Effects of cognitive behavioural therapy and bright light therapy for insomnia in youths with eveningness: study protocol for a randomised controlled trial.

BACKGROUND: Insomnia and eveningness are common and often comorbid conditions in youths. While cognitive behavioural therapy for insomnia (CBT-I) has been suggested as a promising intervention, it remains unclear whether it is sufficient to also address circadian issues in youths. In addition, despite that light has been shown to be effective in phase-shifting one's circadian rhythm, there has been limited data on the effects of bright light therapy and its combination with CBT-I on sleep and circadian outcomes in youths. The current protocol outlines a randomised controlled trial that examines the efficacy of CBT-I and CBT-I plus bright light therapy (BLT) in reducing insomnia severity, improving mood symptoms and daytime functioning (e.g. sleepiness, fatigue, cognitive function), and improving subjective and objective sleep and circadian measures compared to a waitlist control group. METHODS: We will carry out a randomised controlled trial (RCT) with 150 youths aged 12-24 who meet the criteria of insomnia and eveningness. Participants will be randomised into one of three groups: CBT-I with bright light therapy, CBT-I with placebo light, and waitlist control. Six sessions of CBT-I will be delivered in a group format, while participants will be currently asked to use a portable light device for 30 min daily immediately after awakening throughout the intervention period for bright light therapy. The CBT-I with light therapy group will receive bright constant green light (506 lx) while the CBT-I with placebo light group will receive the modified light device with the LEDs emitting less than 10 lx. All participants will be assessed at baseline and post-treatment, while the two active treatment groups will be additionally followed up at 1 month and 6 months post-intervention. The primary outcome will be insomnia severity, as measured by the Insomnia Severity Index. Secondary outcomes include self-reported mood, circadian, daytime functioning, and quality of life measures, as well as sleep parameters derived from actigraphy and sleep diary and neurocognitive assessments. Objective measures of the circadian phase using dim-light melatonin onset assessment and sleep parameters using polysomnography will also be included as the secondary outcomes. DISCUSSION: This study will be the first RCT to directly compare the effects of CBT-I and BLT in youths with insomnia and eveningness. Findings from the study will provide evidence to inform the clinical management of insomnia problems and eveningness in youths. TRIAL REGISTRATION: ClinicalTrials.gov NCT04256915. Registered on 5 February 2020.

Secular trends in sleep and circadian problems among adolescents in Hong Kong: From 2011-2012 to 2017-2019.

OBJECTIVE: The study aimed to investigate secular trends in sleep and circadian problems in Hong Kong Chinese adolescents. METHODS: This study analyzed cross-sectional data from two large-scale school-based sleep surveys conducted in 2011-2012 and 2017-2019. Sleep and circadian problems, including sleep-wake pattern, insomnia, chronotype, social jetlag, daytime sleepiness, and other sleep-related factors, were compared between two survey years. RESULTS: A total of 8082 adolescents (5639 students in 2011-2012 [Mean age: 14.4 years, 50.9% boys] and 2443 students in 2017-2019 [Mean age: 14.7 years, 54.0% boys]) were included in this 7-year study. The average time in bed of Hong Kong adolescents decreased from 8.38 hours to 8.08 hours from 2011-2012 to 2017-2019. There was a 0.28-hour delay in weekday bedtime, 0.54-hour advance in weekend wake-up time, and a 0.36-hour decline in average time in bed, resulting in increased trends of sleep loss (Time in bed <8h: OR = 2.06, 95%CI: 1.44-2.93, p < 0.01; Time in bed <7h: OR = 2.73, 95%CI: 1.92-3.89, p < 0.01), daytime sleepiness (OR = 1.70, 95%CI: 1.34-2.16, p < 0.01), and evening chronotype (OR = 1.26, 95%CI: 1.08-1.48, p < 0.01). The increased trend in insomnia disorder, however, was insignificant when covariates were adjusted. CONCLUSION: A secular trend of reduced time in bed, delay in weekday bedtime, advance in weekend wake-up time, increase in evening chronotype and daytime sleepiness from 2011-2012 to 2017-2019 were observed. There is a timely need for systematic intervention to promote sleep health in adolescents.

An Open-Label Pilot Trial of a Brief, Parent-Based Sleep Intervention in Children With ADHD.

OBJECTIVE: To assess the effects of a brief parent-based behavioral sleep intervention in children with ADHD. METHODS: Families with a child with ADHD and parent-reported sleep problems received a brief parent-based sleep intervention, which involved two one-to-one consultation sessions and one telephone follow-up with the parent/caregiver. Child's sleep and clinical symptoms, and parental sleep and daytime functioning were assessed at baseline, 2-week post-intervention, and 3-month follow-up. RESULTS: Sixty eligible families (mean age of the child: 9.4 ± 1.5 years; boys: 75%) were recruited, and 43 (72%) completed the whole intervention. The intervention resulted in significant improvements in the child's sleep, clinical symptoms, and parental sleep and parenting stress, and these improvements were generally maintained at 3-month follow-up. CONCLUSION: The findings supported the promising effects of a brief parent-based sleep intervention on improving sleep and clinical symptoms in children with ADHD and parental sleep and parenting stress. Further randomized clinical trials with long-term follow-up are needed to test the robustness of the effectiveness of the intervention.

Quantitative and qualitative subgenomic RNA profiles of SARS-CoV-2 in respiratory samples: A comparison between Omicron BA.2 and non-VOC-D614G.

The SARS-CoV-2 Omicron variants are notorious for their transmissibility, but little is known about their subgenomic RNA (sgRNA) expression. This study applied RNA-seq to delineate the quantitative and qualitative profiles of canonical sgRNA of 118 respiratory samples collected from patients infected with Omicron BA.2 and compared with 338 patients infected with non-variant of concern (non-VOC)-D614G. A unique characteristic profile depicted by the relative abundance of 9 canonical sgRNAs was reproduced by both BA.2 and non-VOC-D614G regardless of host gender, age and presence of pneumonia. Remarkably, such profile was lost in samples with low viral load, suggesting a potential application of sgRNA pattern to indicate viral activity of individual patient at a specific time point. A characteristic qualitative profile of canonical sgRNAs was also reproduced by both BA.2 and non-VOC-D614G. The presence of a full set of canonical sgRNAs carried a coherent correlation with crude viral load (AUC â€‹= â€‹0.91, 95% CI 0.88-0.94), and sgRNA ORF7b was identified to be the best surrogate marker allowing feasible routine application in characterizing the infection status of individual patient. Further potentials in using sgRNA as a target for vaccine and antiviral development are worth pursuing.

Effects of childhood obstructive sleep apnea with and without daytime sleepiness on behaviors and emotions.

OBJECTIVE: To investigate the relationship between obstructive sleep apnea (OSA) with and without excessive daytime sleepiness (EDS) and behavioral and emotional outcomes in non-obese prepubertal children. METHODS: This was a retrospective analysis of children aged 5-11 years who presented to our unit for assessment of their sleep-related complaints. All children underwent polysomnography (PSG). They also completed the Pediatric Daytime Sleepiness Scale (PDSS) and a sleep diary. OSA was diagnosed if the obstructive apnea-hypopnea index (OAHI) was ≥1 event/hour. EDS was defined as PDSS >15. Behavioral and emotional outcomes were assessed using the Child Behavioral Checklist (CBCL). RESULTS: Data from 391 children (mean age of 8.6 ± 1.7 years; 67 % male) were analyzed. Seventy children did not have OSA or EDS, 137 had OSA, 50 had reported having EDS but without OSA, and 134 children had both OSA and EDS. There were significantly higher CBCL total problems score in the combined group (61 ± 9) compared to the non-OSA/EDS group (54 ± 10), and the OSA-only group (54 ± 10) (p < 0.001). The presence of EDS was significantly associated with higher CBCL T score and higher odds for clinically significant behavioral problems (T score ≥65) after adjusting for age, sex, BMI z-score and average sleep duration (p < 0.001). CONCLUSION: Excessive daytime sleepiness is an important contributory factor associated with suboptimal behavioral and emotional outcomes in children with OSA.

Development, Reliability, and Structural Validity of the Scale for Knowledge, Attitude, and Practice in Ethics Implementation Among AI Researchers: Cross-Sectional Study.

BACKGROUND: Medical artificial intelligence (AI) has significantly contributed to decision support for disease screening, diagnosis, and management. With the growing number of medical AI developments and applications, incorporating ethics is considered essential to avoiding harm and ensuring broad benefits in the lifecycle of medical AI. One of the premises for effectively implementing ethics in Medical AI research necessitates researchers' comprehensive knowledge, enthusiastic attitude, and practical experience. However, there is currently a lack of an available instrument to measure these aspects. OBJECTIVE: The aim of this study was to develop a comprehensive scale for measuring the knowledge, attitude, and practice of ethics implementation among medical AI researchers, and to evaluate its measurement properties. METHODS: The construct of the Knowledge-Attitude-Practice in Ethics Implementation (KAP-EI) scale was based on the Knowledge-Attitude-Practice (KAP) model, and the evaluation of its measurement properties was in compliance with the COnsensus-based Standards for the selection of health status Measurement INstruments (COSMIN) reporting guidelines for studies on measurement instruments. The study was conducted in 2 phases. The first phase involved scale development through a systematic literature review, qualitative interviews, and item analysis based on a cross-sectional survey. The second phase involved evaluation of structural validity and reliability through another cross-sectional study. RESULTS: The KAP-EI scale had 3 dimensions including knowledge (10 items), attitude (6 items), and practice (7 items). The Cronbach α for the whole scale reached .934. Confirmatory factor analysis showed that the goodness-of-fit indices of the scale were satisfactory (χ2/df ratio:=2.338, comparative fit index=0.949, Tucker Lewis index=0.941, root-mean-square error of approximation=0.064, and standardized root-mean-square residual=0.052). CONCLUSIONS: The results show that the scale has good reliability and structural validity; hence, it could be considered an effective instrument. This is the first instrument developed for this purpose.

Subtyping at-risk adolescents for predicting response toward insomnia prevention program.

BACKGROUND: Previous study has shown that a brief cognitive-behavioral prevention insomnia program could reduce 71% risk of developing insomnia among at-risk adolescents. This study aimed to evaluate the differential response to insomnia prevention in subgroups of at-risk adolescents. METHODS: Adolescents with a family history of insomnia and subthreshold insomnia symptoms were randomly assigned to a 4-week insomnia prevention program or nonactive control group. Assessments were conducted at baseline, 1 week, and 6- and 12-month after the intervention. Baseline sleep, daytime, and mood profiles were used to determine different subgroups by using latent class analysis (LCA). Analyses were conducted based on the intention-to-treat approach. RESULTS: LCA identified three subgroups: (a) insomnia symptoms only, (b) insomnia symptoms with daytime sleepiness and mild anxiety, and (c) insomnia symptoms with daytime sleepiness, mild anxiety, and depression. The incidence rate of insomnia disorder over the 12-month follow-up was significantly reduced for adolescents receiving intervention in subgroup 3 compared with the controls (hazard ratio [HR] = 0.37; 95% confidence interval [CI]: 0.13-0.99; p = .049) and marginally for subgroup 2 (HR = 0.14; 95% CI: 0.02-1.08; p = .059). In addition, adolescents who received intervention in subgroups 2 and 3 had a reduced risk of excessive daytime sleepiness (subgroup 2: adjusted OR [AdjOR] = 0.45, 95% CI: 0.23-0.87; subgroup 3: AdjOR = 0.32, 95% CI: 0.13-0.76) and possible anxiety (subgroup 2: AdjOR = 0.47, 95% CI: 0.27-0.82; subgroup 3: AdjOR = 0.33, 95% CI: 0.14-0.78) compared with the controls over the 12-month follow-up. CONCLUSIONS: Adolescents at risk for insomnia can be classified into different subgroups according to their psychological profiles, which were associated with differential responses to the insomnia prevention program. These findings indicate the need for further phenotyping and subgrouping at-risk adolescents to develop personalized insomnia prevention.

School-Based Sleep Education Program for Children: A Cluster Randomized Controlled Trial.

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.

Sleep and academic performance among students in Hong Kong: Curvilinear relationship suggesting an optimal amount of sleep.

OBJECTIVES: This study aimed to elucidate the association between sleep and academic performance using standardized academic assessment in a large and representative sample of school children and adolescents in Hong Kong. METHODS: This school-based cross-sectional study was conducted in 2016. Students completed territory-wide standardized tests in Chinese, English, and Mathematics and a set of questionnaires covering sleep, academic anxiety and motivation. Parents provided additional information on socioeconomic status and children's study behaviors. Weekday proxy sleep duration was reflected by time-in-bed, the difference between bedtime and wakeup time. RESULTS: The study included 4262 Grade 3 (G.3) (mean age [SD], 9.2 [0.6] years; girls: 49.7%) and 3297 G.9 students (mean age [SD], 15.3 [0.74]; girls: 57.5%) from 77 schools. Apart from showing a general insufficiency of students' sleep in this metropolitan city, there was a significant quadratic relationship (G.3: ß = -0.05, p < .001; G.9: ß = -0.03, p < .01), indicating that students with an optimal level of sleep (9.5 h and 8.5 h in G.3 and G.9, respectively) tend to have better academic performance. The significant association remained after controlling for socioeconomic and study-related variables in that sleeping too little or too much was associated with poor academic performance. CONCLUSIONS: This is the first study to explore the curvilinear association between sleep duration and academic performance by using standardized test and simultaneously examining learning-related controls with a large representative sample in Hong Kong. The findings suggested that there is an inverted U-shaped relationship between sleep duration and academic performance in both school-aged children and adolescents. It is recommended that systematic sleep education and intervention is necessary to encourage the development of optimal sleep pattern, which might have beneficial effect on academic performance for students at both primary and secondary level.

Evaluating the efficacy and safety of transcranial pulse stimulation on adolescents with attention deficit hyperactivity disorder: Study protocol of a pilot randomized, double-blind, sham-controlled trial.

Background: Traditional treatment alone might not effectively control the severity of attention deficit hyperactivity disorder (ADHD) symptoms. Transcranial pulse stimulation (TPS) is a non-invasive brain stimulation (NIBS) technology used on older adults with mild neurocognitive disorders and adults with major depressive disorder. However, there has been no study conducted on young adolescents with ADHD. This will be the first nationwide study evaluating the efficacy and safety of TPS in the treatment of ADHD among young adolescents in Hong Kong. Methods: This study proposes a double-blinded, randomized, sham-controlled trial including TPS as an intervention group and a sham TPS group. Both groups will be measured at baseline (T1), immediately after the intervention (T2), and at the 1-month (T3) and 3-month follow-ups (T4). Recruitment: A total of 30 subjects aged between 12 and 17 years, diagnosed with attention deficit hyperactivity disorder (ADHD), will be recruited in this study. All subjects will be computer randomized into either the intervention group or the sham TPS group on a 1:1 ratio. Intervention: All subjects in each group will have to undertake functional MRI (fMRI) before and after six 30-min TPS sessions, which will be completed in 2 weeks' time. Outcomes: Baseline measurements and post-TPS evaluation of the ADHD symptoms and executive functions will also be conducted on all participants. The 1- and 3-month follow-up periods will be used to assess the long-term sustainability of the TPS intervention. For statistical analysis, ANOVA with repeated measures will be used to analyze data. Missing data were managed by multiple imputations. The level of significance will be set to p < 0.05. Significance of the study: Results emerging from this study will generate new knowledge to ascertain whether TPS can be used as a top-on treatment for ADHD. Clinical trial registration: clinicaltrails.gov, identifier: NCT05422274.

Secular trends of sleep-wake patterns in Hong Kong preschoolers.

OBJECTIVE: To evaluate the secular trends of sleep-wake patterns of Hong Kong preschool children. METHODS: Kindergartens from the four geographical regions of Hong Kong were randomly invited to take part in a sleep survey in 2012 and again in 2018. The parent-completed questionnaire provided information on socioeconomic status (SES), children's, and parental sleep-wake patterns. Secular trends and risk factors associated with short sleep duration in preschoolers were explored. RESULTS: A sample of 5048 preschool children was included in the secular comparison, with 2306 and 2742 from the 2012 and 2018 surveys, respectively. A higher percentage of children in 2018 (41.1% vs 26.7%, p < 0.001) did not achieve the recommended sleep duration. During the survey years, sleep duration decreased by 13 ([95%CI: 18.5 to -8.1]) and 18 min ([95%CI: 23.6 to -12.2]) on weekdays and weekends, respectively. The overall trend of nap decrease was not significant. Sleep onset latency significantly increased on both weekdays (6 min [95%CI: 3.5 to 8.5]) and weekends (7 min [95%CI: 4.7 to 9.9]). Children's sleep duration was positively correlated with parental sleep duration with a correlation coefficient ranging from 0.16 to 0.27 (p < 0.001). CONCLUSIONS: A significant proportion of Hong Kong preschool children did not achieve the recommended amount of sleep. A downward secular trend in sleep duration was observed during the survey period. Public health measures to improve sleep duration in preschool children should be a high priority.

Craniofacial phenotyping by photogrammetry in Chinese prepubertal children with obstructive sleep apnea.

STUDY OBJECTIVES: This 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. METHODS: This 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. RESULTS: This 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). CONCLUSIONS: Craniofacial 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.

The impact of sleep-corrected social jetlag on mental health, behavioral problems, and daytime sleepiness in adolescents.

STUDY OBJECTIVES: This study aimed to examine the effect of sleep-corrected social jetlag (SJLsc) on mental health, behavioral problems, and daytime sleepiness in adolescents. METHODS: This was a cross-sectional study which included 4787 adolescents (Mean age: 14.83±1.6y, 56.0% girls) recruited from 15 secondary schools in Hong Kong. SJLsc was defined as the absolute difference between sleep-corrected midsleep on weekdays and weekends, at which the sleep debt has been considered. It was classified into three groups: low-level ("LSJLsc", <1h), mid-level ("MSJLsc", ≥1h and <2h), and high-level of SJLsc ("HSJLsc", ≥2h). Adolescents' mental health, behavioral problems and daytime sleepiness were measured by the General Health Questionnaire (GHQ-12), the Strengths and Difficulties Questionnaire (SDQ) and the Pediatric Daytime Sleepiness Scale (PDSS). Logistic regression analysis and restricted cubic spline regression (RCS) analysis were applied with consideration of confounders including age, gender, puberty and sleep problems. RESULTS: Nearly half (46.9%) of adolescents had SJLsc for at least 1 h. Greater SJLsc was associated with more behavioral difficulties (MSJLsc: OR: 1.20, p = 0.03; HSJLsc: OR: 1.34, p = 0.02) when controlling for age, sex, puberty, chronotype, insomnia, and time in bed. There was a dose-response relationship in which higher SJLsc had an increased risk of conduct problems and hyperactivity, while only high-level SJLsc was associated with a peer relationship problem. In RCS analysis, SJLsc was associated with a higher likelihood of behavioral difficulties (p = 0.03) but not poor mental health or daytime sleepiness. CONCLUSIONS: Sleep-corrected social jetlag was a unique risk factor for behavioral problems in adolescents. Our findings highlighted the need for interventions to promote healthy sleep-wake patterns in school adolescents.

Blood pressure and childhood obstructive sleep apnea: A systematic review and meta-analysis.

Obstructive sleep apnea (OSA) is an established risk factor for high blood pressure (BP) in adults. However, it remains unclear whether the same association could be found in children and adolescents. Therefore, we conducted a systematic review and meta-analysis of observational studies to evaluate the associations between childhood OSA and BP outcomes. The review protocol was registered in PROSPERO (CRD42021225683). We performed a systematic literature search to identify relevant cross-sectional and longitudinal studies up to July 6, 2021. Of the 4902 identified articles, a total of 12 cross-sectional studies and 2 cohort studies were included in the final analyses. In the cross-sectional analyses, the mean systolic BP (SBP) were significantly higher in children with mild or moderate-to-severe OSA compared to the healthy controls, and these effects were more pronounced during the nighttime. In prospective studies, moderate-to-severe childhood OSA was associated with a risk of elevated SBP in adulthood (Mean difference = 4.02 mm Hg, 95% CI = 1.32 to 6.72). Taken together, our results suggest that moderate-to-severe childhood OSA is associated with a higher risk of adverse SBP outcomes. Early detection and treatment of OSA may promote cardiovascular health in children and adolescents and possibly in future adulthood.

The Associations of Electronic Media Use With Sleep and Circadian Problems, Social, Emotional and Behavioral Difficulties in Adolescents.

Background: Electronic media use (EMU) becomes one of the most common activities in adolescents. The present study investigated the deleterious influence of excessive EMU and EMU before bedtime on social, emotional, and behavioral difficulties (SEBD) in adolescents. The role of sleep and circadian problems in mediating the association of EMU with SEBD was examined. Methods: A cross-sectional survey study was conducted with 3,455 adolescents (55.7% female, mean age = 14.8 ± 1.57 years, 36.6% monthly family income < HK$15,000) between December 2011 and March 2012 in Hong Kong. The associations of EMU with sleep and circadian problems and SEBD were analyzed using multiple binary logistic regression and path analysis. Sleep problems were measured by the Insomnia Severity Index and the reduced Horne and Östberg Morningness and Eveningness Questionnaire. Circadian problems were calculated based on established formulas. SEBD was measured using the Strengths and Difficulties Questionnaire. Participants' mental health status was assessed by the General Health Questionnaire. Results: A longer duration of EMU, excessive EMU (daily duration ≥ 2 h), and bedtime EMU (an hour before bedtime) were associated with the risk of sleep and circadian problems, poor mental health, and SEBD (p < 0.05). Insomnia, eveningness, social jetlag, and sleep deprivation were found to mediate the associations of EMU (including bedtime EMU of computers, electronic game consoles, phones, and televisions, together with excessive EMU of computers for leisure purposes and phones) with mental health and SEBD. Conclusions: The findings suggest the need for setting up guidelines and advocacy for education for appropriate EMU and intervention for the associated sleep and circadian problems to ameliorate EMU-related mental and behavioral health problems in adolescents.

Monthly Motivational Interview Counseling and Nicotine Replacement Therapy for Smoking Parents of Pediatric Patients: A Randomized Controlled Trial.

Background: Parental smoking is the dominant source of passive smoke exposure in the pediatric population. The current randomized controlled trial (RCT) study aimed to evaluate the effectiveness of a multi-component smoking reduction intervention in parental smoking reduction and children's environmental tobacco smoke exposure reduction in clinical settings. Methods: A single-blinded, 6-month randomized controlled trial recruited smoking parents (N = 210) of children who attended the pediatric wards or clinics at the Prince of Wales Hospital. Participants allocated to the intervention group (n = 105) received monthly motivational interviews on smoking reduction with emphasis on health hazards related to children's passive smoke exposure, 8-week nicotine replacement therapy, and referral to smoking cessation service if the parents preferred. The control group (n = 105) received simple verbal advice on smoking cessation. Primary outcomes were parental urine cotinine validated and self-reported ≥50% smoking reduction rates at 6 months. Results: Smoking parents in the intervention group had significantly more biochemically validated ≥50% smoking reduction than the control: 27.1 vs. 10.0% (OR = 3.34, 95% CI: 1.16-9.62, P = 0.02). The rate of self-reported ≥50% smoking reduction was also significantly higher in the intervention group than the control: 51.9 vs. 20.2% (OR = 4.40, 95% CI: 2.38-8.12, P < 0.001). For secondary outcomes, the rate of parental self-reported smoking cessation was higher in the intervention arm: 10.5 vs. 1.0% (OR = 12.17, 95% CI: 1.54-96.07, P < 0.001), however, no differences were detected in biochemically validated cessation and changes in children's passive smoke exposure between the groups. Conclusion: Monthly smoking reduction counseling together with nicotine replacement therapy is more effective than simple verbal cessation advice in the smoking reduction for parents of pediatric patients. However, this study did not demonstrate differences in smoking cessation or reduction in children's passive smoke exposure with a 6-month follow-up. Achievement of a smoke-free environment remains challenging. Trial Registration: Clinicaltrials.gov, identifier: NCT03879889.

The associations of insomnia symptoms with daytime behavior and cognitive functioning in children with attention-deficit/hyperactivity disorder.

STUDY OBJECTIVES: 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). METHODS: 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 and N-back task for working memory, Tower of London (TOL) test for planning skills and Bergs Card Sorting Test (BCST) for set-shifting ability. RESULTS: Children 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 (all P < .05). After controlling for potential confounders, children with ADHD and insomnia symptoms showed poorer performance on the CPT and Letter-digit test as compared with children with ADHD without insomnia and healthy controls (all P < .05). CONCLUSIONS: Insomnia 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. CITATION: 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. J Clin Sleep Med. 2022;18(8):2029-2039.

Investigation of Chromosomal Structural Abnormalities in Patients With Undiagnosed Neurodevelopmental Disorders.

Background: Structural variations (SVs) are various types of the genomic rearrangements encompassing at least 50 nucleotides. These include unbalanced gains or losses of DNA segments (copy number changes, CNVs), balanced rearrangements (such as inversion or translocations), and complex combinations of several distinct rearrangements. SVs are known to play a significant role in contributing to human genomic disorders by disrupting the protein-coding genes or the interaction(s) with cis-regulatory elements. Recently, different types of genome sequencing-based tests have been introduced in detecting various types of SVs other than CNVs and regions with absence of heterozygosity (AOH) with clinical significance. Method: In this study, we applied the mate-pair low pass (∼4X) genome sequencing with large DNA-insert (∼5 kb) in a cohort of 100 patients with neurodevelopmental disorders who did not receive informative results from a routine CNV investigation. Read-depth-based CNV analysis and chimeric-read-pairs analysis were used for CNV and SV analyses. The region of AOH was indicated by a simultaneous decrease in the rate of heterozygous SNVs and increase in the rate of homozygous SNVs. Results: First, we reexamined the 25 previously reported CNVs among 24 cases in this cohort. The boundaries of these twenty-five CNVs including 15 duplications and 10 deletions detected were consistent with the ones indicated by the chimeric-read-pairs analysis, while the location and orientation were determined in 80% of duplications (12/15). Particularly, one duplication was involved in complex rearrangements. In addition, among all the 100 cases, 10% of them were detected with rare or complex SVs (>10 Kb), and 3% were with multiple AOH (≥5 Mb) locating in imprinting chromosomes identified. In particular, one patient with an overall value of 214.5 Mb of AOH identified on 13 autosomal chromosomes suspected parental consanguinity. Conclusion: In this study, mate-pair low-pass GS resolved a significant proportion of CNVs with inconclusive significance, and detected additional SVs and regions of AOH in patients with undiagnostic neurodevelopmental disorders. This approach complements the first-tier CNV analysis for NDDs, not only by increasing the resolution of CNV detection but also by enhancing the characterization of SVs and the discovery of potential causative regions (or genes) contributory to could be complex in composition NDDs.

Efficacy of Email-delivered Versus Face-to-face Group Cognitive Behavioral Therapy for Insomnia in Youths: A Randomized Controlled Trial.

PURPOSE: 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. METHODS: 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. RESULTS: 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. DISCUSSION: 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.

Association of smoking, lung function and COPD in COVID-19 risk: a two-step Mendelian randomization study.

BACKGROUND AND AIMS: Smoking increases the risk of severe COVID-19, but whether lung function or chronic obstructive pulmonary disease (COPD) mediate the underlying associations is unclear. We conducted the largest Mendelian randomization study to date, to our knowledge, to address these questions. DESIGN: Mendelian randomization study using summary statistics from genome-wide association studies (GWAS), FinnGen and UK Biobank. The main analysis was the inverse variance weighted method, and we included a range of sensitivity analyses to assess the robustness of the findings. SETTING: GWAS which included international consortia, FinnGen and UK Biobank. PARTICIPANTS: The sample size ranged from 193 638 to 2 586 691. MEASUREMENTS: Genetic determinants of life-time smoking index, lung function [e.g. forced expiratory volume in 1 sec (FEV1 )], chronic obstructive pulmonary disease (COPD) and different severities of COID-19. RESULTS: Smoking increased the risk of COVID-19 compared with population controls for overall COVID-19 [odds ratio (OR) = 1.19 per standard deviation (SD) of life-time smoking index, 95% confidence interval (CI) = 1.11-1.27], hospitalized COVID-19 (OR = 1.67, 95% CI = 1.42-1.97) or severe COVID-19 (OR = 1.48, 95% CI = 1.10-1.98), with directionally consistent effects from sensitivity analyses. Lung function and COPD liability did not appear to mediate these associations. CONCLUSION: There is genetic evidence that smoking probably increases the risk of severe COVID-19 and possibly also milder forms of COVID-19. Decreased lung function and increased risk of chronic obstructive pulmonary disease do not seem to mediate the effect of smoking on COVID-19 risk.