Background: We aimed to analyze the effects of an antimicrobial stewardship program (ASP) on the proportion of antimicrobial-resistant pathogens in bacteremia, antimicrobial use, and mortality in pediatric patients. Methods: A retrospective single-center study was performed on pediatric inpatients under 19 years old who received systemic antimicrobial treatment from 2001 to 2019. A pediatric infectious disease attending physician started ASP in January 2008. The study period was divided into the pre-intervention (2001–2008) and the post-intervention (2009–2019) periods. The amount of antimicrobial use was defined as days of therapy per 1,000 patientdays, and the differences were compared using delta slope (= changes in slopes) between the two study periods by an interrupted time-series analysis. The proportion of resistant pathogens and the 30-day overall mortality rate were analyzed by the χ2 . Results: The proportion of extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae bacteremia increased from 17% (39 of 235) in the pre-intervention period to 35% (189 of 533) in the post-intervention period (P < 0.001). The total amount of antimicrobial use significantly decreased after the introduction of ASP (delta slope value = −16.5; 95% confidence interval [CI], −30.6 to −2.3; P = 0.049). The 30-day overall mortality rate in patients with bacteremia did not increase, being 10% (55 of 564) in the pre-intervention and 10% (94 of 941) in the post-intervention period (P = 0.881). Conclusion The introduction of ASP for pediatric patients reduced the delta slope of the total antimicrobial use without increasing the mortality rate despite an increased incidence of ESBL-producing gram-negative bacteremia.

Objectives: The Panbio COVID-19 Ag Rapid Test Device (Panbio COVID-19 Ag, Abbott Rapid Diagnostics) is a lateral flow immunochromatographic assay targeting the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleoprotein in nasopharyngeal specimens for the diagnosis of coronavirus disease 2019 (COVID-19). This study aimed to verify the performance of the Panbio COVID-19 Ag for implementation in clinical laboratories. Methods: Sixty nasopharyngeal swab specimens (30 positive and 30 negative) dipped in transport medium, and COVID-19 was confirmed using real-time RT-PCR using Allplex SARS-CoV-2 assay (Seegene), were tested using the Panbio COVID-19 Ag. Reproducibility was evaluated using positive and negative control materials. Sensitivity and specificity were calculated based on the results of realtime RT-PCR as the standard test method. Results: Reproducibility was confirmed by the consistent results of repeated tests of the quality control materials. The overall sensitivity and specificity of Panbio COVID-19 Ag were 50.0% and 100.0%, respectively. Panbio COVID-19 Ag demonstrated high sensitivity (88.2%) in analyzing the detection limit cycle threshold (Ct) value of 26.67 provided by the manufacturer as a positive criterion, and the sensitivity was 100.0% for the positive criterion of Ct values <25, although it was less sensitive for Ct ≥ 25. Conclusion Considering the high sensitivity for positive samples with Ct values <25 and the rapid turnaround of results, Panbio COVID-19 Ag can be used in clinical laboratories to diagnose COVID-19 in limited settings.

Purpose: We performed this study to determine whether the degree of neutropenia after the first chemotherapy cycle can be used as a surrogate marker of individual susceptibility to chemotherapeutic agents affecting treatment outcome in patients with neuroblastoma. Materials and Methods: The study included 313 patients who received the first cycle chemotherapy with a CEDC (cisplatin+etoposide+doxorubicin+cyclophosphamide) regimen and had absolute neutrophil count (ANC) data available. The cumulative incidences of progression and treatment-related mortality (TRM) were estimated. To identify genetic variations associated with the ANC, a genome-wide association study (GWAS) was performed. Results: An ANC of 32.5/μL was determined as the cutoff point to categorize patients into the good and poor prognosis subgroups in terms of progression. Patients with a high nadir ANC had a higher cumulative incidence of progression than those with a low nadir ANC (p < 0.001). In multivariate analysis, high nadir ANC, age, bone marrow involvement, and unfavorable histology were poor prognostic factors. With regard to the TRM, patients with a low nadir ANC (ANC < 51.0/μL) had a higher cumulative incidence of TRM than those with a high nadir ANC (p=0.010). In GWAS, single-nucleotide polymorphisms of LPHN2 and CRHR1 were significantly associated with the nadir ANC. Conclusion In neuroblastoma patients, the degree of neutropenia after the first chemotherapy cycle can be used as a surrogate marker to predict an individual’s susceptibility to chemotherapeutic agents. Tailoring of treatment based on the degree of neutropenia needs to be considered.

We aimed to investigate associations of dietary diversity (DD) with gut microbial diversity and the development of hen's egg allergy (HEA) in infants. We enrolled 68 infants in a highrisk group and 32 infants in a control group based on a family history of allergic diseases. All infants were followed from birth until 12 months of age. We collected infant feeding data, and DD was defined using 3 measures: the World Health Organization definition of minimum DD, food group diversity, and food allergen diversity. Gut microbiome profiles and expression of cytokines were evaluated by bacterial 16S rRNA sequencing and real-time reverse transcriptase-polymerase chain reaction. High DD scores at 3 and 4 months were associated with a lower risk of developing HEA in the high-risk group, but not in the control group. In the high-risk group, high DD scores at 3, 4, and 5 months of age were associated with an increase in Chao1 index at 6 months. We found that the gene expression of IL-4, IL-5, IL-6, and IL-8 were higher among infants who had lower DD scores compared to those who had higher DD scores in high-risk infants. Additionally, high-risk infants with a higher FAD score at 5 months of age showed a reduced gene expression of IL-13. Increasing DD within 6 months of life may increase gut microbial diversity, and thus reduce the development of HEA in infants with a family history of allergic diseases.

Objectives: ：The high lifetime prevalence of depression in Korea is related to problems such as suicide and decreased productivity, as well as the cost of disease due to increased use of medical services, which can cause great socioeconomic loss. Therefore, in this study, the burden of disease of depression and the importance of managing mental health diseases, which are increasing day by day, are suggested to be helpful in determining priorities in health policy establishment. Methods: ：In this study, the socio-economic cost of depression was calculated by dividing it into direct cost and indirect cost. For statistical data, data from the National Health Insurance Service of the public and statistics on diseases of national interest were mainly used. Results: ：As a result, the socio-economic cost of depression in 2019 estimated in this study was calculated to be a total of KRW 4.83 trillion, with direct costs 692.9 billion won and indirect costs 4.13 trillion won. Among them, the cost due to decrease in work performance accounted for the largest portion, accounting for 65.5%. Conclusions ：As the socio-economic burden due to depression is expected to increase in the future, it is necessary to establish a systematic funding plan for the treatment and management of depressed patients in daily life.

Background: and PurposeSleep disturbance is common in patients with primary headache disorders. We were interest in whether poor sleep quality affects patients directly or via increases in the frequency and severity of headaches. To that end, we investigated the direct and indirect effects of sleep quality on the headache-related impact among patients with primary headache disorders. Methods: We analyzed migraine and tension-type headache (TTH) in patients included in the headache registry of our headache clinic from October 2015 to May 2018. We collected information on the headache frequency, severity, and psychological status. Sleep quality and headache-related impact were measured using the Pittsburgh Sleep Quality Index and Headache Impact Test-6, respectively. We performed path analyses with headache frequency and severity as covariates to determine the direct effect of sleep quality on the headache-related impact, and the indirect effects mediated by increases in the headache frequency and severity. Results: This study included 915 patients: 784 with migraine and 131 with TTH. Worse sleep quality was independently associated with greater headache-related impact in both patients with migraine and those with TTH. Path analysis revealed a direct effect (β=0.207,p<0.001) of sleep quality and an indirect effect mediated by headache frequency and severity (β=0.067, p=0.004) on the headache-related impact in migraine. In TTH, only direct effects of sleep quality on the headache-related impact were significant (β=0.224, p=0.004). Conclusions We suggest that poor sleep quality can directly increase the headache-related impact in both patients with migraine and TTH as well as indirectly by increasing the headache frequency and severity in patients with migraine.

There have been few studies investigating the association between atopic dermatitis (AD) and prenatal exposure to heavy metals. We aimed to evaluate whether prenatal exposure to heavy metals is associated with the development or severity of AD in a birth cohort study. A total of 331 subjects were followed from birth for a median duration of 60.0 months. The presence and severity of AD were evaluated at ages 6 and 12 months, and regularly once a year thereafter. The concentrations of lead, mercury, chromium, and cadmium in umbilical cord blood were measured by inductively coupled plasma mass spectrometry. Cord blood mononuclear cells (CBMCs) were isolated and stimulated for analysis of cytokine production using ELISA. Heavy metal levels in cord blood were not associated with the development of AD until 24 months of age. However, a positive correlation was observed between the duration of AD and lead levels in cord blood (p=0.002). AD severity was also positively associated with chromium concentrations in cord blood (p=0.037), while cord blood levels of lead, mercury, and cadmium were not significantly associated with AD severity (p=0.562, p=0.054, and p=0.055, respectively). Interleukin-13 production in CBMCs was positively related with lead and chromium levels in cord blood (p=0.021 and p=0.015, respectively). Prenatal exposure to lead and chromium is associated with the persistence and severity of AD, and the immune reaction toward a Th2 polarization.
Cacao ; Cadmium ; Chromium ; Cohort Studies ; Dermatitis, Atopic ; Enzyme-Linked Immunosorbent Assay ; Fetal Blood ; Interleukin-13 ; Mass Spectrometry ; Metals, Heavy ; Parturition ; Plasma ; Umbilical Cord

OBJECTIVE: Extrapyramidal signs (EPS) are common in patients with mild cognitive impairment (MCI). However, few studies have assessed the effect of EPS on the clinical course of MCI. We aimed to evaluate whether patients with EPS show more frequent progression from MCI to Alzheimer's disease (AD) and to other types of dementia. METHODS: Participants (n=882) with MCI were recruited, and were followed for up to 5 years. The EPS positive group was defined by the presence of at least one EPS based on a focused neurologic examination at baseline. RESULTS: A total of 234 converted to dementia during the follow-up period. The risk of progression to AD was lower in the patients with EPS after adjusting for potential confounders [hazard ratio (HR)=0.70, 95% confidence interval (CI)=0.53–0.93, p=0.01]. In contrast, the patients with EPS had a six-fold elevated risk of progression to dementia other than AD (HR=6.33, 95%CI=2.30–17.39, p < 0.001). CONCLUSION: EPS in patients with MCI is a strong risk factor for progression of MCI to non-Alzheimer dementia. The careful neurologic examination for EPS in patients with MCI can yield important clinical information for prognosis.
Alzheimer Disease ; Dementia* ; Follow-Up Studies ; Humans ; Korea* ; Mild Cognitive Impairment* ; Neurologic Examination ; Prognosis ; Risk Factors

The present study aimed to investigate the distribution of total serum immunoglobulin E (IgE) levels in Korean schoolchildren and to evaluate its utility in the prediction of atopy and allergic diseases. A nationwide, cross-sectional survey was conducted in first grade students from randomly selected elementary and middle schools. Total IgE levels were measured by ImmunoCAP. Skin prick tests were performed for 18 common inhalant allergens to determine the presence of atopy. Children aged 12–13 years and parents of children aged 6–7 years were asked to complete questionnaire assessing allergic diseases. The cut-off levels of total IgE were determined by analyzing receiver operating characteristic curves. The median total IgE level was 86.7 kU/L (range: 1.5–4,523.1) in 3,753 children aged 6–7 years and 94.7 kU/L (range: 1.5–3,000.0) in 3,930 children aged 12–13 years. Total IgE concentrations were higher in children with atopy or allergic diseases than in those without (all P < 0.001). At the cut-off value of 127.7 kU/L, sensitivity, specificity, and positive and negative predictive values (PPV and NPV) were 67.1%, 75.4%, 65.4%, and 76.7%, respectively, in elementary schoolchildren. At the cut-off value of 63.0 kU/L, sensitivity, specificity, PPV, and NPV were 81.9%, 66.6%, 75.0%, and 75.1%, respectively, in middle schoolchildren. PPV and NPV were ≥ 70% when cut-offs of 258.8 kU/L and 38.4 kU/L were used for the diagnosis of atopy in 6–7 year-olds and 12–13 year-olds, respectively. This nationwide population-based study provided the first normal reference ranges of total IgE in Korean schoolchildren.
Allergens ; Child ; Cross-Sectional Studies ; Diagnosis ; Humans ; Hypersensitivity ; Immunoglobulin E* ; Immunoglobulins* ; Korea ; Parents ; Reference Values* ; ROC Curve ; Sensitivity and Specificity ; Skin

BACKGROUND AND PURPOSE: Patients with active cancer are at an increased risk for stroke. Hypercoagulability plays an important role in cancer-related stroke. We aimed to test whether 1) hypercoagulability is a predictor of survival, and 2) correction of the hypercoagulable state leads to better survival in patients with stroke and active cancer. METHODS: We recruited consecutive patients with acute ischemic stroke and active systemic cancer between January 2006 and July 2015. Hypercoagulability was assessed using plasma D-dimer levels before and after 7 days of anticoagulation treatment. The study outcomes included overall and 1-year survival. Plasma D-dimer levels before and after treatment were tested in univariate and multivariate Cox regression models. We controlled for systemic metastasis, stroke mechanism, age, stroke severity, primary cancer type, histology, and atrial fibrillation using the forward stepwise method. RESULTS: A total of 268 patients were included in the analysis. Patients with high (3rd–4th quartiles) pre-treatment plasma D-dimer levels showed decreased overall and 1-year survival (adjusted HR, 2.19 [95% CI, 1.46–3.31] and 2.70 [1.68–4.35], respectively). After anticoagulation treatment, post-treatment D-dimer level was significantly reduced and independently associated with poor 1-year survival (adjusted HR, 1.03 [95% CI, 1.01–1.05] per 1 μg/mL increase, P=0.015). The successful correction of hypercoagulability was a protective factor for 1-year survival (adjusted HR 0.26 [CI 0.10–0.68], P=0.006). CONCLUSIONS: Hypercoagulability is associated with poor survival after stroke in patients with active cancer. Effective correction of hypercoagulability may play a protective role for survival in these patients.
Atrial Fibrillation ; Humans ; Methods ; Mortality* ; Neoplasm Metastasis ; Plasma ; Prognosis ; Protective Factors ; Stroke* ; Thrombophilia*