Increased Risk of Osteoporotic Fracture in Patients With Autoimmune Hepatitis.

INTRODUCTION: Few large-scale studies have been published regarding the association between autoimmune hepatitis (AIH) and risk of osteoporotic fracture. This study aimed to determine the risk of developing an osteoporotic fracture in patients with AIH. METHODS: We used claims data from the Korean National Health Insurance Service between 2007 and 2020. Patients with AIH (n = 7,062) were matched with controls (n = 28,122) based on age, sex, and duration of follow-up using a ratio of 1:4. Osteoporotic fractures included fractures of the vertebrae, hip, distal radius, and proximal humerus. The incidence rate (IR) and IR ratio of osteoporotic fracture were compared between the 2 groups, and their associated factors were evaluated. RESULTS: During a median follow-up period of 5.4 years, 712 osteoporotic fractures occurred in patients with AIH with an IR of 17.5 per 1,000 person-years. Patients with AIH had a significantly higher risk of osteoporotic fractures than matched controls, with an IR ratio of 1.24 (95% confidence intervals, 1.10-1.39, P < 0.01) in the multivariable analysis. Female sex, older age, history of stroke, presence of cirrhosis, and use of glucocorticoids were associated with an increased risk of osteoporotic fractures. In the 2-year landmark analysis, longer duration of glucocorticoid exposure was associated with an incremental increased risk of osteoporotic fracture. DISCUSSION: Patients with AIH had an increased risk of osteoporotic fracture compared with controls. The presence of cirrhosis and long-term use of glucocorticoids further adversely affected osteoporotic fracture in patients with AIH.

Comparison of anticholinergic burden with chronic polypharmacy on functional decline and mortality in Korean older people: a retrospective nationwide cohort study.

BACKGROUND: We aimed to evaluate the association of anticholinergic burden and chronic polypharmacy with the incidence of functional decline and all-cause mortality, and to determine the difference between anticholinergic burden and chronic polypharmacy among Korean older people. METHODS: This nationwide cohort study included 42,132 older people aged ≥ 65 years who underwent Korean National Health Insurance Service health examinations from 2007 to 2008. Odds ratios (ORs) and 95% confidence intervals (CIs) for abnormal Timed Up and Go (TUG) test results were assessed using multivariate logistic regression analyses. Hazard ratios (HRs) and 95% CIs for all-cause mortality until the end of 2015 were estimated using multivariable Cox proportional hazards regression analysis. RESULTS: Of the participants, 37.19% had abnormal TUG test results, and 7.66% of those died during the 5.7-year mean follow-up. The abnormal TUG test results OR increased by 27% among individuals with Korean Anticholinergic Burden Scale (KABS) scores ≥ 3 (OR 1.27, 95% CI 1.02-1.58) compared to those with KABS scores of 0. The HRs for all-cause mortality increased for individuals with higher KABS scores (P for trend < 0.001) or chronic polypharmacy (P for trend < 0.001) compared to those for individuals without these conditions. The combination of a higher KABS or chronic polypharmacy and abnormal TUG test results increased the risk of all-cause mortality (All P for trend < 0.001). CONCLUSION: Anticholinergic drug burden shows a better association with functional decline than chronic polypharmacy, and the use of medications and functional decline may be important risk factors for all-cause mortality among older people.

COVID-19 Outcome and Tobacco Product Use: Case-Control and Retrospective Cohort Studies Using Nationwide Samples.

BACKGROUND: Conflicting evidence exists regarding the association between smoking and the risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We investigated the association between combustible cigarette (CC) smoking, noncombustible tobacco product (NCTP) use, and the use of any tobacco product with various coronavirus disease 2019 (COVID-19) outcomes. METHODS: A case-control study was conducted using the Korea Disease Control and Prevention Agency-COVID19-National Health Insurance Service (NHIS) cohort. A retrospective cohort study was conducted using 12,571,698 individuals from the NHIS cohort. Logistic regression evaluated the association between CC smoking, NCTP use, and use of any tobacco product with SARS-CoV-2 infection. Poisson regression evaluated the association between these forms of tobacco product use and COVID-19-related hospitalization and mortality. RESULTS: In the case-control study, we identified 30,878 cases of SARS-CoV-2 infection. The odds ratios (95% confidence intervals [CIs]) for SARS-CoV-2 infection were lower among current CC smokers (0.51, 0.48-0.54), current- and former-NCTP users (0.80, 0.74-0.88; 0.82, 0.74-0.91), and current users of any tobacco product (0.52, 0.49-0.55) relative to never user controls. In retrospective cohort study, we identified 16,521 COVID-19-related hospitalization and 362 COVID-19-related deaths. The relative risks (95% CIs) for COVID-19-related hospitalization were lower among current CC smokers (0.51, 0.48-0.54) and current users of any tobacco product (0.53, 0.50-0.56) relative to never user controls. There was no association between the use of tobacco product and COVID-19-related mortality. CONCLUSION: Current CC smokers and current users of any tobacco product showed reduced risk of SARS-CoV-2 infection and COVID-19-related hospitalization. It remains uncertain whether these relationships are causal.

Stratification of Nontuberculous Mycobacterial Disease Risk in Type 2 Diabetes Based on Metformin Use: a Population-Based Cohort Study in South Korea.

In a 1:4 case-control matched analysis of data from a nationwide population-based cohort in South Korea, we evaluated whether metformin use mitigates the risk of nontuberculous mycobacterial disease in patients with type 2 diabetes. Multivariable analysis revealed no significant association of metformin use with a diminished risk for incident nontuberculous mycobacterial disease in patients with type 2 diabetes.

Liver Cirrhosis Increases the Risk of Herpes Zoster: A Nationwide Population-Based Cohort Study.

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.

Epidemiology and comorbidities in idiopathic pulmonary fibrosis: a nationwide cohort study.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is frequently accompanied by comorbidities, with the management of these comorbidities crucial for clinical outcomes. This study investigated the prevalence, incidence, changes over time, and clinical impact of comorbidities in IPF patients, based on nationwide claims data in South Korea. METHODS: This retrospective cohort study utilised nationwide health claim data in South Korea between 2011 and 2019. Patients with IPF were defined as those with ICD-10 code J84.1 and Rare Intractable Disease code V236 who made at least one claim per year. Patients were classified by sex, age, pirfenidone use and burden of comorbidities, and differences among groups were determined. RESULTS: The yearly prevalence rate of IPF increased from 7.50 to 23.20 per 100,000 people, and the yearly incidence rate increased from 3.56 to 7.91 per 100,000 person-years over time. The most common respiratory comorbidity was chronic obstructive pulmonary disease (37.34%), followed by lung cancer (3.34%), whereas the most common non-respiratory comorbidities were gastro-oesophageal reflux disease (70.83%), dyslipidaemia (62.93%) and hypertension (59.04%). The proportion of some comorbidities differed by sex, age and use of pirfenidone. The proportion of lung cancer was higher in patients treated with pirfenidone, whereas the proportion of anxiety and depression were lower in patients not treated with pirfenidone. Charlson comorbidity index ≥ 4 was associated with increases in hospitalisations and total medical costs. CONCLUSIONS: The yearly prevalence and incidence of IPF and comorbidities in Korea increased over time. These comorbidities affected the use of pirfenidone and medical resources.

Association Between Body Weight Changes and Subsequent Development of Out-of-Hospital Cardiac Arrest: A Population-Based Nested Case-Control Study.

BACKGROUND: Body weight is a modifiable demographic factor. Although the association of body mass index (BMI) categories with sudden cardiac death was reported, dynamic changes of BMI and the risk of cardiac arrest remain unknown. This study aimed to evaluate the association between the out-of-hospital cardiac arrest (OHCA) occurrence within a year and the percent changes of BMI preceding the OHCA. METHODS: This population-based nested case-control study used the National Health Insurance Service Data of Korea. In all, 24,465 patients with non-traumatic OHCA between 2010 and 2018, who underwent national health check-up twice (one within a year and the other within 2-4 years before OHCA) and 32,434 controls without OHCA, were matched for age and sex. The association between the risk of OHCA and BMI percent change stratified by sex was investigated. RESULTS: All the BMI percent changes of ≥ 5% significantly increased the OHCA occurrence with a reverse J-shaped association. Compared to individuals with a stable weight, those with severe (> 15%) BMI decrease had the highest odds ratio (OR) of 4.29 (95% confidence intervals [CIs], 3.72-4.95) for OHCA occurrence followed by those with moderate (10-15%) weight loss (OR, 2.80; 95% CI, 2.55-3.08) and those with severe (> 15%) weigh gain (OR, 2.24; 95% CI, 1.96-2.57), respectively. The impact of weight loss on the cardiac arrest occurrence was more prominent in men, while the impact of weight gain was more prominent in women. CONCLUSION: Significant weight changes increase the risk of OHCA within a year with a reverse J-shaped association. Significant weight loss might be a warning sign for OHCA especially for men.

Treatment Outcomes of Patients With Ruptured Abdominal Aortic Aneurysms.

BACKGROUND: Ruptured abdominal aortic aneurysm (rAAA) is a serious complication of abdominal aortic aneurysm associated with high operative mortality and morbidity rates. The present study evaluated the perioperative and long-term outcomes of Korean patients with rAAA based on national health insurance claims data. METHODS: The National Health Insurance Service (NHIS) database was searched retrospectively to identify patients with rAAA who underwent endovascular aneurysm repair (EVAR) and open surgical repair (OSR) from 2009 to 2018. Perioperative (≤ 30 days), early postoperative (≤ 3 month), and long-term (> 3 month) survival, reinterventions, and complications were assessed. RESULTS: The search identified 1,034 patients with rAAA, including 594 who underwent EVAR and 440 who underwent OSR. When the study period was divided into two, the total numbers of patients with rAAA, patients who underwent EVAR, and octogenarians were higher during the second half. The perioperative mortality rate was 29.8% in the EVAR and 35.0% in the OSR group (P = 0.028). Hartmann's procedure for bowel infarction was performed more frequently in the OSR than in the EVAR group (adjusted odds ratio, 6.28; 95% confidence interval [CI], 2.33-21.84; P = 0.001), but other complication rates did not differ significantly. All-cause mortality during the entire observation period did not differ significantly in the EVAR and OSR groups (adjusted hazard ratio, 1.17; 95% CI, 0.98-1.41; P = 0.087). Abdominal aortic aneurysm-related reintervention rate was significantly lower in the OSR group (adjusted hazard ratio, 0.31; 95% CI, 0.14-0.70; P = 0.005). CONCLUSION: Although EVAR showed somewhat superior perioperative outcomes for rAAA, the long-term outcomes of EVAR after excluding initial 3 months were significantly worse than OSR. When anatomically feasible for both treatments, the perioperative mortality risk and reasonable prospects of long-term survival should be considered in rAAA.

High Risk of Fractures Within 7 Years of Diagnosis in Asian Patients With Inflammatory Bowel Diseases.

BACKGROUND & AIMS: In this nationwide population-based study, we investigated the risk of vertebral and hip fractures in patients with inflammatory bowel disease (IBD). METHODS: Using data from the Korean National Health Insurance claims database gathered between 2007 and 2016, we calculated the incidence rate ratios (IRRs) of vertebral and hip fractures in patients with newly diagnosed IBD (n = 18,228; 64.1% male, 65.9% ulcerative colitis) compared with an age- and sex-matched control population (matching ratio, 1:10; n = 186,871). RESULTS: During a median follow-up period of 4.5 years, the incidence rate and IRR of vertebral and hip fractures in patients with IBD were 2.88 per 1000 person-years and 1.24 (95% CI, 1.08-1.42), respectively. The cumulative risk of vertebral and hip fractures in IBD patients was 0.6%, 1.4%, and 1.9% at 2, 5, and 7 years after diagnosis, respectively, and this risk of fracture in IBD patients was higher than that in matched controls (P = .002). The use of corticosteroids further increased the risk of fractures in IBD patients (IRR, 1.37; 95% CI, 1.13-1.65) compared with matched controls. The risk of fractures was significantly higher in patients with Crohn's disease (CD) (IRR, 1.56; 95% CI, 1.19-2.04) than in matched controls, and this risk remained higher in patients with CD without corticosteroid exposure (IRR, 1.62; 95% CI, 1.12-2.34). The risk of fracture increased with age and was particularly high in females and in those with comorbidities. CONCLUSIONS: The risk of fractures was significantly high in newly diagnosed IBD patients, especially in those with CD regardless of corticosteroid exposure.

Association of the atherogenic index of plasma with cardiovascular risk beyond the traditional risk factors: a nationwide population-based cohort study.

BACKGROUND: The atherogenic index of plasma (AIP) is composed of triglycerides and high-density lipoprotein cholesterol and is a novel marker for assessing the risk of atherogenicity and cardiometabolic health. An association between AIP and greater frequency of major adverse cardiovascular events (MACEs) in patients with type 2 diabetes mellitus and high cardiovascular (CV) disease risk has been reported. However, only few studies have examined the correlation between AIP and CV risk in general populations. We thus aimed to evaluate the relationship between AIP and CV diseases using a large-scale population dataset from the Korean National Health Insurance Service-National Health Screening Cohort (NHIS-HEALS). METHODS: A total of 514,866 participants were enrolled from the NHIS-HEALS and classified according to the AIP quartiles. We performed univariate and multivariate Cox proportional hazards regression analyses to determine the association between AIP and MACEs, CV events, and CV mortality. RESULTS: During follow-up, we documented 12,133, 11,055, and 1942 cases of MACEs, CV events, and CV mortality, respectively. The multivariate-adjusted hazard ratios [HRs; 95% confidence interval (CI)] for MACEs gradually and significantly increased with the AIP quartiles [1.113 (1.054-1.175) in Q2, 1.175 (1.113-1.240) in Q3, and 1.278 (1.209-1.350) in Q4], following an adjustment for the conventional CV risk factors, including age, sex, body mass index, smoking, alcohol drinking, physical activities, household income, fasting glucose, systolic blood pressure, low-density lipoprotein cholesterol, and estimated glomerular filtration rate. In subgroup analyses, the association of AIP with MACEs and CV events was particularly outstanding in patients with diabetes. CONCLUSIONS: AIP was significantly associated with CV risks after adjusting for the traditional risk factors. Therefore, it may be used as an effective mass screening method to identify patients at a high risk of CV events.

National prescription patterns of antidepressants among patients with amyotrophic lateral sclerosis: An analysis of the Korean National Health Insurance database.

INTRODUCTION/AIMS: The current status of antidepressant use in patients with amyotrophic lateral sclerosis (ALS), such as the prevalence and factors associated with it, has not been systematically investigated. We aimed to analyze the prevalence and patterns of antidepressant prescriptions in patients with ALS and depression, and to identify factors associated with antidepressant prescriptions after the diagnosis of ALS. METHODS: The data of patients with ALS and the prescription of antidepressants were retrieved from the Korean National Health Insurance claims data. A multivariate logistic regression model was used to identify factors associated with antidepressant prescriptions. RESULTS: In total, 533 of 2955 patients had depressive disorders, and 426 were prescribed antidepressants. Selective serotonin reuptake inhibitors and tricyclic antidepressants were the most frequently prescribed drugs. Adjusted odds ratios (ORs) were 1.379 for the prescription of antidepressants in females. For various age groups, compared with those aged 80 years and older, adjusted ORs were 1.889 for those in their 70s, 2.319 for those in their 60s, 2.872 for those in their 50s, 2.854 for those in their 40s, and 3.363 for those under 40 years of age. Adjusted ORs were 1.662 for patients with a history of a psychiatric disorder and 1.861 for those with a history of psychiatric pharmacotherapy (all P < .05). DISCUSSION: Most patients with ALS who had depression received antidepressant prescriptions. In young females with a previous psychiatric disorder or pharmacotherapy, an in-depth evaluation for a depressive disorder should be performed.

The smoking population is not hardening in South Korea: a study using the Korea Community Health Survey from 2010 to 2018.

INTRODUCTION: The hardening hypothesis proposes that the proportion of hardcore smokers increases when smoking prevalence declines. To evaluate whether such hardening occurs in South Korea, we examined the association between quitting behaviours, the number of cigarettes smoked per day and the proportion of hardcore smokers and smoking prevalence among local districts in South Korea. METHODS: This study used the cross-sectional data from the Korea Community Health Survey (2010-2018) to examine local district-level associations between smoking prevalence and quit attempts, quit plans, quit ratios, cigarettes smoked per day and the proportion of hardcore smokers. Panel regression analysis was performed using the indicators of hardcore smoking (quit attempts, quit plans, quit ratios, cigarettes smoked per day and proportion of hardcore smokers) as the outcome variables, and prevalence of smoking, local districts, age and sex as predictor variables. RESULTS: When the smoking prevalence of the districts decreased by 1%, quit attempts, quit plans and quit ratios increased by 0.24% (95% CI 0.11 to 0.37), 0.37% (95% CI 0.26 to 0.47) and 1.71% (95% CI 1.65 to 1.76), respectively. Cigarette consumption decreased by 0.17 cigarettes per day (95% 0.15 to 0.19), and the prevalence of hardcore smokers decreased by 0.88% (95% CI 0.78 to 0.98) when smoking prevalence decreased by 1%. CONCLUSION: Hardening of smoking did not occur in South Korea when smoking prevalence declined, which suggests tobacco control policies in South Korea have been effective in reducing smoking prevalence without increasing the proportion of hardcore smokers.

Risk factors for rebleeding in Crohn's disease patients with acute severe lower gastrointestinal bleeding: With special reference to the role of anti-tumor necrosis factor therapy.

BACKGROUND AND AIM: Acute severe lower gastrointestinal bleeding (LGIB) in patients with Crohn's disease (CD) is uncommon; however, it is a potentially life-threatening complication, and its recurrence is common. We thus aimed to identify the predictors for rebleeding in CD patients with acute severe LGIB and particularly focused on whether anti-tumor necrosis factor (TNF) therapy lowers the risk of rebleeding compared with conventional medical therapy (CMT) or surgery. METHODS: The risk of rebleeding was analyzed in 131 CD patients with acute severe LGIB. Patients were classified into the CMT group (n = 99), anti-TNF therapy group (n = 22), and surgery group (n = 10). No patients in the surgery group received anti-TNF therapy. RESULTS: During the median follow-up of 98 months after the first episode of acute severe LGIB, rebleeding occurred in 50.5%, 18.2%, and 30.0% of the CMT group, anti-TNF therapy group, and surgery group, respectively (P = 0.015). The cumulative risks of rebleeding at 1 and 10 years were 20.0% and 64.7% in the CMT group, 13.6% and 18.4% in the anti-TNF therapy group, and 0% and 40.7% in the surgery group, respectively (P = 0.020). Multivariable Cox regression analysis showed that anti-TNF therapy was associated with a lower risk of rebleeding compared with CMT (hazard ratio, 0.303; 95% confidence interval, 0.108-0.849; P = 0.023). CONCLUSIONS: In CD patients with acute severe LGIB, anti-TNF therapy may reduce the risk of rebleeding compared with CMT. Although surgery is considered effective in preventing early rebleeding, concomitant anti-TNF therapy may be helpful in further lowering the long-term risk of rebleeding.

Clinical outcomes and long-term prognosis of perianal Crohn's disease in an Asian population.

BACKGROUND AND AIM: The clinical impact of perianal Crohn's disease (CD) (pCD), a well-known poor prognostic factor of CD, has not been fully evaluated in Asian patients. We investigated the outcomes of CD in Korean patients according to the presence of pCD at CD diagnosis. METHODS: Using 2010-2014 data from the national health insurance claims database, we evaluated the disease course of CD according to the presence of pCD at CD diagnosis. The results were verified in a hospital-based cohort of 2923 patients. RESULTS: The cumulative risk of intestinal resection was lower in patients with pCD at diagnosis than in those without, in the population-based cohort (9.1% vs 14.7% at 5 years after diagnosis, P < 0.001), but it was similar between the two groups in the hospital-based cohort (36.8% vs 36.8% at 10 years after diagnosis, P = 0.950). Moreover, the cumulative risk of behavioral progression was not significantly different between the two groups in the hospital-based cohort (43.4% vs 41.6% at 10 years after diagnosis, P = 0.366). On multivariable analysis, pCD at CD diagnosis was not a predictor of intestinal resection, behavioral progression, CD-related hospital admission, or diverting surgery; however, it was an independent predictor of proctectomy (hazard ratio [HR] 3.210, P < 0.001) and anorectal cancer (HR 3.104, P = 0.047). CONCLUSIONS: Although the presence of pCD increased the risk of proctectomy and anorectal cancer in Asian patients, the clinical impact of pCD on the overall outcomes of patients with CD may be less significant in Asian patients compared with Western patients.

Effect of multiple comorbidities on mortality in chronic obstructive pulmonary disease among Korean population: a nationwide cohort study.

BACKGROUND: The effects of comorbidities on chronic obstructive pulmonary disease (COPD) have been usually studied individually in the past. In this study, we aimed to investigate the comorbidities associated with mortality, the effect of multimorbidity on mortality and other factors associated with mortality among Korean COPD population. METHODS: The Korean National Health Insurance Service-National Sample Cohort version 2.0, collected between 2002 and 2015, was used. Among COPD patients [entire cohort (EC), N = 12,779], 44% of the participants underwent additional health examination, and they were analysed separately [health-screening cohort (HSC), N = 5624]. Fifteen comorbidities previously reported as risk factors for mortality were studied using Cox proportional hazards regression models. RESULTS: Total mortality rates were 38.6 per 1000 person-years (95% CI 37.32-40.01) and 27.4 per 1000 person-years (95% CI 25.68-29.22) in EC and HSC, respectively. The most common causes of death were disease progression, lung cancer, and pneumonia. Only some of the comorbidities had a direct impact on mortality. Multimorbidity, assessed by the number of comorbid diseases, was an independent risk factor of all-cause mortality in both cohorts and was a risk factor of respiratory mortality only in HSC. The Kaplan-Meier analysis showed significant differences in survival trajectories according to the number of comorbidities in all-cause mortality but not in respiratory mortality. Low BMI, old age and male sex were independent risk factors for both mortalities in both cohorts. CONCLUSIONS: The number of comorbidities might be an independent risk factor of COPD mortality. Multimorbidity contributes to all-cause mortality in COPD, but the effect of multimorbidity is less evident on respiratory mortality.

Exploring the impact of number and type of comorbidities on the risk of severe COPD exacerbations in Korean Population: a Nationwide Cohort Study.

BACKGROUND: It is difficult to assess the impact of multiple comorbidities on clinical outcomes in chronic obstructive pulmonary disease (COPD). In this study, we aimed to investigate exacerbation-associated comorbidities, determine whether the number of comorbidities is an independent risk factor for exacerbation, and identify other exacerbation-associated factors in a Korean COPD population using a nationwide population-based cohort. This study focused on severe exacerbations that required hospitalisation or emergency room visits. METHODS: The National Health Insurance Service-National Sample Cohort, version 2.0, data sampled between 2002 and 2015 were analysed. Data from two years after the diagnosis of COPD were analysed for each participant (N = 12,554, entire cohort). Moreover, 42% of the participants underwent additional health examinations (N = 5306, health-screening cohort). Fifteen comorbidities that were previously reported as risk factors for exacerbations were examined. A logistic regression model was used to analyse association with exacerbations. RESULTS: Asthma (1.57 [1.39-1.76] and 1.24 [1.06-1.44]), lung cancer (1.84 [1.30-2.59] and 2.28 [1.54-3.37]), and heart failure (1.39 [1.16-1.67] and 1.52 [1.18-1.97]) were associated with exacerbation in both cohorts (odds ratio [95% confidence interval] in the entire cohort and health-screening cohort, respectively). The number of comorbidities was an independent risk factor, and old age, male sex, low body mass index, and current smoking were also independent risk factors. High cholesterol levels and body mass index exerted protective effects against exacerbation. CONCLUSIONS: The number of comorbidities, certain comorbidities such as asthma, lung cancer and heart failure, and low BMI were associated with an increased risk of severe exacerbation in COPD patients.

Incidence and Outcomes of Perianal Disease in an Asian Population with Crohn's Disease: A Nationwide Population-Based Study.

BACKGROUND: Little is known about the natural history of perianal fistulas in Asian populations with Crohn's disease (CD). AIMS: We investigated the incidence and outcomes of perianal CD (pCD) in Korean CD patients. METHODS: A nationwide population-based cohort of 6265 CD patients diagnosed in 2010-2014 was analyzed to investigate the incidence and outcomes of pCD. The results were validated in a hospital-based cohort of 2923 CD patients diagnosed in 1981-2015. Factors associated with pCD development were analyzed. The incidence and outcomes of pCD were compared between the prebiologic and biologic eras. RESULTS: pCD occurred in 39.2% of the population-based cohort and 56.1% of the hospital-based cohort during the median follow-up of 4.2 and 8.5 years, respectively. The cumulative incidence of pCD was 40.0% at 5 years after CD diagnosis in the population-based cohort and 62.5% at 20 years in the hospital-based cohort. In multivariate analysis, pCD development was positively associated with male sex, younger age and colonic involvement at diagnosis, early diagnosis, and CD diagnosis in the prebiologic era. The cumulative probability of proctectomy at 10, 20, and 30 years after pCD diagnosis was 2.9%, 12.2%, and 16.2%, respectively. The cumulative incidence of pCD occurring after CD diagnosis and the cumulative probability of proctectomy were significantly lower in the biologic era than in the prebiologic era (p < 0.001 and p = 0.03, respectively). CONCLUSIONS: Compared with Western patients with CD, Korean patients show a high incidence of pCD but have a low probability of proctectomy, suggesting the favorable course of pCD.

Pulmonary alveolar proteinosis in Korea: analysis of prevalence and incidence via a nationwide population-based study.

BACKGROUND: Pulmonary alveolar proteinosis (PAP) is a very rare lung disease and its prevalence and incidence remain unclear. The prevalence and incidence of PAP were investigated by using nationwide claims data from the Korean Health Insurance Review and Assessment service. METHODS: Data were extracted for adults who visited any secondary or tertiary medical institute between 2010 and 2016 with the PAP-related Korean Classification of Disease, 7th edition code J84.0 and the Rare Intractable Disease exempted calculation code V222. To robust case definition, a narrow case definition was made when all following factors were met: 1) more than two PAP-coded visits within 1 year of the first claim, and 2) more than one claim for both chest computed tomography and diagnostic procedures (bronchoscopy or surgical lung biopsy) within 90 days before or after the first claim. RESULTS: A total of 182 patients (narrow, n = 82) with PAP-related codes were identified from 2010 to 2016 and 89 new patients (narrow, n = 66) visited medical institutes between 2012 and 2015. The prevalence of PAP was 4.44 (narrow: 2.27) per 106 population, with a peak age of 60-69 years. The incidence of PAP was 0.56 (narrow: 0.41) per 106 population at risk, with a peak age of 50-59 years. Among incident cases, the male-to-female ratio was 1.52 and about two-thirds had comorbidities, dyslipidaemia being the most common. CONCLUSIONS: The prevalence and incidence of PAP in Korea are low, similar to those in other countries; however, Korean patients with PAP are characterized by older diagnostic age and a lower male-to-female ratio.

Epidemiology of Antiphospholipid Syndrome in Korea: a Nationwide Population-based Study.

BACKGROUND: Antiphospholipid syndrome (APS) is a systemic autoimmune disorder characterized by arterial and venous thrombosis or pregnancy morbidity in patients with persistent antiphospholipid antibodies. However, nationwide population-based epidemiology studies regarding APS are still unavailable. METHODS: We analyzed claims data extracted from the Korean Health Insurance and Review Agency (HIRA) covering more than 52 million Koreans, between January 1, 2008, and December 31, 2017. Patients diagnosed with APS, as determined by the Korean Classification of Disease, 7th edition (D68.6), and a rare intractable disease program (V253), were identified in HIRA. RESULTS: A total of 3,088 newly diagnosed incident cases of 1,215 men and 1,873 women were identified during 2009-2016. The mean age was 44.6 ± 16.6 (men, 47.4 ± 16.3; women, 42.8 ± 16.6) years. The incidence was 0.75 per 105 person-year (95% confidence interval, 0.73-0.78). The prevalence in 2016 was 6.19 per 105 people. For incident cases, women showed incidence peak at ages of 30-39 years and 70-79 years, whereas for men, it was highest at ages of 70-79 years only. Of all patients, 1,766 (57%, 810 men and 956 women) had primary APS, 1,322 (43%, 405 men and 917 women) had secondary APS, and 845 (27%, 216 men and 629 women) were associated with systemic lupus erythematosus (SLE). CONCLUSION: The incidence of APS differs according to age groups and gender. The incidence of primary APS was higher than that of secondary APS in both gender. Furthermore, as already reported, secondary APS is highly associated with SLE; however, we observed that rheumatoid arthritis is also highly related.

Early discontinuation of ethambutol in pulmonary tuberculosis treatment based on results of the GenoType MTBDRplus assay: A prospective, multicenter, non-inferiority randomized trial in South Korea.

No studies have investigated whether discontinuation of ethambutol (EMB) based on the susceptibility to isoniazid and rifampin as determined by the GenoType MTBDRplus assay would be appropriate. We aimed to determine the feasibility of discontinuing EMB before the end of intensive phase treatment based on the result of MTBDRplus assay in patients with pulmonary tuberculosis (PTB). This prospective, multicenter non-inferiority randomized trial was conducted at 12 referral centers in South Korea in drug-susceptible PTB patients who initiated the standard four-drug regimen for PTB. Based on the results of the assay, EMB was discontinued in the MTBDRplus group after the confirmation that M. tuberculosis isolate was susceptible to isoniazid and rifampin. The timepoint for EMB discontinuation in the Guideline group was determined using the results of the phenotypic drug susceptibility test based on the Korean National TB Guidelines. The primary outcome was treatment success. Secondary outcomes included the 1-year rates of recurrence and adverse events. Of 600 randomized patients, the treatment outcome analysis was performed for 493 patients (MTBDRplus group, 244; Guideline group, 249). Treatment success rates were 93.9% (229/224) in the MTBDRplus group and 93.6% (233/249) in the Guideline group and did not differ between groups; relative risk 1.00 (95% CI 0.95-1.06). The 1-year recurrence rate between the two groups (0.9% vs. 0.5%, respectively) and differences in adverse drug reactions did not differ between groups. In conclusion, early discontinuation of EMB based on the results of the MTBDRplus assay did not affect the treatment outcomes in PTB.