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Background/aims: The predictive value of the estimated pulse wave velocity (ePWV) for the development of metabolic syndrome has not yet been extensively explored. This study aimed to fill this gap by evaluating ePWV as a potential predictor of metabolic syndrome development in middle-aged Korean adults., Methods: Using prospective data obtained from the Ansan-Ansung cohort database, participants without metabolic syndrome at baseline were studied. ePWV was calculated using specific equations based on age and blood pressure. The primary outcome was the incidence of metabolic syndrome during a median follow-up period of 187 months., Results: Among the 6,186 participants, 2,726 (44.1%) developed metabolic syndrome during the follow-up period. ePWV methvalues were categorized into tertiles to assess their predictive value for the development of metabolic syndrome. An ePWV cut-off of 7.407 m/s was identified as a predictor of metabolic syndrome development, with a sensitivity of 0.743 and a specificity of 0.464. Participants exceeding this cut-off, especially those in the third tertile (8.77-14.63 m/s), had a notably higher risk of developing metabolic syndrome. Specifically, the third tertile exhibited a 52.8% cumulative incidence compared with 30.8% in the first tertile. After adjustments, those in the third tertile faced a 1.530-fold increased risk of metabolic syndrome (95% confidence interval, 1.330-1.761)., Conclusion: ePWV is a significant predictor of the development of metabolic syndrome. This finding underscores the potential of ePWV as a cardiometabolic risk assessment tool and can thus provide useful information for primary prevention strategies.

Objective: To improve the current recommendations for the diagnosis of canine heartworm (Dirofilaria immitis) disease., Animals: Blood samples collected from 35 shelter dogs in the Republic of Korea., Methods: Samples were tested for the presence of microfilaria using the modified Knott (MK) test and D immitis DNA using species-specific loop-mediated isothermal amplification (LAMP) PCR. The blood samples were additionally assessed for the presence of heartworm antigens using the Antigen Rapid Canine Heartworm AG Test Kit 2.0 (Bionote Co). The performance of the MK test and LAMP PCR was assessed through statistical analysis, with a paired McNemar test utilized for comparison., Results: The heartworm antigen was detected in 28.5% of the subjects. Of the 10 positive animals, the MK test detected microfilaria in 4 of 35 (11.4%) animals, and LAMP PCR detected D immitis DNA in 6 of 35 (17.1%). The results of this study indicate that the LAMP PCR showed more positive results in samples compared to the conventional MK test., Clinical Relevance: The D immitis-specific LAMP PCR assay has the potential to function as an alternative to current detection methods. It could complement the existing antigen detection tests in diagnosing canine heartworm infections.

Objective: This study aimed to compare and characterize the safety profiles of new antiseizure medications (ASMs) using a nationwide pharmacovigilance database from a long-term perspective in Korea., Methods: We reviewed adverse event reports from the Korea Adverse Event Reporting System database between January 2013 and December 2022 for descriptive analysis of six new ASMs (lacosamide, levetiracetam, lamotrigine, oxcarbazepine, topiramate, and zonisamide). We investigated the frequency and characteristics of adverse drug reactions (ADRs) based on the MedDRA terminology, system organ classes, and modified WHO classification., Results: We identified 5,733 reported cases of ADRs. The commonly reported ADRs associated with total ASMs were rash/urticaria (1,822, 31.8 %), dizziness (409, 7.1 %), somnolence/drowsiness (311, 5.4 %), and hepatotoxic effects (273, 4.8 %). Type B (idiosyncratic) effects (2,932; 51.1 %) were more commonly reported than Type A (related to known drug mechanisms) effects (2,613; 45.6 %). Skin and subcutaneous tissue disorders and type B effects were most commonly reported for lamotrigine and oxcarbazepine, whereas nervous system disorders and type A effects were most commonly reported for lacosamide, topiramate, and zonisamide. The pediatric group (<18 years) exhibited skin and subcutaneous tissue disorders and type B effects relatively more frequently than the adult and older adult groups., Conclusion: Hypersensitivity skin reactions and type B effects remained significant ADRs in the new ASMs; however, type A effects were more commonly reported in some ASMs. The pediatric group showed a higher rate of type B effects. Overall, new ASMs should also be used with caution., 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.)

Backgruound: This study evaluated the usefulness of indices for metabolic syndrome, non-alcoholic fatty liver disease (NAFLD), and insulin resistance (IR), as predictive tools for cardiovascular disease in middle-aged Korean adults., Methods: The prospective data obtained from the Ansan-Ansung cohort database, excluding patients with major adverse cardiac and cerebrovascular events (MACCE). The primary outcome was the incidence of MACCE during the follow-up period., Results: A total of 9,337 patients were included in the analysis, of whom 1,130 (12.1%) experienced MACCE during a median follow-up period of 15.5 years. The metabolic syndrome severity Z-score, metabolic syndrome severity score, hepatic steatosis index, and NAFLD liver fat score were found to significantly predict MACCE at values above the cut-off point and in the second and third tertiles. Among these indices, the hazard ratios of the metabolic syndrome severity score and metabolic syndrome severity Z-score were the highest after adjusting for confounding factors. The area under the receiver operating characteristic curve (AUC) of the 10-year atherosclerotic cardiovascular disease (ASCVD) score for predicting MACCE was 0.716, and the metabolic syndrome severity Z-score had an AUC of 0.619., Conclusion: The metabolic syndrome severity score is a highly reliable indicator and was closely associated with the 10-year ASCVD risk score in predicting MACCE in the general population. Given the specific characteristics and limitations of metabolic syndrome severity scores as well as the indices of NAFLD and IR, a more practical scoring system that considers these factors is essential to achieve greater accuracy in forecasting cardiovascular outcomes.

We employed a detection method to quantify Alexandrium catenella (Group I), one of the causative species for paralytic shellfish poisoning (PSP) in Jinhae-Masan Bay, Korea, targets sxtA4, via chip-based digital PCR. Additionally, we explored the dynamics of Alexandrium during the spring of 2022 using an rDNA-based quantitative PCR (qPCR) assay to enhance the performance of the dPCR assay. In matching dPCR results with PSP monitoring reports, we optimized a cell regulatory threshold of 102 cells L -1 , the maximum cell density when shellfish harvesting was permitted, for the dPCR assay. This threshold functioned similar to the PST threshold used in mouse bioassays (MBAs). Furthermore, we validated a total concordance rate of 83.8 % between the two assays for 2020-2022, reaching a maximum of 96.2 % in 2020. Thus, the result of dPCR could complement MBAs, facilitating the early detection of PSP outbreaks., 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 Ltd. All rights reserved.)

Introduction: Fragmented cancer care, defined as receipt of care from multiple hospitals, has been shown to be associated with poor patient outcomes and high expense. However, evidence regarding the effects of hospital choice by patients with cancer on overall survival are lacking. Thus, we investigated the relationship between patterns of fragmented care and five-year mortality in patients with gastric cancer., Materials and Methods: Using the Korean National Health Insurance senior cohort of adults aged ≥60 years, we identified patients with gastric cancer who underwent gastrectomy during 2007-2014. We examined the distribution of the study population by five-year mortality, and used Kaplan-Meier survival curves/log-rank test and Cox proportional hazard model to compare five-year mortality with fragmented cancer care., Results: Among the participants, 19.5% died within five years. There were more deaths among patients who received fragmented care, especially those who transferred to smaller hospitals (46.6%) than to larger ones (40.0%). The likelihood of five-year mortality was higher in patients who received fragmented cancer care upon moving from large to small hospitals than those who did not transfer hospitals (hazard ratio, 1.28; 95% confidence interval, 1.10-1.48, P = .001). Moreover, mortality was higher among patients treated in large hospitals or in the capital area for initial treatment, and this association was greater for patients from rural areas., Discussion: Fragmentation of cancer care was associated with reduced survival, and the risk of mortality was higher among patients who moved from large to small hospitals., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Tuberous sclerosis complex (TSC) is an autosomal dominant multisystem disorder, caused by a loss-of-function of either TSC1 or TSC2 gene. However, in 10%-15% TSC patients there is no pathogenic variant identified in either TSC1 or TSC2 genes based on standard clinical testing., Methods: In this study, genome sequencing was performed for families with clinical diagnosis of TSC with negative results from TSC1 and TSC2 single-gene tests., Results: Herein, we report a family presenting a classical TSC phenotype with an unusual, complex structural variant involving the TSC1 gene: an intrachromosomal inverted insertion in the long arm of chromosome 9. We speculate that the inverted 9q33.3q34.13 region was inserted into the q31.2 region with the 3'-end of the breakpoint of the inversion being located within the TSC1 gene, resulting in premature termination of TSC1., Conclusions: In this study, we demonstrate the utility of genome sequencing for the identification of complex chromosomal rearrangement. Because the breakpoints are located within the deep intronic/intergenic region, this copy-neutral variant was missed by the TSC1 and TSC2 single-gene tests and contributed to an unknown etiology. Together, this finding suggests that complex structural variants may be underestimated causes for the etiology of TSC., (© 2023 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.)

Objectives: The escalating burden of cardiovascular disease (CVD) is a critical public health issue worldwide. CVD, especially acute myocardial infarction (AMI) and stroke, is the leading contributor to morbidity and mortality in Korea. We aimed to develop algorithms for identifying AMI and stroke events from the National Health Insurance Service (NHIS) database and validate these algorithms through medical record review., Methods: We first established a concept and definition of "hospitalization episode," taking into account the unique features of health claims-based NHIS database. We then developed first and recurrent event identification algorithms, separately for AMI and stroke, to determine whether each hospitalization episode represents a true incident case of AMI or stroke. Finally, we assessed our algorithms' accuracy by calculating their positive predictive values (PPVs) based on medical records of algorithm- identified events., Results: We developed identification algorithms for both AMI and stroke. To validate them, we conducted retrospective review of medical records for 3,140 algorithm-identified events (1,399 AMI and 1,741 stroke events) across 24 hospitals throughout Korea. The overall PPVs for the first and recurrent AMI events were around 92% and 78%, respectively, while those for the first and recurrent stroke events were around 88% and 81%, respectively., Conclusions: We successfully developed algorithms for identifying AMI and stroke events. The algorithms demonstrated high accuracy, with PPVs of approximately 90% for first events and 80% for recurrent events. These findings indicate that our algorithms hold promise as an instrumental tool for the consistent and reliable production of national CVD statistics in Korea.

The pediatric population with comorbidities is a high-risk group for severe coronavirus disease 2019 (COVID-19). As of January 2023, the COVID-19 vaccination rate for at least two doses among Korean children 5-11 years is low at 1.1%. We summarized the COVID-19 vaccination status for the pediatric population (5-17 years) with comorbidities through July 2022 using the National Health Insurance Service database. Pediatric patients with comorbidities had higher vaccination rates than the general pediatric population (2.4% vs. 1.1% in 5-11-year-olds [ P < 0.001], 76.5% vs. 66.1% in 12-17-year-olds [ P < 0.001]). However, there were substantial differences according to comorbidity category, and the 2-dose vaccination rate was lowest among children with immunodeficiency in all age groups (1.1% in 5-11-year-olds, 51.2% in 12-17-year-olds). The COVID-19 vaccination rate among Korean children has remained stagnant at a low proportion despite ongoing outreach. Thus, more proactive strategies are needed alongside continuous surveillance., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2023 The Korean Academy of Medical Sciences.)

Objective: To assess the effectiveness and tolerability of perampanel monotherapy following conversion from adjunctive therapy., Methods: This was a multicenter, retrospective, non-interventional study of Korean patients aged ≥12 years with focal-onset seizures (FOS) with or without focal to bilateral tonic-clonic seizures. Data were extracted from electronic medical records of perampanel-treated patients from 1 February 2016 to 31 October 2020. Kaplan-Meier estimated retention rates, effectiveness, and safety were recorded., Results: Subjects (n = 66, mean age 46.2 years) were mostly male (68.2%) with focal to bilateral tonic-clonic seizure (71.2%). Mean duration of illness was 86.3 months. Retention rates after conversion to perampanel monotherapy at 3, 6, and 12 months (primary outcome) were 96.0%, 96.0%, and 75.6%, respectively. Overall retention rates in patients receiving perampanel as adjunctive or monotherapy at 3, 6, 12, 18, and 24 months after perampanel add-on were 100%, 98.3%, 95.9%, 92.6%, and 92.6%, respectively. Mean retention duration was 41.2 months (overall perampanel administration) and 21.4 months (monotherapy). Mean seizure frequency/28 days in the Full Analysis Set (n = 61) was comparable for adjunctive and monotherapy (0.2 ± 0.79 vs 0.2 ± 0.64; change between adjunctive and monotherapy periods: 0.0 ± 0.59; p = 0.498). Perampanel was well tolerated and no new safety signals were identified. Dizziness (4.6%), only reported during adjunctive therapy, was the most common treatment-emergent adverse event., Conclusions: Conversion to perampanel monotherapy from adjunctive therapy showed promising results in subjects with FOS with/without focal to bilateral tonic-clonic seizures; further studies in a larger population are needed to confirm these encouraging data., Competing Interests: Declaration of Competing Interest JP and YL are employees of Eisai Korea Inc. All other 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 © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

To contain the surge of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the South Korean government has implemented non-pharmacological interventions as well as border restrictions. The efficacy of entry restrictions should be evaluated to facilitate their preparation for new variants of SARS-CoV-2. This study explored the impact of border policy changes on overseas entrants and local cases of SARS-CoV-2 variants. Data from the Korea Disease Control and Prevention Agency randomly collected between April 11, 2021 and August 20, 2022 were evaluated using the Granger causality model. The results showed that the outbreak gap of delta variants between international and domestic cases was 10 weeks, while that of omicron variants was approximately 2 weeks, meaning that the quarantine policy helped contain delta variants rather than more transmissible variants. It is recommended that countries implement quarantine policies based on particular purposes accounting for the specific features of different variants to avoid potential negative impacts on the economy., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2023 The Korean Academy of Medical Sciences.)

The genus Hapalochlaena, including the blue-lined octopus Hapalochlaena fasciata (H. fasciata), is highly toxic. Venomous, blue-lined octopuses were recently found in Korea, but their toxicity, toxin composition, and distribution remain largely unknown. Here we estimated the geographic distribution of the organisms along the Korean coast and clarified their toxicity. Tetrodotoxin (TTX) was present in all three specimens of H. fasciata examined, although the toxicity varied largely between individuals. The mean TTX concentration in the whole body of the three specimens was 6.5 ± 2.2 μg/g (range 3.3-8.5 μg/g). Among the body parts examined, the salivary glands exhibited the highest concentration (22.4 ± 9.7 μg/g). From 2012 to 2021, 26 individuals were obtained nearly every month from different regions of the Korean coast. A non-fatal case of a blue-lined octopus bite was reported along the Korean coast in June 2015. This is the first report on the widespread distribution of blue-lined octopuses on the Korean coast and TTX detection. The widespread distribution of the TTX-bearing H. fasciata along the Korean coast within the temperate zone indicates that the species may soon become a serious health issue in Korea. The toxicity of this species is also a potentially significant human health risk.

Purpose: Fragmented cancer care (FC) means that patients visit multiple providers for treatment, which is common in cancer care. While FC is associated with poor health outcomes in patients with colorectal cancer (CRC) worldwide, there is still a lack of evidence in South Korea. We investigated the association between FC and 5-year morality in patients with CRC using population-based claims data., Methods: The study population was followed up from 2002 to 2015. Data were collected from Korea National Health Insurance claims. Participants comprised patients with CRC diagnosed with International Classification of Diseases (ICD)-10 (C18.x-C20.x) and a special claim code for cancer (V193). Data were analyzed using the Kaplan-Meier curve with a log-rank test and Cox proportional hazard model. The effect of FC on patients' 5-year survival was examined., Results: Of 3467 patients with CRC, 20.0% had experienced FC. FC was significantly associated with an increased risk of 5-year mortality (hazard ratio 1.516, 95% confidence interval 1.274-1.804). FC was prevalent in those who had a low income level, underwent chemotherapy, did not undergo radiation therapy, and did not visit a tertiary hospital for their first treatment., Conclusion: Efforts to decrease FC and integrate complex cancer care within appropriate healthcare delivery systems may improve survivorship among patients with CRC., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Importance: Infections are proposed to be triggering factors for Kawasaki disease (KD), although its etiological factors remain unknown. Recent reports have indicated a 4- to 6-week lag between SARS-CoV-2 infection and multisystem inflammatory syndrome in children with a similar presentation to that of KD., Objective: To investigate the temporal correlation between KD and viral infections, focusing on respiratory viruses., Design, Setting, and Participants: This cohort study was conducted among individuals aged 0 to 19 years diagnosed with KD between January 2010 and September 2020 from the Korean National Health Insurance Service. Data on infectious disease outbreaks from 2016 to 2019 were collected from the Korea Disease Control and Prevention Agency, Korean Influenza and Respiratory Virus Monitoring System, Korea Enteroviruses Surveillance System, and the Enteric Pathogens Active Surveillance Network in South Korea. Data were analyzed from December 2020 to October 2021., Main Outcomes and Measures: National databases for infectious diseases were used for a time-series analysis of the correlation between viral infections and KD. The temporal correlation between infectious disease outbreaks and KD outbreaks was evaluated using the Granger causality test (G-test), which is a useful tool to estimate correlations between 2 time series of diseases based on time lags., Results: Overall, 53 424 individuals with KD were identified, including 22 510 (42.1%) females and 30 914 (57.9%) males and 44 276 individuals (82.9%) younger than 5 years. Intravenous immunoglobulin-resistant KD was identified in 9042 individuals (16.9%), and coronary artery abnormalities were identified in 384 individuals (0.7%). Of 14 infectious diseases included in the analyses, rhinovirus infection outbreaks were identified as significantly correlated at 1 to 3 months before KD outbreaks in South Korea (r = 0.3; 1 month: P < .001; 2 months: P < .001; 3 months: P < .001). Outbreaks of respiratory syncytial virus infection were identified as significantly correlated with KD outbreaks by 2 months (r = 0.5; 2 months: P < .001). Additionally, varicella outbreaks were identified as significantly correlated at 2 and 3 months before KD outbreaks (r = 0.7; 2 months: P < .001; 3 months: P < .001)., Conclusions and Relevance: In this cohort study with a time series analysis of children and youth in South Korea with KD, respiratory infections caused by rhinovirus and respiratory syncytial virus and varicella outbreaks were significantly correlated with KD at 1 to 3 months before KD outbreaks.

Background: Benefits of intensive blood pressure lowering on health outcomes have been demonstrated in high-risk patients. However, little is known about such benefits in patients with left ventricular hypertrophy (LVH)., Objectives: This study sought to investigate the association of on-treatment blood pressure with cardiovascular disease (CVD) risk in adults with hypertension and LVH., Methods: From a nationwide health examination database, this study identified 95,545 participants aged 40-79 years who were taking antihypertensive medication and had LVH on baseline electrocardiography. Using Cox models, HRs and 95% CIs for CVD events were calculated according to systolic blood pressure (SBP) or diastolic blood pressure (DBP)., Results: Over a median follow-up of 11.5 years, 12,035 new CVD events occurred. An SBP of <130 mm Hg and DBP of <80 mm Hg were associated with the lowest risk for CVD events in cubic spline models. When the group with SBP of 120-129 mm Hg was the reference, multivariable-adjusted HRs were 1.31 (95% CI: 1.24-1.38) in the ≥140 mm Hg group, 1.08 (95% CI: 1.02-1.15) in the 130-139 mm Hg group, and 1.03 (95% CI: 0.93-1.15) in the <120 mm Hg group. Likewise, when the group with DBP of 70-79 mm Hg was the reference, multivariable-adjusted HRs were 1.30 (95% CI: 1.24-1.37) in the ≥90 mm Hg group, 1.06 (95% CI: 1.01-1.12) in the 80-89 mm Hg group, and 1.08 (95% CI: 0.96 to 1.20) in the <70 mm Hg group., Conclusions: In adults with hypertension and LVH, the risk for CVD events was the lowest at SBP <130 mm Hg and DBP <80 mm Hg. Further randomized trials are warranted to establish optimal blood pressure-lowering strategies for these patients., Competing Interests: Funding Support and Author Disclosures This work was supported by the Korea Health Technology Research and Development Project through the Korea Health Industry Development Institute funded by the Ministry of Health and Welfare, Republic of Korea (grant HI13C0715). The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Increased body mass index (BMI) has been associated with a higher risk of severe coronavirus disease 2019 (COVID-19) infections. However, whether obesity is a risk factor for contracting COVID-19 has hardly been investigated so far., Methods: We examined the association between BMI level and the risk of COVID-19 infection in a nationwide case-control study comprised of 3788 case patients confirmed to have COVID-19 between 24 January and 9 April 2020 and 15 152 controls matched by age and sex, who were aged 20 years or more and underwent National Health Insurance Service (NHIS) health examinations between 2015-2017, using data from the Korean NHIS with linkage to the Korea Centers for Disease Control and Prevention data. Our primary exposure of interest was BMI level, categorized into 4 groups: <18.5 (underweight), 18.5-22.9 (normal weight), 23-24.9 (overweight), and ≥25 kg/m2 (obese)., Results: Of the entire 18 940 study participants, 11 755 (62.1%) were women, and the mean age of the study participants was 53.7 years (standard deviation, 13.8). In multivariable logistic regression models adjusted for sociodemographic, comorbidity, laboratory, and medication data, there was a graded association between higher BMI levels and higher risk of COVID-19 infection. Compared to normal-weight individuals, the adjusted odds ratios in the overweight and obese individuals were 1.13 (95% confidence interval [CI], 1.03-1.25) and 1.26 (95% CI, 1.15-1.39), respectively. This association was robust across age and sex subgroups., Conclusions: Higher BMI levels were associated with a higher risk of contracting COVID-19., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Non-pharmaceutical interventions (NPIs) have been widely implemented to mitigate the spread of COVID-19. We assessed the effect of NPIs on hospitalisations for pneumonia, influenza, COPD and asthma. This retrospective, ecological study compared the weekly incidence of hospitalisation for four respiratory conditions before (January 2016-January 2020) and during (February-July 2020) the implementation of NPI against COVID-19. Hospitalisations for all four respiratory conditions decreased substantially during the intervention period. The cumulative incidence of admissions for COPD and asthma was 58% and 48% of the mean incidence during the 4 preceding years, respectively., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Dasatinib is administered at a fixed starting dosage of 100 mg once daily regardless of patient-specific factors. However, such fixed dosing may not be optimal for the treatment of Asian patients with chronic myeloid leukemia in chronic phase (CP-CML)., Patients and Methods: The dose-limiting toxicities (DLTs) and molecular responses (MRs) of dasatinib therapy were evaluated using clinical data obtained from 102 patients newly diagnosed with CP-CML at 17 hospitals in South Korea., Results: By 36 months after the initiation of a fixed dose regimen of dasatinib 100 mg once daily as the first-line therapy, 55.9% of patients experienced at least one type of DLT. The 3 most frequent DLTs were thrombocytopenia (45.5%), pericardial or pleural effusion (30.9%), and anemia (7.3%). Patients with higher dasatinib dose adjusted for body weight (Dose/BW) had a greater rate of DLT occurrence (logit [P] = 1.58 × [Dose/BW] - 2.27, P = .03). As median Dose/BW increased from 1.23 to 2.00 mg/kg, the rate of DLT occurrence increased from 43.5% to 66.7% (P = .03). However, Dose/BW did not affect the achievement rate of major MR (60.9% to 69.6%, P = .92)., Conclusion: The starting dosage of dasatinib may need to be reduced (eg, 80 mg once daily or lower) for Asian patients with CP-CML, especially with lighter BW, to alleviate the risk of DLT occurrence without compromising the achievement of MR., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background/aims: Although it is near concluded that renin-angiotensin system inhibitors do not have a harmful effect on coronavirus disease 2019 (COVID-19), there is no report about whether angiotensin receptor blockers (ARBs) and angiotensin-converting enzyme inhibitors (ACEIs) offer any protective role. This study aimed to compare the association of ARBs and ACEIs with COVID-19-related mortality., Methods: All patients with COVID-19 in Korea between January 19 and April 16, 2020 were enrolled. The association of ARBs and ACEIs with mortality within 60 days were evaluated. A comparison of hazard ratio (HR) was performed between COVID-19 patients and a retrospective cohort of pneumonia patients hospitalized in 2019 in Korea., Results: Among 10,448 COVID-19 patients, ARBs and ACEIs were prescribed in 1,231 (11.7%) and 57 (0.6%) patients, respectively. After adjusting for age, sex, and history of comorbidities, the ARB group showed neutral association (HR, 1.034; 95% CI, 0.765 to 1.399; p = 0.8270) and the ACEI groups showed no significant associations likely owing to the small population size (HR, 0.736; 95% CI, 0.314 to 1.726; p = 0.4810). When comparing HR between COVID-19 patients and a retrospective cohort of patients hospitalized with pneumonia in 2019, the trend of ACEIs showed similar benefits, whereas the protective effect of ARBs observed in the retrospective cohort was absent in COVID-19 patients. Meta-analyses showed significant positive correlation with survival of ACEIs, whereas a neutral association between ARBs and mortality., Conclusion: Although ARBs or ACEIs were not associated with fatal outcomes, potential beneficial effects of ARBs observed in pneumonia were attenuated in COVID-19.

While several studies have explored nutrient intake and dietary habits associated with depression, few studies have reflected recent trends and demographic factors. Therefore, we examined how nutrient intake and eating habits are associated with depression, according to gender and age. We performed simple and multiple regressions using nationally representative samples of 10,106 subjects from the Korea National Health and Nutrition Examination Survey. The results indicated that cholesterol, dietary fiber, sodium, frequency of breakfast, lunch, dinner, and eating out were significantly associated with depression ( p -value < 0.05). Moreover, depression was associated with nutrient intake and dietary habits by gender and age group: sugar, breakfast, lunch, and eating out frequency in the young women's group; sodium and lunch frequency among middle-age men; dietary fibers, breakfast, and eating out frequency among middle-age women; energy, moisture, carbohydrate, lunch, and dinner frequency in late middle-age men; breakfast and lunch frequency among late middle-age women; vitamin A, carotene, lunch, and eating out frequency among older age men; and fat, saturated fatty acids, omega-3 fatty acid, omega-6 fatty acid, and eating out frequency among the older age women's group ( p -value < 0.05). This study can be used to establish dietary strategies for depression prevention, considering gender and age.

[Figure: see text].

Objectives: This study aimed to identify the survival rate and explore factors affecting survival among early COVID-19 patients in South Korea., Methods: Data reported by the Korea Disease Control and Prevention Agency (KDCA), up to 15 July, when COVID-19 was confirmed were used as research data in connection with the National Health Insurance Service's (NHIS) national health information database. The final analysis targets were 12,646 confirmed patients and 303 deaths. The survival rate of patients with COVID-19 was estimated through Kaplan-Meier survival analysis. Cox proportional hazard regression analysis was performed to search for factors affecting survival., Results: When looking at the survival rate by age group for men and women, the 28-day survival rate for men aged >80 years was 77% and 73% at 42 days, while 83% and 81% for women. Men had a worse survival rate than women. For chronic diseases, the highest risk of mortality was observed in malignant neoplasms of the respiratory and urogenital systems, followed by diseases of the urinary system and diabetes., Conclusions: The number of COVID-19 deaths was highest the next day after initial diagnosis. The case fatality rate was high in males, older age, and chronic diseases., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Vaccines against coronavirus disease 2019 (COVID-19) are raising concerns about vaccine safety, particularly in the context of large-scale immunization. To address public concerns, we measured the baseline incidence rates of major conditions potentially related to vaccine-related adverse events (VAEs). We aimed to provide a basis for evaluating VAEs and verifying causality., Methods: Conditions of interest were selected from the US Vaccine Adverse Event Reporting System Table of Reportable Events and a recent report from a European consortium on vaccine surveillance. We used the National Health Insurance Service database in Korea to identify the monthly numbers of cases with these conditions. Data from January 2006 to June 2020 were included. Prediction models were constructed from the observed incidences using an autoregressive integrated moving average. We predicted the incidences of the conditions and their respective 95% confidence intervals (CIs) for January through December 2021. In addition, subgroup analysis for the expected vaccination population was conducted., Results: Mean values (95% CIs) of the predicted monthly incidence of vasovagal syncope, anaphylaxis, brachial neuritis, acute disseminated encephalomyelitis, Bell's palsy, Guillain-Barré syndrome, encephalopathy, optic neuritis, transverse myelitis, immune thrombocytopenic purpura, and systemic lupus erythematosus in 2021 were 23.89 (19.81-27.98), 4.72 (3.83-5.61), 57.62 (51.37-63.88), 0.03 (0.01-0.04), 8.58 (7.90-9.26), 0.26 (0.18-0.34), 2.13 (1.42-2.83), 1.65 (1.17-2.13), 0.19 (0.14-0.25), 0.75 (0.61-0.90), and 3.40 (2.79-4.01) cases per 100,000 respectively. The majority of the conditions showed an increasing trend with seasonal variations in their incidences., Conclusion: We measured the incidence of a total of 11 conditions that could potentially be associated with VAEs to predict the monthly incidence in 2021. In Korea, conditions that could potentially be related to VAEs occur on a regular basis, and an increasing trend is observed with seasonality., Competing Interests: The authors have no conflicts of interest to declare., (© 2021 The Korean Academy of Medical Sciences.)

Background: As the COVID-19 pandemic continues, an initial risk-adapted allocation is crucial for managing medical resources and providing intensive care., Objective: In this study, we aimed to identify factors that predict the overall survival rate for COVID-19 cases and develop a COVID-19 prognosis score (COPS) system based on these factors. In addition, disease severity and the length of hospital stay for patients with COVID-19 were analyzed., Methods: We retrospectively analyzed a nationwide cohort of laboratory-confirmed COVID-19 cases between January and April 2020 in Korea. The cohort was split randomly into a development cohort and a validation cohort with a 2:1 ratio. In the development cohort (n=3729), we tried to identify factors associated with overall survival and develop a scoring system to predict the overall survival rate by using parameters identified by the Cox proportional hazard regression model with bootstrapping methods. In the validation cohort (n=1865), we evaluated the prediction accuracy using the area under the receiver operating characteristic curve. The score of each variable in the COPS system was rounded off following the log-scaled conversion of the adjusted hazard ratio., Results: Among the 5594 patients included in this analysis, 234 (4.2%) died after receiving a COVID-19 diagnosis. In the development cohort, six parameters were significantly related to poor overall survival: older age, dementia, chronic renal failure, dyspnea, mental disturbance, and absolute lymphocyte count <1000/mm 3 . The following risk groups were formed: low-risk (score 0-2), intermediate-risk (score 3), high-risk (score 4), and very high-risk (score 5-7) groups. The COPS system yielded an area under the curve value of 0.918 for predicting the 14-day survival rate and 0.896 for predicting the 28-day survival rate in the validation cohort. Using the COPS system, 28-day survival rates were discriminatively estimated at 99.8%, 95.4%, 82.3%, and 55.1% in the low-risk, intermediate-risk, high-risk, and very high-risk groups, respectively, of the total cohort (P<.001). The length of hospital stay and disease severity were directly associated with overall survival (P<.001), and the hospital stay duration was significantly longer among survivors (mean 26.1, SD 10.7 days) than among nonsurvivors (mean 15.6, SD 13.3 days)., Conclusions: The newly developed predictive COPS system may assist in making risk-adapted decisions for the allocation of medical resources, including intensive care, during the COVID-19 pandemic., (©Sung-Yeon Cho, Sung-Soo Park, Min-Kyu Song, Young Yi Bae, Dong-Gun Lee, Dong-Wook Kim. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 22.02.2021.)

Objective: To evaluate the risk of stroke associated with intravitreal ranibizumab in age-related macular degeneration (AMD)., Methods: A nationwide retrospective case-crossover study was performed using data from the Korean National Health Insurance Service (KNHIS) database, which included patients with exudative AMD in South Korea (n = 41,860). The index date was the date of hospitalization for stroke. We defined the case period as 60 days and four control periods before the index date. A pharmacy prescription database was searched for ranibizumab use during the case and control periods. We calculated adjusted odds ratios (ORs) and 95% confidence intervals (CIs) with a conditional logistic regression model., Results: A total of 865 patients with AMD and incident stroke were included. Of all the patients, 12.02% had been treated during the preceding 60-day case period, compared with 9.25-10.29% during control periods. The adjusted OR of stroke associated with intravitreal ranibizumab during the case period was 1.285 (95% CI 0.979-1.686) (p = 0.07). In the subgroup analysis, the risk of hemorrhagic stroke had an OR of 2.252 (95% CI 1.068-4.749, p = 0.033). Further analyses based on patient gender, age, and different risk periods of 15 and 30 days yielded no increase in the risk of stroke associated with intravitreal ranibizumab., Conclusions: This case-crossover analysis revealed no evidence of increased risk of hospitalization for stroke within 60 days of intravitreal ranibizumab injection in AMD patients. A secondary analysis indicated the possibility of an increased risk of hemorrhagic stroke, with borderline significance. Further research is needed regarding the underlying biological mechanisms and drug safety.

Researchers have been interested in probing how the environmental factors associated with allergic diseases affect the use of medical services. Considering this demand, we have constructed a database, named the Allergic Disease Database, based on the National Health Insurance Database (NHID). The NHID contains information on demographic and medical service utilization for approximately 99% of the Korean population. This study targeted 3 major allergic diseases, including allergic rhinitis, atopic dermatitis, and asthma. For the target diseases, our database provides daily medical service information, including the number of daily visits from 2013 and 2017, categorized by patients' characteristics such as address, sex, age, and duration of residence. We provide additional information, including yearly population, a number of patients, and averaged geocoding coordinates by eup, myeon, and dong district code (the smallest-scale administrative units in Korea). This information enables researchers to analyze how daily changes in the environmental factors of allergic diseases (e.g., particulate matter, sulfur dioxide, and ozone) in certain regions would influence patients' behavioral patterns of medical service utilization. Moreover, researchers can analyze long-term trends in allergic diseases and the health effects caused by environmental factors such as daily climate and pollution data. The advantages of this database are easy access to data, additional levels of geographic detail, time-efficient data-refining and processing, and a de-identification process that minimizes the exposure of identifiable personal information. All datasets included in the Allergic Disease Database can be downloaded by accessing the National Health Insurance Service data sharing webpage (https://nhiss.nhis.or.kr).

Background: This study aimed to determine the infection risk of coronavirus disease 2019 (COVID-19) in patients with diabetes (according to treatment method)., Methods: Claimed subjects to the Korean National Health Insurance claims database diagnosed with COVID-19 were included. Ten thousand sixty-nine patients with COVID-19 between January 28 and April 5, 2020, were included. Stratified random sampling of 1:5 was used to select the control group of COVID-19 patients. In total 50,587 subjects were selected as the control group. After deleting the missing values, 60,656 subjects were included., Results: Adjusted odds ratio (OR) indicated that diabetic insulin users had a higher risk of COVID-19 than subjects without diabetes (OR, 1.25; 95% confidence interval [CI], 1.03 to 1.53; P=0.0278). In the subgroup analysis, infection risk was higher among diabetes male insulin users (OR, 1.42; 95% CI, 1.07 to 1.89), those between 40 and 59 years (OR, 1.66; 95% CI, 1.13 to 2.44). The infection risk was higher in diabetic insulin users with 2 to 4 years of morbidity (OR, 1.744; 95% CI, 1.003 to 3.044)., Conclusion: Some diabetic patients with certain conditions would be associated with a higher risk of acquiring COVID-19, highlighting their need for special attention. Efforts are warranted to ensure that diabetic patients have minimal exposure to the virus. It is important to establish proactive care and screening tests for diabetic patients suspected with COVID-19 for timely disease diagnosis and management.

The rapid spread of COVID-19 has resulted in the shortage of medical resources, which necessitates accurate prognosis prediction to triage patients effectively. This study used the nationwide cohort of South Korea to develop a machine learning model to predict prognosis based on sociodemographic and medical information. Of 10,237 COVID-19 patients, 228 (2.2%) died, 7772 (75.9%) recovered, and 2237 (21.9%) were still in isolation or being treated at the last follow-up (April 16, 2020). The Cox proportional hazards regression analysis revealed that age > 70, male sex, moderate or severe disability, the presence of symptoms, nursing home residence, and comorbidities of diabetes mellitus (DM), chronic lung disease, or asthma were significantly associated with increased risk of mortality (p ≤ 0.047). For machine learning, the least absolute shrinkage and selection operator (LASSO), linear support vector machine (SVM), SVM with radial basis function kernel, random forest (RF), and k-nearest neighbors were tested. In prediction of mortality, LASSO and linear SVM demonstrated high sensitivities (90.7% [95% confidence interval: 83.3, 97.3] and 92.0% [85.9, 98.1], respectively) and specificities (91.4% [90.3, 92.5] and 91.8%, [90.7, 92.9], respectively) while maintaining high specificities > 90%, as well as high area under the receiver operating characteristics curves (0.963 [0.946, 0.979] and 0.962 [0.945, 0.979], respectively). The most significant predictors for LASSO included old age and preexisting DM or cancer; for RF they were old age, infection route (cluster infection or infection from personal contact), and underlying hypertension. The proposed prediction model may be helpful for the quick triage of patients without having to wait for the results of additional tests such as laboratory or radiologic studies, during a pandemic when limited medical resources must be wisely allocated without hesitation.

Objectives: To delineate clinical characteristics of asymptomatic and symptomatic patients confirmed with COVID-19 in South Korea., Methods: Data were obtained from the Korean National Health Insurance Service database linked to the Korea Centers for Disease Control and Prevention data., Results: Among 10,237 patients (mean [SD] age, 45.0 [19.8] years; 60.1% female) who met the eligibility criteria for the study, 6,350 (62.0%) patients were asymptomatic, and 3,887(38.0%) patients were symptomatic. The mean and median age were similar between asymptomatic and symptomatic patients. Notably, we observed a U-shaped association between age group and the proportion of asymptomatic patients, with the nadir at 57.3% in the 40-49 age group. This U-shaped distribution was largely similar between men and women. The overall prevalence of asymptomatic individuals was higher, regardless of sex, residential area, income levels, and comorbid conditions., Conclusions: In this national cohort of over 10,000 patients with COVID-19, more than 60% of all cases in South Korea reported no symptoms at the time of diagnosis. Expanding criteria for contact tracing and testing to capture potential transmission before symptom onset should be urgently considered to inform control strategies for COVID-19., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Purpose: To report incidence rates of primary congenital glaucoma in Korea and evaluate comorbidity and mortality from 2001 to 2015., Methods: This study is a nationwide and retrospective population-based study. We used claims data from the Korean National Health Insurance Service database between 2001 and 2015. Data for all patients diagnosed with primary congenital glaucoma were retrieved using the Korean Electronic Data Interchange and Korean Standard Classification of Diseases-6 codes., Results: The number of patients with primary congenital glaucoma between 2001 and 2015 was 776, of which 437 were male (56.31%) and 339 were female (43.69%). The annual prevalence demonstrated a general decreasing trend since 2011, but this was not significant. Over the total survey period, the incidence rate was 11.0 per 100,000 births, with 12.0 cases among males and 10.0 among females. The incidence according to age was 518 (68.78%) patients at age 0, 112 (13.66%) at 1 year, 70 (8.39%) at 2 years, and 76 (9.17%) at 3 years. Of the 776 patients diagnosed with primary congenital glaucoma in the study population, 27 died. The observed mortality per 100,000 people is about 10 times higher than that of the general infant and child population under the age of 4 years. Visual impairment was the most common accompanying disability, followed by brain lesion., Conclusions: Our study's estimates of the nationwide population-based incidence of primary congenital glaucoma in a Korean population will expand our understanding of the disease and allow healthcare systems to plan for primary congenital glaucoma., Competing Interests: No potential conflict of interest relevant to this article was reported., (© 2020 The Korean Ophthalmological Society.)

Background: Mortality of coronavirus disease 2019 (COVID-19) is a major concern for quarantine departments in all countries. This is because the mortality of infectious diseases determines the basic policy stance of measures to prevent infectious diseases. Early screening of high-risk groups and taking action are the basics of disease management. This study examined the correlation of comorbidities on the mortality of patients with COVID-19., Methods: We constructed epidemiologic characteristics and medical history database based on the Korean National Health Insurance Service Big Data and linked COVID-19 registry data of Korea Centers for Disease Control & Prevention (KCDC) for this emergent observational cohort study. A total of 9,148 patients with confirmed COVID-19 were included. Mortalities by sex, age, district, income level and all range of comorbidities classified by International Classification of Diseases-10 based 298 categories were estimated., Results: There were 3,556 male confirmed cases, 67 deaths, and crude death rate (CDR) of 1.88%. There were 5,592 females, 63 deaths, and CDR of 1.13%. The most confirmed cases were 1,352 patients between the ages of 20 to 24, followed by 25 to 29. As a result of multivariate logistic regression analysis that adjusted epidemiologic factors to view the risk of death, the odds ratio of death would be hemorrhagic conditions and other diseases of blood and blood-forming organs 3.88-fold (95% confidence interval [CI], 1.52-9.88), heart failure 3.17-fold (95% CI, 1.88-5.34), renal failure 3.07-fold (95% CI, 1.43-6.61), prostate malignant neoplasm 2.88-fold (95% CI, 1.01-8.22), acute myocardial infarction 2.38-fold (95% CI, 1.03-5.49), diabetes was 1.82-fold (95% CI, 1.25-2.67), and other ischemic heart disease 1.71-fold (95% CI, 1.09-2.66)., Conclusion: We hope that this study could provide information on high risk groups for preemptive interventions. In the future, if a vaccine for COVID-19 is developed, it is expected that this study will be the basic data for recommending immunization by selecting those with chronic disease that had high risk of death, as recommended target diseases for vaccination., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2020 The Korean Academy of Medical Sciences.)

Background: There is a controversy whether it is safe to continue renin-angiotensin system blockers in patients with coronavirus disease 2019 (COVID-19). We analyzed big data to investigate whether angiotensin-converting enzyme inhibitors and/or angiotensin II receptor blockers have any significant effect on the risk of COVID-19. Population-based cohort study was conducted based on the prescription data from nationwide health insurance records., Methods: We investigated the 1,374,381 residents aged ≥ 40 years living in Daegu, the epicenter of the COVID-19 outbreak, between February and March 2020. Prescriptions of antihypertensive medication during the year before the outbreak were extracted from the National Health Insurance Service registry. Medications were categorized by types and stratified by the medication possession ratios (MPRs) of antihypertensive medications after controlling for the potential confounders. The risk of COVID-19 was estimated using a difference in difference analysis., Results: Females, older individuals, low-income earners, and recently hospitalized patients had a higher risk of infection. Patients with higher MPRs of antihypertensive medications had a consistently lower risk of COVID-19 than those with lower MPRs of antihypertensive medications and non-users. Among patients who showed complete compliance, there was a significantly lower risk of COVID-19 for those prescribed angiotensin II receptor blockers (relative risk [RR], 0.751; 95% confidence interval [CI], 0.587-0.960) or calcium channel blockers (RR, 0.768; 95% CI, 0.601-0.980)., Conclusion: Renin-angiotensin system blockers or other antihypertensive medications do not increase the risk of COVID-19. Patients should not stop antihypertensive medications, including renin-angiotensin system blockers, because of concerns of COVID-19., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2020 The Korean Academy of Medical Sciences.)

Purpose: This study aimed to evaluate the risk of acute myocardial infarction (AMI) associated with intravitreal ranibizumab in age-related macular degeneration (AMD)., Methods: This nationwide retrospective case-crossover study using data from the Korean National Health Insurance Service database included patients diagnosed with exudative AMD using the registration code for exudative AMD (V201) from 2009 to 2014. We identified all incident AMI cases among these exudative AMD cases from inpatient claims and defined the index date as the date of hospitalization. For each patient, we defined the case period as one to 60 days and four control periods as 121 to 180, 181 to 240, 241 to 300, and 301 to 361 days, respectively, before the index date. A prescription of ranibizumab was searched for during the case and control periods. We calculated the adjusted odds ratios and their 95% confidence intervals using a conditional logistic regression model., Results: From a cohort of patients with exudative AMD (n = 41,860), a total of 181 AMI patients with exudative AMD were included. Among all the patients, 11.05% were treated during the 2 months preceding the index date as compared with 8.29% to 9.39% treated during control periods. The adjusted odds ratio of AMI associated with intravitreal ranibizumab during the preceding 2 months was 1.22 (95% confidence interval, 0.673-2.213; p = 0.5124). Analyses based on case periods of 15 days and 1 month yielded similar results., Conclusions: Intravitreal ranibizumab injection does not appear to increase the risk of hospitalization for AMI within 60 days in exudative AMD patients., Competing Interests: No potential conflict of interest relevant to this article was reported., (© 2020 The Korean Ophthalmological Society.)

Objective: The aim of this study was to gather the expert opinions of Korean epileptologists regarding the treatment of adult patients with epilepsy., Methods: A total of 42 neurologists who specialized in epilepsy were surveyed. They completed an online questionnaire describing multiple patient scenarios. Using these scenarios, they evaluated treatment strategies and gave their preference for specific antiepileptic drugs (AEDs) used to treat genetically mediated generalized epilepsy and focal epilepsy., Results: Initial AED monotherapy, followed by a second form of alternative monotherapy or an add-on combination therapy, was the preferred treatment strategy. The experts reached consensus for 87.2% of the items. The most commonly selected AEDs for the initial monotherapy for patients with generalized epilepsy were levetiracetam or valproate. For those with focal epilepsy, levetiracetam, oxcarbazepine, or lamotrigine were the most popular selections. Ethosuximide was the treatment of choice only for patients with generalized epilepsy with prominent absence seizures. Levetiracetam was preferred as an add-on therapy for both generalized and focal epilepsy. For special populations of patients, such as elderly adults or those with comorbid diseases, levetiracetam or lamotrigine was selected as the treatment of choice., Conclusion: Most of the survey results were in accordance with the US expert opinion survey published in 2016. This survey can assist clinicians in making clinical decisions when treating individual adult patients with epilepsy., Competing Interests: Declaration of competing interest None., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Central line-associated bloodstream infections (CLABSIs) are preventable health care-associated infections that can lead to increased mortality. Therefore, we investigated trends in CLABSI rates, and the factors associated with changing trends over a 10-year period using the Korean National Healthcare-associated Infections Surveillance System (KONIS)., Methods: We investigated annual CLABSI rates from 2006 to 2015 in 190 KONIS-participating intensive care units (ICUs) from 107 participating hospitals. We collected data associated with hospital and ICU characteristics and analyzed trends using generalized autoregressive moving average models., Results: The CLABSI pooled mean rate decreased from 3.40 in 2006 to 2.20 in 2015 (per 1,000 catheter-days). The trend analysis also showed a significant decreasing trend in CLABSI rates in unadjusted models (annual increase, -0.137; P < .001). After adjusting for hospital and ICU characteristics, significant decreasing trends were identified (annual increase, -0.109; P < .001). However, there were no significant changes in subgroups with non-university-affiliated hospitals, hospitals in metropolitan areas near Seoul, small hospitals (300-699 beds), or surgical ICUs., Conclusions: In South Korea, CLABSI rates have shown significant reductions in the past 10 years with participation in the KONIS. However, CLABSI rates may be reduced by encouraging more hospitals to participate in the KONIS and by improved policy support for hospitals lacking infection control resources., (Copyright © 2019 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Severe and life-threatening drug eruptions include drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN). One class of medications that has been highly associated with such drug eruptions is antiepileptic drugs (AEDs). We attempt to investigate drug eruptions associated with AEDs as a class, as well as with individual AEDs, in Korea., Methods: We used the Korea Institute of Drug Safety and Risk Management - Korea Adverse Event Reporting System (KIDS-KAERS) database, a nationwide database of adverse events reports, between January 2008 and December 2017 to investigate the reporting count of all drug eruptions and calculated the ratio of DRESS/SJS/TEN reports for each AED., Results: Among a total of 2,942 reports, most were of rash/urticaria (2,702, 91.8%), followed by those of DRESS (109, 3.7%), SJS (106, 3.6%), and TEN (25, 0.85%). The common causative AEDs were lamotrigine (699, 23.8%), valproic acid (677, 23%), carbamazepine (512, 17.4%), oxcarbazepine (320, 10.9%), levetiracetam (181, 6.2%), and phenytoin (158, 5.4%). In limited to severe drug eruptions (DRESS, SJS, and TEN; total 241 reports), the causative AEDs were carbamazepine (117, 48.8%), lamotrigine (57, 23.8%), valproic acid (20, 8.3%), phenytoin (15, 6.3%), and oxcarbazepine (10, 4.2%). When comparing aromatic AED with non-aromatic AED, aromatic AEDs were more likely to be associated with severe drug eruption (aromatic AEDs: 204/1,793 versus non-aromatic AEDs: 37/1,149; OR, 3.86; 95% CI, 2.7-5.5). Death was reported in 7 cases; DRESS was the most commonly reported adverse event (n = 5), and lamotrigine was the most common causative AED (n = 5)., Conclusion: Although most cutaneous drug eruptions in this study were rash or urticaria, approximately 8% of reports were of severe or life-threatening adverse drug reactions, such as SJS, TEN, or DRESS. When hypersensitivity skin reactions occurred, aromatic AEDs were associated with 4 fold the risk of SJS/TEN/DRESS compared with non-aromatic AEDs. Our findings further emphasize that high risk AEDs should be prescribed under careful monitoring, and early detection and prompt interventions are needed to prevent severe complications., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2020 The Korean Academy of Medical Sciences.)

Background/aims: Chronic obstructive pulmonary disease (COPD) is a major cause of mortality in the world. There are no population-based studies on longterm mortality in COPD patients in Korea., Methods: Using the large, population-based, National Health Insurance Service- National Sample Cohort (NHIS-NSC), we identified COPD patients using the International Classification of Disease-Tenth Revision (ICD-10) and prescription details in the NHIS-NSC during 2003 to 2013. We analyzed the survival curves of COPD patients by sex, age, and cause of death., Results: A total of 14,127 individuals older than 40 years were diagnosed with COPD. There were a total of 3,695 deaths (26.2%) in COPD patients during the study period. The 5-year mortality of COPD patients was 25.4% (29.9% in males and 19.1% in females). The mortality rate increased rapidly with age. The most common cause of death in COPD was chronic lower respiratory disease., Conclusion: This study described long-term mortality in COPD patients in Korea. Higher mortality was observed in males, and it was closely related to age.

Nitrogen use efficiency in modern agriculture is very low. It means that a lot of synthetic chemicals are wasted rather than utilized by crops. This can cause more problems where the soil surface is thin and rocky like Jeju Island in the Republic of Korea. This is because overly used nitrogen fertilizer can be washed into the underground water and pollute it. Thus, it would be important to monitor the nitrogen deficiency of crops in the field to provide the right amount of nitrogen in a timely manner so that nitrogen waste can be limited. To achieve this, the normalized difference vegetation index (NDVI) was used to monitor chlorophyll content, which is tightly associated with nitrogen content in the buckwheat field. The NDVI was calculated with the data obtained by a low-resolution camera mounted on an unmanned aerial vehicle. The results showed that the NDVI can estimate the chlorophyll content of buckwheat. These simple but clear results imply that precision agriculture could be achieved even with a low-resolution camera in a cost-effective manner to reduce the pollution of underground water., Competing Interests: The authors declare no conflicts of interest.

Background/aim: The aim of this study was to estimate the nationwide incidence of clinically diagnosed exudative age-related macular degeneration (AMD) and associated use of ranibizumab and aflibercept in South Korea., Methods: In this retrospective, population-based cohort study, claims data for 2010-2015 were analysed in a randomly selected sample of 519 661 adults aged ≥40 years. The incidence per 10 000 person-years was estimated, along with the 95% CI. Incident exudative AMD was defined based on the registration code for rare intractable diseases. Use of ranibizumab and aflibercept and the incidence of exudative AMD were recorded., Results: Nine hundred and twelve patients were newly diagnosed with exudative AMD in 2010-2015. The 6-year incidence in the general population aged ≥40 years was 2.9 (95% CI 2.8 to 3.0) per 10 000 person-years. The incidence was highest in individuals aged 75-79 years (12.0, 95% CI 10.3 to 13.8). The incidence was higher in men than in women in all age groups. Six hundred and twenty-five (69%) of the 912 newly diagnosed patients started ranibizumab or aflibercept as a first-line treatment. The average number of injections administered was 6.1 (SD 3.9; minimum of 1 injection and maximum government-supported limit of 14) during 2010-2015; the number increased with increasing government funding support (from 5 to 10 and from 10 to 14 in 2013 and 2014, respectively)., Conclusions: This study describes the incidence of exudative AMD in South Korea and its treatment under the national health insurance system in this country. Its findings could be used for reference purposes and be useful when planning treatment for exudative AMD., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Aims: Long-term results on hepatitis B virus (HBV) reactivation in patients with resolved infection during anti-cancer therapy are unknown. This study investigated long-term risk and therapeutic endpoints including hepatitis B surface antigen (HBsAg) seroclearance following antiviral therapy in patients developing reactivation of resolved HBV., Methods: The study included 528 consecutive HBsAg-negative/hepatitis B core antibody-positive patients who underwent rituximab treatment or hematopoietic stem cell transplantation (HSCT) between 2006 and 2016. Long-term outcomes of patients with reactivation after antiviral therapy were examined in comparison with 37 HBsAg-positive chronic carriers under the same medical settings., Results: The 7-year cumulative rate of HBV reactivation was 10.8% and 57.9% in patients receiving rituximab treatment and HSCT, respectively. After antiviral initiation, patients with reactivation of resolved HBV showed significantly higher 1-year cumulative rates of hepatitis B e antigen seroconversion (69.2% vs. 22.6%, P = 0.008) and HBsAg seroclearance (61.8% vs. 3.3%, P < 0.001) than chronic HBsAg carriers. Reactivation of resolved HBV was independently predictive of HBsAg seroclearance in a combined group of reactivated patients and chronic HBsAg carriers. Low viral load at reactivation was predictive of HBsAg seroclearance in reactivated patients. The majority of patients with HBsAg seroclearance developed anti-HBs. None of the reactivated patients who achieved HBsAg seroclearance relapsed after cessation of antiviral therapy., Conclusions: HBsAg seroclearance rapidly occurs following antiviral therapy for reactivation of resolved HBV infection, suggesting distinct clinical phenotypes as well as shorter duration of HBV infection associated with this particular disease setting-HBV reactivation.

Background: Hyperglycemic crisis is a metabolic emergency associated with diabetes mellitus. However, accurate epidemiologic information on cases of hyperglycemic crisis in Korea remains scarce. We evaluated trends in hyperglycemic crisis hospitalizations and in- and out-of-hospital mortality in Korea. We also predicted future trends., Methods: We extracted claims data with hyperglycemic crisis as the principal diagnosis from the National Health Insurance Service database in Korea from January 2004 to December 2013. We investigated the numbers of claims with hyperglycemic crisis and identified trends in hyperglycemic crisis based on those claims data. We predicted future trends by statistical estimation., Results: The total annual number of claims of hyperglycemic crisis increased from 2,674 in 2004 to 5,540 in 2013. Statistical analysis revealed an increasing trend in hyperglycemic crisis hospitalizations ( P for trend <0.01). In contrast, the hospitalization rate per 1,000 diabetes cases showed a decreasing trend ( P for trend <0.01) during this period. The mortality rate per 1,000 diabetes cases also showed a decreasing trend ( P for trend <0.0001). However, no distinct linear trend in the case-related fatality rate at <60 days over the last decade was observed. The predicted number of annual claims of hyperglycemic crisis will increase by 2030., Conclusion: The number of hyperglycemic crisis hospitalizations in Korea increased in the last decade, although the hospitalization rate per 1,000 diabetes cases and mortality rate decreased. Also, the predicted number of annual claims will increase in the future. Thus, it is necessary to establish long-term healthcare policies to prevent hyperglycemic crisis., Competing Interests: No potential conflict of interest relevant to this article was reported., (Copyright © 2019 Korean Endocrine Society.)

Purpose: To assess changes in clinical practice patterns after implementing diagnosis-related group (DRG) payment system in July 2013 and its effect on the quality of care for pelvic organ prolapse (POP)., Materials and Methods: Using the 2011-2016 administrative database from National Health Insurance claim data, we reviewed medical information of 7362 patients who underwent hysterectomies for POP in Korean tertiary hospitals. We compared changes in several variables including length of stay, concomitant procedures, outpatient visits and readmission within 30 days after discharge, and retreatment for POP or stress urinary incontinence within postoperative 1 year before and after DRG system., Results: After the introduction of DRG system, the average length of stay decreased (7.74 ± 2.88 to 6.63 ± 2.18 days, p<0.001) without increasing readmission rates. However, the number of outpatient visits increased (2.78±2.33 to 2.98±2.47, p<0.001). Regarding concomitant procedures, the rates of colpopexy and midurethral slings significantly decreased (7.87% and 9.84% to 4.93% and 2.93%, respectively, all p<0.001). Even though there was no difference in the reoperation rates, pessary insertion for recurrent POP significantly increased after the introduction of DRG system (0.10% to 0.38%, p = 0.015)., Conclusion: The implementation of DRG in Korean tertiary hospitals has led to increase of outpatient visits and reduced surgical management for POP, which indicates that the uniform application of DRG influences the quality of care for POP patients., Competing Interests: The authors have declared that no competing interests exist.

Objective: The objective of this trial was to compare the effectiveness of levetiracetam (LEV) and topiramate (TPM) as adjunctive treatment for patients with focal seizures in Korea., Methods: In this Phase IV, open-label, multicenter trial (NCT01229735), adults were randomized to treatment with LEV (1000-3000 mg/day) or TPM (200-400 mg/day). Only patients achieving LEV ≥1000 mg/day or TPM ≥100 mg/day after a 4-week up-titration entered the 20-week dose-finding and subsequent 28-week maintenance periods. The primary outcome was the 52-week retention rate; others included safety and exploratory efficacy outcomes., Results: Of 343 randomized patients (LEV 177; TPM 166), 211 (61.5%) completed the trial. In the full analysis set (FAS), retention rate was 59.1% with LEV vs 56.6% with TPM (p = 0.7007), while in the prespecified sensitivity analysis, based on data from patients who received drug doses in the recommended range (LEV 176; TPM 113), it was 59.1% with LEV vs 42.5% with TPM (p = 0.0086). In the FAS, median percent reduction in seizure frequency from baseline was 74.47% with LEV and 67.86% with TPM (p = 0.0665); ≥50% responder rate was 69.0% vs 64.8% (p = 0.4205), and the 6-month seizure-freedom rate was 35.8% vs 22.3% (p = 0.0061). In the sensitivity analysis, differences between groups were greater, favoring LEV. Incidences of treatment-emergent adverse events (TEAEs) were 70.6% with LEV vs 77.1% with TPM; most frequently somnolence (20.3%), dizziness (18.1%), and nasopharyngitis (13.6%) with LEV; and decreased appetite (15.7%), dizziness (14.5%), and headache (14.5%) with TPM. Discontinuations due to TEAEs were 7.9% with LEV and 12.7% with TPM., Conclusions: In this open-label trial, the 52-week retention rate was not significantly different between LEV and TPM. However, LEV was associated with a substantially higher seizure freedom rate and a more favorable safety profile than TPM in this population of Korean patients with focal seizures., (Copyright © 2019. Published by Elsevier Inc.)

Background: Our purpose was to compare the risk of tooth loss caused by periodontal disease between diabetic and nondiabetic individuals and to estimate the relative risk of tooth loss according to the severity and control of diabetes., Methods: We selected 10,215 individuals who were diagnosed as diabetics in the Korean National Health Insurance Service-National Sample Cohort (NHIS-NSC) database in 2003 and the same number of individuals who had never been diagnosed with diabetes during the period covered by the NHIS-NSC (2002-2013) with propensity score matching. Diabetic individuals were divided into two groups according to the treatment modality. We counted the number of teeth lost in each group to determine the difference in the risk of tooth loss among groups and used the Cox proportional hazards model to calculate hazard ratios (HRs) of tooth loss caused by periodontitis., Results: Diabetic individuals had a higher risk of tooth loss than nondiabetic individuals (HR = 1.298, 95% confidence interval [CI]: 1.233 ≤ HR ≤ 1.366; P < 0.01). The severer the degree of diabetes, the higher the risk of tooth loss. As the number of dental visits increased, the risk of tooth loss declined (HR = 0.998, 95% CI: 0.996 ≤ HR ≤ 0.999; P < 0.01)., Conclusions: Within the limits of this retrospective cohort study, the risk of tooth loss among diabetic individuals was higher than that among nondiabetic individuals. The risk of tooth loss declined with increasing numbers of dental visits and increased with the severity of diabetes., (© 2018 American Academy of Periodontology.)

Purpose: The association between long-term cardioprotective aspirin use and neovascular age-related macular degeneration (AMD) is controversial. This study was undertaken to estimate the risk of neovascular AMD with long-term regular use of low-dose aspirin., Design: Retrospective population-based study, using a nationwide cohort from a variety of clinics and hospitals in South Korea., Participants: Nonregular aspirin users and regular aspirin users under national health insurance, aged ≥45 years, who were followed from 2010 to 2015, were identified., Methods: Incidence per 10 000 person-years for neovascular AMD was estimated. Long-term regular use of low-dose aspirin was defined as sustained intake of ≤100 mg aspirin with ≥1044 days prescription between 2005 and 2009. Nonregular aspirin users included occasional users or nonusers. The analyses included a propensity score-adjusted analysis in a large, randomly selected, unmatched whole cohort (n = 482 613); propensity score-matched analysis in a matched cohort (n = 74 196); and maximally adjusted analysis in the unmatched whole cohort (n = 482 613)., Main Outcome Measures: Incidence of newly developed neovascular AMD using the registration code for intractable disease under national health insurance., Results: Incidence of neovascular AMD was 3.5 among nonregular aspirin users and 7.2 among regular aspirin users per 10 000 person-years in the unmatched whole cohort. However, propensity score-adjusted analyses revealed no association between aspirin use and neovascular AMD (adjusted hazard ratio [HR], 0.98; 95% confidence interval [CI], 0.73-1.30). Likewise, propensity score-matched analyses showed no association; incidences of neovascular AMD were 7.5 and 7.1 among nonregular aspirin users and regular aspirin users (crude HR, 0.94; 95% CI, 0.70-1.28), respectively. A maximally adjusted model, including age, sex, income, residential area, and history of 100 randomly selected types of generic drugs, showed no association (adjusted HR, 0.95; 95% CI, 0.71-1.28)., Conclusions: We found no association between long-term regular use of low-dose aspirin for 5 years and future incidence of neovascular AMD. Thus, this large-scale study suggests that regular, long-term use of low-dose aspirin appears to be safe with respect to the new development of neovascular AMD., (Copyright © 2018 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)