Data_Sheet_1_Identifying major predictors for parenting stress in a caregiver of autism spectrum disorder using machine learning models.DOCX

IntroductionPrevious studies have investigated predictive factors for parenting stress in caregivers of autism spectrum disorder (ASD) patients using traditional statistical approaches, but their study settings and results were inconsistent. Herein, this study aimed to identify major predictors for parenting stress in this population by developing explainable machine learning models.MethodsStudy participants were collected from the Department of Child and Adolescent Psychiatry, Severance Hospital, Yonsei University College of Medicine, Seoul, the Republic of Korea between March 2016 and October 2020. A total of 36 model features were used, which include subscales of the Minnesota Multiphasic Personality Inventory-2 (MMPI-2) for caregivers’ psychopathology, Social Responsiveness Scale-2 for core symptoms, and Child Behavior Checklist (CBCL) for behavioral problems. Machine learning classifiers [eXtreme Gradient Boosting (XGBoost), random forest (RF), logistic regression, and support vector machine (SVM) classifier] were generated to predict severe total parenting stress and its subscales (parental distress, parent-child dysfunctional interaction, and difficult child). Model performance was assessed by area under the receiver operating curve (AUC), sensitivity, specificity, accuracy, positive predictive value, and negative predictive value. We utilized the SHapley Additive exPlanations tree explainer to investigate major predictors.ResultsA total of 496 participants were included [mean age of ASD patients 6.39 (SD 2.24); 413 men (83.3%)]. The best-performing models achieved an AUC of 0.831 (RF model; 95% CI 0.740–0.910) for parental distress, 0.814 (SVM model; 95% CI 0.720–0.896) for parent-child dysfunctional interaction, 0.813 (RF model; 95% CI 0.724–0.891) for difficult child, and 0.862 (RF model; 95% CI 0.783–0.930) for total parenting stress on the test set. For the total parenting stress, ASD patients’ aggressive behavior and anxious/depressed, and caregivers’ depression, social introversion, and psychasthenia were the top 5 leading predictors.ConclusionBy using explainable machine learning models (XGBoost and RF), we investigated major predictors for each subscale of the parenting stress index in caregivers of ASD patients. Identified predictors for parenting stress in this population might help alert clinicians whether a caregiver is at a high risk of experiencing severe parenting stress and if so, providing timely interventions, which could eventually improve the treatment outcome for ASD patients.</p

Comparative efficacy and optimal duration of first-line antibiotic regimens for acute otitis media in children and adolescents: a systematic review and network meta-analysis of 89 randomized clinical trials

Introduction Antibiotic use for acute otitis media (AOM) is one of the major sources of antimicrobial resistance. However, the effective minimal antibiotic duration for AOM remains unclear. Moreover, guidelines often recommend broad ranges (5–10 days) of antibiotic use, yet the clinical impact of such a wide window has not been assessed. Methods We systematically searched PubMed/MEDLINE, Embase, Scopus, Web of Science, and Cochrane Library from database inception to 6 October 2021. Network meta-analysis was conducted on randomized controlled trials that assessed antibiotic treatment for AOM in children (PROSPERO CRD42020196107). Results For amoxicillin and amoxicillin–clavulanate, 7-day regimens were noninferior to 10-day regimens in clinical responses [amoxicillin: risk ratio (RR) 0.919 (95% CI 0.820–1.031), amoxicillin–clavulanate: RR 1.108 (0.957–1.282)], except for ≤ 2 years. For the third-generation cephalosporins, 7-day and 10-day regimens had similar clinical responses compared to placebo [7-day: RR 1.420 (1.190–1.694), 10-day: RR 1.238 (1.125–1.362) compared to placebo]. However, 5-day regimens of amoxicillin–clavulanate and third-generation cephalosporins were inferior to 10-day regimens. Compared to amoxicillin, a shorter treatment duration was tolerable with amoxicillin–clavulanate. Conclusions Our findings indicated that 10 days of antibiotic use may be unnecessarily long, while the treatment duration should be longer than 5 days. Otherwise, 5-day regimens would be sufficient for a modest treatment goal. Our findings revealed that the current wide range of recommended antibiotic durations may have influenced the clinical outcome of AOM, and a narrower antibiotic duration window should be re-established

Comparative efficacy and optimal duration of first-line antibiotic regimens for acute otitis media in children and adolescents: a systematic review and network meta-analysis of 89 randomized clinical trials

Introduction Antibiotic use for acute otitis media (AOM) is one of the major sources of antimicrobial resistance. However, the effective minimal antibiotic duration for AOM remains unclear. Moreover, guidelines often recommend broad ranges (5–10 days) of antibiotic use, yet the clinical impact of such a wide window has not been assessed. Methods We systematically searched PubMed/MEDLINE, Embase, Scopus, Web of Science, and Cochrane Library from database inception to 6 October 2021. Network meta-analysis was conducted on randomized controlled trials that assessed antibiotic treatment for AOM in children (PROSPERO CRD42020196107). Results For amoxicillin and amoxicillin–clavulanate, 7-day regimens were noninferior to 10-day regimens in clinical responses [amoxicillin: risk ratio (RR) 0.919 (95% CI 0.820–1.031), amoxicillin–clavulanate: RR 1.108 (0.957–1.282)], except for ≤ 2 years. For the third-generation cephalosporins, 7-day and 10-day regimens had similar clinical responses compared to placebo [7-day: RR 1.420 (1.190–1.694), 10-day: RR 1.238 (1.125–1.362) compared to placebo]. However, 5-day regimens of amoxicillin–clavulanate and third-generation cephalosporins were inferior to 10-day regimens. Compared to amoxicillin, a shorter treatment duration was tolerable with amoxicillin–clavulanate. Conclusions Our findings indicated that 10 days of antibiotic use may be unnecessarily long, while the treatment duration should be longer than 5 days. Otherwise, 5-day regimens would be sufficient for a modest treatment goal. Our findings revealed that the current wide range of recommended antibiotic durations may have influenced the clinical outcome of AOM, and a narrower antibiotic duration window should be re-established

Correlations between sleep problems, core symptoms, and behavioral problems in children and adolescents with autism spectrum disorder: a systematic review and meta-analysis

Children and adolescents with autism spectrum disorder (ASD) experience various sleep problems. Sleep problems co-occur in a bidirectional relationship with ASD core symptoms and behavioral problems. However, studies on how these three factors are intricately linked to each other are limited. This meta-analysis examined the differential relationship between specific sleep problems, core symptoms, and behavioral problems in this population. This study was registered in PROSPERO (CRD42022339695). We systematically searched the PubMed/MEDLINE, Web of Science, and Scopus databases from inception to April 27, 2022. Observational studies that reported correlations between measures of sleep problems, ASD core symptoms, or ASD behavioral problems were included, and participants aged 18 years or below were enrolled. The correlation coefficient (r) was assessed as the primary effect metric. Total 22 cross-sectional studies were included, which comprised 2655 participants (mean age = 6.60 years old; mean percentage of boys = 80.64%). We found correlations between total sleep problems and total core symptoms (r 0.293 [95% confidence interval − 0.095 to 0.604]), total sleep problems and total behavioral problems (r 0.429 [0.299–0.544]), and total core symptoms and total behavioral problems (r − 0.050 [− 0.177 to 0.079]) and identified statistically significant correlations between specific components of sleep problems, ASD core symptoms, and ASD behavioral problems. Each specific sleep problem showed a unique association with core symptoms and behavioral problems. Sleep problems in ASD should be explored in detail, and the closely linked core symptoms and behavioral problems should be common therapeutic targets.</p

Correlations between sleep problems, core symptoms, and behavioral problems in children and adolescents with autism spectrum disorder: a systematic review and meta-analysis

Children and adolescents with autism spectrum disorder (ASD) experience various sleep problems. Sleep problems co-occur in a bidirectional relationship with ASD core symptoms and behavioral problems. However, studies on how these three factors are intricately linked to each other are limited. This meta-analysis examined the differential relationship between specific sleep problems, core symptoms, and behavioral problems in this population. This study was registered in PROSPERO (CRD42022339695). We systematically searched the PubMed/MEDLINE, Web of Science, and Scopus databases from inception to April 27, 2022. Observational studies that reported correlations between measures of sleep problems, ASD core symptoms, or ASD behavioral problems were included, and participants aged 18 years or below were enrolled. The correlation coefficient (r) was assessed as the primary effect metric. Total 22 cross-sectional studies were included, which comprised 2655 participants (mean age = 6.60 years old; mean percentage of boys = 80.64%). We found correlations between total sleep problems and total core symptoms (r 0.293 [95% confidence interval − 0.095 to 0.604]), total sleep problems and total behavioral problems (r 0.429 [0.299–0.544]), and total core symptoms and total behavioral problems (r − 0.050 [− 0.177 to 0.079]) and identified statistically significant correlations between specific components of sleep problems, ASD core symptoms, and ASD behavioral problems. Each specific sleep problem showed a unique association with core symptoms and behavioral problems. Sleep problems in ASD should be explored in detail, and the closely linked core symptoms and behavioral problems should be common therapeutic targets.</p

Characterization of Novel <i>O</i>‑Glycans Isolated from Tear and Saliva of Ocular Rosacea Patients

<i>O</i>-Glycans in saliva and tear isolated from patients suffering from ocular rosacea, a form of inflammatory ocular surface disease, were profiled, and their structures were elucidated using high resolution mass spectrometry. We have previously shown that certain structures, particularly sulfated oligosaccharides, increased in the tear and saliva of rosacea patients. In this study, the structures of these glycans were elucidated using primarily tandem mass spectrometry. There were important similarities in the glycan profiles of tears and saliva with the majority of the structures in common. The structures of the most abundant species common to both tear and saliva, which were also the most abundant species in both, were elucidated. For sulfated species, the positions of the sulfate groups were localized. The majority of the structures were new, with the sulfated glycans comprising mucin <i>core 1</i>- and <i>core 2</i>-type structures. As both saliva and tear are rich in mucins, it is suggested that the <i>O</i>-glycans are mainly components of mucins. The study further illustrates the strong correspondence between the glycans in the tear and saliva of ocular rosacea patients

Subjective and objective sleep alterations in medication-naïve children and adolescents with autism spectrum disorder: a systematic review and meta-analysis

Aims This study aimed to summarize the evidence on sleep alterations in medication-naïve children and adolescents with autism spectrum disorder (ASD). Methods We systematically searched PubMed/Medline, Embase and Web of Science databases from inception through March 22, 2021. This study was registered with PROSPERO (CRD42021243881). Any observational study was included that enrolled medication-naïve children and adolescents with ASD and compared objective (actigraphy and polysomnography) or subjective sleep parameters with typically developing (TD) counterparts. We extracted relevant data such as the study design and outcome measures. The methodological quality was assessed through the Newcastle-Ottawa Scale (NOS). A meta-analysis was carried out using the random-effects model by pooling effect sizes as Hedges’ g. To assess publication bias, Egger’s test and p-curve analysis were done. A priori planned meta-regression and subgroup analysis were also performed to identify potential moderators. Results Out of 4277 retrieved references, 16 studies were eligible with 981 ASD patients and 1220 TD individuals. The analysis of objective measures showed that medication-naïve ASD patients had significantly longer sleep latency (Hedges’ g 0.59; 95% confidence interval [95% CI] 0.26 to 0.92), reduced sleep efficiency (Hedges’ g −0.58; 95% CI −0.87 to −0.28), time in bed (Hedges’ g −0.64; 95% CI −1.02 to −0.26) and total sleep time (Hedges’ g −0.64; 95% CI −1.01 to −0.27). The analysis of subjective measures showed that they had more problems in daytime sleepiness (Hedges’ g 0.48; 95% CI 0.26 to 0.71), sleep latency (Hedges’ g 1.15; 95% CI 0.72 to 1.58), initiating and maintaining sleep (Hedges’ g 0.86; 95% CI 0.39 to 1.33) and sleep hyperhidrosis (Hedges’ g 0.48; 95% CI 0.29 to 0.66). Potential publication bias was detected for sleep latency, sleep period time and total sleep time measured by polysomnography. Some sleep alterations were moderated by age, sex and concurrent intellectual disability. The median NOS score was 8 (interquartile range 7.25–8.75). Conclusion We found that medication-naïve children and adolescents with ASD presented significantly more subjective and objective sleep alterations compared to TD and identified possible moderators of these differences. Future research requires an analysis of how these sleep alterations are linked to core symptom severity and comorbid behavioural problems, which would provide an integrated therapeutic intervention for ASD. However, our results should be interpreted in light of the potential publication bias.</p

Pharmacological and non-pharmacological interventions for irritability in autism spectrum disorder: a systematic review and meta-analysis with the GRADE assessment

No description supplied</p

Pharmacological and non-pharmacological interventions for irritability in autism spectrum disorder: a systematic review and meta-analysis with the GRADE assessment

No description supplied</p

Subjective and objective sleep alterations in medication-naïve children and adolescents with autism spectrum disorder: a systematic review and meta-analysis

Aims This study aimed to summarize the evidence on sleep alterations in medication-naïve children and adolescents with autism spectrum disorder (ASD). Methods We systematically searched PubMed/Medline, Embase and Web of Science databases from inception through March 22, 2021. This study was registered with PROSPERO (CRD42021243881). Any observational study was included that enrolled medication-naïve children and adolescents with ASD and compared objective (actigraphy and polysomnography) or subjective sleep parameters with typically developing (TD) counterparts. We extracted relevant data such as the study design and outcome measures. The methodological quality was assessed through the Newcastle-Ottawa Scale (NOS). A meta-analysis was carried out using the random-effects model by pooling effect sizes as Hedges’ g. To assess publication bias, Egger’s test and p-curve analysis were done. A priori planned meta-regression and subgroup analysis were also performed to identify potential moderators. Results Out of 4277 retrieved references, 16 studies were eligible with 981 ASD patients and 1220 TD individuals. The analysis of objective measures showed that medication-naïve ASD patients had significantly longer sleep latency (Hedges’ g 0.59; 95% confidence interval [95% CI] 0.26 to 0.92), reduced sleep efficiency (Hedges’ g −0.58; 95% CI −0.87 to −0.28), time in bed (Hedges’ g −0.64; 95% CI −1.02 to −0.26) and total sleep time (Hedges’ g −0.64; 95% CI −1.01 to −0.27). The analysis of subjective measures showed that they had more problems in daytime sleepiness (Hedges’ g 0.48; 95% CI 0.26 to 0.71), sleep latency (Hedges’ g 1.15; 95% CI 0.72 to 1.58), initiating and maintaining sleep (Hedges’ g 0.86; 95% CI 0.39 to 1.33) and sleep hyperhidrosis (Hedges’ g 0.48; 95% CI 0.29 to 0.66). Potential publication bias was detected for sleep latency, sleep period time and total sleep time measured by polysomnography. Some sleep alterations were moderated by age, sex and concurrent intellectual disability. The median NOS score was 8 (interquartile range 7.25–8.75). Conclusion We found that medication-naïve children and adolescents with ASD presented significantly more subjective and objective sleep alterations compared to TD and identified possible moderators of these differences. Future research requires an analysis of how these sleep alterations are linked to core symptom severity and comorbid behavioural problems, which would provide an integrated therapeutic intervention for ASD. However, our results should be interpreted in light of the potential publication bias.</p