Sleep and the gut microbiota in preschool aged children

Sleep plays a significant role in the mental and physical development of children. Emerging evidence in animals and human adults indicates a relationship between sleep and the gut microbiota; however, it is unclear whether the sleep of preschoolers during a key developmental period, associates with features of their gut microbiota. The objective of this study was to assess the relationship between sleep and gut microbiota in preschool aged children (4.37 ±0.48 years, n=143). Sleep measures included total nighttime sleep (TST), sleep efficiency (SE), and wake-time after sleep onset (WASO) assessed using actigraphy. Beta-diversity differences between children with low and high TST (p =0.048) suggest gut microbiota community differences. Particularly, relative abundance of Bifidobacterium was higher in the high TST group and Bacteroides, was higher in children who had higher SE and low WASO (LDA score >2). In contrast, some Lachnospiraceae members including Blautia and Coprococcus 1 were associated with shorter nighttime sleep duration and less efficiency, respectively. We also found a group of faecal metabolites, including specific neuroactive compounds and immunomodulating metabolites were associated with greater sleep efficiency and less time awake at night. Notably, tryptophan and its metabolizing products were higher in children who had higher SE or lower WASO (LDA score >2); concentration of propionate was higher in children with lower WASO (p =0.036). Overall, our results reveal a novel association between sleep and gut microbiota in preschool aged children. Longer nighttime sleep and greater sleep efficiency were associated with specific commensal bacteria that may regulate sleep through modulating neurotransmitter metabolism and the immune system.

Classical complement pathway factor alterations in narcolepsy

Objective: Narcolepsy is a chronic sleep disorder long hypothesised to be an autoimmune disease. Complement-mediated immune mechanisms have not been investigated in detail in narcolepsy. Our aim was to establish the significance of classical pathway activation in narcolepsy. Methods: Sera of 42 narcolepsy patients and 26 healthy controls were screened with ELISA to determine the levels of C1q, C3a, C4d and complement component 4 binding protein (C4BP). A home-made ELISA method was developed to detect antibodies to C4BP-alpha (anti-C4BPA). The correlation between complement levels and clinical findings was examined. Results: C1q levels were significantly higher in narcolepsy patients while C4d and C4BP levels were significantly lower compared to healthy controls. C3a levels were comparable among patients and controls. Eleven narcolepsy patients showed serum anti-C4BPA levels. Total rapid eye movements (REM) time, sleep onset latency, REM sleep latency, sleep activity, percentage of wakefulness after sleep onset and Epworth sleepiness scale scores were correlated with levels of different complement factors. Conclusion: Complement-mediated immune mechanisms might partake in narcolepsy pathogenesis. The precise role of autoantibodies on complement level alterations needs to be investigated. Levels of complement factors and degradation products may potentially be utilised as biomarkers to predict the clinical severity of narcolepsy.

Sleep Characteristics in Esport Players and Associations With Game Performance: Residual Dynamic Structural Equation Modeling

The current study aimed to examine sleep characteristics of esport players and the stipulated effects of game performance on consecutive sleep characteristics using residual dynamic structural equation modeling (RDSEM). A sample of 27 Counterstrike players with a mean age of 18½ years participated in the current study. Sleep was detected over a period of 56 days with a Somnofy sleep monitor that utilizes an impulse radio ultra-wideband puls radar and Dopler technology, and weekly game performance was reported by the players. The results showed that esport players' sleep characteristics were in the lower levels of recommended guidelines and that sleep onset started later and sleep offset ended later in the morning compared with athletes from other traditional sports. The esport players displayed stable patterns in sleep onset, sleep offset, time in bed, sleep efficiency and non-REM respiration rates per minute (NREM RPM). On the between-person level, esport players with better game performance spent more time sleeping (r = 0.55) and scored lower on NREM RPM (r = −0.44). Unstandardized within-person cross-lagged paths showed that better game performance predicted subsequent earlier sleep offset. The within-level standardized estimates of the cross-lagged paths revealed that participants with better game performance spent subsequently more time in deep sleep (0.20), less time in light sleep (−0.14), less time in bed (−0.16), and displayed lower NREM RPM (−0.21), earlier sleep offset (−0.21), and onset (−0.09). The findings of better game performance being related to better sleep are discussed in terms of existing knowledge on how stress responses elicitated by poor performance might impact on non-REM respiration rates and sleep.

A double-blind, randomized, placebo-controlled trial of suvorexant for the treatment of vasomotor symptom-associated insomnia disorder in midlife women

Study Objectives The neuropeptide orexin promotes wakefulness, modulates thermoregulation, increases after menopause, and is normalized in women receiving estrogen therapy, suggesting a role for orexin antagonism as a treatment for vasomotor symptom (VMS)-associated insomnia disorder. We tested the efficacy of the dual orexin receptor antagonist suvorexant for chronic insomnia related to nighttime VMS. Methods In a double-blind, placebo-controlled trial, 56 women with chronic insomnia associated with nighttime VMS, Insomnia Severity Index (ISI) scores ≥15, and >30 minutes of diary-rated wake after sleep-onset (WASO) were randomized to receive oral suvorexant 10-20 mg (n=27) or placebo (n=29) nightly for 4 weeks. Analysis of within-person change in ISI was adjusted for baseline ISI and race. Results Mean baseline ISI scores were 18.1 (95% CI, 16.8-19.4) and 18.3 (95% CI, 17.2-19.5) in the suvorexant and placebo groups, respectively (p=0.81). The average 4-week ISI within-person decrease from baseline was greater on suvorexant [-8.1 (95% CI, -10.2 to -6.0)] compared to placebo [-5.6 (95% CI, -7.4 to -3.9), p=0.04]. Compared to placebo, nighttime diary-rated VMS frequency was significantly reduced with suvorexant (p<0.01). While diary-rated WASO and total sleep time trended toward improvement on suvorexant, findings were not significant after adjustment for multiple comparison. Daytime VMS and other sleep-related outcomes did not differ between groups. Suvorexant was well tolerated. Conclusion These results suggest that suvorexant is likely a well-tolerated and efficacious treatment for VMS-associated insomnia disorder and reduces nighttime VMS. Antagonism of orexin receptors could provide a novel therapeutic option for midlife women with VMS-associated chronic insomnia.

Modulation of Sleep Architecture by Whole-Body Static Magnetic Exposure: A Study Based on EEG-Based Automatic Sleep Staging

A steady increase in sleep problems has been observed along with the development of society. Overnight exposure to a static magnetic field has been found to improve sleep quality; however, such studies were mainly based on subjective evaluation. Thus, the presented data cannot be used to infer sleep architecture in detail. In this study, the subjects slept on a magneto-static mattress for four nights, and self-reported scales and electroencephalogram (EEG) were used to determine the effect of static magnetic field exposure (SMFE) on sleep. Machine learning operators, i.e., decision tree and supporting vector machine, were trained and optimized with the open access sleep EEG dataset to automatically discriminate the individual sleep stages, determined experimentally. SMEF was found to decrease light sleep duration (N2%) by 3.51%, and sleep onset latency (SOL) by 15.83%, while it increased deep sleep duration (N3%) by 8.43%, compared with the sham SMFE group. Further, the overall sleep efficiency (SE) was also enhanced by SMFE. It is the first study, to the best of our knowledge, where the change in sleep architecture was explored by SMFE. Our findings will be useful in developing a non-invasive sleep-facilitating instrument.

Importance of characterising sleep breaks within the 24-h movement behaviour framework

Accelerometers measure the acceleration of the body part they are attached and allow to estimate time spent in activity levels (sedentary behaviour, light, and moderate-to-vigorous physical activity) and sleep over a 24-h period for several consecutive days. These advantages come with the challenges to analyse the large amount of data while integrating dimensions of both physical activity/sedentary behaviour and sleep domains. This commentary raises the questions of 1) how to classify sleep breaks (i.e. wake after sleep onset) during the night within the 24-h movement behaviour framework and 2) how to assess their impact on health while also accounting for night time sleep duration and time in sedentary behaviour and physical activity during the day. The authors advocate for future collaborations between researchers from the physical activity/sedentary behaviour and sleep research fields to ensure appropriate analysis and interpretation of the tremendous amount of data recorded by the newer generation accelerometers. This is the only way forward to provide meaningfully accurate evidence to inform future 24-h movement behaviour guidelines.

Sleep disturbances in early clinical stages of psychotic and bipolar disorders: A meta-analysis

Objective: To provide a qualitative view and quantitative measure of sleep disturbances across and between early stages – clinical ultra high-risk and first episode – of psychotic and bipolar disorders. Methods: Electronic databases (PubMed, Cochrane, Embase, PsychINFO) were searched up to March 2021 for studies comparing sleep measures between individuals with an early stage and controls. Standard mean deviations (Cohen’s d effect sizes) were calculated for all comparisons and pooled with random-effects models. Chi-square tests were used for direct between-subgroups (ultra high-risk vs first episode) comparisons of standard mean deviations. The effects of age, sex ratio, symptoms and treatment were examined in meta-regression analyses. Results: A database search identified 13 studies that contrasted sleep measures between individuals with an early stage ( N = 537) and controls ( N = 360). We observed poorer subjective sleep quality (standard mean deviation = 1.32; 95% confidence interval, [1.01, 1.62]), shorter total sleep time (standard mean deviation =−0.44; 95% confidence interval, [−0.67, −0.21]), lower sleep efficiency (standard mean deviation = −0.72; 95% confidence interval, [−1.08, −0.36]), longer sleep onset latency (standard mean deviation = 0.75; 95% confidence interval, [0.45, 1.06]) and longer duration of wake after sleep onset (standard mean deviation = 0.49; 95% confidence interval, [0.21, 0.77]) were observed in early stages compared to controls. No significant differences were observed for any of the reported electroencephalographic parameters of sleep architecture. No significant between-subgroups differences were observed. Meta-regressions revealed a significant effect of the age and the antipsychotic status on subjective measures of sleep. Conclusion: The early stage population presents with significant impairments of subjective sleep quality continuity, duration and initiation. Systematic assessments of sleep in early intervention settings may allow early identification and treatment of sleep disturbances in this population.

The “Sleep Well, Lincolnshire” Project: Evaluation of an Online Sleep Practitioner Clinic

Objectives: Poor sleep is associated with adverse outcomes during childhood. Behavioral insomnia is the most common sleep difficulty experienced by children. The coronavirus disease 2019 (COVID-19) global pandemic in 2020 has profoundly affected children’s sleep patterns. This project aimed to evaluate a one-toone sleep service delivered via online clinics by community sleep practitioners in the UK.Methods: This was an observational pre- and post-evaluation study over a 12-month period. The intervention derived from aspects of cognitive-behavioral therapy for insomnia. The evaluation was questionnaire-based and assessed sleep parameters and well-being.Results: 104 parents returned completed questionnaires. The average time of sleep onset was 1 hour and 39 minutes pre-intervention and 20 minutes post-intervention. The average number of nights per week that children woke up was 3.9 pre-intervention and 0.9 post-intervention; the number of night awakenings fell from 1.9 to 0.5 and the time that children were awake after sleep onset fell from 66.8 minutes to 5.8 minutes. The average time that children were asleep was 8.0 hours per night pre-intervention and 10.2 hours post-intervention. The improvement in all sleep parameters was statistically significant (p<0.05). All parameters of parental and children’s well-being improved significantly (p<0.05), except for perceived ability to drive (p=0.07). All parents stated that they would recommend sleep support and 20% already had done so.Conclusions: The COVID-19 pandemic has accelerated the development of remote health care solutions, and in the case of children’s sleep clinics, the online mode of intervention delivery that is as effective, acceptable, and accessible as face-to-face delivery.

Systematic Review and Meta-analysis of Efficacy and Safety of Melatonin and Triclofos for Inducing Adequate Sedation for Sleep Electroencephalogram in Children

Introduction Triclofos and melatonin are commonly used oral sedatives in children for obtaining a sleep electroencephalogram (EEG) record. There has been no systematic review till now to compare the efficacy and safety of these two medications. Objectives The review intended to compare the efficacy of oral triclofos and melatonin in children <18 years of age for inducing adequate sedation for obtaining a sleep EEG record. We also attempted to compare the adverse effects, impact on EEG record, the yield of epileptiform abnormalities, and sleep onset latency in both groups. Methods A systematic search was conducted on “MEDLINE/PUBMED, Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE, Web of Science, and Google Scholar” till November 30, 2020, with the following keywords/the Medical Subject Headings (MESH) terms while searching: “sleep EEG,” “electroencephalogram,” “triclofos,” “melatonin” OR “ramelteon” AND “epilepsy,” “seizure,” OR “convulsion.” ROB 2.0 and ROBINS-I tool was used to determine the risk of bias. To assess heterogeneity in studies, Higgins and Thompson's I 2 method was utilized. When I 2 was more than 50%, a random effects model was utilized and a fixed-effect model was used for other parameters. To assess the presence of publication bias, Egger's test was used. Results For describing the efficacy of triclofos in 1,284 and melatonin in 1,532 children, we selected 16 articles. The indirect comparison between the pooled estimate of all children receiving individual medications revealed comparable efficacy in obtaining successful sleep EEG record with a single dose (90 vs. 76%, p = 0.058) and repeat dose (p = 0.054), detection of epileptiform abnormalities (p = 0.06), and sleep onset latency (p = 0.06), but more proportion of children receiving triclofos had adverse effects (p = 0.001) and duration of sleep was also higher with triclofos (p = 0.001). Conclusion Efficacy of triclofos and melatonin are comparable in inducing sleep for recording EEG in children, although triclofos is more likely to cause adverse effects. However, the level of evidence is low for this conclusion and the weak strength of recommendation for the results of this review is likely to change in the future after completion of controlled trials exploring these two medications.