Regional and annual patterns in respiratory virus co-infection etiologies and antibiotic prescriptions for pediatric mycoplasma pneumoniae pneumonia

Objective: Mycoplasma pneumoniae (M. pneumoniae) pneumonia is the second-most common cause of community-acquired pneumonia (CAP). This study aimed at investigating into the prevalence of macrolide-resistant M. pneumoniae (MRMP) with respiratory virus co-infection and the antibiotic prescriptions in children with CAP in four provinces in Korea, and to assess the variations in the findings across regions and throughout the year. Patients and methods: This prospective study was conducted in 29 hospitals in Korea between July 2018 and June 2020. Among the enrolled 1,063 children with CAP, all 451 patients with M. pneumoniae underwent PCR assays of M. pneumoniae and respiratory viruses, and the presence of point mutations of residues 2063 and 2064 was evaluated. Results: Gwangju-Honam (88.6%) showed the highest prevalence of MRMP pneumonia, while Daejeon-Chungcheong (71.3%) showed the lowest, although the differences in prevalence were not significant (p=0.074). Co-infection of M. pneumoniae pneumonia and respiratory virus was observed in 206 patients (45.4%), and rhinovirus co-infection (101 children; 22.2%) was the most frequent. The prevalence of MRMP pneumonia with respiratory virus co-infection and the antibiotic prescriptions differed significantly among the four provinces (p 0.05) during the study period. Conclusions: The prevalence of M. pneumoniae pneumonia with virus co-infection and antibiotic prescriptions could differ according to region, although the MRMP pneumonia rate showed no difference within Korea.ope

Efficacy of glucocorticoids for the treatment of macrolide refractory mycoplasma pneumonia in children: meta-analysis of randomized controlled trials

Background: Mycoplasma pneumoniae is one of the most common pathogens causing community acquired pneumonia in children. Although the rate of macrolide-refractory Mycoplasma pneumoniae (MRMP) has increased, systemic glucocorticoids as a treatment option has not been validated yet. The purpose of this study was to assess the efficacy of glucocorticoids add-on in the treatment of MRMP in children through systematic review and meta-analysis. Methods: Data sources A systematic literature search was conducted using ten electronic bibliographic databases including English, Korean, Chinese and Japanese languages, up to March 8, 2018. Study selection The study was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist and selected randomized control trials which compared the efficacy of glucocorticoids add-on to macrolide in the treatment of MRMP in children. Data extraction Two independent reviewers extracted: primary outcomes as hospital days, fever duration, and change in C-reactive protein (CRP) and main analysis was performed through meta-analysis with random effects model. Results: Twenty-four unique randomized controlled trials met the inclusion criteria. The mean length of hospital stay in glucocorticoids treatment group was significantly shorter than that in conventional macrolide-treatment group (Weighted mean difference (WMD) = - 4.03 days). The mean length of fever duration was significantly shorter in the glucocorticoid treatment group in comparison with the conventional treatment group (WMD = -3.32 days). Level of CRP after treatment was significantly lower in the glucocorticoid treatment group than that in the conventional treatment group (WMD = -16.03). Sensitivity analysis and subgroup analysis showed no significant improvement in heterogeneity. As limitations of the study, most of the studies included were from a single country and we were unable to control for heterogeneity across interventions, lack of standardized measures, and different time points of assessments across studies. Conclusions: Glucocorticoid add-on treatment for MRMP can significantly shorten the duration of fever and hospital stay and decrease the level of CRP. These results should be confirmed by adequately powered studies in the future.ope

Clinical characteristics of pediatric patients infected with SARS-CoV-2 versus common human coronaviruses: a national multicenter study

Background: Human coronaviruses (HCoV) cause mild upper respiratory infections; however, in 2019, a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged, causing an acute respiratory disease pandemic. Coronaviruses exhibit marked epidemiological and clinical differences. Purpose: This study compared the clinical, laboratory, and radiographic findings of children infected with SARS-CoV-2 versus HCoV. Methods: SARS-CoV-2 data were obtained from the Korea Disease Control and Prevention Agency (KDCA) registry and 4 dedicated coronavirus disease 2019 (COVID-19) hospitals. Medical records of children admitted with a single HCoV infection from January 2015 to March 2020 were collected from 10 secondary/tertiary hospitals. Clinical data included age, sex, underlying disease, symptoms, test results, imaging findings, treatment, and length of hospital stay. Results: We compared the clinical characteristics of children infected with HCoV (n=475) to those of children infected with SARS-CoV-2 (272 from KDCA, 218 from COVID-19 hospitals). HCoV patients were younger than KDCA patients (older than 9 years:3.6% vs. 75.7%; P<0.001) and patients at COVID-19 hospitals (2.0±2.9 vs 11.3±5.3; P<0.001). Patients with SARS-CoV-2 infection had a lower rate of fever (26.6% vs. 66.7%; P<0.001) and fewer respiratory symptoms than those with HCoV infection. Clinical severity, as determined by oxygen therapy and medication usage, was worse in children with HCoV infection. Children and adolescents with SARS-CoV-2 had less severe symptoms. Conclusion: Children and adolescents with COVID-19 had a milder clinical course and less severe disease than those with HCoV in terms of symptoms at admission, examination find-ings, and laboratory and radiology results. © 2023 by The Korean Pediatric Society.ope

Continuous Renal Replacement Therapy (CRRT) in Children and the Specialized CRRT Team: A 14-Year Single-Center Study

Continuous renal replacement therapy (CRRT) has been used as an important intervention in critically ill children. Our center has the only specialized CRRT team (SCT) for children in Korea, which consists of pediatric intensivists, a pediatric nephrologist and CRRT-specialized-nurses. This study was a retrospective single-center analysis, including all pediatric patients admitted to the intensive care unit (ICU) of Severance hospital in Korea and received CRRT between 2003 and 2016, grouped as before SCT (group A, n = 51) and after SCT (group B, n = 212). We obtained the data for sex, age, weight, diagnosis, blood flow rate or type of CRRT machine used, administration of inotropic agents or anticoagulants, and ICU duration before CRRT (hours). A total of 263 patients were included. The age was significantly younger (p < 0.001) and blood flow rate was lower (p = 0.001) in group B than group A. Vasopressors (p < 0.001), continuous veno-venous hemodiafiltration (CVVHDF) (p < 0.001), nafamostat mesilate (p < 0.001), and extracorporeal membrane oxygenation (ECMO)-CRRT (p = 0.004) were more frequently used in group B. Based on our 14-year experience, we conclude that SCT operation could have played an important role in increasing the amount of CRRT utilization.ope

Validation of Pediatric Index of Mortality 3 for Predicting Mortality among Patients Admitted to a Pediatric Intensive Care Unit

Background : The objective of this study was to evaluate the usefulness of the newest version of the pediatric index of mortality (PIM) 3 for predicting mortality and validating PIM 3 in Korean children admitted to a single intensive care unit (ICU). Methods : We enrolled children at least 1 month old but less than 18 years of age who were admitted to the medical ICU between March 2009 and February 2015. Performances of the pediatric risk of mortality (PRISM) III, PIM 2, and PIM 3 were evaluated by assessing the area under the receiver operating characteristic (ROC) curve, conducting the Hosmer-Lemeshow test, and calculating the standardized mortality ratio (SMR). Results : In total, 503 children were enrolled; the areas under the ROC curve for PRISM III, PIM 2, and PIM 3 were 0.775, 0.796, and 0.826, respectively. The area under the ROC curve was significantly greater for PIM 3 than for PIM 2 (P<0.001) and PRISM III (P=0.016). There were no significant differences in the Hosmer-Lemeshow test results for PRISM III (P=0.498), PIM 2 (P=0.249), and PIM 3 (P=0.337). The SMR calculated using PIM 3 (1.11) was closer to 1 than PIM 2 (0.84). Conclusions : PIM 3 showed better prediction of the risk of mortality than PIM 2 for the Korean pediatric population admitted in the ICU.ope

Prescription Patterns and Burden of Pediatric Asthma in Korea

PURPOSE: This study aimed to estimate the prevalence, prescription pattern and burden of pediatric asthma in Korea by analyzing the National Health Insurance (NHI) claims data. METHODS: We retrospectively analyzed the insurance claim records from the Korean NHI claims database from January 2010 to December 2014. Asthmatic patients were defined as children younger than 18 years, with appropriate 10th Revision of the International Classification of Diseases codes (J45 or J46) and a prescription for 1 or more asthma maintenance medications at the same date. Hospitalization and emergency department visits for asthma were defined as use of short-acting beta₂-agonists during hospital visits among asthmatic patients. RESULTS: There were 1,172,807 asthmatic children in 2010, which increased steadily to 1,590,228 in 2014 in Korea. The prevalence showed an increasing trend annually for all ages. The mean prevalence by age in those older than 2 years decreased during the study period (from 39.4% in the 2-3 year age group to 2.6% in the 15-18 year age group). In an outpatient prescription, leukotriene receptor antagonists were the most commonly prescribed medication for all ages. Patients older than 6 years for whom inhaled corticosteroids were prescribed comprised less than 15% of asthmatic patients. The total direct medical cost for asthma between 2010 and 2014 ranged from $376 to$483 million. Asthma-related medical cost per person reached its peak in $366 in 2011 and decreased to$275 in 2014. CONCLUSIONS: The prevalence of pediatric asthma increased annually and decreased with age. Individual cost of asthma showed a decreasing trend in Korean children.ope

A deep learning model for real-time mortality prediction in critically ill children

BACKGROUND: The rapid development in big data analytics and the data-rich environment of intensive care units together provide unprecedented opportunities for medical breakthroughs in the field of critical care. We developed and validated a machine learning-based model, the Pediatric Risk of Mortality Prediction Tool (PROMPT), for real-time prediction of all-cause mortality in pediatric intensive care units. METHODS: Utilizing two separate retrospective observational cohorts, we conducted model development and validation using a machine learning algorithm with a convolutional neural network. The development cohort comprised 1445 pediatric patients with 1977 medical encounters admitted to intensive care units from January 2011 to December 2017 at Severance Hospital (Seoul, Korea). The validation cohort included 278 patients with 364 medical encounters admitted to the pediatric intensive care unit from January 2016 to November 2017 at Samsung Medical Center. RESULTS: Using seven vital signs, along with patient age and body weight on intensive care unit admission, PROMPT achieved an area under the receiver operating characteristic curve in the range of 0.89-0.97 for mortality prediction 6 to 60 h prior to death. Our results demonstrated that PROMPT provided high sensitivity with specificity and outperformed the conventional severity scoring system, the Pediatric Index of Mortality, in predictive ability. Model performance was indistinguishable between the development and validation cohorts. CONCLUSIONS: PROMPT is a deep model-based, data-driven early warning score tool that can predict mortality in critically ill children and may be useful for the timely identification of deteriorating patients.ope

Usefulness of bronchodilator response as an index of asthma control in children

Purpose: Assessing asthma control is important for proper management, and various indices for objective assessment of asthma control, such as fractional exhaled nitric oxide (FeNO) and asthma control test (ACT) score have been proposed. Recently, bronchodilator response (BDR) was reported as a marker of poor asthma control in adults. This study aimed to assess the usefulness of BDR as a biomarker for childhood asthma. Methods: A total of 305 children diagnosed with asthma were included. Spirometry with bronchodilator test was done at the time of diagnosis and about 14 months after asthma treatment. All children were evaluated by childhood asthma control test (c-ACT) and FeNO after asthma treatment. The patients were divided into 2 groups according to BDR results: the positive and negative BDR groups. Various biomarkers for asthma control, such as c-ACT, FeNO and changes of forced expiratory volume in 1 second (FEV1), were compared between the 2 groups. Results: Of the 305 patients, 143 (46.9%) were positive and 162 (53.1%) were negative for BDR. The BDR-positive group showed lower FEV1. In the BDR positive group, FEV1 was significantly increased after asthma treatment, especially in children with airflow limitation which was defined as below 80% of FEV1 or atopy. In atopic children, BDR showed a significant negative correlation with c-ACT and a positive correlation with FeNO. Conclusion: In asthmatic children with airflow limitation at the time of diagnosis, BDR can be a useful index for predicting improvement in lung function by asthma maintenance treatment. BDR could be a reliable marker for the assessment of asthma control in atopic children.ope

High-Sensitivity C-Reactive Protein Can Reflect Small Airway Obstruction in Childhood Asthma.

PURPOSE: High-sensitivity assays enabled the identification of C-reactive protein (hs-CRP) at levels that were previously undetectable. We aimed to determine if hs-CRP could reflect airway inflammation in children, by comparing hs-CRP with spirometry and impulse oscillometry (IOS) parameters and symptomatic severities. MATERIALS AND METHODS: A total of 276 asthmatic children who visited Severance Children's Hospital from 2012-2014 were enrolled. Serum hs-CRP and pulmonary function tests were performed on the same day. Patients were divided into hs-CRP positive and negative groups (cut-off value, 3.0 mg/L). RESULTS: Of the 276 asthmatic children [median age 7.5 (5.9/10.1) years, 171 boys (62%)], 39 were hs-CRP positive and 237 were negative. Regarding spirometry parameters, we observed significant differences in maximum mid-expiratory flow, % predicted (FEF₂₅₋₇₅) (p=0.010) between hs-CRP positive and negative groups, and a negative correlation between FEF₂₅₋₇₅ and hs-CRP. There were significant differences in the reactance area (AX) (p=0.046), difference between resistance at 5 Hz and 20 Hz (R5-R20) (p=0.027), resistance at 5 Hz, % predicted (R5) (p=0.027), and reactance at 5 Hz, % predicted (X5) (p=0.041) between hs-CRP positive and negative groups. There were significant positive correlations between hs-CRP and R5 (r=0.163, p=0.008), and X5 (r=0.164, p=0.007). Spirometry and IOS parameters had more relevance in patients with higher blood neutrophil levels in comparison to hs-CRP. CONCLUSION: Hs-CRP showed significant correlation with FEF₂₅₋₇₅, R5, and X5. It can reflect small airway obstruction in childhood asthma, and it is more prominent in neutrophil dominant inflammation.ope

Etiology and clinical feature of oral allergy syndrome in children

Purpose: Oral allergy syndrome (OAS) is a unique allergic reaction to fresh fruits or vegetables, which is caused by cross-reactivity between foods and pollens. This study was conducted to investigate the clinical feature of OAS and relevant pollen allergens as well as the association between them in Korean children. Methods: This single-center study included 290 children who were sensitized to pollens at Severance Hospital, and the clinical characteristics of children with and without OAS were compared. A multicenter study included 97 children who were diagnosed with OAS at 3 hospitals between January 2008 and June 2014. The details of clinical features were collected by retrospective medical record reviews using a standardized case report form. The relevant pollen allergens were identified by skin prick tests and/or serum specific IgE levels. Results: The most commonly sensitized allergen was Japanese hop in pollen-sensitized children. Children with OAS were most commonly sensitized to birch and oak, and 12.4% of the pollen-sensitized children had OAS in the single center. The number of children who were newly diagnosed with OAS has increased over the past 7 years. The most common causative food of OAS was apple. More than 60% of patients with OAS had oral allergic reactions to multiple foods. Conclusion: OAS may be relatively common in pollen-sensitized children. OAS should be considered in children with allergic disease and sensitization to pollens.ope