High prevalence of exon-13 variants in USH2A-related retinal dystrophies in Taiwanese population.

BACKGROUND: Biallelic pathogenic variants in USH2A lead to Usher syndrome or non-syndromic retinitis pigmentosa, and shown to have geographical and ethnical distribution in previous studies. This study provided a deeper understanding of the detailed clinical features using multimodal imaging, genetic spectrum, and genotype-phenotype correlations of USH2A-related retinal dystrophies in Taiwan. RESULTS: In our cohort, the mean age at first visit was 47.66 ± 13.54 years, and the mean age at symptom onset, which was referred to the onset of nyctalopia and/or visual field constriction, was 31.21 ± 15.24 years. Among the variants identified, 23 (50%) were missense, 10 (22%) were splicing variants, 8 (17%) were nonsense, and 5 (11%) were frameshift mutations. The most predominant variant was c.2802T>G, which accounted for 21% of patients, and was located in exon 13. Patients with truncated alleles had significantly earlier symptom onset and seemly poorer disease progression regarding visual acuity, ellipsoid zone line length, and hypofluorescent lesions in the macula than those who had the complete gene. However, the clinical presentation revealed similar progression between patients with and without the c.2802T>G variant. During long-term follow-up, the patients had different ellipsoid zone line progression rates and were almost evenly distributed in the fast, moderate, and slow progression subgroups. Although a younger onset age and a smaller baseline intact macular area was observed in the fast progression subgroup, the results showed no significant difference. CONCLUSIONS: This is the first cohort study to provide detailed genetic and longitudinal clinical analyses of patients with USH2A-related retinal dystrophies in Taiwan. The mutated allele frequency in exon 13 was high in Taiwan due to the predominant c.2802T>G variant. Moreover, truncated variants greatly impacted disease progression and determined the length of therapeutic windows. These findings provide insight into the characteristics of candidates for future gene therapies.

Corneal Endothelial Morphology and Ocular Biometric Indexes in Premature Children With and Without Retinopathy of Prematurity.

Purpose: The purpose of this study was to analyze human corneal endothelial cells (HCECs) morphology and ocular biometrics in premature (PM) children with or without retinopathy of prematurity (ROP). Methods: Retrospective data on patient demographics, HCECs status, and ocular biometrics with at least 2 visits between 2016 and 2021 were reviewed. The main outcomes were endothelial cell density (ECD), coefficient of variation (CV), hexagonal cell ratio (HEX), central corneal thickness (CCT), axial length, anterior chamber depth, keratometry, corneal diameter, pupil diameter, and refraction status. Generalized estimating equation was used to evaluate the differences between PM no-ROP and ROP groups. We also analyzed the trend of ECD, CV, HEX, and CCT change with age between groups. Results: The study included 173 PM patients without ROP and 139 patients with ROP. A total of 666 and 544 measurements were recorded in the PM no-ROP and ROP groups, respectively. The ROP group had higher spherical power, myopic spherical equivalent (SE), and steeper steep keratometry (K; P < 0.05). The ROP group had higher CV (P = 0.0144), lower HEX (P = 0.0012) and thicker CCT (P = 0.0035). In the HCECs parameters, the ROP group had slower ECD decrement (P < 0.0001), faster CV decrement (P = 0.0060), and faster HEX increment (P = 0.0001). A difference in corneal morphology changes between the ROP and PM no-ROP groups were prominent in patients with lower gestational age (GA) in the subgroup analysis. Conclusions: Worse HCECs morphology and higher myopic status were initially observed in patients with prior ROP but not in PM patients with no-ROP. ECD and HCECs morphology improved with age, especially in patients with low GA.

Effects of modafinil on nocturnal sleep patterns in patients with narcolepsy: A cohort study.

BACKGROUND: Patients with narcolepsy often experience disturbed nighttime sleep. Modafinil is commonly prescribed for hypersomnolence, but its impacts on nocturnal sleep remain unclear. This study uses actigraphy to examine the effect of modafinil on both hypersomnolence and nocturnal sleep patterns in patients with narcolepsy. METHODS: Prior to treatment, 87 patients with narcolepsy wore an actigraphy for 7-14 days to assess their nighttime sleep. After evaluation, they received a daily dose of 200-400 mg of modafinil in the morning and wore an actigraphy again six months after initiating treatment. Questionnaires, including the Epworth-Sleepiness-Scale (ESS), the Visual-Analogue-for-Hypersomnolence (VAS), and the Short-Form-36-Health-Survey (SF-36), were used to evaluate hypersomnolence and quality of life both before and after treatment. Paired t-tests and independent samples t-tests were used for pre- and post-treatment comparisons and subgroup analysis. We used the Pearson's correlation test to measure the correlations between the sleep parameters of the actigraphy and data of the questionnaires. RESULTS: Improvements in hypersomnolence were noted following modafinil treatment, and we observed no significant deterioration in nocturnal sleep parameters by the actigraphy. The total number of awakenings by actigraphy significantly decreased (p = 0.005), especially in females (p = 0.008), while sleep onset latency significantly increased in children/adolescents (p = 0.014). Correlations were found between the sleep parameters of the actigraphy and ESS, VAS, and SF-36 scores. CONCLUSION: Modafinil treatment may not worsen nighttime sleep in patients with narcolepsy. However, it should be administered with care in children and adolescents.

The application of machine learning on brain imaging features of different narcolepsy subtypes.

STUDY OBJECTIVES: Narcolepsy is a central hypersomnia disorder, and differential diagnoses between its subtypes can be difficult. Hence, we applied machine learning to analyze the positron emission tomography (PET) data of patients with type 1 or type 2 narcolepsy, and patients with type 1 narcolepsy and comorbid schizophrenia, to construct predictive models to facilitate the diagnosis. METHODS: This is a retrospective and prospective case-control study of adolescent and young adult patients with type 1 or type 2 narcolepsy, and type 1 narcolepsy and comorbid schizophrenia. All participants received 18-F-fluorodeoxy glucose PET, sleep studies, neurocognitive tests, sleep questionnaires, and human leukocyte antigen typing. The collected PET data were analyzed by feature selections and classification methods in machine learning to construct predictive models. RESULTS: A total of 314 participants with narcolepsy were enrolled; 204 had type 1 narcolepsy, 90 had type 2 narcolepsy, and 20 had type 1 narcolepsy and comorbid schizophrenia. We used three filter methods for feature selection followed by a comparative analysis of classification methods. To apply a small number of regions of interest (ROI) and high classification accuracy, the Naïve Bayes classifier with the Term Variance as feature selection achieved the goal with only three ROIs (left basal ganglia, left Heschl, and left striatum) and produced an accuracy of higher than 99%. CONCLUSIONS: The accuracy of our predictive model of PET data are promising and can aid clinicians in the diagnosis of narcolepsy subtypes. Future research with a larger sample size could further refine the predictive model of narcolepsy.

Validity of Diagnostic Support Model for Attention Deficit Hyperactivity Disorder: A Machine Learning Approach.

An accurate and early diagnosis of attention deficit hyperactivity disorder can improve health outcomes and prevent unnecessary medical expenses. This study developed a diagnostic support model using a machine learning approach to effectively screen individuals for attention deficit hyperactivity disorder. Three models were developed: a logistic regression model, a classification and regression tree (CART), and a neural network. The models were assessed by using a receiver operating characteristic analysis. In total, 74 participants were enrolled into the disorder group, while 21 participants were enrolled in the control group. The sensitivity and specificity of each model, indicating the rate of true positive and true negative results, respectively, were assessed. The CART model demonstrated a superior performance compared to the other two models, with region values of receiver operating characteristic analyses in the following order: CART (0.848) > logistic regression model (0.826) > neural network (0.67). The sensitivity and specificity of the CART model were 78.8% and 50%, respectively. This model can be applied to other neuroscience research fields, including the diagnoses of autism spectrum disorder, Tourette syndrome, and dementia. This will enhance the effect and practical value of our research.

Whole Genome Sequencing Revealed Inherited Rare Oligogenic Variants Contributing to Schizophrenia and Major Depressive Disorder in Two Families.

Schizophrenia and affective disorder are two major complex mental disorders with high heritability. Evidence shows that rare variants with significant clinical impacts contribute to the genetic liability of these two disorders. Also, rare variants associated with schizophrenia and affective disorders are highly personalized; each patient may carry different variants. We used whole genome sequencing analysis to study the genetic basis of two families with schizophrenia and major depressive disorder. We did not detect de novo, autosomal dominant, or recessive pathogenic or likely pathogenic variants associated with psychiatric disorders in these two families. Nevertheless, we identified multiple rare inherited variants with unknown significance in the probands. In family 1, with singleton schizophrenia, we detected four rare variants in genes implicated in schizophrenia, including p.Arg1627Trp of LAMA2, p.Pro1338Ser of CSMD1, p.Arg691Gly of TLR4, and Arg182X of AGTR2. The p.Arg691Gly of TLR4 was inherited from the father, while the other three were inherited from the mother. In family 2, with two affected sisters diagnosed with major depressive disorder, we detected three rare variants shared by the two sisters in three genes implicated in affective disorders, including p.Ala4551Gly of FAT1, p.Val231Leu of HOMER3, and p.Ile185Met of GPM6B. These three rare variants were assumed to be inherited from their parents. Prompted by these findings, we suggest that these rare inherited variants may interact with each other and lead to psychiatric conditions in these two families. Our observations support the conclusion that inherited rare variants may contribute to the heritability of psychiatric disorders.

Dietary profile of pediatric obstructive sleep apnea patients, effects of routine educational counseling, and predictors for outcomes.

Background: Dietary behavior is a main contributing yet modifiable factor to the body weight status of children and may be involved in the pathophysiology of childhood obstructive sleep apnea (OSA). This study aimed to investigate the dietary profile of pediatric OSA patients, effects of educational counseling after adenotonsillectomy, and predictor for disease resolution. Methods: This observational study included 50 pediatric OSA patients undergoing adenotonsillectomy with routine educational counseling (Group 1), 50 pediatric OSA patients undergoing adenotonsillectomy without formal educational counseling (Group 2), and 303 healthy children without OSA (Control). The three groups were matched by age. The consumption frequency of 25 food items/groups was assessed by the Short Food Frequency Questionnaire. Quality of life was evaluated by the OSA-18 questionnaire. Sleep architecture and OSA severity were measured by standard polysomnography. Between- and within-group comparisons were analyzed by non-parametric approaches and generalized estimating equations. Prediction of disease recovery was performed by multivariable logistic regression models. Results: Group 1 children consumed fruit drinks with sugar, vegetables, sweets, chocolate, rice, and noodles more frequently than Control Group children. At baseline, the distributions of sex, weight status, OSA-18 scores, and polysomnographic variables were comparable between Group 1 and Group 2. After a 12-month follow-up, Group 1 had better improvements in physical suffering, caregiver concerns, sleep architecture, and mean peripheral oxygen saturation compared to Group 2. Furthermore, Group 1 no longer had excessive consumption of fruit drinks with sugar, chocolate, and noodles; however, food consumption frequencies did not change significantly. Notably, younger age and reduced intake of butter/margarine on bread and noodles were independent predictors of cured OSA in Group 1. Conclusion: The present study preliminarily characterized an unhealthy dietary profile among pediatric OSA patients and suggested that routine educational counseling in addition to adenotonsillectomy yielded some clinical benefits. Certain items/groups of food frequencies may be associated with disease recovery and further investigations are warranted.

Impact of Taiwan's 2021 COVID-19 lockdown on the symptom severity and quality of life of patients with narcolepsy.

COVID-19 lockdowns can influence the sleep quality and daytime condition of patients with narcolepsy. Using data from our cohort study, we investigated changes in the quality of life and the symptom severity of patients with narcolepsy during Taiwan's 2021 lockdown and investigated differences by narcolepsy subtype, sex, and age. Patients with type 1 and type 2 narcolepsy (NT1 and NT2, respectively) aged 6-40 years were retrospectively recruited from our narcolepsy cohort study. These patients were regularly evaluated using the Short Form 36 Health Survey questionnaire (SF-36), the Epworth Sleepiness Scale (ESS), the visual analog scale (VAS) for hypersomnolence, the VAS for cataplexy and sleep diary. We compared the differences between the lockdown and the prelockdown periods by narcolepsy subtype, sex, and age. We used a paired t test analysis to compare differences in the SF-36, ESS, VAS scores and data of sleep diary between the prelockdown and lockdown periods (p1), and an independent t test analysis was used to compare the changes in different subgroups between the prelockdown and lockdown periods (p2). A total of 120 patients with narcolepsy were recruited (mean age 24.22 ± 6.87 years; 58% male); 80 of the patients had NT1 (mean age 25.25 ± 6.79 years; 60% male) and 40 had NT2 (mean age 22.16 ± 6.64, 53% male). During the lockdown period, the ESS score of total patients was decreased (p = 0.039) and body mass index was increased (p = 0.02). The NT1 group decreased significantly (p1 = 0.017), especially in men (p1 = 0.016) and adults (p1 = 0.04); scores for the VT domain of the SF-36 increased significantly in male and adult patients with NT2 (p1 = 0.048 and 0.012). Additionally, male patients with NT2 exhibited significantly decreased scores in the physical and emotional role functioning domains (p1 = 0.028, 0.024). The children and adolescents with NT1 had significantly decreased scores in the general health domain of the SF-36, but no significant change was noted in that of adults (p1 = 0.027, p2 = 0.012). We observed both negative and positive impacts of Taiwan's 2021 lockdown on patients with narcolepsy. A more flexible but structured daily routine with adequate sleep time should be considered for this population during lockdown and nonlockdown periods.

Narcolepsy risk loci outline role of T cell autoimmunity and infectious triggers in narcolepsy.

Narcolepsy type 1 (NT1) is caused by a loss of hypocretin/orexin transmission. Risk factors include pandemic 2009 H1N1 influenza A infection and immunization with Pandemrix®. Here, we dissect disease mechanisms and interactions with environmental triggers in a multi-ethnic sample of 6,073 cases and 84,856 controls. We fine-mapped GWAS signals within HLA (DQ0602, DQB1*03:01 and DPB1*04:02) and discovered seven novel associations (CD207, NAB1, IKZF4-ERBB3, CTSC, DENND1B, SIRPG, PRF1). Significant signals at TRA and DQB1*06:02 loci were found in 245 vaccination-related cases, who also shared polygenic risk. T cell receptor associations in NT1 modulated TRAJ*24, TRAJ*28 and TRBV*4-2 chain-usage. Partitioned heritability and immune cell enrichment analyses found genetic signals to be driven by dendritic and helper T cells. Lastly comorbidity analysis using data from FinnGen, suggests shared effects between NT1 and other autoimmune diseases. NT1 genetic variants shape autoimmunity and response to environmental triggers, including influenza A infection and immunization with Pandemrix®.

Effect of Preoperative Weight Status and Disease Presentation on Postoperative Elevated Blood Pressure After Childhood Adenotonsillectomy.

OBJECTIVE: To investigate the risk factors of postoperative elevated blood pressure (BP) in children with childhood obstructive sleep apnea syndrome (OSAS) after adenotonsillectomy (AT). STUDY DESIGN: Case series with planned data collection. SETTING: Tertiary referral center. METHODS: Two hundred forty-five consecutive children (180 boys and 65 girls, median age 6.6 years) with polysomnography-diagnosed OSAS who underwent AT between January 2010 and August 2019. Clinical, polysomnographic, and evening BP data were assessed preoperatively and postoperatively (≥3 months after AT). Changes in the variables before and after AT and between individuals with and without hypertension were compared. RESULTS: Postoperatively, the median (interquartile range) apnea-hypopnea index significantly decreased from 10.4 (5.3-22.6) to 2.2 (1.0-3.8) events/h. In addition, the mean (standard deviation) evening diastolic BP z-score significantly decreased from 0.7 (0.94) to 0.5 (0.81) in the overall cohort, and both systolic (2.1 [0.94]-1.0 [1.31]) and diastolic BP z-scores (1.6 [0.98]-0.7 [0.85]) significantly decreased in the preoperative elevated BP subgroup. Multivariate logistic regression analysis showed that preoperative obesity (adjusted odds ratio = 4.36, 95% confidence interval = 2.24-8.49) and mean peripheral oxygen saturation <95% during sleep (adjusted odds ratio = 2.73, 95% confidence interval = 1.29-5.79) were independently associated with postoperative elevated BP. CONCLUSION: Preoperative obesity and mean peripheral oxygen saturation <95% during sleep were significantly associated with postoperative elevated BP in the children with OSAS, further indicating the importance of careful BP monitoring in this subgroup despite AT treatment.

Adenotonsillectomy-related changes in systemic inflammation among children with obstructive sleep apnea.

BACKGROUND: Adenotonsillar hypertrophy is the most common cause of pediatric obstructive sleep apnea (OSA). Although adenotonsillectomy considerably reduces OSA and systemic inflammation, whether and how systemic inflammation influences the effects of adenotonsillectomy on OSA has yet to be determined. METHODS: This study investigated the associations between changes in anatomical variables, % changes in subjective OSA-18 questionnaire scores, % changes in 11 polysomnographic parameters, and % changes in 27 systemic inflammatory biomarkers in 74 children with OSA. RESULTS: Fifty-six (75.6%) boys and 18 (24.4%) girls with the mean age of 7.4 ± 2.2 years and apnea-hypopnea index (AHI) of 14.2 ± 15.9 events/h were included in the statistical analysis. The mean period between before and after adenotonsillectomy was 5.6 ± 2.6 months. After adenotonsillectomy, the OSA-18 score, eight of 11 polysomnographic parameters, and 20 of 27 inflammatory biomarkers significantly improved (all p < 0.005). Notably, there were significant associations between change in tonsil size and % change in AHI ( r = 0.23), change in tonsil size and % changes in interleukin-8 (IL-8) ( r = 0.34), change in tonsil size and % change in and IL-10 ( r = -0.36), % change in IL-8 and % change in C-C chemokine ligand 5 (CCL5) ( r = 0.30), and % change in CCL5 and % change in AHI ( r = 0.38) (all p < 0.005). Interestingly, % change in IL-8 and % change in CCL5 serially mediated the relationship between change in tonsil size and % change in AHI (total effect: ß = 16.672, standard error = 8.274, p = 0.048). CONCLUSION: These preliminary findings suggest that systemic inflammation is not only a complication of OSA but also that it mediates the surgical effects, which may open avenues for potential interventions to reduce tonsil size and OSA severity through the regulation of IL-8 and CCL5.

Using sleep heart rate variability to investigate the sleep quality in children with obstructive sleep apnea.

Background: Obstructive sleep apnea (OSA) is associated with impaired sleep quality and autonomic dysfunction. Adenotonsillectomy significantly improves subjective and objective sleep quality in children with OSA. However, the postoperative changes in heart rate variability (HRV) indices (indicators of cardiac autonomic function) and their importance remain inconclusive in childhood OSA. This retrospective case series aimed to investigate the association of sleep HRV indices, total OSA-18 questionnaire score (a subjective indicator of sleep quality) and polysomnographic parameters (objective indicators of sleep quality), and effects of adenotonsillectomy on HRV indices, total OSA-18 questionnaire score and polysomnographic parameters in children with OSA. Methods: Seventy-six children with OSA were included in baseline analysis, of whom 64 (84%) completed at least 3 months follow-up examinations after adenotonsillectomy and were included in outcome analysis. Associations between baseline variables, and relationships with treatment-related changes were examined. Results: Multivariable linear regression models in the baseline analysis revealed independent relationships between tonsil size and obstructive apnea-hypopnea index (OAHI), adenoidal-nasopharyngeal ratio and very low frequency (VLF) power of HRV (an indicator of sympathetic activity), and normalized low frequency power (an indicator of sympathetic activity) and OAHI. The outcome analysis showed that adenotonsillectomy significantly improved standard deviation of all normal-to-normal intervals, and high frequency power, QoL (in terms of reduced total OSA-18 questionnaire score), OAHI and hypoxemia. Using a conceptual serial multiple mediation model, % change in OSA-18 questionnaire score and % change in VLF power serially mediated the relationships between change in tonsil size and % change in OAHI. Conclusions: The improvement in OAHI after adenotonsillectomy was serially mediated by reductions in total OSA-18 questionnaire score and VLF power. These preliminary findings are novel and provide a direction for future research to investigate the effects of VLF power-guided interventions on childhood OSA.

Correlation Analysis of Attention and Intelligence of Preterm Infants at Preschool Age: A Premature Cohort Study.

OBJECTIVE: Developmental delay in neurocognitive function has been reported in premature children. This cohort study prospectively followed preterm infants following birth, and herein we present the four-year longitudinal follow-up data of cognitive development at preschool age and analyze correlated factors. METHODS: Term and preterm children received regular clinical evaluations and development assessments after birth, and at age 4 ± 1 years, they received the Wechsler-preschool and primary scale of intelligence, Fourth Edition (WPPSI-IV), excluding those with full-scale intelligence quotient < 70. A total of 150 participants received Conners Kiddie Continuous Performance Test (K-CPT), while 129 participants received ophthalmic evaluation. We adopted Chi-square test, ANOVA, and post hoc analysis to compare group differences. Correlations with K-CPT and WPPSI-IV were analyzed using Pearson's correlation. RESULTS: Group 1 consisted of 25 full-term children, group 2 had 94 preterm children with birth-weight of ≥ 1500 g, and group 3 had 159 preterm children with birth-weight of < 1500 g. Group 1 was the healthiest group and had the best performance in attention and intelligence, while group 3 had the worst physical condition and cognitive performance. The correlation analysis revealed that perinatal factors, including gestational age, birth weight, Apgar scores, and physical conditions, significantly correlated with WPPSI-IV and K-CPT variables. Gender significantly correlated with object assembly of WPSSI-IV and clinical index of K-CPT. Among vision-related variables, best corrected visual acuity correlated most with K-CPT, including clinical index, Omission, and hit reaction time standard error of K-CPT, as well as significantly correlated with information and bug search of WPPSI-IV. CONCLUSIONS: Preterm children at preschool age still had poorer cognitive performance than full-term children, especially those with birth BW less than 1500 g. Gender and vision are correlated with cognitive deficits. Continuous monitoring with comprehensive assessments is recommended.

Changed epidemiology of narcolepsy before, during, and after the 2009 H1N1 pandemic: a nationwide narcolepsy surveillance network study in mainland China, 1990-2017.

STUDY OBJECTIVES: Increased 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. METHODS: Individual 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. RESULTS: Average 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. CONCLUSIONS: Increased 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.

The impact of COVID-19 lockdown on sleep patterns, emotions, and behaviors of children and adolescents in Taiwan.

Background: The lockdown in May 2021 was the first and only lockdown implemented in Taiwan during the COVID-19 pandemic. The epidemic in Taiwan has been maintained under relatively better control and this study aimed to examine the impact of the lockdown on sleep and emotional and behavior disturbances in children and adolescents in Taiwan. Material and methods: Participants over 6 years old were recruited retrospectively from a cohort study, and their parents completed questionnaires including the Children's Sleep Habits Questionnaire (CSHQ), the Child Behavior Checklist (CBCL), the Swanson, Nolan and Pelham-IV Teacher and Parent Rating Scale (SNAP-IV), and the function assessment. A total of 217 children and adolescents whose parents completed questionnaires during both the lockdown period and the pre-lockdown period were included. We used paired t-test and independent t test; to analyze the differences between the lockdown and pre-lockdown periods and between different subgroups. Results: The mean age of all participants was 11.87 ± 3.97 years, with 69.6% male. The results of CSHQ indicated that our participants had significantly increased total sleep time (p = 0.000), more sleep onset delay (p = 0.011), fewer sleep duration problems (p = 0.029), less parasomnia (p = 0.018), fewer sleep breathing problems (p = 0.028), and less daytime sleepiness (p = 0.000) during the lockdown, especially males and children. We observed trends but no significant changes of all participants in CBCL and SNAP during the lockdown. The change of the inattention index reached a significant level between children and adolescents (p 2 = 0.017). The results of the functional assessment showed more interferences in home living (p = 0.021) of all participants, especially males (p 1 = 0.002). Conclusions: The lockdown significantly impacted children and adolescents' sleep and functioning. We also observed trends of increased emotion, behavior and inattention problems, and significantly increased interference in home living. Male gender and younger age may be associated factors for sleep and functional disturbances of the lockdown.

Quality of life changes and their predictors in young adult narcolepsy patients after treatment: A real-world cohort study.

Background: We conducted a five-year prospective follow-up study to track the real-world quality of life of patients with narcolepsy after medication and analyzed predictors. Methods: The study ultimately included 157 participants who completed 5-year follow-up, 111 had type 1 narcolepsy (NT1) and 46 had type 2 narcolepsy (NT2). Polysomnography, multiple sleep latency test, actigraphy and HLA-typing were conducted. The Short Form 36 Health Survey Questionnaire (SF-36), the Stanford Center for Narcolepsy Sleep Inventory, the Epworth Sleepiness Scale (ESS), the visual analog for hypersomnolence (VAS), and Conners' Continuous Performance Test were used. Descriptive statistics, repeated measures, and hierarchical linear models were applied for analysis. Results: Most demographic and clinical data did not significantly differ between groups, but the NT1 group had significantly more overweight, more severe narcoleptic symptoms, more positive HLA typing, shorter mean sleep latency, and more sleep onset rapid eye movement periods. No significant change to the physical domains of SF-36 was found in the total group, but we observed significant changes in emotional role functioning and social function. The NT1 group showed significant improvements in physical role functioning, emotional role functioning, and social function. The NT2 group demonstrated significant improvements in emotional role functioning. At the baseline, the NT2 group had significantly better scores, but there was no significant group difference after treatment, except for physical and social function. ESS and VAS were significantly improved during follow-up. At the baseline, the NT1 group had significantly higher ESS and VAS scores, and continuously significantly higher ESS scores during follow-up. Narcolepsy types, HLA typing, age of onset, symptom severity, attention and vigilance were significantly correlated with SF-36. Conclusion: Symptom control greatly associates with the quality of life in narcoleptic patients, and medication can play the most important role. Management targeting narcoleptic symptoms, attention impairment, and drug adherence should be provided.

The effect of electromagnetic field on sleep of patients with nocturia.

INTRODUCTION: Accumulated studies revealed that electromagnetic field can affect human brain and sleep. We explored the effectiveness of electromagnetic field [Schumann resonance (SR)] on nocturia symptoms, quality of life, and sleep in patients with nocturia. METHODS: This is a randomized, open-label, and active-controlled study, in which 35 participants were randomized into 2 groups. Group A received oxybutynin and the SR device for 12 weeks, while the active-control group received only the medication. We followed these patients every 4 weeks with a number of questionnaires, including the Pittsburgh sleep quality index (PSQI) and Epworth sleepiness scale (ESS) for sleep, the American Urological Association Symptom Score (AUASS) for nocturia symptoms, and the Nocturia-Quality-of-Life-questionnaire (N-QOL) for quality of life. Descriptive statistics, pair t-tests, Chi-squared tests, and repeated measures were applied for data analysis. RESULTS: No significant difference was found in the demographic data between the 2 groups. The AUASS, N-QOL, PSQI, and ESS total scores were significantly improved in the SR-sleep-device group (P < .001, P = .005, P < .001, P = .001) after treatment, but no significant change was found in the active-control group. Several variables of AUASS in the SR-sleep-device group were significantly improved, especially streaming and sleeping (both P = .001), and subjective sleep quality and sleep efficiency also demonstrated significant improvement (both P < .001). CONCLUSIONS: Our study revealed that electromagnetic field (SR) as an add-on can improve not only sleep and quality of life but also nocturia symptoms in patients with nocturia. These findings suggest that SR can be effective for sleep disturbance secondary to physical disease, which can be a new application of the electromagnetic field.

Genotypes Influence Clinical Progression in EYS-Associated Retinitis Pigmentosa.

Purpose: The purpose of this study was to investigate the genetic and clinical characteristics of eyes shut homolog (EYS)-associated retinitis pigmentosa (RP). Methods: This was a retrospective cross-sectional observational study of 36 patients with EYS-associated autosomal recessive RP (arRP). Results: The gene sequencing results revealed that c.6416G>A (p.Cys2139Tyr) and c.7228+1G>A were the two most predominant variants in our cohort and that variants near the C-terminus, which contains alternating laminin and epidermal growth factor (EGF) domains, accounted for the majority of the allele counts (58 of a total of 72) and relative allele frequencies (81%). Over half of the patients presented with pericentral-type RP (n = 19, 60%), which frequently occurred in combination with macular lesions (n = 10, 52%). Patients having both variants within the alternating laminin and EGF domains near the C-terminus had a more severe disease progression (average 0.045 logMAR increase per year) than those having one variant in the N-terminus and the other in the C-terminus (average 0.001 logMAR increase per year). Conclusions: Pericentral RP was the major phenotype in patients with EYS-associated arRP. There was also a statistically significant relationship between the location of the variants and the severity of the disease. Translational Relevance: This study may aid patients with EYS-associated arRP to predict future vision acuity based on their genetic and clinical features.

Pediatric Narcolepsy-A Practical Review.

Pediatric narcolepsy is a chronic sleep-wakefulness disorder. Its symptoms frequently begin in childhood. This review article examined the literature for research reporting on the effects of treatment of pediatric narcolepsy, as well as proposed etiology and diagnostic tools. Symptoms of pediatric narcolepsy include excessive sleepiness and cataplexy. In addition, rapid-eye-movement-related phenomena such as sleep paralysis, sleep terror, and hypnagogic or hypnapompic hallucinations can also occur. These symptoms impaired children's function and negatively influenced their social interaction, studying, quality of life, and may further lead to emotional and behavioral problems. Therefore, early diagnosis and intervention are essential for children's development. Moreover, there are differences in clinical experiences between Asian and Western population. The treatment of pediatric narcolepsy should be comprehensive. In this article, we review pediatric narcolepsy and its treatment approach: medication, behavioral modification, and education/mental support. Pharmacological treatment including some promising newly-developed medication can decrease cataplexy and daytime sleepiness in children with narcolepsy. Other forms of management such as psychosocial interventions involve close cooperation between children, school, family, medical personnel, and can further assist their adjustment.

Craniofacial Morphologic Predictors for Passive Myofunctional Therapy of Pediatric Obstructive Sleep Apnea Using an Oral Appliance with a Tongue Bead.

We conducted this retrospective study to identify potential clinical, polysomnographic, and cephalometric predictors for the treatment outcomes of a tongue-beaded oral appliance (OA) in children with obstructive sleep apnea syndrome (OSAS). In total, 63 patients­50 boys and 13 girls ranging in age from 4 to 16 years­underwent OA treatment nightly for at least 6 months. A baseline digital lateral cephalometric radiograph was obtained for each patient. Multivariate logistic regression analysis was performed to examine predictors for the treatment outcome based on the clinical and cephalometric measurements. Overall, 28 patients responded to the treatment (post-treatment improvement > 50% or apnea−hypopnea index (AHI) < 1/h), and 35 did not (post-treatment improvement < 50% and AHI ≥ 1/h). Significantly larger cranial base angle (SNBa), smaller lower gonial angle (LGo Angle), and shorter length of anterior cranial base (SN) were found in responders. Smaller lower gonial angle (LGo Angle) and smaller anterior cranial base (SN) predict a favorable outcome for pediatric OSAS using a tongue-beaded OA. This finding will equip practitioners with additional insights when selecting suitable candidates for OA therapy in pediatric patients.