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CONTEXT Approximately 10% to 20% of patients with Kawasaki disease (KD) are refractory to initial intravenous immunoglobulin (IVIG) therapy. KD is mainly associated with coronary artery abnormalities. OBJECTIVES To identify and evaluate all developed prediction models for IVIG resistance in patients with KD and synthesize evidence from external validation studies that evaluated their predictive performances. DATA SOURCES PubMed Medline, Dialog Embase, the Cochrane Central Register of Controlled Trials, the World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov were searched from inception until October 5, 2021. STUDY SELECTION All cohort studies that reported patients diagnosed with KD who underwent an initial IVIG of 2 g/kg were selected. DATA EXTRACTION Study and patient characteristics and model performance measures. Two authors independently extracted data from the studies. RESULTS The Kobayashi, Egami, Sano, Formosa, and Harada scores were the only prediction models with 3 or more external validation of the161 model analyses in 48 studies. The summary C–statistics were 0.65 (95% confidence interval [CI]: 0.57–0.73), 0.63 (95% CI: 0.55–0.71), 0.58 (95% CI: 0.55–0.60), 0.50 (95% CI: 0.36–0.63), and 0.63 (95% CI: 0.44–0.78) for the Kobayashi, Egami, Sano, Formosa, and Harada models, respectively. All 5 models showed low positive predictive values (0.14–0.39) and high negative predictive values (0.85–0.92). LIMITATIONS Potential differences in the characteristics of the target population among studies and lack of assessment of calibrations. CONCLUSIONS None of the 5 prediction models with external validation accurately distinguished between patients with and without IVIG resistance.

Whether reducing exposure to varicella by the implementation of the routine varicella vaccination program for children leads to increased incidence of herpes zoster (HZ) remains controversial. The aim of the present study was to identify the trend in the hospitalization associated with HZ before and after the introduction of routine varicella vaccination by using nationally representative data from an inpatient database in Japan. Data were obtained on the number of inpatients hospitalized for HZ from the "Survey on the effect of the introduction of Diagnosis Procedure Combination (DPC) database" and the total population in Japan from the Population Estimates created by the former Statistics Bureau between fiscal years 2013 and 2018. The data from the DPC hospitals only and all hospitals in the survey were analyzed separately. The trends in the annual incidence of HZ hospitalization were identified. The trends in the annual hospitalization for HZ per 100,000 persons were then analyzed by age group (0-20, 21-40, 41-60, 61-79, and ≥80 years of age). The annual number of hospitalizations for HZ was approximately 20,000 in the DPC hospitals and 25,000 in all hospitals, showing no upward trend. The age-specific annual hospitalization rate for HZ did not increase in all the age groups. As age increased, the hospitalization rate also increased. This study presents no upward trend in the hospitalizations for HZ after the implementation of the routine varicella vaccination program in Japan.

An endovascular arteriovenous fistula is a recent technological advancement in hemodialysis vascular access. This systematic review and meta-analysis aimed to investigate the efficacy and safety of endovascular arteriovenous fistula (eAVF) creation compared with surgical arteriovenous fistula (sAVF) creation among patients with chronic kidney disease. We searched Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Clinical Trials.gov, and the WHO International Clinical Trials Registry Platform until May 2021 to perform meta-analyses using random-effects models. Pre-specified primary outcomes were fistula maturation, procedure-related complications, and patient satisfaction. Secondary outcomes were procedural technical success, procedure time, all adverse events, and medical expenditure. The risk of bias in non-randomized studies of the interventions assessment tool, and the Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) approach were used to assess the quality of individual studies and the body of evidence, respectively. In seven studies including 860 patients, endovascular arteriovenous fistula creation had little to no effect on fistula maturation (odds ratio, 0.58; 95% confidence intervals, 0.05 to 6.91). Meta-analysis could not be performed for procedure-related complications and patient satisfaction due to insufficient data. For secondary outcomes, endovascular arteriovenous fistula resulted in a slight to no difference in procedural technical success (odds ratio, 0.69: 95% confidence intervals, 0.04 to 11.98) and all adverse events (odds ratio, 6.31; 95% confidence intervals, 0.64 to 62.22). Endovascular fistula creation incurred less medical expenditure than sAVF (mean difference, USD 12760; 95% confidence intervals, -19710 to -5820). Meta-analysis for procedure time was not performed because one of the studies had a critical risk of bias. All of these outcomes were of low certainty of evidence or very low certainty of evidence. There was limited evidence for supporting endovascular arteriovenous fistula creation over conventional surgical arteriovenous fistula creation for patients with chronic kidney disease. Multicenter randomized controlled trials are needed to confirm the efficacy and safety of eAVFs in selected populations.

Influenza vaccination is the most effective method for preventing influenza virus infection. The incidence of influenza is higher in schoolchildren than other age groups. This study evaluated the effectiveness of seasonal inactivated influenza vaccination (IIV) in a community population of schoolchildren during two seasons. This study was a cross-sectional survey of public schoolchildren based on data collected in the 2012/2013 and 2014/2015 seasons. The questionnaire was distributed to all public schoolchildren of target grade in a survey area, and 7945 respondents were included in the analysis. The vaccination status and influenza onset were defined based on the self-reported questionnaire by parents or guardians. Generalized linear mixed models were used to adjust clustering within schools and individual covariates and calculate odds ratios (ORs) and 95% confidence intervals (CIs) for associations between vaccination status and influenza onset. The influenza incidence was higher in the 2015 than the 2013 survey (25% versus 17%), although the vaccination rates were comparable between the two seasons. Receiving one- or two-dose vaccination was more protective against influenza than non-vaccination in both the 2013 (OR, 0.77; 95%CI, 0.65–0.92) and 2015 (OR, 0.88; 95%CI, 0.75–1.02) surveys. Full vaccination was also more protective in both the 2013 (OR, 0.75; 95%CI, 0.62–0.89) and 2015 (OR, 0.86; 95%CI, 0.74–1.00) surveys. Seasonal IIV was protective against influenza for Japanese schoolchildren in a community-based real-world setting. The difference in clinical effectiveness of IIV between the two seasons was likely due to the antigenic mismatch between the circulating and vaccine strains.

This systemic review and meta-analysis aimed to evaluated existing evidence on the clinical efficacy and safety of endovascular arteriovenous fistula creation by directly comparing it with surgical arteriovenous fistula creation among patients with chronic kidney disease requiring hemodialysis.

To the Editor,Harandian et al. [1] reviewed the prevalence of immediate adverse reactions to penicillin antibiotics in patients with reported penicillin allergy in 2016. They assessed the effect of...

Background Neonatal jaundice and phototherapy have been associated with the development of allergic diseases. It has been suggested, however, that effect estimates of the associations might be smaller than expected. We sought to update the evidence of their associations including recently published large longitudinal studies. Methods We sought published and unpublished observational studies through the major databases. We used a random-effect meta-analysis model weighted by the inverse variance estimate, the Quality in Prognosis Studies tool to assess the methodological quality for each study, and the Grading of Recommendations, Assessment, Development, and Evaluation approach to assess the certainty of evidence (COE). Results Nineteen studies were enrolled in the qualitative syntheses, and fourteen studies were synthesized in the meta-analyses. Neonatal jaundice was associated with a higher risk of childhood-onset asthma (odds ratio [OR], 1.46; 95% confidence interval [95% CI], 1.39-1.53; COE, moderate), atopic dermatitis (AD; OR, 1.30; 95% CI, 1.07-1.57; COE, moderate), and allergic rhinitis (AR; OR, 3.01; 95% CI, 0.8810.30; COE, low). Neonatal phototherapy was also associated with a higher risk of childhood-onset asthma (OR, 1.24; 95% CI, 1.11-1.38; COE, moderate), AD (OR, 1.31; 95% CI, 1.24-1.39; COE, moderate), and AR (OR, 1.38; 95% CI, 0.93-2.04; COE, very low). There were no studies that reported effect estimates of the associations between childhood-onset food allergies and neonatal jaundice and phototherapy. Conclusion Neonatal jaundice and phototherapy were probably a prognostic factor of childhood-onset allergic diseases; however, the associations were likely to be smaller than previously estimated.

We constructed an optimal machine learning (ML) method for predicting intravenous immunoglobulin (IVIG) resistance in children with Kawasaki disease (KD) using commonly available clinical and laboratory variables. We retrospectively collected 98 clinical records of hospitalized children with KD (2–109 months of age). We found that 20 (20%) children were resistant to initial IVIG therapy. We trained three ML techniques, including logistic regression, linear support vector machine, and eXtreme gradient boosting with 10 variables against IVIG resistance. Moreover, we estimated the predictive performance based on nested 5-fold cross-validation (CV). We also selected variables using the recursive feature elimination method and performed the nested 5-fold CV with selected variables in a similar manner. We compared ML models with the existing system regardless of their predictive performance. Results of the area under the receiver operator characteristic curve were in the range of 0.58–0.60 in the all-variable model and 0.60–0.75 in the select model. The specificities were more than 0.90 and higher than those in existing scoring systems, but the sensitivities were lower. Three ML models based on demographics and routine laboratory variables did not provide reliable performance. This is possibly the first study that has attempted to establish a better predictive model. Additional biomarkers are probably needed to generate an effective prediction model.

BackgroundAutism spectrum disorder (ASD) has phenotypically and genetically heterogeneous characteristics. A simulation study demonstrated that attempts to categorize patients with a complex disease into more homogeneous subgroups could have more power to elucidate hidden heritability.MethodsWe conducted cluster analyses using the k-means algorithm with a cluster number of 15 based on phenotypic variables from the Simons Simplex Collection (SSC). As a preliminary study, we conducted a conventional genome-wide association study (GWAS) with a dataset of 597 ASD cases and 370 controls. In the second step, we divided cases based on the clustering results and conducted GWAS in each of the subgroups vs controls (cluster-based GWAS). We also conducted cluster-based GWAS on another SSC dataset of 712 probands and 354 controls in the replication stage.ResultsIn the preliminary study, we observed no significant associations. In the second step of cluster-based GWASs, we identified 65 chromosomal loci, which included 30 intragenic loci located in 21 genes and 35 intergenic loci that satisfied the threshold of P−8. Some of these loci were located within or near previously reported candidate genes for ASD: CDH5, CNTN5, CNTNAP5, DNAH17, DPP10, DSCAM, FOXK1, GABBR2, GRIN2A5, ITPR1, NTM, SDK1, SNCA and SRRM4. Of these 65 significant chromosomal loci, rs11064685 located within the SRRM4 gene had a significantly different distribution in the cases vs. controls in the replication cohort.ConclusionsThese findings suggest that clustering may successfully identify subgroups with relatively homogeneous disease etiologies. Further cluster validation and replication studies are warranted in larger cohorts.

Background: The association between eczema and mental health problems in schoolchildren has been underexplored. We aimed to investigate this association with the validated questionnaires. Methods: Of 46,648 invited children, we analyzed 9954 (21.3%) in the 2nd to the 8th grades from the ToMMo Child Health Study conducted in 2014 and 2015, a cross-sectional survey in Miyagi Prefecture, Japan. We defined eczema status as “normal,” “mild/moderate,” or “severe,” based on the presence of persistent flexural eczema and sleep disturbance, according to the International Study of Asthma and Allergies in Childhood (ISAAC) Eczema Symptom Questionnaire. Clinical ranges of Strengths and Difficulties Questionnaire (SDQ) total difficulties scores and four SDQ subcategories of emotional symptoms, conduct problems, hyperactivity/inattention, and peer problems were defined as scores ≥16, ≥5, ≥5, ≥7, and ≥5, respectively. Results: The mean SDQ total difficulties score significantly increased as eczema status worsened (all P ≤ 0.004 for trend). The OR of scores in the clinical range for SDQ total difficulties were 1.51 (95% CI, 1.31–1.74) for mild/moderate eczema and 2.63 (95% CI, 1.91–3.63) for severe eczema (P

Objective:We aimed to investigate the association between types of housing and allergic symptoms at 3–4 years following the Great East Japan Earthquake.Methods:Our study was based on the ToMMo Child Health Study conducted in 2014 and 2015, a cross-sectional survey of public school children in Miyagi Prefecture, Japan. Of the 46 648 invited schoolchildren in the 2nd to 8th grades, 9884 were included. Presence of eczema, wheezing, and mental health symptoms was defined with questionnaires. To calculate odds ratios (ORs) and 95% CIs for the associations between types of housing and eczema or respiratory symptoms, we fitted generalized linear mixed models, included a random effect for municipality of residence, and adjusted for sex, school grade, survey year, and mental health symptoms.Results:Prefabricated temporary housing was significantly associated with eczema symptoms (OR, 1.46; 95% CI, 1.06–2.02). Even after adjusting for the presence of mental health symptoms, our analysis produced similar results (OR, 1.42; 95% CI, 1.03–1.96). Conversely, it was not significantly associated with respiratory symptoms (OR, 0.97; 95% CI, 0.61–1.54).Conclusions:Children living in prefabricated temporary housing had a higher prevalence of eczema symptoms; however, prevalence of respiratory symptoms was not significantly higher.

Backgrounds: The effect of breastfeeding on weight status of individuals after a large-scale natural disaster in a developed country is unclear. We aimed to investigate the association of ...

Background Serious isolated laryngeal injuries are uncommon in children. Case Report We describe the case of an 8-year-old boy with laryngeal injury and pneumomediastinum due to minor blunt neck trauma. He presented to the emergency department complaining of odynophagia and hoarseness, but without respiratory distress. Emphysema was seen between the trachea and vertebral body on initial cervical spine x-ray study, and flexible laryngoscopy revealed erythema and mild edema of both the right vocal cord and the arytenoid region. He recovered with conservative management only. Why Should an Emergency Physician Be Aware of This? We conclude that it is important to recognize subtle evidence of laryngeal injury secondary to blunt neck trauma to ensure early diagnosis. Initial cervical spine x-ray assessment should exclude both cervical spine fracture and local emphysema after blunt neck trauma. If patients with blunt neck trauma have evidence of a pneumomediastinum, the clinician should consider the possibility of aerodigestive injury.

Background: The objective of this study was to investigate the accuracy of diffusion-weighted whole-body imaging with background body signal suppression (DWIBS) as a diagnostic test for acute pyelonephritis (APN) in children. Methods: Among inpatients under 15 years of age in a primary care setting, we retrospectively reviewed the medical records for 29 febrile children subjected to DWIBS to confirm or exclude APN. To assess the diagnostic value of DWIBS, the subjects were divided into 13 patients clinically diagnosed with APN and 16 non-APN patients. DWIBS findings were divided into positive, indeterminate, and negative based on visual observation. Results: Likelihood ratios for positive, indeterminate, and negative prediction were 6.15 (95% CI, 1.90–19.97), 0.49 (95% CI, 0.13–1.83) and 0.14 (95% CI, 0.03–0.65), respectively. Conclusions: This study is the first to estimate the accuracy of DWIBS for the detection of APN. Initial DWIBS is a sensitive method for the diagnosis of APN and can improve diagnostic performance.

A ten-month-old male infant fell onto the floor from a chair of 50 cm in height and hit his head on the day before hospitalization. He was admitted due to acute subdural hematoma, which was associated with arachnoid cyst. Head CT conducted on the 4th day confirmed that the hematoma had not enlarged. After discharge, enlargement of the hematoma was detected on MR imaging conducted on the 65th day after injury, followed by the diminution without surgical treatment. MR images were obtained on the 192nd day. In the case of head injury associated with arachnoid cyst, the risk of subdural hematoma as well as its ensuing enlargement in subacute or chronic phase needs to be considered.

Gouty arthritis is uncommon in childhood and adolescence. On the other hand, there has been no report of cases with development of gouty arthritis with post-streptococcal acute glomerulonephritis (PSAGN) in pediatric patients. Here we report the case of a mildly obese 12-year-old boy with PSAGN complicated by gouty arthritis of the left first metatarsophalangeal joint. On follow-up, it was confirmed that as serum C3 level returned to normal, urinary excretion of uric acid increased and serum uric acid level decreased, thereby resolving the burning pain of the left big toe. In this case, not only did renal insufficiency associate with PSAGN but also mild obesity may have led to hyperuricemia and gouty arthritis. In conclusion, clinicians should be aware that PSAGN may be complicated by gouty arthritis in obese pediatric patients.