Beta-lactam allergy and drug challenge test in children: a systematic review and meta-analysis.

BACKGROUND: Most cases of beta-lactam allergy in children are likely to be mislabeled. This study aimed to assess the prevalence of true positives, as determined by drug challenge tests, and the rate of false negatives in children with suspected allergies and confirm the safety of the drug challenge test. METHODS: We conducted a systematic review and meta-analysis according to established procedures. Study participants were children with suspected beta-lactam allergy who underwent a drug challenge. PubMed MEDLINE, Dialog EMBASE, Cochrane Central Register of Controlled Trials, World Health Organization International Clinical Trials Registry Platform, and clinicaltrials.gov were searched from inception until March 5, 2021. RESULTS: The pooled prevalence of (a) positive results in the first challenge was 0.049 (95% CI, 0.041-0.057; I2 = 71%) from 78 studies; (b) serious adverse events was 0.00 (95% CI, 0.00-0.00; I2 = 0.0%) from 62 studies; and (c) positive results in the second challenge after the first negative result was 0.028 (95% CI, 0.016-0.043; I2 = 38%) from 18 studies. CONCLUSIONS: The prevalence of children with suspected beta-lactam allergy with true-positive results and false-negative results from the drug challenge test was very low. Serious adverse events resulting from drug challenge tests were also very rare. IMPACT: Most children with suspected beta-lactam allergy were likely to be mislabeled. Serious adverse events caused by the drug challenge test were rare. Few false-negative results were obtained from the drug challenge test.

Neonatal jaundice, phototherapy and childhood allergic diseases: An updated systematic review and meta-analysis.

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 METHODS: We sought published and unpublished observational studies through the major databases.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.

Severity of eczema and mental health problems in Japanese schoolchildren: The ToMMo Child Health Study.

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 < 0.001 for trend), adjusted for sex, school grade, current wheeze, and disaster-related factors, using normal eczema as a reference. The association between severity of eczema and four SDQ subcategories showed a similar trend (all P ≤ 0.017 for trend). CONCLUSIONS: We found a significant association between severity of eczema and mental health problems. The presence of eczema was associated with four SDQ subcategories.

Laryngeal Injury and Pneumomediastinum Due to Minor Blunt Neck Trauma: Case Report.

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.

[An infant with acute subdural hematoma after a minor head injury associated with arachnoid cyst].

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.

A Case With Typical Clinical Manifestations of Kawasaki Disease and Multisystem Inflammatory Syndrome in Children Temporally Associated With SARS-CoV-2 Infection.

Whether Kawasaki disease (KD) and multisystem inflammatory syndrome in children (MIS-C) temporally associated with SARS-CoV-2 infection are two distinct syndromes or part of the same spectrum is not fully understood. In this report, we present the case of a five-year-old boy who fully satisfied the diagnostic criteria for both KD and MIS-C associated with SARS-CoV-2 infection. He tested positive for SARS-CoV-2 on an oropharyngeal swab antigen test approximately four weeks before the onset of symptoms. He had severe abdominal pain. Abdominal ultrasound showed ascites. He improved with initial (2 g/kg) and additional (1 g/kg) intravenous immunoglobulin (IVIG) therapy and intravenous methylprednisolone (initial dose, 2 mg/kg/day). Our case may lead to clarification of the pathogenesis of both diseases. Additionally, the recent history of SARS-CoV-2 infection for children with prolonged fever and no clear focus of infection should be checked, and, if present, clinicians should consider MIS-C temporally associated with SARS-CoV-2 infection. IVIG therapy is important for children with MIS-C who meet the diagnostic criteria for KD, even if diagnosed with MIS-C.

Prevalence of Drug Fever among Cases of Nosocomial Fever: A Systematic Review and Meta-analysis.

Objective Drug fever is defined as a fever that temporally coincides with the start of a culprit drug and disappears after discontinuation of the drug. It is a common cause of nosocomial fever, which refers to a fever that develops beyond the first 48 h after hospital admission. However, the exact prevalence of drug fever among cases of nosocomial fever is unclear, as is the variation in prevalence depending on the clinical setting and most common causative drugs. Methods PubMed MEDLINE, Dialog EMBASE, Cochrane Central Register of Controlled Trials, World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov were systematically searched. Studies that reported the prevalence of drug fever in patients with nosocomial fever were included. Two of the four reviewers conducted independent assessments of the inclusion, data extraction, and quality. Pooled adjusted odds ratios were generated using a random-effects model and presented with 95% confidence intervals (CIs). Results Fifteen meta-analysis from 15 studies were included. Ten studies did not report the definition of drug fever or excluded febrile patients who were admitted to the hospital within 24-48 h. The pooled prevalence of drug fever among cases of nosocomial fever was 3.0% (95% CI, 0.6-6.8%), which was largely consistent across the settings, except for at oriental medicine hospital. Only four studies reported the causative agents, and antibiotics were the most frequently reported. Conclusions The prevalence of drug fever is low in patients with nosocomial fever. Clinicians should recognize that drug fever is a diagnosis of exclusion, even in cases of nosocomial fever.

Mortality After Hip and Spine Fractures in Patients With End-Stage Kidney Disease: A Systematic Review and Meta-Analysis.

Fractures represent a major cause of disability in the elderly, and patients with fractures exhibit a higher mortality rate than those without. Fractures are also an important health problem among patients with end-stage kidney disease (ESKD) requiring hemodialysis, peritoneal dialysis, or kidney transplantation. To the best of our knowledge, no study in the literature has yet quantitatively summarized the mortality rates, and a summary of evidence on post-hip and spine fracture mortality in patients with ESKD is lacking. The purpose of this study is to quantitatively evaluate the mortality rate, one-year mortality rate, and five-year mortality rate after hip and spine fractures in patients with ESKD receiving kidney replacement therapy. The MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), Embase, and ClinicalTrials.gov databases were comprehensively searched for reports on mortality rate and time-period mortality in patients with ESKD after hip or spine fractures up to June 2022. Prospective and retrospective cohort studies, as well as case series involving four or more patients, were included. Pooled mortality rate, one-year rate, and five-year mortality rate with 95% confidence intervals (CIs) were examined using a random-effects model. The risk of bias was assessed using the Joanna Briggs Institute (JBI) Prevalence Critical Appraisal Tool. Additionally, heterogeneity between studies was evaluated. A total of 26 studies were included in this meta-analysis. The one-year and five-year mortality rates after hip and spine fractures were 215.35-774.0 per 1,000 person-year and 148-194.1 per 1,000 person-year, respectively. After hip fractures, the one-year mortality rate was 27% (95% CI: 18-38%, I2 = 98%), whereas the five-year mortality rate was 56% (95% CI: 41-71%, I2 = 99%). After spine fractures, the one-year mortality rate was 10% (95% CI: 4-17%, I2 = 70%), whereas the five-year mortality rate was 48.3%. The post-fracture mortality rate was high in patients with ESKD, particularly within one year after the occurrence of fractures. Additionally, the five-year mortality rate after hip femoral or spine fractures was high at approximately 50%.

Prediction Models for Intravenous Immunoglobulin Resistance in Kawasaki Disease: A Meta-analysis.

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.

A Comparison Between the Efficacy and Safety of Endovascular Arteriovenous Fistula Creation and Surgical Fistula Creation: A Systematic Review and Meta-Analysis.

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.

Regional variation in the development of neonatal hyperbilirubinemia and relation with sunshine duration in Japan: an ecological study.

BACKGROUND: Few studies have investigated the regional variations in the development of neonatal hyperbilirubinemia. This study aimed to investigate regional variations in medical costs for neonatal hyperbilirubinemia and the correlations between sunshine duration and medical care costs for neonatal hyperbilirubinemia in an ecological study, using the National Database of Japan. METHODS: We obtained data on the annual medical costs for neonatal hyperbilirubinemia, annual live births, and annual sunshine duration in each prefecture from the National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB) Open Data, Vital Statistics in Japan, and System of Social and Demographic Statistics Prefectural Data Basic Data from 2014 to 2017. We created choropleth maps showing the regional variations (quartiles) in the annual medical costs for neonatal hyperbilirubinemia per 10 live births and the annual sunshine duration in each prefecture. We used Pearson's correlation coefficients to evaluate the associations between the annual sunshine duration and annual medical care costs for neonatal hyperbilirubinemia per 10 live births in each prefecture. RESULTS: The Tohoku region (on the Sea of Japan side) and the Hokuriku region were likely to have higher medical care costs for neonatal hyperbilirubinemia and shorter sunshine duration than the rest of the country. There were weak and negative correlations between the annual sunshine duration and the annual medical care costs for neonatal hyperbilirubinemia. The correlation coefficients ranged from -0.086 to -0.33. CONCLUSION: There could be regional variations in the medical care costs for neonatal hyperbilirubinemia in Japan. Short sunshine duration could be a prognostic factor for the development of neonatal hyperbilirubinemia.

Routine varicella vaccination program and hospitalization for herpes zoster in Japan.

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.

Comparison of Machine Learning Models for Prediction of Initial Intravenous Immunoglobulin Resistance in Children With Kawasaki Disease.

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.

Effectiveness of seasonal inactivated influenza vaccination in Japanese schoolchildren: an epidemiologic study at the community level.

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.

Clustering by phenotype and genome-wide association study in autism.

Autism 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. We 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 data set 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 data set of 712 probands and 354 controls in the replication stage. In the preliminary study, which was conducted in conventional GWAS design, 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 < 5.0 × 10-8. 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. These findings suggest that clustering may successfully identify subgroups with relatively homogeneous disease etiologies. Further cluster validation and replication studies are warranted in larger cohorts.

Association of Feeding Practice with Childhood Overweight and/or Obesity in Affected Areas Before and After the Great East Japan Earthquake.

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 breastfeeding with childhood overweight and/or obesity in areas affected by the Great East Japan Earthquake. Materials and Methods: From health examination records of 15,563 children, we retrospectively obtained anthropometric and feeding practice (formula, mixed, and breastfeeding) data during early childhood. According to their age at the time of the earthquake, we subdivided the children into study groups 1 (42-48 months), 2 (18-24 months), and 3 (<3 months). Overweight, obesity, and underweight were defined on the basis of body mass index. To assess the association between feeding practice at 3 months of age and the risk of overweight and/or obesity at 3 years of age, we developed generalized linear mixed models that included a random effect of the municipality of residence; for this analysis, we combined "mixed feeding" and "formula feeding" into a single category: "mixed plus formula feeding." Results: Mixed- plus formula-fed children had a significantly higher risk of overweight and/or obesity than breastfed children in all three study groups (odds ratios, 1.20-2.22; all p ≤ 0.047). The rate of underweight at 3 years of age was ≤0.3%, irrespective of feeding practices. Conclusion: Breastfeeding, even during a large-scale natural disaster in a developed country, maintained its protective effect against overweight and/or obesity in childhood.