX, USA; 26IRCCS Fondazione Santa Lucia, Rome, ItalyCorrespondence: Brigitte Holzinger, Tel +43 699 101 99 042, Email brigitte.holzinger@meduniwien.ac.atPurpose: The COVID-19 pandemic affects mental health and sleep, resulting in frequent nightmares. Therefore, identifying factors associated with nightmare frequency is important, as it can indicate mental health issues. The study aimed to investigate increases in nightmare frequency comparing the pre-pandemic and pandemic period, and identify its risk factors. Further, the mediating role of post-traumatic stress disorder symptoms between the pandemic and nightmares is explored.Patients and Methods: For this cross-sectional survey data were obtained via self-rating online survey (ICOSS: details in Partinen et al, 2021), which was open to anyone older than 18 years. The final volunteer sample consisted of 15,292 participants, divided according to their nightmare frequency (high: ≥ 1– 2 nights/week; low: < 1– 2 nights/week). A total of 9100 participants were excluded if answers on variables of interest were missing or receiving rewards for participation. Chi-square tests identified changes of nightmare frequency. Predictors of high nightmare frequency were assessed using logistic regression and presented as Odds Ratios. Post-hoc mediation models were used to investigate the role of post-traumatic stress symptoms (PTSS).Results: The mean age was 41.63 (SD=16.55) with 64.05% females. High nightmare frequency increased significantly from 13.24% to 22.35% during the pandemic. Factors associated with it included self-reported PTSS (OR=2.11), other mental disorders and various sleep disorders or problems. Financial burden due to the pandemic, confinement, having had COVID-19, and work situation during the pandemic were associated with nightmare frequency, those relations were partly mediated through PTSS.Conclusion: Our results display the pandemic influence on nightmare frequency, which in turn connects to multiple mental health and sleep factors. These relations were partly mediated through PTSS. The COVID-19 pandemic appears to have caused traumatization of a substantial proportion of society. Health care workers should consider nightmares in their screening routines, as it might indicate PTSS and/or other mental and sleep disorders.Keywords: COVID-19, nightmares, mental health, sleep, post-traumatic stress disorder, collective trauma

Study ObjectivesIncreased incidence of narcolepsy was reported in children during the 2009 H1N1 pandemic following Pandemrix, a H1N1 flu vaccine. A link with A(H1N1) pdm09 infections remains controversial. Using nationwide surveillance data from China (1990 to 2017), the epidemiology of narcolepsy was analyzed.MethodsIndividual records of narcolepsy patients were collected from 15 of 42 hospitals across China known to diagnose cases. Incidence was estimated assuming the representativeness of these hospitals. Age-specific incidence, epidemiological and clinical characteristics of patients were evaluated before, during, and after the 2009 H1N1 pandemic. Sensitivity analyses were conducted by including NT1 cases only and excluding the effect of the 2009 H1N1 vaccination.ResultsAverage annual incidence was 0.79 per 100 000 person-years (PY) from 1990 to 2017 and 1.08 per 100 000 PY from 2003 to 2017. Incidence increased 4.17 (95% CI 4.12, 4.22) and 1.42 (95% CI 1.41, 1.44) fold during and after the 2009 H1N1 pandemic when compared to baseline. These results were robust in sensitivity analyses. Patients with the onset of narcolepsy during the pandemic period were younger (notably in 5–9-year-old strata), and the age shift toward younger children reversed to baseline following the pandemic.ConclusionsIncreased incidence of narcolepsy was observed during the 2009 H1N1 pandemic period. This is likely to be associated with the circulation of the wild type A(H1N1)pdm09 virus. This observation should be considered for future influenza pandemic preparedness plans.