Search

Background: The Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is known to be more infectious and less severe than the other variants. Despite the increasing number of symptomatic patients, severe neurological complications in children with the Omicron variant have been reported rarely, unlike with wild-type or Delta variants. This study aimed to investigate severe neurological complications in children with Omicron variant infection., Methods: We conducted a retrospective study of 17 pediatric patients with severe neurological manifestations associated with coronavirus disease 2019 in Korea during the Omicron variant prevalence, from January 1 to April 30, 2022., Results: Among the 17 patients, 11 had pre-existing neurological disabilities and nine met the criteria for multisystem inflammatory syndrome in children (MIS-C). Four of the five vaccine-eligible patients (12 years and older) were unvaccinated. Severe neurological manifestations included acute necrotizing encephalopathy, acute fulminant cerebral edema, acute disseminated encephalomyelitis, basal ganglia encephalitis, unclassified severe encephalopathy/encephalitis, and refractory status dystonicus. Patients with MIS-C and underlying neurological disabilities had longer median hospital and intensive care unit stays compared with those without these conditions. Five patients survived with new neurological deficits at the one-year follow-up, and three died, all of whom had underlying neurological disabilities., Conclusions: This study shows that severe neurological complications in pediatric patients with the Omicron variant of SARS-CoV-2 occur infrequently but may lead to significant morbidity and mortality, especially among those with pre-existing neurological disabilities and unvaccinated individuals. Continued efforts are necessary to prevent and manage such complications in these vulnerable populations., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: We examined how responsibility (the "duty to inform relatives about genetic testing results") is understood and enacted among Swiss and Korean women carrying BRCA1 or BRCA2 pathogenic variants., Methods: In-depth interviews and/or focus groups with 46 Swiss and 22 Korean carriers were conducted, using an identical interview guide. Data were analyzed inductively and translated into English for cross-country comparisons., Results: We identified five modes of responsibility in both samples: Persuader, Enabler, Relayer, Delayer, and Decliner. The Enabler and Relayer modes were the most common in both countries. They followed the rational imperative of health and norms of competence and self-determination, respectively. The Relayer mode transmitted information without trying to influence relatives' decisions. The Delayer and Decliner modes withheld information, deeming it the best way to safeguard the family during that specific moment of its trajectory. Responsibility to disclose testing results was influenced by culturally diverging conceptions of the family unit and socio-contextual norms., Conclusion: Responsibility primarily reflects the imperative of health prevention; findings demonstrate various interpretations, including the sense of family caring achieved through controlled disclosure of genetic information., Practice Implications: Findings offer healthcare providers socio-anthropological insights to assist probands navigate the disclosure of genetic information within their families., Trial Registration Number: NCT04214210 (registered Nov 2, 2020), KCT 0005643 (registered Nov 23, 2020)., Competing Interests: Declaration of Competing Interest None, (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

The Korean Genetic Diagnosis Program for Rare Disease (KGDP) enrolled 1890 patients with rare diseases between March 2017 and October 2022. Children and adolescents accounted for the majority of the patients, and systemic disease was the most common presenting symptom. The exome-based virtual disease-specific multigene panel was the most frequently used analytical method, with an overall diagnostic yield of 33.3%. A total of 629 positive cases were diagnosed, involving 297 genes. All 297 genes identified in these cases were confirmed to be known genes listed in the OMIM database. The nationwide KGDP network and its cooperation with the Korean Undiagnosed Diseases Program (KUDP) provide a more comprehensive genetic analysis of undiagnosed cases. The partnership between the KGDP and KUDP has the potential to improve the diagnosis and treatment options for patients. In conclusion, KGDP serves as the primary access point or gateway to KUDP., (© 2023. The Author(s), under exclusive licence to European Society of Human Genetics.)

α-Dystroglycanopathies are a clinically and genetically heterogeneous group of muscular dystrophies associated with the defective glycosylation of α-dystroglycan (α-DG). Eighteen genes associated with α-dystroglycanopathies have been identified, and the relative prevalence of genetic subtypes varies with ethnicity. Here, we investigated the clinical and genetic characteristics of α-DG-related muscular dystrophy in the Korean pediatric population. We analyzed the clinical characteristics and variant profiles of 42 patients with α-DG-related muscular dystrophies diagnosed by either reduced glycosylation of α-DG and/or genetic confirmation. Genotype-phenotype correlations were explored by a retrospective medical record review. The muscle-eye-brain disease/Fukuyama congenital muscular dystrophy was the most common phenotype (28/42, 66.7%). Homozygous or compound heterozygous variants were detected in 37 patients belonging to 34 unrelated families (37/42; 88.1%). Pathogenic variants were identified in FKTN (n = 24), POMGNT1 (n = 4), GMPPB (n = 4), FKRP (n = 2), POMT1 (n = 2), and ISPD (n = 1). Compound heterozygous retrotransposal insertions and deep-intronic variants in FKTN were the most common genotypes and were associated with severe phenotypes. This study suggests that α-DG-related muscular dystrophy has a wide range of genotypes and phenotypes according to ethnicity. A stratified genetic test according to ethnicity should be considered to diagnose α-DG-related muscular dystrophy., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have influenced the work reported in this study., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Phase I of the Korean Undiagnosed Diseases Program (KUDP), performed for 3 years, has been completed. The Phase I program aimed to solve the problem of undiagnosed patients throughout the country and develop infrastructure, including a data management system and functional core laboratory, for long-term translational research. Herein, we share the clinical experiences of the Phase I program and introduce the activities of the functional core laboratory and data management system., Results: During the program (2018-2020), 458 patients were enrolled and classified into 3 groups according to the following criteria: (I) those with a specific clinical assessment which can be verified by direct testing (32 patients); (II) those with a disease group with genetic and phenotypic heterogeneity (353 patients); and (III) those with atypical presentations or diseases unknown to date (73 patients). All patients underwent individualized diagnostic processes based on the decision of an expert consortium. Confirmative diagnoses were obtained for 242 patients (52.8%). The diagnostic yield was different for each group: 81.3% for Group I, 53.3% for Group II, and 38.4% for Group III. Diagnoses were made by next-generation sequencing for 204 patients (84.3%) and other genetic testing for 35 patients (14.5%). Three patients (1.2%) were diagnosed with nongenetic disorders. The KUDP functional core laboratory, with a group of experts, organized a streamlined research pipeline covering various resources, including animal models, stem cells, structural modeling and metabolic and biochemical approaches. Regular data review was performed to screen for candidate genes among undiagnosed patients, and six different genes were identified for functional research. We also developed a web-based database system that supports clinical cohort management and provides a matchmaker exchange protocol based on a matchbox, likely to reinforce the nationwide clinical network and further international collaboration., Conclusions: The KUDP evaluated the unmet needs of undiagnosed patients and established infrastructure for a data-sharing system and future functional research. The advancement of the KUDP may lead to sustainable bench-to-bedside research in Korea and contribute to ongoing international collaboration., (© 2022. The Author(s).)

Background: We aimed to examine the delay in antiviral initiation in rapid antigen test (RAT) false-negative children with influenza virus infection and to explore the clinical outcomes. We additionally conducted a medical cost-benefit analysis., Methods: This single-center, retrospective study included children (aged < 10 years) with influenza-like illness (ILI), hospitalized after presenting to the emergency department during three influenza seasons (2016-2019). RAT-false-negativity was defined as RAT-negative and polymerase chain reaction-positive cases. The turnaround time to antiviral treatment (TAT) was from the time when RAT was prescribed to the time when the antiviral was administered. The medical cost analysis by scenarios was also performed., Results: A total of 1,430 patients were included, 7.5% were RAT-positive (n = 107) and 2.4% were RAT-false-negative (n = 20). The median TAT of RAT-false-negative patients was 52.8 hours, significantly longer than that of 4 hours in RAT-positive patients (19.2-100.1, P < 0.001). In the multivariable analysis, TAT of ≥ 24 hours was associated with a risk of severe influenza infection and the need for mechanical ventilation (odds ratio [OR], 6.8, P = 0.009 and OR, 16.2, P = 0.033, respectively). The medical cost varied from $11.7-187.3/ILI patient., Conclusion: Antiviral initiation was delayed in RAT-false-negative patients. Our findings support the guideline that children with influenza, suspected of having severe or progressive infection, should be treated immediately., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2022 The Korean Academy of Medical Sciences.)

Background: Quality of life (QOL) has become an important indicator for evaluating patients' symptoms and their overall satisfaction with life. Thus, examining QOL is essential for fully understanding the life satisfaction of breast cancer survivors (BCS). However, selecting the appropriate instrument for QOL measurement is challenging, and few studies have compared disease-specific and generic QOL measures and how they reflect the impact of cancer-related symptoms on QOL in BCS. We examined QOL in BCS using both disease-specific and generic instruments and compared their representation of the QOL impacts of anxiety, depression, sleep, fatigability, and posttraumatic growth., Methods: This study involved analysis of follow-up data for an exercise intervention called the BLESS (Better Life after cancer, Energy, Strength, and Support) program, which included 40 BCS treated at 1 medical center in South Korea. Their QOL was assessed using both the Functional Assessment of Cancer Therapy-Breast (FACT-B) and Quality of Life Index (QLI)., Results: Both FACT-B and QLI total scores revealed that Korean BCS had low levels of QOL. Furthermore, both FACT-B and QLI total scores were significantly related to anxiety, depression, sleep, fatigability, and posttraumatic growth in the participants. Notably, multivariate regression analysis of FACT-B and QLI total scores showed different predictors for QOL: with the FACT-B, depression was the only significant predictor, while with the QLI, posttraumatic growth was the only significant predictor., Conclusion: The selection of a given QOL instrument may affect the overall findings and interpretation of the impacts of related symptoms. The FACT-B should be considered for studies of symptoms such as depression, while the QLI is more appropriate for examining overall QOL and posttraumatic growth.

Abstract: Asthma is a heterogeneous disease characterized by chronic airway inflammation with a genetic predisposition. Butyrophilin-like 2 (BTNL2) is a member of the immunoglobulin superfamily that plays an important role in regulating T cell activation and immune homeostasis. Here, we aimed to investigate the association of the genetic variants of BTNL2 with childhood asthma and asthma-related traits by utilizing extreme asthma phenotypes and employing a genome-wide association study. Our study included 243 children with well-defined moderate to severe atopic asthma and 134 healthy children with no history of allergic diseases and allergic sensitization. DNA from these subjects was genotyped using AxiomTM Genome-Wide Array Plates. Although no single nucleotide polymorphisms (SNPs) reached a genome-wide threshold of significance, 3 SNPs, rs3817971, rs41355746, and rs41441651, at BTNL2 were significantly associated with moderate to severe atopic asthma after performing Bonferroni correction. These SNPs were also associated with the risk of allergic sensitization toward house dust mites and the presence and degree of bronchial hyperresponsiveness. Thus, we identified that BTNL2 was associated with atopic moderate to severe persistent asthma in Korean children, and this may play an important role in disease development and susceptibility., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background Breast density at mammography is an established risk factor for breast cancer, but it cannot be used to distinguish between glandular and fibrous tissue. Purpose To evaluate the association between the glandular tissue component (GTC) at screening breast US and the risk of future breast cancer in women with dense breasts and the association between the GTC and lobular involution. Materials and Methods Screening breast US examinations performed in women with no prior history of breast cancer and with dense breasts with negative findings from mammography from January 2012 to December 2015 were retrospectively identified. The GTC was reported as being minimal, mild, moderate, or marked at the time of the US examination. In women who had benign breast biopsy results, the degree of lobular involution in normal background tissue was categorized as not present, mild, moderate, or complete. The GTC-related breast cancer risk in women with a cancer diagnosis or follow-up after 6 months was estimated by using Cox proportional hazards regression. Cumulative logistic regression was used to evaluate the association between the GTC and lobular involution. Results Among 8483 women (mean age, 49 years ± 8 [standard deviation]), 137 developed breast cancer over a median follow-up time of 5.3 years. Compared with a minimal or mild GTC, a moderate or marked GTC was associated with an increased cancer risk (hazard ratio, 1.5; 95% CI: 1.05, 2.1; P = .03) after adjusting for age and breast density. The GTC had an inverse association with lobular involution; women with no, mild, or moderate involution had greater odds (odds ratios of 4.9 [95% CI: 1.5, 16.6], 2.6 [95% CI: 0.95, 7.2], and 1.8 [95% CI: 0.7, 4.6], respectively) of a moderate or marked GTC than those with complete involution ( P = .004). Conclusion The glandular tissue component was independently associated with the future breast cancer risk in women with dense breasts and reflects the lobular involution. It should be considered for risk stratification during screening breast US. © RSNA, 2021 Online supplemental material is available for this article.

Background: Rubinstein-Taybi syndrome (RSTS) is a rare congenital malformation syndrome with clinical characteristics such as hypertrichosis, high arched eyebrows, large beaked nose, and broad thumbs and halluces. RSTS patients showed intellectual disability and health problems such as short stature, ophthalmologic abnormalities, congenital heart defects, genitourinary defects, and variable types of tumors. Although mutations in CREBBP and EP300 genes are associated with RSTS features, genetic causation is still unknown in 30% of patients., Methods: We present clinical and molecular genetic characteristics of 25 unrelated Korean patients clinically diagnosed with RSTS. Sanger sequencing analysis and multiplex ligation-dependent probe amplification for CREBBP in 25 patients and exome sequencing of CREBBP-negative cases were performed in nine patients successively., Results: Causative variants were identified in 20 (80%) patients: 16 (64%) in CREBBP and 4 (16%) in EP300. All the identified variants predict protein truncation (11 frameshift, 2 nonsense, 1 splicing-site, and 6 large intragenic deletions); there are no repeatedly identified sequence variants. Four of the CREBBP and all four EP300 variants are novel. Intellectual disability was noted in 24/25 patients (96%); no difference was found between CREBBP and EP300 groups. One patient with a CREBBP variant (4%) had malignant tumor., Conclusions: To date, this is the largest cohort of patients with RSTS including EP300-related patients in Korea. Future large-scale studies to find genetic mutation of molecularly unsolved patients and long-term prospective studies are required to validate our results., (© 2021 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.)

Abstract: Low specificity and operator dependency are the main problems of breast ultrasound (US) screening. We investigated the added value of deep learning-based computer-aided diagnosis (S-Detect) and shear wave elastography (SWE) to B-mode US for evaluation of breast masses detected by screening US.Between February 2018 and June 2019, B-mode US, S-Detect, and SWE were prospectively obtained for 156 screening US-detected breast masses in 146 women before undergoing US-guided biopsy. S-Detect was applied for the representative B-mode US image, and quantitative elasticity was measured for SWE. Breast Imaging Reporting and Data System final assessment category was assigned for the datasets of B-mode US alone, B-mode US plus S-Detect, and B-mode US plus SWE by 3 radiologists with varied experience in breast imaging. Area under the receiver operator characteristics curve (AUC), sensitivity, and specificity for the 3 datasets were compared using Delong's method and McNemar test.Of 156 masses, 10 (6%) were malignant and 146 (94%) were benign. Compared to B-mode US alone, the addition of S-Detect increased the specificity from 8%-9% to 31%-71% and the AUC from 0.541-0.545 to 0.658-0.803 in all radiologists (All P < .001). The addition of SWE to B-mode US also increased the specificity from 8%-9% to 41%-75% and the AUC from 0.541-0.545 to 0.709-0.823 in all radiologists (All P < .001). There was no significant loss in sensitivity when either S-Detect or SWE were added to B-mode US.Adding S-Detect or SWE to B-mode US improved the specificity and AUC without loss of sensitivity., Competing Interests: The authors have no conflicts of interests to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: Autosomal dominant (AD) guanosine triphosphate cyclohydrolase 1 (GCH1) deficiency is the most common cause of dopa-responsive dystonia (DRD). Patients with GCH1 deficiency are likely to experience diagnostic delay, but its consequences have not been described thoroughly in patients with early-onset disease. We describe the diagnostic delay and residual motor signs (RMS) observed in patients with early-onset (before 15 years of age) disease., Methods: Twelve patients with early-onset AD GCH1 deficiency from a single center were included in the case series analysis. For the meta-analysis, the PubMed database was searched for articles on early-onset AD GCH1 deficiency published from 1995 to 2019., Results: In the case series, the mean duration of diagnostic delay was 5.6 years. Two patients exhibited RMS, and four patients underwent orthopedic surgery. The literature search yielded 137 AD GCH1 deficiency cases for review; gait disturbance was reported in 92.7% of patients, diurnal fluctuation of symptoms in 91.9%, and RMS in 39%. The mean duration of diagnostic delay was 14.6 years overall: 12.0 years in RMS-negative patients and 21.2 years in RMS-positive patients., Conclusions: Diagnostic delay in early-onset AD GCH1 deficiency is more closely associated with later RMS. Early clinical suspicion, timely diagnosis, and levodopa treatment may reduce the occurrence of RMS in patients with early-onset AD GCH1 deficiency., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021. Published by Elsevier B.V.)

Background: Fatigue is one of the most common and burdensome symptoms experienced by cancer patients. In interventions intended to reduce fatigue in such patients, fatigability, or perception of fatigue contextualized to activities of fixed intensity and duration, may also be measured. This study investigated the effects of a 15-month intervention on fatigue and fatigability in breast cancer survivors (BCS); explored the fatigue-fatigability relationship; and evaluated the impacts of fatigue and fatigability on anxiety, depression, sleep disturbance, and endocrine symptoms., Methods: A randomized controlled trial design was applied to an exercise program called BLESS (Better Life after cancer, Energy, Strength, and Support). The intervention included this 12-week exercise program and four follow-up contacts intended to promote exercise adherence over the following year. Participants were women aged 20 to 69 who had been diagnosed with stage I, II, or III breast cancer; had completed active treatment; and had moderate or higher fatigue. At the completion of the intervention, the survey responses of 40 BCS were evaluated using the chi-square test and multiple regression analysis. The Korean versions of the Revised Piper Fatigue Scale and Pittsburgh Fatigability Scale were used to measure fatigue and fatigability, respectively., Results: There was no significant difference in fatigue or fatigability between the experimental and control groups at intervention completion. However, the control group showed a stronger association than the experimental group between fatigue and physical fatigability. In the control group, fatigue and fatigability were significantly associated with anxiety, depression, sleep disturbance, and endocrine symptoms. In the experimental group, only the cognitive/mood fatigue score and depression were significantly associated. Only endocrine symptoms influenced mental fatigability (B = - 0.185, P < 0.05), and only depression influenced cognitive/mood fatigue (B = 1.469, P < 0.05)., Conclusions: Fatigue and fatigability showed different correlations with cancer-related symptoms after the exercise intervention. Future assessments of fatigability in intervention studies will allow measurement of the spectrum of patients' abilities to overcome fatigue at various physical activity levels while capturing different aspects of cancer-related symptoms., Trial Registration: This study was retrospectively registered on Clinical Research Information Service ( KCT0005763 ; date of registration: 31/12/2020)., (© 2021. The Author(s).)

The current study was conducted to investigate mental health levels in Korean adults during the coronavirus 2019 (COVID-19) pandemic and determine their predictors. The study was conducted online, and 334 adults from 14 locations in Korea participated. Data collection was conducted from May 19 to May 24, 2020, using a questionnaire consisting of general and COVID-19-related characteristics, perceived physical health, individual and community resilience, and mental health. For data analysis, descriptive statistics, t test, one-way analysis of variance, and hierarchical regression were used. In cases where women were more vulnerable to mental health problems and gender was controlled, regression analysis showed that individual resilience (β = -0.212, p < 0.001), perceived physical health (β = -0.160, p = 0.004), and community resilience (β = -0.119, p = 0.031) had an effect on mental health. Following the COVID-19 pandemic, communities should screen groups vulnerable to mental health problems and develop an integrated mental health program that incorporates predictors of mental health difficulties. [Journal of Psychosocial Nursing and Mental Health, 59(3), 18-27.]., (Copyright 2020, SLACK Incorporated.)

Evidence from cohort studies on the effects of long-term exposure to air pollution on mortality is limited in South Korea, which has high concentration of particles compared to North America, Western Europe, and Japan, and low exposure compared to China. To reduce knowledge gaps between other countries and South Korea, we investigated the association between all-cause, cardiovascular, and respiratory mortality and long-term exposure to PM 10 and, as a surrogate for fine particles from local emission sources, SO 2 and NO 2 . Participants comprised 18,220 subjects (97,114.4 person-years) residing in 73 districts of seven major cities of South Korea who were assigned to measurements of fixed-site monitoring stations and followed up. We applied Cox proportional hazard models with time-varying exposure up to three years average of air pollutants. We adjusted for individual and district-level covariates measured at baseline such as age, sex, socioeconomic positions, and health behaviors. We found that hazard ratios of PM 10 and SO 2 for all-cause mortality leveled off over approximately 5 ppb of SO 2 and 35-50 μg/m 3 of PM 10 . Interquartile range increases of PM 10 (5.05 μg/m 3 ), SO 2 (2.09 ppb), and NO 2 (11.41 ppb) were associated with 14.4% (95% CI: -0.4, 31.4), 18.1% (-4.5, 46.0), and 18.9% (-8.7, 54.7) increases in cardiovascular mortality, respectively. We did not find positive associations for respiratory mortality. The increase in cardiovascular mortality varied by sex (for PM 10 , in females, 27.4% (5.8, 53.5) increase), smoking (in non-smokers, 35.9% (12.7, 64.0) increase), drinking (in drinkers, 24.5% (2.1, 51.8) increase), marital status (in those not married, 23.1% (1.1, 49.9)), employment status (for SO 2 , in those employed, 79.4% (16.1, 177.3) increase), body mass index (in those ≥23, 47.6% (10.4, 97.3) increase), and community deprivation (for PM 10 , in less deprived communities, 21.0% (1.3, 44.4) increase). In summary, long-term exposure to air pollution is associated with mortality risk in South Korea. Our results suggest that the health effect of long-term exposure to air pollution may not be equal by sex, health behaviors and socioeconomic positions., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Previous studies have consistently reported an increase in mortality risk, even at low levels of blood lead. The average blood lead concentration in the Korean population has steadily decreased but is still higher than that of developed countries. The purpose of this study was to examine the associations between mortality and blood lead concentrations for adults in Korea. We used the Korea National Health and Nutrition Examination Survey (2008-2013) linked Cause of Death data, which are followed by 2018. A total of 7308 subjects who aged over 30 at the baseline examination were included in the analyses. Cox proportional hazard model was used to estimate the hazard ratios of mortality from non-accidental causes and cancer mortality. The estimated hazard ratios (95% CI) for comparison of the second and third tertile group with the lowest tertile group were 2.01 (1.20, 3.40) and 1.91 (1.13, 3.23) for non-accidental mortality and 3.42 (95% CI: 1.65, 7.08) and 2.27 (95% CI: 1.09, 4.70) for cancer mortality, respectively. The dose-response relationship also showed significant increase in the risk of mortality at blood lead level between 1.5 and 6.0 μg/dL. Our findings suggest that potent policies to lower lead exposure are required for the general Korean population.

Background: Previous studies have investigated the predictors for home discharge without considering stroke severity., Objectives: To develop a practical assessment tool that predicts home discharge for moderate stroke patients after subacute rehabilitation therapy in the tertiary hospitals., Methods: Stroke patients with National Institutes of Health Stroke Scale scores of 6 to 13 were included in this prospective cohort study. Various demographic, clinical, and functional factors were analyzed as potential predictive factors. A weighted scoring model was developed through the following three-step process: 1) selection of the factors by logistic regression analyses, 2) development of a weighted scoring model, and 3) validation of the generalizability of the model., Results: The home discharge rate was 51% (n = 372), and the overall mean length of stay of hospitalization was 32.5 days. 1) The Cognitive Functional Independence Measure, 2) the Functional Ambulation Categories, 3) the modified Charlson Comorbidity Index, and 4) marital status were independent predictors of home discharge. The coefficient value for marital status was adjusted to 1 in the scoring system, and the values of the other parameters were proportionally converted to the nearest integer. Possible total scores ranged from 0 to 13 in the model, with a higher score indicating a higher probability of home discharge. With a cutoff point of 7, this model showed 87.0% sensitivity and 86.2% specificity (area under the curve = 0.90)., Conclusions: This novel assessment tool can be useful in predicting home discharge after subacute rehabilitation of moderate stroke patients.

Background: Traditional Korean medicine (TKM) has been employed for the treatment of children with cerebral palsy in Korea; however, the addition of TKM to usual rehabilitation (UR) treatment is hindered by insufficient evidence of clinical improvement with TKM in patients with cerebral palsy. In this study, we will evaluate the effectiveness and safety of integrative medicine rehabilitation (IMR) for cerebral palsy through a randomized controlled clinical study., Methods: Eighty children (2-6 years old) diagnosed with cerebral palsy will be recruited and randomly divided into groups A and B. Patients in group A will receive IMR with UR, while those in group B will receive only UR during weeks 1-12 of the study. IMR includes acupuncture treatment (head and limb acupuncture) three times a week and the administration of herbal medicine (Yukgunza-tang and Yukmijihwang-tang extracts) twice a day in parallel with UR. Evaluations will be conducted at the beginning of the study and at 12 and 24 weeks (follow-up). The primary outcome is the Gross Motor Function Measure-88 score, and the secondary outcomes are the scores for the Goal Attainment Scale, Korean Bayley Scales of Infant Development III, and the Pediatric Quality of Life Inventory, and adverse events., Discussion: This will be the first pragmatic randomized controlled trial to evaluate the efficacy and safety of IMR in children with cerebral palsy in Korea. The results will help to demonstrate if IMR is an effective therapeutic approach for cerebral palsy., Trial Registration: Ministry of Food and Drug Safety 31361 ( http://www.mfds.go.kr ). Registered on 29 June 2017. Clinical Research Information Service KCT0002620 ( https://cris.nih.go.kr/cris/search/search&#95;result&#95;st01.jsp?seq=9819 ). Registered on 29 December 2017.

The purpose of the present study was to compare the health behaviors, general health, and mental health of South Korean employees according to their employment status, and to examine how these associations vary across genders using the latest Korean National Examination Health and Nutrition Survey data. Logistic regression analyses were performed using employment status-permanent job, temporary job, and unemployed-as predictor variables and health-related variables as the outcome variables. Results indicated that temporary workers and the unemployed have higher odds of poor mental health regardless of gender. On the other hand, only male permanent workers were found to have a higher risk of problematic drinking compared to precarious workers and the unemployed. Meanwhile, only women showed a higher risk of current smoking in the temporary job and unemployed groups compared with permanent employees. Regarding general health, women, not men, in the temporary job group reported poorer general health (i.e., low health-related quality of life and higher self-perceived poor health) than those in other groups. These findings suggest that the development and implementation of intervention services, as well as organizational actions, need to consider differential impacts of unfavorable employment status on health issues according to gender.

A substantial portion of Mendelian disease patients suffers from genetic variants that are inherited in a recessive manner. A precise understanding of pathogenic recessive variants in a population would assist in pre-screening births of such patients. However, a systematic understanding of the contribution of recessive variants to Mendelian diseases is still lacking. Therefore, genetic diagnosis and variant discovery of 553 undiagnosed Korean patients with complex neurodevelopmental problems (KND for Korean NeuroDevelopmental cohort) were performed using whole exome sequencing of patients and their parents. Disease-causing variants, including newly discovered variants, were identified in 57.5% of the probands of the KND cohort. Among the patients with the previous reported pathogenic variants, 35.1% inherited these variants in a recessive manner. Genes that cause recessive disorders in our cohort tend to be less constrained by loss-of-function variants and were enriched in lipid metabolism and mitochondrial functions. This observation was applied to an estimation that approximately 1 in 17 healthy Korean individuals carry at least one of these pathogenic variants that develop severe neurodevelopmental problems in a recessive manner. Furthermore, the feasibility of these genes for carrier screening was evaluated. Our results will serve as a foundation for recessive variant screening to reduce occurrences of rare Mendelian disease patients. Additionally, our results highlight the utility and necessity of whole exome sequencing-based diagnostics for improving patient care in a country with a centralized medical system.

This study investigated change in depression and revealed factors related to change using one-year follow-up data. A sample of 108 North Korean Refugee Youths (NKRYs) aged 13 to 26 years (66 females) was recruited from two alternative schools for NKRYs in South Korea. Based on the Center for Epidemiologic Studies Depression Scale cut-off score of 16, respondents were grouped based on change in depression score after one year as stable low, alleviated, deteriorated, or prolonged. Multinomial logistic regression assessed the influence of baseline psychological scores (resilience, emotional regulation strategy, and self-esteem), and reported social support (psychological/practical) on the odds of group classification. With the stable low group as the reference category, those with alleviated depression at Time 2 had significantly higher odds of expressive suppression and tended to have lower self-esteem at Time 1. The deteriorated depression group was more likely than the stable low group to have lower resilience and cognitive appraisal scores. Those with prolonged high depression were more likely than the stable low group to have lower resilience, less practical social support, and lower self-esteem. Psychological interventions, particularly those focused on increasing self-esteem and resilience, could be helpful for NKRYs with potential risk of depression. In addition, practical support should be provided on an as-needed basis to prevent chronic depression among NKRYs.

Background: The number of children using home mechanical ventilation (HMV) has increased markedly in Europe and North America, but little is known about the situation in Korea. We described the clinical characteristics of children using HMV and investigated the current situation of HMV utilization in children., Methods: Data on HMV prescriptions in year 2016 for children under the age of 19 was retrieved from the National Health Insurance Service for nationwide information. For more detailed information, data from year 2016 to 2018 was also retrieved from a tertiary center, Severance Children's Hospital., Results: Nationwide, 416 children were prescribed with HMV in 2016, with an estimated prevalence of 4.4 per 100,000 children, of which 64.2% were male and mean age was 6-year-old. The estimated number of patients using invasive ventilators via tracheostomy was 202 (49%). Neuromuscular diseases were the most frequent cause (217; 52%), followed by central nervous system diseases (142; 34%), and cardiopulmonary diseases (57; 14%). In the tertiary center, a total of 62 children were prescribed with HMV (19 [31%] with non-invasive ventilation; 43 [69%] with invasive ventilation]. The number of children with HMV increased from 11 in 2016 to 29 in 2018. The mean age for initiation of HMV was 3.1 years and male patients comprised 65%. The most frequent diagnostic reason for HMV was central nervous system diseases (68%), followed by cardiopulmonary diseases (19%) and neuromuscular diseases (13%). Five patients died during the study period and five patients weaned from HMV., Conclusion: This study provides insights on the present situation of HMV utilization in Korean children., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2019 The Korean Academy of Medical Sciences.)

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.

Objective: To investigate the rate of return to work and identify key factors associated with return to work between 3 months and 2 years after stroke., Design: Prospective cohort study., Setting: The Korean Stroke Cohort for Functioning and Rehabilitation (KOSCO) in Korea., Participants: A total of 193 persons with first-ever stroke who reported working status at 3 months after stroke., Outcome Measures: Data on baseline characteristics were collected from medical records. Functional assessments were performed using the National Institutes of Health Stroke Scale, the modified Rankin Scale, the Fugl-Meyer Assessment, the Functional Ambulatory Category, the Korean Mini-Mental State Examination, the Korean version of the Frenchay Aphasia Screening Test, the American Speech-Language-Hearing Association National Outcomes Measurement System, the Korean-Modified Barthel Index, the Geriatric Depression Scale-Short Form and the EuroQol-5 dimensions. An enumeration survey included the Reintegration to Normal Living Index, the Psychosocial Well-being Index-Short Form (, the Family Support Index and the Caregivers Burden Index., Results: Overall, 145 (75.1%) patients who had a stroke in the "Continuously-Employed" group and 48 (24.9%) in the "Employed-Unemployed" group returned to work between 3 months and 2 years after stroke. Multivariate logistic analysis demonstrated that in patients who had a stroke, characteristics such as age, PWI-SF Score, and caregiver characteristics, including age, sex (female) and living arrangements, were significantly associated with return to work between 3 months and 2 years after stroke., Conclusion: Age and PWI-SF Score of patients who had a stroke, as well as the age, sex and living arrangements of caregivers, are key factors influencing the return to work after stroke., Trial Registration Number: NCT03402451., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The Korean Undiagnosed Diseases Program (KUDP) was launched in January 2017 as a one-year pilot project to address the increasing global interest in patients with undiagnosed rare diseases. The purpose of this paper is to summarize the project results and emphasize the unmet research needs among patients with undiagnosed rare diseases in Korea., Results: Patient enrollment, assessment, and diagnostic processes were determined by the KUDP clinical expert consortium. Patients followed a diagnostic workflow after being categorized into one of four groups: I) insufficient clinical information or lack of standard diagnostic processes; II) undiagnosed due to low disease awareness; III) clinically diagnosed but unconfirmed genetically due to genetic heterogeneities; or IV) unknown disease due to complex, atypical clinical presentations. After excluding two patients from group I, 97 patients were enrolled, including 10 in group II, 67 in group III, and 20 in group IV. Most of them (92 of 97, 94.8%) were pediatric patients (< 18 years old) and 59 (60.8%) were male. The primary symptoms for 80 patients (82.5%) were neurologic. During the one-year pilot study, 72 patients completed a diagnostic assessment including clinical and molecular genetic analyses; some patients also underwent pathological or biochemical analysis. Twenty-eight of these patients (28/72, 38.9%) achieved molecular genetic diagnosis. Thirteen patients were diagnosed based on traditional tests, including biochemical assay, single or targeted genetic analysis, and chromosomal microarray. We performed whole exome sequencing on 52 patients, among whom 15 (28.8%, 15/52) reached a final diagnosis. One new disorder was identified via international collaboration., Conclusions: Using an efficient clinical diagnostic workflow, this KUDP pilot study resulted in a fair diagnostic success rate, improving the potential for additional diagnoses and new scientific discovery of complex and rare diseases. KUDP also satisfied unmet needs for rare diseases with multisystem involvement, highlighting the value of emerging genomic technologies for further research into rare and still-undiagnosed conditions.

Objective: The aim of the study was to investigate the correlation between spasticity severity and functional outcomes during the first year after stroke., Design: The Korean Stroke Cohort for Functioning and Rehabilitation is a large, multicenter, prospective cohort study of all patients with acute first-ever stroke admitted to participating hospitals in nine Korean areas. To investigate the correlation between spasticity severity and functional status measured by using the Institutes of Health Stroke Scale (NIHSS), Modified Barthel Index (MBI), Functional Independence Measurement (FIM), Fugl-Meyer Assessment (FMA), Functional Ambulatory Category (FAC), modified Rankin scale (mRS), and American Speech-Language Hearing Association National Outcome Measurement System Swallowing Scale (ASHA-NOMS), data were analyzed at 3, 6, and 12 mos after the occurrence of stroke., Results: A total of 7359 stroke patients, 3056 were finally included. Prevalence rates of spasticity in patients after stroke were 6.8% at 3 mos, 6.9% at 6 mos, and 7.6% at 12 mos. The scores of mRS and NIHSS were higher and those of K-MBI, FIM, FMA, and ASHA-NOMS were lower in more severe spastic patients, indicating poorer functional outcomes (P < 0.05)., Conclusions: This study demonstrated the coexistence of spasticity and poor functional outcome during the first year after first-ever stroke patients.

Objective: The Children's Depression Rating Scale-Revised (CDRS-R) is a valid instrument for the assessment of depressive symptoms in youth, but this measure is yet to be validated in Korea. Thus, the present study aimed to evaluate the validity of the Korean version of the CDRS-R and to determine its factor structures., Methods: This study included 66 youths between 12 and 17 years of age who participated as part of an ongoing study investigating biomarkers of the antidepressant response and suicidal events in depressed youth. At baseline, the participants were assessed using the Kiddie-Schedule for Affective Disorders and Schizophrenia-Present and Lifetime version (K-SADS-PL), CDRS-R, Children's Depression Inventory (CDI), Beck Depression Inventory (BDI), Clinical Global Impressions-Severity (CGI-S), Children's Global Assessment Scale (CGAS), and Child Behavior Checklist (CBCL). Based on their diagnosis, each participant was assessed either five (major depressive disorder [MDD], n = 36) or two (non-MDD, n = 30) more times with the CDRS-R, CDI, BDI, CGI-S, and CGAS; thus, 306 assessments were included in the final analyses of the present study. Pearson's r and Cronbach's α values were used to determine validity and internal consistency, and exploratory factor analysis was performed to determine the factor structures of the Korean version of the CDRS-R., Results: The CDRS-R score was significantly correlated with scores on the K-SADS-PL depression subscale (r = 0.93, p < 0.01), CDI (r = 0.86, p < 0.01), BDI (r = 0.85, p < 0.01), CGI-S (r = 0.84, p < 0.01), and CGAS (r = -0.86, p < 0.01), indicating that this measure has strong criterion validity. In addition, the high correlation of the CDRS-R with the depression subscale of the CBCL (r = 0.67, p < 0.01) and lower correlations with the subscales of the CBCL that assess delinquent behavior, aggressive behavior, and externalizing problem support the discriminant validity of this instrument (r s ≤ 0.50, p < 0.01). Internal consistency was high, as evidenced by a Cronbach's α of 0.91, and the exploratory factor analysis revealed that the Korean version of the CDRS-R comprised three factors as follows: subjective depressed mood, daily functional impairment, and observed depressive affect. These factors differed from those used in previous studies, which were performed with the English version of the CDRS-R., Conclusions: This study of the Korean version of the CDRS-R provides initial promising data regarding its criterion validity, discriminant validity, internal consistency, and factor structures. These properties were significantly strong, which suggests that the Korean version of the CDRS-R is a valid and reliable instrument for the assessment of depressive symptoms in youth.

Background: Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is a rare inherited disorder characterized by infantile-onset macrocephaly, slow neurologic deterioration, and seizures. Mutations in the causative gene, MLC1, are found in approximately 75% of patients and are inherited in an autosomal recessive manner. We analyzed MLC1 mutations in five unrelated Korean patients with MLC., Methods: Direct Sanger sequencing was used to identify MLC1 mutations. A founder effect of the p.Ala275Asp variant was demonstrated by haplotype analysis using single-nucleotide polymorphic (SNP) markers. Multiple ligation-dependent probe amplification (MLPA) and comparative genomic hybridization plus SNP array were used to detect exonic deletions or uniparental disomy (UPD)., Results: The most prevalent pathogenic variant was c.824C>A (p.Ala275Asp) found in 7/10 (70%) alleles. Two pathogenic frameshift variants were found: c.135delC (p.Cys46Alafs*12) and c.337&#95;353delinsG (p.Ile113Glyfs*4). Haplotype analysis suggested that the Korean patients with MLC harbored a founder mutation in p.Ala275Asp. The p.(Ile113Glyfs*4) was identified in a homozygous state, and a family study revealed that only the mother was heterozygous for this variant. Further analysis of MLPA and SNP arrays for this patient demonstrated loss of heterozygosity of chromosome 22 without any deletion, indicating UPD. The maternal origin of both chromosomes 22 was demonstrated by haplotype analysis., Conclusions: This study is the first to describe the mutational spectrum of Korean patients with MLC, demonstrating a founder effect of the p.Ala275Asp variant. This study also broadens our understanding of the mutational spectrum of MLC1 by demonstrating a homozygous p.(Ile113Glyfs*4) variant resulting from UPD of chromosome 22., Competing Interests: No potential conflicts of interest relevant to this article were reported., (© The Korean Society for Laboratory Medicine)