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.

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.

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.

Rare but life-threatening cause of massive haemoptysis in an adolscent with tuberculosis: Rasmussen's aneurysm.

Rasmussen's aneurysm is a rare yet fatal cause of massive haemoptysis in pulmonary tuberculosis. Early identification and timely intervention are of utmost importance to reduce the associated mortality. A girl in early adolescence presented with persistent fever and massive haemoptysis who required intubation and was subsequently confirmed to have tuberculosis. CT pulmonary angiogram showed the presence of pseudoaneurysms in the left upper and lower lobes. The haemoptysis resolved following the embolisation of the culprit's vessel. Residual lung destruction was evident on CT after a 12-month course of antituberculosis therapy. Rasmussen's aneurysm is a significant vascular complication of cavitary tuberculosis and needs to be considered in patients presenting with massive haemoptysis.

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.

The impacts of intra-individual daily sleep variability on daytime functioning and sleep architecture in healthy young adults: An experimental study.

Sleep variability is commonly seen in the young populations. This study aimed to examine the impacts of experimentally induced sleep variability on sleepiness, mood, cognitive performance and sleep architectures among young adults. Thirty-six healthy individuals (aged 18-22 years) were randomly assigned to either variable sleep schedule (n = 20) or control (n = 16) groups. The protocol involved 1 week of regular sleep (time in bed = 7.5 hr) in the home setting, followed by one adaptation night (time in bed = 7.5 hr), one baseline night (time in bed = 7.5 hr), and 6 nights of sleep manipulation in the laboratory monitored by polysomnography (three cycles of variable sleep schedule by changing daily time in bed alternating between 6 hr and 9 hr for variable sleep schedule group versus fixed sleep schedule with daily time in bed for 7.5 hr for control group). Sleepiness, mood, sustained attention, processing speed, response inhibition and working memory were measured every morning and evening. The variable sleep schedule group reported a higher level of sleepiness, especially in the mornings, and increased negative mood in the evenings. There were no significant differences in positive mood, cognitive performance and sleep macro- and micro-structures. Our results showed the negative effects of sleep variability on daytime functioning especially sleepiness and negative mood, suggesting the need to address variable sleep schedules through sleep intervention.

Early-Life Skin Microbial Biomarkers for Eczema Phenotypes in Chinese Toddlers.

Eczema is a common inflammatory skin disorder during infancy. Evidence has shown that skin-microbiome fluctuations may precede eczema development, but their predictive value for eczema phenotypes remains unknown. We aimed to investigate the early-life evolution of the skin microbiome and its temporal associations with different pairs of eczema phenotypes (transient versus persistent, atopic versus non-atopic) in Chinese children. We followed 119 term Chinese infants from birth to 24 months old within a Hong Kong birth cohort. The skin microbes at the left antecubital fossa were serially sampled by flocked swabs at 1, 6, and 12 months for bacterial 16S rRNA gene sequencing. The atopic sensitization at 12 months was strongly associated with eczema persisting to 24 months (odds ratio 4.95, 95% confidence interval 1.29-19.01). Compared with those with non-atopic eczema, the children with atopic eczema had reduced alpha diversity at 12 months (p < 0.001) and transiently higher abundance of the genus Janibacter at 6 months (p < 0.001). Our findings suggest that atopic sensitization at 12 months may predict persistent eczema by 24 months, and atopic eczema at 12 months is associated with unique skin microbiome profiles at 6 and 12 months. Non-invasive skin-microbiome profiling may have predictive value for atopic eczema.

Effect of surgical intervention for childhood OSA on blood pressure: A randomized controlled study.

OBJECTIVE: To investigate the effect of surgical intervention on 24-h ABP in children with OSA. It was hypothesized that blood pressure would improve following adenotonsillectomy. METHODS: This was a two-centered investigator-blinded randomized controlled trial. Non-obese pre-pubertal children aged 6-11 years with OSA (obstructive apnea-hypopnea index, OAHI >3/h) underwent 24-h ABP monitoring at baseline and 9 months after the randomly assigned intervention, i.e. Early Surgery (ES) or Watchful Waiting (WW). Intention-to-treat analysis was performed. RESULTS: 137 subjects were randomized. Sixty-two (Age: 7.9y ± 1.3, 71% boys) and 47 (Age: 8.5y ± 1.6, 77% boys) participants from the ES and WW groups, respectively completed the study. Changes in ABP parameters were similar in the ES and WW groups (nighttime systolic BP z-scores: +0.03 ± 0.93 vs. -0.06 ± 1.04, p = 0.65; nighttime diastolic BP z-scores: -0.20 ± 0.95 vs. -0.02 ± 1.00, p = 0.35) despite a greater improvement in OSA in the ES group. However, a reduction in nighttime diastolic BP z-score correlated with improvements in OSA severity indexes (r = 0.21-0.22, p < 0.05), and a significant improvement in nighttime diastolic BP z-score [-0.43 ± 1.01, p = 0.027] following surgery was observed in participants with severe preoperative OSA (OAHI ≥10/h). The ES group had a significant increase in body mass index z-score after surgery [+0.27 ± 0.57, p < 0.001], which correlated with the increase in daytime systolic BP z-score (r = 0.2, p < 0.05). CONCLUSION: Surgical treatment did not lead to significant improvements in ABP in OSA children except in those with more severe disease. The improvement in BP was partially masked by the weight gain following surgery. CLINICAL TRIAL REGISTRATION: The trial was registered with the Chinese Clinical Trial Registry (http://www.chictr.org.cn. REGISTRATION NUMBER: ChiCTR-TRC-14004131).

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.

Human milk oligosaccharides in Chinese lactating mothers and relationship with allergy development in offspring.

BACKGROUND: The health benefits of breastfeeding are partly contributed by human milk oligosaccharides (HMOs), but there is limited data on breast milk (BM) HMO composition in Chinese. OBJECTIVE: This study investigated the association between early-life HMO intake and allergy occurrence in Chinese children. METHODS: 103 healthy Chinese pregnant women regardless of allergy history were recruited into this birth cohort. Their babies were followed until 24 months old. Concentrations of 2'-fucosyllactose (2'-FL), lacto-N-neotetraose (LNnT), -sialyllactose (3'-SL) and 6'-sialyllactose (6'-SL) in BM collected at 1-month postpartum were measured by liquid chromatography-mass spectrometry. The associations between these HMOs and allergy occurrence by 24 months were analyzed by multivariate regression analyses. RESULTS: Twenty-nine percent and 19% of participants had eczema at 12 and 24 months old respectively. Eighty BM samples were analyzed, with 2'-FL being the most abundant HMO (median 1447 ppm, interquartile range [IQR] 291-1906 ppm), and median (IQR) levels of LNnT, 6'-SL and 3'-SL in ppm were 738 (580-950), 20.5 (12.7-38.8) and 23.0 (17.8-27.6) respectively. Participants with eczema by 24 months consumed BM with higher 2'-FL concentration at 1-month (P = 0.008), and also lower 6'-SL concentration in exclusively breastfed infants (P = 0.012) but higher 6'-SL concentration for those with mixed feeding at 1 month (P = 0.043). Food allergic children at 12 months consumed BM with higher 2'-FL concentrations at 1 month (P = 0.048). CONCLUSIONS: BM 2'-FL concentration is higher in children who develops eczema by 24 months and food allergy during infancy. The relationship for 6'-SL is divergent depending on mode of feeding in infants.

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.

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.

Profiling of SARS-CoV-2 Subgenomic RNAs in Clinical Specimens.

SARS-CoV-2 transcribes a set of subgenomic RNAs (sgRNAs) essential for the translation of structural and accessory proteins to sustain its life cycle. We applied RNA-seq on 375 respiratory samples from individual COVID-19 patients and revealed that the majority of the sgRNAs were canonical transcripts with N being the most abundant (36.2%), followed by S (11.6%), open reading frame 7a (ORF7a; 10.3%), M (8.4%), ORF3a (7.9%), ORF8 (6.0%), E (4.6%), ORF6 (2.5%), and ORF7b (0.3%); but ORF10 was not detected. The profile of most sgRNAs, except N, showed an independent association with viral load, time of specimen collection after onset, age of the patient, and S-614D/G variant with ORF7b and then ORF6 being the most sensitive to changes in these characteristics. Monitoring of 124 serial samples from 10 patients using sgRNA-specific real-time RT-PCR revealed a potential of adopting sgRNA as a marker of viral activity. Respiratory samples harboring a full set of canonical sgRNAs were mainly collected early within 1 to 2 weeks from onset, and most of the stool samples (90%) were negative for sgRNAs despite testing positive by diagnostic PCR targeting genomic RNA. ORF7b was the first to become undetectable and again being the most sensitive surrogate marker for a full set of canonical sgRNAs in clinical samples. The potential of using sgRNA to monitor viral activity and progression of SARS-CoV-2 infection, and hence as one of the objective indicators to triage patients for isolation and treatment should be considered. IMPORTANCE Attempts to use subgenomic RNAs (sgRNAs) of SARS-CoV-2 to identify active infection of COVID-19 have produced diverse results. In this work, we applied next-generation sequencing and RT-PCR to profile the full spectrum of SARS-CoV-2 sgRNAs in a large cohort of respiratory and stool samples collected throughout infection. Numerous known and novel discontinuous transcription events potentially encoding full-length, deleted and frameshift proteins were observed. In particular, the expression profile of canonical sgRNAs was associated with genomic RNA level and clinical characteristics. Our study found sgRNAs as potential biomarkers for monitoring infectivity and progression of SARS-CoV-2 infection, which provides an alternative target for the management and treatment of COVID-19 patients.

Reduced tongue mobility: an unrecognized risk factor of childhood obstructive sleep apnea.

STUDY OBJECTIVES: Childhood obstructive sleep apnea (OSA) is an important and prevalent disease. A short lingual frenulum is a risk factor for OSA, but whether tongue mobility also plays a role in OSA etiology remains unknown. This study aimed to examine tongue mobility in children with and without OSA. We hypothesized that reduced tongue mobility was associated with OSA. We also evaluated the relationship between tongue mobility and craniofacial profile. METHODS: This was a cross-sectional case-control study. Prepubertal Chinese children aged 5-12 years, suspected to have OSA were recruited from our sleep disorder clinic. All subjects underwent overnight polysomnography. The lingual frenulum was evaluated based on tongue mobility and free tongue length. Craniofacial measurements were assessed by lateral cephalometry. RESULTS: Eighty-two subjects (mean age: 8.32 ± 1.70 years, 57 males) were recruited. The mean tongue mobility was 58.2 (±19)% and 67.4 (±15)% (p = 0.019) in subjects with and without OSA, respectively. Tongue mobility was inversely correlated with OAHI (r = -0.218, p = 0.049). In multivariate logistic regression, low tongue mobility was independently associated with a higher risk of OSA after adjustment for age, sex, body mass index z-score, presence of large tonsils and turbinates, and nocturnal oral breathing (odds ratio = 3.65, 95% CI = 1.22 to 11.8). Tongue mobility was found to correlate with the cranial base angle (Ba-S-N) (r = 0.262, p = 0.018), which determines the relative position of the mandible. CONCLUSIONS: In prepubertal children, reduced tongue mobility is associated with the occurrence and severity of OSA. Assessing tongue mobility is recommended in childhood OSA management.

Parental Knowledge, Attitude, and Practice on Tobacco Use, Smoking Cessation, and Children's Environmental Tobacco Smoke Exposure.

Background: Environmental tobacco smoke (ETS) exposure in children ranks one of the major public health problems in our time. Poor parental knowledge, attitude, and practice (KAP) on ETS often contribute to worse exposure of the kids. Thus, we aimed to document parental KAP regarding tobacco use, smoking cessation and children's ETS exposure, and to analyse how knowledge and attitude relate to practice. Methods: Self-administered KAP questionnaires were distributed to smoking parents recruited from the pediatric unit at the Prince of Wales Hospital, which provides pediatric service to a population of 1.2 million in Hong Kong. The 60-item questionnaire had a range of 0-38 for knowledge, 0-44 for attitude, and 0-40 for practice. Descriptive analyses were performed for KAP response, regression analyses were performed for the exploration of associations and identification of predictive indicators. Results: 145 smoking parents (mean age: 38.0 ± 6.7 yrs.; male: 85.5%) were included. Less than half (39.3%) of them reported a smoke-free policy at home. Among those parents who had private cars, less than half (45.2%) of them had smoke-free policy in their car that they never smoked in the car. Only 25.5% of the participants correctly answered ≥70% of the knowledge questions, and 11.8 % of the participants gave favorable responses to ≥70% of the attitude questions. The total knowledge and the total attitudes score were positively associated (r = 0.49, 95% CI: 0.35-0.79, p < 0.001), yet they were only modestly correlated with parental practice on children's ETS exposure. By multivariate regressions, potential predictive factors for more favorable parental KAP included higher household income, lower parental nicotine dependence level and breastfeeding practice. Conclusions: Parental KAP related to tobacco use and children's ETS exposure needs improvement to address the significant gap between recommended and actual practice. The weak association between knowledge and practice suggested that parental education alone is not adequate to combat ETS exposure in children.

Associations of circadian factors with insomnia symptoms and emotional and behavioral problems among school-age children.

STUDY OBJECTIVES: To examine the associations of circadian characteristics (ie, chronotype and social jetlag) with insomnia symptoms and emotional and behavioral problems among school-age children. METHODS: A total of 620 primary school children (medianage = 10.06, standard deviation = 1.16, 58.7% boys) were recruited and assessed by a set of parent-report questionnaires, including Children's Sleep Habit Questionnaire for measuring sleep-wake patterns and insomnia symptoms (bedtime resistance, sleep onset delay, and night waking), Children's Chronotype Questionnaire for assessing the child's chronotype preference, and Strength and Difficulties Questionnaire for assessing emotional and behavioral problems. Linear regression models were applied to examine the associations of chronotype and social jetlag with insomnia symptoms and mental health outcomes, in which age, sex, family income, and average sleep duration were entered as covariates. RESULTS: Evening chronotype was significantly associated with bedtime resistance and sleep onset delay, while social jetlag was not related to insomnia symptoms. Evening chronotype was also significantly associated with externalizing symptoms after controlling for potential confounders. CONCLUSIONS: Evening chronotype, but not social jetlag, was the risk factor for insomnia symptoms, and evening chronotype was further associated with increased behavioral problems in school-age children. Our findings underscored the roles of circadian factors in relation to sleep and mental health problems in this young population. CITATION: Sun W, Kwok NTT, Chan NY, et al. Associations of circadian factors with insomnia symptoms and emotional and behavioral problems among school-age children. J Clin Sleep Med. 2021;17(10):2107-2114.