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Background: Immune checkpoint inhibitors (ICIs) are one of the main pillars of cancer therapy. Since other studies such as clinical trial and retrospective study have limitations for detecting the immune-related adverse events (irAEs) characterized by unpredictable onset, nonspecific symptoms and wide clinical spectrum, we aimed to identify the incidence of irAEs and to detect and evaluate the signals using real-world data. Methods: Cancer patients treated with anticancer medications were analyzed using the nationwide health insurance claims database of South Korea from 2017 to 2019, and Clinical Data Warehouse (CDW) database of Asan Medical Center (AMC), a tertiary referral hospital, from 2012 to 2019. AEs of ICI users were compared with those of non-ICI anticancer medication users. PD-1 inhibitors (nivolumab and pembrolizumab) and PD-L1 inhibitors (atezolizumab) were evaluated. We defined an AE as a newly added diagnosis after the ICI prescription using an ICD-10 diagnostic code. A signal was defined as an AE that was detected by any one of the four indices of data mining: hazard ratio (HR), proportional claims ratio (PCR), claims odds ratio (COR), or information component (IC). All detected signals were reviewed and classified into wellknown or potential irAEs. Signal verification was performed for targeted AEs using CDW of AMC using diagnostic codes and text mining. Results: We identified 118 significant signals related to ICI use. We detected 31 well-known irAEs, most of which were endocrine diseases and skin diseases. We also detected 33 potential irAEs related to disorders in the nervous system, eye, circulatory system, digestive system, skin and subcutaneous tissues, and bones. Especially, portal vein thrombosis and bone disorders such as osteoporosis with pathological fracture and fracture of shoulder, upper arm, femur, and lower leg showed high HR in ICI users than in non-ICI users. The signals from hospital database were verified using diagnostic codes and text mining. Conclusion: This real-world data analysis demonstrated an efficient approach for signal detection and evaluation of ICI use. An effective realworld pharmacovigilance system of the nationwide claims database and the EMR could complement each other in detecting significant AE signals. [ABSTRACT FROM AUTHOR]

Background/Aims: Although an association between achalasia and esophageal cancer has been reported, whether achalasia confers a substantial increase in mortality is unknown. Moreover, the causes of death related to achalasia have not been investigated. We performed this nationwide, population-based cohort study on achalasia because no such study has been performed since the introduction of high-resolution manometry in 2008. Methods: This study was performed using data extracted from the Korean National Health Insurance Service database, covering a 9-year period from 2009 to 2017. Control participants without a diagnostic code for achalasia were randomly selected and matched by sex and birth year at a case-to-control ratio of 1:4. Data on the cause of death from Statistics Korea were also analyzed. Results: The overall incidence of achalasia was 0.68 per 100,000 person-years, and the prevalence was 6.46 per 100,000 population. Patients with achalasia (n=3,063) had significantly higher adjusted hazard ratio (aHR) for esophageal cancer (aHR, 3.40; 95% confidence interval [CI], 1.25 to 9.22; p=0.017), pneumonia (aHR, 2.30; 95% CI, 1.89 to 2.81; p<0.001), aspiration pneumonia (aHR, 3.92; 95% CI, 2.38 to 6.48; p<0.001), and mortality (aHR, 1.68; 95% CI, 1.44 to 1.94; p<0.001). Esophageal cancer carried the highest mortality risk (aHR, 8.82; 95% CI, 2.35 to 33.16; p=0.001), while pneumonia had the highest non-cancer mortality risk (aHR, 2.28; 95% CI, 1.31 to 3.96; p=0.004). Conclusions: In this nationwide study, achalasia was associated with increased risk of mortality. Esophageal cancer and pneumonia were the most common comorbidities and the major causes of death in patients with achalasia. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Limited data are available regarding the association between liver cirrhosis (LC) and the risk of herpes zoster (HZ). This study aimed to determine the risk of HZ in patients with LC. METHODS: HZ was defined as the presence of the International Classification of Diseases-10th revision code for HZ and concomitant prescription of antiviral medication. The incidence rates and standardized incidence ratios (SIRs) of HZ in patients with LC were analyzed using data from the Health Insurance Review and Assessment Service in Korea claims database from 2009 to 2019. RESULTS: A total of 504,986 Korean patients with LC were included. The mean age was 52.4 years, and 60.8% were men. Chronic hepatitis B was the most common cause of LC. The incidence rates for HZ and HZ-related hospitalization were 21.6 of 1,000 and 1.81 of 1,000 person-years, respectively. The SIRs for HZ and HZ-related hospitalization were 1.09 (95% confidence interval [CI]: 1.08-1.09) and 1.48 (95% CI: 1.44-1.52), respectively, which were significantly higher than those in the general population. Patients with LC aged 20-29, 30-39, and 40-49 years had SIRs for HZ of 1.41 (95% CI: 1.33-1.48), 1.16 (1.13-1.19), and 1.17 (1.13-1.19), respectively. In multivariable analysis, woman (adjusted hazard ratio [AHR]: 1.48), steroid (AHR: 1.20), immunosuppressant use (AHR: 1.26), and combined comorbidities were associated with an increased risk of HZ among patients with LC. DISCUSSION: Patients with LC, particularly those who are not currently recommended for HZ vaccination, were at an increased risk of HZ and HZ-related hospitalization compared with the general Korean population. [ABSTRACT FROM AUTHOR]

Background: Cambaroides similis is an endangered candidate species living in the stream of South Korea. Freshwater crayfish is known to decline rapidly not only domestically, but also internationally. Its decline is projected to be further exacerbated due to climate change. Understanding physical characteristics of the habitat is crucial for the conservation of an organism. However, comprehensive data regarding the distribution and physical habitat characteristics of C. similis are currently unavailable in South Korea. Thus, the objective of this study was to ascertain preferred ranges for water depth, current velocity, and streambed substrate of C. similis using Weibull model. Results: In this study, C. similis was found at 59 sites across 12 regions in South Korea. Its optimal water depth preferences ranged from 11.9 cm to 30.1 cm. Its current velocity preferences ranged from 9.8 cm s-1 to 29.1 cm s-1. Its substrate preferences ranged from -5.1 Fm to -2.5 Fm. Median values of central tendency were determined as follows: water depth of 21.4 cm, current velocity of 21.2 cm s-1, and substrate of -4.1 Fm. Mean values of central tendency were determined as follows: water depth of 21.8 cm, current velocity of 22.0 cm s-1, and substrate of -4.4 Fm. Mode values of central tendency were determined as follows: water depth of 21.7 cm, current velocity of 20.1 cm s-1, and substrate of -3.7 Fm. Conclusions: Based on habitat suitability analysis, physical microhabitat characteristics of C. similis within a stream were identified as Run section with coarse particle substrate, low water depth, and slow current velocity. Due to high sensitivity of these habitats to environmental changes, prioritized selection and assessment of threats should be carried out as a primary step. [ABSTRACT FROM AUTHOR]

Background/Aims: The long-term course of Crohn’s disease (CD) has never been evaluated in non-Caucasian population-based cohorts. The aim of the present study was to evaluate the longterm prognosis of Korean CD patients in the well-defined population-based Songpa-Kangdong inflammatory bowel disease cohort. Methods: Outcomes of disease and their predictors were evaluated for 418 patients diagnosed with CD between 1986 and 2015. Results: During a median of 123 months, systemic corticosteroids, thiopurines, and anti-tumor necrosis factor (TNF) agents were administered to 58.6%, 81.3%, and 37.1% of patients, respectively. Over time, the cumulative probability of starting corticosteroids significantly decreased (p=0.001), whereas that of starting thiopurines and anti-TNFs significantly increased (both p<0.001). The cumulative probability of behavioral progression was 54.5% at 20 years, and it significantly decreased during the anti-TNF era. Intestinal resection was required for 113 patients (27.0%). The cumulative probabilities of intestinal resection at 1, 5, 10, 20, and 25 years after CD diagnosis were 12.7%, 16.5%, 23.8%, 45.1%, and 51.2%, respectively. Multivariable Cox regression analysis identified stricturing behavior at diagnosis (adjusted hazard ratio [aHR], 2.70; 95% confidence interval [CI], 1.55 to 4.71), penetrating behavior at diagnosis (aHR, 11.15; 95% CI, 6.91 to 17.97), and diagnosis of CD during the anti-TNF era (aHR, 0.51; 95% CI, 0.35 to 0.76) as independently associated with intestinal resection. The standardized mortality ratio among CD patients was 1.36 (95% CI, 0.59 to 2.68). Conclusions: The long-term prognosis of Korean patients with CD is at least as good as that of Western CD patients, as indicated by the low intestinal resection rate. Moreover, behavioral progression and intestinal resection rates have decreased over the past 3 decades. [ABSTRACT FROM AUTHOR]

Background: Epidemiological data have shown that vitamin D deficiency is highly prevalent in Korea. Genetic factors influencing vitamin D deficiency in humans have been studied in Europe but are less known in East Asian countries, including Korea. We aimed to investigate the genetic factors related to vitamin D levels in Korean people using a genome-wide association study (GWAS). Methods: We included 12,642 subjects from three different genetic cohorts consisting of Korean participants. The GWAS was performed on 7,590 individuals using linear or logistic regression meta- and mega-analyses. After identifying significant single nucleotide polymorphisms (SNPs), we calculated heritability and performed replication and rare variant analyses. In addition, expression quantitative trait locus (eQTL) analysis for significant SNPs was performed. Results: rs12803256, in the actin epsilon 1, pseudogene (ACTE1P) gene, was identified as a novel polymorphism associated with vitamin D deficiency. SNPs, such as rs11723621 and rs7041, in the group-specific component gene (GC) and rs11023332 in the phosphodiesterase 3B (PDE3B) gene were significantly associated with vitamin D deficiency in both meta- and mega-analyses. The SNP heritability of the vitamin D concentration was estimated to be 7.23%. eQTL analysis for rs12803256 for the genes related to vitamin D metabolism, including glutamine-dependent NAD(+) synthetase (NADSYN1) and 7-dehydrocholesterol reductase (DHCR7), showed significantly different expression according to alleles. Conclusion: The genetic factors underlying vitamin D deficiency in Korea included polymorphisms in the GC, PDE3B, NADSYN1, and ACTE1P genes. The biological mechanism of a non-coding SNP (rs12803256) for DHCR7/NADSYN1 on vitamin D concentrations is unclear, warranting further investigations. [ABSTRACT FROM AUTHOR]

배경 Streptococcus pneumoniae (S. pneumoniae) is the most common organism of respiratory tract infection in community. In the post-pneumococcal vaccination (PCV) era, various serotype of S. pneumoniae and multidrug resistance pneumococcal disease increased compared with those in the pre-PCV era. To choose adequate empirical antibiotics, it is important to know the changing trend in antibiotic susceptibility of S. pneumoniae in a homogenous population in isolated region. 방법 We introduced a retrospective study about the changing trend of antimicrobial resistance to penicillin, erythromycin, ceftriaxone, levofloxacin, and vancomycin and multidrug resistance (MDR) of S. pneumoniae in all aged patients at a single teaching hospital in Jeju Island during 10 years (2009 – 2018). 결과 Of 1,460 S. pneumoniae isolates from 1,454 patients, pneumonia was the most common diagnosis (55.2%), 1,178 (81%) patients were origin of community onset. The overall antimicrobial resistance rate of S. pneumoniae to penicillin, erythromycin, ceftriaxone, levofloxacin, and vancomycin were 16.2%, 84.7%, 25.9 %, 3.3%, and 0%, respectively and MDR S. pneumoniae isolates were 98 (6.7%). The resistance to erythromycin and ceftriaxone and MDR rate significantly increased compared to 10 years ago. The resistance rate to erythromycin and ceftriaxone were significantly lower in both age group of 19 to 64 years and 65 years or older compare with those of in the age group 0 to 18 years. However, the resistance rate to levofloxacin and MDR rate were higher in both age group of 19 to 64 years and 65 years or older compared with those of in the age group 0 to 18 years. In addition, MDR rate increased significantly in the isolates from patients who had the history of hospital admission in 90 days. (OR = 3.45, CI = 1.86-6.36), invasive pneumococcal diseases (OR = 2.52, CI = 1.32-4.84) and sinusitis (OR = 5.68, CI = 2.19-14.74). 결론 The resistance for antibiotics of S. pneumoniae significantly increased compared to 10 years ago. However, the distribution of the individual antimicrobial resistance rate and MDR rate of S. pneumoniae significantly differed according to the age groups. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to compare differences in spiritual needs (SNs) and factors influencing SNs between patients with progressive terminal kidney disease and their family caregivers. Methods: An explorative comparative survey was used to identify the SNs of patients (N=102) with progressive terminal kidney disease undergoing hemodialysis and their family caregivers (N=88) at a general hospital located in Seoul, South Korea. The data were analyzed using descriptive statistics, the chi-square test, the independent t-test, one way analysis of variance, the Scheffé test, and multiple regression with dummy variables. Results: The SNs among family caregivers were higher than in the patient group. SNs were higher among those who were religious in both groups. Loving others was the highest-ranked subdimension in the patient group, followed in descending order by maintaining positive perspective, finding meaning, Reevaluating beliefs and life, asking "why?", receiving love and spiritual support, preparing for death, and relating to God. In the family group, the corresponding order was maintaining positive perspective, loving others, finding meaning, receiving love and spiritual support, preparing for death, relating to God, and asking "why?". The factors that had a negative influence on the level of SNs were not being religious in the patient group and having only a middle school level of education in the family group. Conclusion: The results of this study may serve as evidence that spiritual care for non-cancer patients' family caregivers should be considered as an important part of hospice and palliative care. [ABSTRACT FROM AUTHOR]

Passive surveillance (PS) is a traditional approach to communicable disease surveillance. To complement the approach, several countries have adopted active surveillance (AS) systems that involve the voluntary participation of physicians. This study compares AS versus PS systems in Korea based on the systems' reporting propensity of chickenpox. A mail questionnaire survey was conducted with a random sample of physicians involved in the PS system (N=1,955) and all sentinel physicians of the AS system (N=193). Multiple regression analysis was conducted to identify factors associated with reporting propensity. The reporting propensity of physicians in the AS system was significantly higher than that in the PS surveillance system, 2.7 versus 1.9 on a 5-point Likert scale (p<0.05). Multiple regression analysis showed that, in addition to the type of the surveillance system, physician knowledge of chickenpox as a notifiable disease and the type of institution with which a physician was affiliated were significant factors for a physician's reporting propensity. For both systems, the common barriers for reporting were 'lack of confidence in diagnosis,' 'burden from interference by the public health department following reporting,' and 'complexity of the reporting system.' In conclusion, AS of communicable diseases appeared to have a significantly better performance compared to PS in Korea in the case of chickenpox reporting. These findings would be useful for countries concerned with developing more effective strategies for improving the reporting rate of notifiable diseases. [ABSTRACT FROM AUTHOR]

Recent guidelines identified recovery from cardiac arrest as an additional link in the chain of survival. However, data on the disability level and long-term survivorship in such patients are limited. We aimed to determine the long-term disability level, including disability type and severity, in patients with out-of-hospital cardiac arrest (OHCA) 1 month after discharge. This nationwide observational study used data from the National Health Insurance Service of Korea. We included adult OHCA patients who presented to the emergency departments (ED) of all hospitals in Korea between 2009 and 2018. The main outcome was disability level between 1 month after discharge and the 2-year follow-up. The average disability level was divided into six grades: most severe (grade 1) to mild (grade 6). Among 224,520 OHCA patients, 25,598 (11.4%) survived at 30 days. After excluding 3143 patients with a follow-up less than 2 years, 22,455 patients were included. Newly-developed disabilities were observed in 2664 patients (11.9%) and were more frequent in 1-year survivors than non-survivors (16.7% vs. 4.4%, p < 0.01). The most common type of disability was encephalopathic (54.2%), followed by renal (16.1%), physical (10.5%), and cardiac (4.2%) disabilities. Grade 1 disability was most frequent, followed by grade 2 and 3 (45.7%, 23.5%, 10.9%, respectively). Among patients who survived at 30 days after OHCA, 11.9% developed disabilities, including encephalopathic, physical, renal, and cardiac disabilities. Physicians should be aware of the risk of these disabilities and efforts to treat these disabilities in OHCA survivors should be increased. [ABSTRACT FROM AUTHOR]