Evolving trends in treatment patterns for hepatocellular carcinoma in Korea from 2008 to 2022: a nationwide population-based study.

Background/Aims: The treatment landscape for hepatocellular carcinoma (HCC) has significantly evolved over the past decade. We aimed to analyze trends in treatment patterns for HCC using a nationwide claims database from the Korean Health Insurance Review and Assessment Service. Methods: This retrospective population-based cohort study analyzed 171,002 newly diagnosed HCC patients between 2008 and 2022. Etiologies and treatment modalities were categorized based on the ICD-10 codes and insurance data. Results: The annual incidence decreased from 11,814 in 2008 to 10,443 in 2022. However, patients aged ≥ 70 increased noticeably, with those aged ≥ 80 rising from 3.8% in 2008 to 13.1% in 2022. From 2008 to 2022, the predominant cause of hepatitis B virus decreased from 68.9% to 59.7%, whereas nonalcoholic fatty liver disease increased from 8.9% to 15.8%. The initial treatment trends shifted: surgical resection and systemic therapy increased from 12.2% to 21.3% and from 0.2% to 9.6%, whereas transarterial therapy decreased from 49.9% to 36.6%. Best supportive care decreased from 31.7% to 21.3%. In the subgroup analysis, laparoscopic resection rate increased from 10.6% to 60.6% among the surgical resections. Sorafenib initially accounted for 100%, lenvatinib peaked at 36.5% in 2021, and atezolizumab-bevacizumab became the most widely used (63.1%) by 2022 among the systemic therapies. Conclusions: This study demonstrates the temporal changes in the treatment patterns of Korean HCC patients. Surgical resection, particularly laparoscopic liver resection, and systemic therapy has increased significantly. These changes may have been influenced by reimbursement policies and advances in clinical research.

Tenofovir disoproxil fumarate versus tenofovir alafenamide on risk of osteoporotic fracture in patients with chronic hepatitis B: A nationwide claims study in South Korea.

BACKGROUND: As tenofovir disoproxil fumarate (TDF) requires long-term use, a reduction in bone density should be considered a possibility when treating patients with chronic hepatitis B (CHB) with aging and systemic diseases. Patients treated with tenofovir alafenamide (TAF) have improved bone mineral density loss compared to patients treated with TDF. Although improvements in bone density caused by TAF have been reported, studies on the actual reduction of fractures are insufficient. AIM: To evaluate the impact of TAF on the risk of osteoporotic fractures in comparison with that of TDF. METHODS: Using the national claims data of the Health Insurance Review and Assessment Service, we conducted a retrospective cohort study of 32,582 patients with CHB who had been initially treated with TDF or TAF between November 2017 and December 2020. The numbers of patients treated with TDF and TAF were 20,877 and 11,705, respectively. The annual fracture rate per 100 patients in each group was calculated, and the Cox proportional hazard ratio (HR) was analysed after applying inverse probability treatment weights (IPTW) for both groups. RESULTS: Among 32,582 patients, the average age was 47.8 ± 11.2 years, 64.5% were men, and the follow-up period was 24.4 ± 11.6 months. The incidence of osteoporotic fractures was 0.78 and 0.49 per 100 person-years in the TDF and TAF groups, respectively. After application of IPTW, the HR was 0.68 (95% confidence interval 0.55-0.85, p = 0.001). CONCLUSION: TAF-treated patients with CHB had a significantly lower risk of osteoporotic fracture than TDF-treated patients.

Risk factors for severe postpartum hemorrhage requiring blood transfusion after cesarean delivery for twin pregnancy: a nationwide cohort study.

BACKGROUND: Postpartum hemorrhage (PPH) is a leading cause of maternal morbidity and mortality. Twin pregnancy and cesarean delivery are well-known risk factors for PPH. However, few studies have investigated PPH risk factors in mothers who have undergone cesarean delivery for twin pregnancies. Therefore, this study investigated the risk factors associated with severe PPH after cesarean delivery for twin pregnancies. METHODS: We searched and reviewed the Korean Health Insurance Review and Assessment Service's claims data from July 2008 to June 2021 using the code corresponding to cesarean delivery for twin pregnancy. Severe PPH was defined as hemorrhage requiring red blood cell (RBC) transfusion during the peripartum period. The risk factors associated with severe PPH were identified among the procedure and diagnosis code variables and analyzed using univariate and multivariate logistic regressions. RESULTS: We analyzed 31,074 cesarean deliveries for twin pregnancies, and 4,892 patients who underwent cesarean deliveries for twin pregnancies and received RBC transfusions for severe PPH were included. According to the multivariate analysis, placental disorders (odds ratio, 4.50; 95% confidence interval, 4.09- 4.95; P < 0.001), general anesthesia (2.33, 2.18-2.49; P < 0.001), preeclampsia (2.20, 1.99-2.43; P < 0.001), hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome (2.12, 1.22-3.68; P = 0.008), induction failure (1.37, 1.07-1.76; P = 0.014), and hypertension (1.31, 1.18-1.44; P < 0.001) predicted severe PPH. CONCLUSIONS: Placental disorders, hypertensive disorders such as preeclampsia and HELLP syndrome, and induction failure increased the risk of severe PPH after cesarean delivery for twin pregnancy.

Beyond Acute COVID-19: Investigating the Incidence of Subacute Thyroiditis in Long COVID-19 in Korea.

BACKGRUOUND: The correlation between acute coronavirus disease 2019 (COVID-19) and subacute thyroiditis (SAT) has not been clearly investigated in "long COVID" patients. We aimed to investigate the incidence of SAT during convalescence and after the acute phase of COVID-19, comparing with that of the general population. METHODS: Data from a total of 422,779 COVID-19 patients and a control group of 2,113,895 individuals were analyzed. The index date was defined as the date 3 months after confirmation of COVID-19. The incidence rate (IR) of SAT and hazard ratios (HRs) were calculated per 100,000 persons. Subgroup analysis included analysis of HRs 90-179 and 180 days post-COVID-19 diagnosis; and additional analysis was conducted according to hospitalization status, sex, and age group. RESULTS: The IR of SAT was 17.28 per 100,000 persons (95% confidence interval [CI], 12.56 to 23.20) in the COVID-19 group and 8.63 (95% CI, 6.37 to 11.45) in the control group. The HR of COVID-19 patients was 1.76 (95% CI, 1.01 to 3.06; P=0.045). The HR of SAT was 1.39 (95% CI, 0.82 to 2.34; P=0.220) up to 6 months after the index date and 2.30 (95% CI, 1.60 to 3.30; P<0.001) beyond 6 months. The HR for SAT among COVID-19 patients was 2.00 (95% CI, 1.41 to 2.83) in hospitalized patients and 1.76 (95% CI, 1.01 to 3.06) in non-hospitalized patients compared to the control group. The IR of SAT was 27.09 (95% CI, 20.04 to 35.82) for females and 6.47 (95% CI, 3.34 to 11.30) for males. In the 19 to 64 age group, the IR of SAT was 18.19 (95% CI, 13.70 to 23.67), while the IR was 9.18 (95% CI, 7.72 to 10.84) in the 65 to 69 age group. CONCLUSION: SAT could be a potential long-term complication of COVID-19. Long-term surveillance for thyroid dysfunction is needed especially in hospitalized, female and young-aged subjects.

Pituitary Diseases and COVID-19 Outcomes in South Korea: A Nationwide Cohort Study.

The pituitary gland is either directly or indirectly impacted by SARS-CoV-2 infection. As a consequence of SARS-CoV-2 infection, hypothalamic-pituitary dysfunction or pituitary apoplexy can occur. This study aimed to investigate severe COVID-19 outcomes and COVID-19-related mortality in patients with underlying pituitary disease in Korea using a nationwide cohort database. The data required for this study were obtained from the Health Insurance Review and Assessment Service of Korea. Patients with SARS-CoV-2 infection between January 2020 and December 2021 were divided into the following three groups and analyzed: Group A, those who were hospitalized for SARS-CoV-2 infection without underlying pituitary disease (n = 725,170); Group B, those who were hospitalized for SARS-CoV-2 infection with underlying pituitary disease without exposure to systemic steroids (n = 1509); and Group C, patients with underlying pituitary disease and exposure to systemic steroids (n = 365). Differences in severe COVID-19, requirement for oxygen therapy, intensive care unit admission, application of invasive ventilation or use of extracorporeal membrane oxygenation, and COVID-19-related deaths between groups were then analyzed. Group C had the highest rates of hospitalization after COVID-19 infection (82.2%) and mortality within 30 days of infection (6.8%). Group B had a 1.3-fold increase in severe COVID-19 outcomes compared to Group A. Group C had 1.8-fold and 1.3-fold increases in severe COVID-19 outcomes compared to Group A and Group B, respectively. Group C also had 2.34 and 3.24 times higher mortality rates within 30 days of COVID-19 infection than Group A and Group B, respectively. In conclusion, patients with pituitary disease who are receiving systemic steroids have poorer outcomes and higher mortality associated with COVID-19. Therefore, thorough COVID-19 infection control is required in these patients.

Risk for Newly Diagnosed Type 2 Diabetes Mellitus after COVID-19 among Korean Adults: A Nationwide Matched Cohort Study.

BACKGRUOUND: Coronavirus disease 2019 (COVID-19) can cause various extrapulmonary sequelae, including diabetes. However, it is unclear whether these effects persist 30 days after diagnosis. Hence, we investigated the incidence of newly diagnosed type 2 diabetes mellitus (T2DM) in the post-acute phase of COVID-19. METHODS: This cohort study used data from the Health Insurance Review and Assessment Service, a representative national healthcare database in Korea. We established a cohort of 348,180 individuals diagnosed with COVID-19 without a history of diabetes between January 2020 and September 2021. The control group consisted of sex- and age-matched individuals with neither a history of diabetes nor COVID-19. We assessed the hazard ratios (HR) of newly diagnosed T2DM patients with COVID-19 compared to controls, adjusted for age, sex, and the presence of hypertension and dyslipidemia. RESULTS: In the post-acute phase, patients with COVID-19 had an increased risk of newly diagnosed T2DM compared to those without COVID-19 (adjusted HR, 1.30; 95% confidence interval [CI], 1.27 to 1.33). The adjusted HRs of non-hospitalized, hospitalized, and intensive care unit-admitted patients were 1.14 (95% CI, 1.08 to 1.19), 1.34 (95% CI, 1.30 to 1.38), and 1.78 (95% CI, 1.59 to 1.99), respectively. The risk of T2DM in patients who were not administered glucocorticoids also increased (adjusted HR, 1.29; 95% CI, 1.25 to 1.32). CONCLUSION: COVID-19 may increase the risk of developing T2DM beyond the acute period. The higher the severity of COVID-19 in the acute phase, the higher the risk of newly diagnosed T2DM. Therefore, T2DM should be included as a component of managing long-term COVID-19.

Comparison of the Persistence of Anti-TNF Agents and Ustekinumab in Patients with Crohn's Disease: A Study Based on the Korean National Database.

BACKGROUND: Biologics play an important role in the treatment of moderate to severe Crohn's disease (CD). Ustekinumab was approved for such patients in the Republic of Korea on 1 December 2018. Therefore, we need to compare the efficacy of ustekinumab and anti-TNF inhibitors. METHODS: We compared one-year persistence rates between anti-TNF inhibitors and ustekinumab in moderate-to-severe CD patients using Korean National Health Insurance Service data from 1 December 2016 to 30 November 2021. We also analysed the risk factors for the non-persistence of biologics. RESULTS: The one-year persistence rates with index therapy in bio-naïve and bio-experienced patients were 87.7% and 69.7% for infliximab (p < 0.001), 85.1% and 72.8% for adalimumab (p < 0.001), and 92.1% and 89.8% for ustekinumab (p = 0.333), respectively. The risk factors for non-persistence were older age, non-use of an immune modulator, and previous biologic exposure in both the infliximab and adalimumab groups. The one-year persistence rate of ustekinumab was higher than that of anti-TNF inhibitors in bio-naïve patients (hazard ratio [HR] 0.53; 95% confidence interval [CI] 0.35-0.81; p = 0.003) and bio-experienced patients (HR 0.32; 95% CI 0.22-0.45; p < 0.001). CONCLUSIONS: Ustekinumab was superior in bio-naïve CD patients compared to anti-TNF inhibitors. However, the follow-up time was relatively short; further studies should continuously collect and analyse data.

Association of scrub typhus with incidence of dementia: a nationwide population-based cohort study in Korea.

BACKGROUND: Scrub typhus is a mite-borne infectious rickettsial disease that can occur in rural and urban areas, with an especially high prevalence in older populations. This disease causes systemic vasculitis that can invade the central nervous system. Considering these characteristics, here we examined whether scrub typhus was associated with the occurrence of dementia, using large population-based cohort data. METHOD: This population-based cohort study enrolled patients aged 60-89 years using data from the Health Insurance Review and Assessment database of South Korea between 2009 and 2018. We defined scrub typhus and dementia using International Classification of Diseases, Tenth Edition diagnostic codes. The control group was stratified according to age and sex at a ratio of 1:5 to the case group in the study population. The index date was set after 90 days beyond the date of the scrub typhus diagnosis, while the observation period was from the time of the index appointment to December 31, 2020. The primary outcome was newly diagnosed dementia. The secondary outcome was dementia classification, such as Alzheimer's disease, vascular dementia, and other. All analyses were conducted by matching age, gender, and comorbidity. RESULTS: During the observation period, 10,460 of 71,047 (14.7%) people who had a history of scrub typhus versus 42,965 of 355,235 (12.1%) people in the control group, that is, with no history of scrub typhus, were diagnosed with dementia (adjusted hazard ratio, 1.12; 95% confidence interval, 1.10-1.15, p < 0.001). The Kaplan-Meier curves for time to cumulative incidence of dementia showed that the dementia incidence in both groups increased over time, while individuals with a past history of scrub typhus had a higher incidence of dementia than the control group. Second, the risk of Alzheimer's disease was significantly higher among patients with a history of scrub typhus (adjusted hazard ratio, 1.15; 95% confidence interval 1.13-1.18, p < 0.001). CONCLUSION: In conclusion, a history of scrub typhus infection in old age is significantly associated with an increase in dementia, especially Alzheimer's disease. Our results suggest that prevention and appropriate treatment of scrub typhus should be emphasized as a dementia prevention measure.

Mortality and Severity of Coronavirus Disease 2019 in Patients with Long-Term Glucocorticoid Therapy: A Korean Nationwide Cohort Study.

BACKGRUOUND: The severity of coronavirus disease 2019 (COVID-19) among patients with long-term glucocorticoid treatment (LTGT) has not been established. We aimed to evaluate the association between LTGT and COVID-19 prognosis. METHODS: A Korean nationwide cohort database of COVID-19 patients between January 2019 and September 2021 was used. LTGT was defined as exposure to at least 150 mg of prednisolone (≥5 mg/day and ≥30 days) or equivalent glucocorticoids 180 days before COVID-19 infection. The outcome measurements were mortality, hospitalization, intensive care unit (ICU) admission, length of stay, and mechanical ventilation. RESULTS: Among confirmed patients with COVID-19, the LTGT group (n=12,794) was older and had a higher proportion of comorbidities than the control (n=359,013). The LTGT group showed higher in-hospital, 30-day, and 90-day mortality rates than the control (14.0% vs. 2.3%, 5.9% vs. 1.1%, and 9.9% vs. 1.8%, respectively; all P<0.001). Except for the hospitalization rate, the length of stay, ICU admission, and mechanical ventilation proportions were significantly higher in the LTGT group than in the control (all P<0.001). Overall mortality was higher in the LTGT group than in the control group, and the significance remained in the fully adjusted model (odds ratio [OR], 5.75; 95% confidence interval [CI], 5.31 to 6.23) (adjusted OR, 1.82; 95% CI, 1.67 to 2.00). The LTGT group showed a higher mortality rate than the control within the same comorbidity score category. CONCLUSION: Long-term exposure to glucocorticoids increased the mortality and severity of COVID-19. Prevention and early proactive measures are inevitable in the high-risk LTGT group with many comorbidities.

Risk of cancer in Korean patients with psoriatic arthritis: a nationwide population-based cohort study.

OBJECTIVE: While many studies on the increased risk of cancer in patients with psoriasis are available, data on the risk of cancer in patients with psoriatic arthritis (PsA) are still scarce. We assessed the risk of cancer in patients with PsA in a nationwide population-based cohort in Korea. METHODS: From 2010 to June 2021, patients newly diagnosed with PsA and 1:10 age-matched and sex-matched controls were included in this study. The outcome was the incidence of overall and specific cancers. RESULTS: Total 162 cancers occurred in 4688 PsA patients (incidence rate 83.2 (95% CI 70.8 to 97.0) per 10 000 person-years) and 1307 cancers occurred in 46 880 controls (incidence rate 66.9 (95% CI 63.3 to 70.6) per 10 000 person-years). The adjusted HR (aHR) of overall cancer in PsA patients was 1.20 (95% CI 1.02 to 1.41). However, this significance disappeared when non-melanoma skin cancer (NMSC) was excluded (aHR 1.16, 95% CI 0.98 to 1.37). Among specific cancers, the risk of NMSC (aHR 3.64 (95% CI 1.61 to 8.23)), lymphoma (aHR 2.63 (95% CI 1.30 to 5.30)) and thyroid cancer (aHR 1.83 (95% CI 1.18 to 2.85)) was higher in patients with PsA than in controls. CONCLUSION: The risk of overall cancer was higher in patients with PsA than in the general population. Patients with PsA had increased risks of NMSC, lymphoma and thyroid cancer compared with the general population. Our findings suggest a need to conduct cancer screening by a detailed history and comprehensive clinical examination in patients with PsA.

Risk of acute myocardial infarction, stroke, and venous thromboembolism among patients with anti-neutrophil cytoplasmic antibody-associated vasculitis in South Korea: A nationwide population-based study.

OBJECTIVES: To investigate the incidence and risk of cerebro-cardiovascular comorbidities (stroke, acute myocardial infarction, venous thromboembolism, and pulmonary embolism) in anti-neutrophil cytoplasmic antibody-associated vasculitis using nationwide Korean population-based medical claims data. METHODS: We identified 1905 patients with newly diagnosed anti-neutrophil cytoplasmic antibody-associated vasculitis during 2009-2019. Incidence rates and hazard ratios with 95% confidence intervals were calculated to estimate the risk of cerebro-cardiovascular comorbidities in these patients and compared to age- and sex-matched controls (1:10) using the Cox proportional hazards model. RESULTS: Most patients had microscopic polyangiitis (42.5%), followed by granulomatosis with polyangiitis (29.1%) and eosinophilic granulomatosis with polyangiitis (28.4%). The annual incidence rate of anti-neutrophil cytoplasmic antibody-associated vasculitis in 2019 was 0.55 per 100,000 person-years. Cerebro-cardiovascular comorbidities occurred in 12.6%. Stroke was most common (64.6%), followed by venous thromboembolism (34.6%), pulmonary embolism (18.3%), and acute myocardial infarction (5.4%). Korean patients with anti-neutrophil cytoplasmic antibody-associated vasculitis were at a significantly (2.3 times) higher overall risk for cerebro-cardiovascular comorbidities than the general population (adjusted hazard ratios, 4.5, 3.1, and 2.0 times higher for pulmonary embolism, venous thromboembolism, and stroke, respectively). These findings were similar for patients with each subtype of anti-neutrophil cytoplasmic antibody-associated vasculitis. CONCLUSIONS: This is the first nationwide population-based study to demonstrate a significant risk of cerebro-cardiovascular comorbidities as complications of anti-neutrophil cytoplasmic antibody-associated vasculitis in Korean patients. Knowing these risks may enable personalized patient care and improve overall survival.

Incidence of major depressive disorder over time in patients with liver cirrhosis: A nationwide population-based study in Korea.

There is yet to be a large-scale longitudinal study on the course of depression incidence within the duration of cirrhosis. The aim of this study is to analyze the incidence of depression from before to after diagnosis of cirrhosis over time. Incidence Rate (IR) was defined as the number of newly diagnosed patients with MDD divided by the sum of observation periods by using claims database in Korea. Incidence Rate Ratio (IRR) was defined as the IR in the specific interest period divided by the IR in the control period. The control period was defied as 1 to 2 years before diagnosis of cirrhosis. The IRs before and after cirrhosis diagnosis were 3.56 and 7.54 per 100 person-year, respectively. The IRR was 2.12 (95% confidence Interval: 2.06-2.18). The IRR of developing depression mildly increased before diagnosis of cirrhosis (-360 days to -181 days, IRR 1.14, p < 0.001; -180 days to -90 days, IRR 1.24, p < 0.001; -90 days to -31 days, IRR 1.56, p < 0.001) and rapidly increased immediately after diagnosis of cirrhosis (+30 days to +89 days, IRR 2.12, 95% confidence interval: 2.06-2.18, p < 0.001). The pattern of increasing depression immediately after the diagnosis of cirrhosis was observed equally in all sexes and ages. Thus, clinicians must pay close attention to screening for depression within the first three months of liver cirrhosis diagnosis.

Risk of Breast Cancer in Association with the Use of Second-generation Antipsychotics.

Objective: Previous studies regarding the relationship between the risk of breast cancer (BC) and antipsychotics use have reported inconsistent findings. Insufficient sample size and/or observation period may have hindered revealing the risk of BC associated with antipsychotics use. We aimed to investigate whether the use of second-generation antipsychotics (SGA) is associated with increased risk of BC. Methods: We used the Health Insurance Review Agency database in South Korea between 2008 and 2018. The index date was determined as the date of the first antipsychotic prescription. We selected women prescribed SGAs for more than 30 days within a year from the index date and age-matched controls, yielding 498,970 cases and 997,940 controls. The Cox proportional hazards regression model was used for estimating the risk. Results: The incidence rates of BC were 109.74 and 101.51 per 100,000 person-years in the case and control groups, respectively. There was an increased risk of BC in the case group (hazard ratio [HR] = 1.08, 95% confidence interval [CI] 1.04-1.13). There was a higher risk of BC in subjects prescribed with ≥ 10,000 mg of olanzapine equivalent dose (HR = 1.29, 95% CI 1.14-1.46) than those with < 10,000 mg (HR = 1.05, 95% CI 1.00-1.11). The increased risk of BC in the case group became significant after six years of the observation period (≥ 6 years: HR = 1.24, 95% CI 1.14-1.35, 3 to < 6 years: HR = 1.06, 95% CI 0.97-1.15, < 3 years: HR = 1.02, 95% CI 0.95-1.09). Conclusion: This study indicated that the use of SGAs is associated with increased risk of BC in a long-term relationship with a dose-response pattern.

Risk of infective endocarditis associated with invasive dental procedures in patients with cardiac rhythm devices.

AIMS: The incidence of infective endocarditis related to cardiac implantable electronic devices (CIEDs) has gradually increased. The risk associated with dental procedures in patients with CIED implantation and the need for prevention of infective endocarditis remain unclear. The present study investigated the incidence and risk of infective endocarditis associated with invasive dental procedures in patients with CIEDs. METHODS AND RESULTS: We analysed a nationwide population-based cohort of patients with CIEDs who underwent dental procedures. We performed a self-controlled case series analysis and evaluated the incidence rate ratio of infective endocarditis 3 months after dental procedures. Of a total of 62 019 patients who underwent CIED implantation, 32 536 patients underwent at least one dental procedure during follow-up, and the mean number of dental procedures was 3.4 per patient. They were 152 infections with an incidence of 445 per 100 000 person-years in the dental procedure period and 500 events at an incidence of 255 per 100 000 person-years in the non-dental procedure period. The CIED-related infective endocarditis in the dental procedure period occurred significantly more frequently than during non-dental procedure periods (odds ratio, 1.75; 95% confidence interval, 1.48-2.05; P < 0.001). The mean time interval from dental procedure to infective endocarditis was 59.6 ± 47.3 days. CONCLUSION: Invasive dental procedures are associated with an increased risk of infective endocarditis in those who underwent CIED implantation. Appropriate preventive therapy might be needed in these patients.

The Comparative Risk of Serious Adverse Events With Tofacitinib and TNF Inhibitors in Patients With Ulcerative Colitis: The Korean Experience as Revealed by a National Database.

Tofacitinib is an oral, small-molecule Janus kinase inhibitor approved in South Korea for the treatment of moderate to severe ulcerative colitis (UC) on May 1, 2019. However, safety data are lacking. We investigated the incidence of serious adverse events (SAEs) in patients with UC using tofacitinib from the National Health Insurance Service database. In all, 1,026 UC patients were enrolled in this study. The overall incidences (100 person-years; 95% confidence interval) of SAEs were 4.06 (1.63-8.36) and 6.30 (4.59-8.43) in the tofacitinib and anti-TNFi groups, respectively. No thromboembolic event occurred and major cardiovascular events occurred in only three patients (two unstable angina and one congestive heart failure) in the tofacitinib group. The incidence of herpes zoster and tuberculosis did not differ between the two groups. There was no difference in the overall incidence of SAEs, including thromboembolic events, between tofacitinib- and TNFi-treated UC patients.

Effect of single tablet regimen on prescription trends for treatment-naïve patients with HIV/AIDS in Korea.

Single-tablet regimens (STRs) should be considered for patients with HIV/AIDS to increase medication compliance and improve clinical outcomes. This study compared variations in the prescription trends between STRs and multiple-tablet regimens (MTRs) for treatment-naïve patients with HIV/AIDS after the approval of the new STRs, a proxy indicator for improvement in medication adherence. The medical and pharmacy claim data were retrospectively obtained from the Health Insurance Review and Assessment service, which contains basic information on the patients' sociodemographic characteristics and treatment information for the entire Korean population. From 2013 to 2018, a total of 6737 patients with HIV/AIDS were included. Most patients were men (92.8%, n = 6251) and insured through the National Health Insurance (95.1%, n = 6410). The mean number of pills in their antiretroviral treatment regimens decreased from 2.8 ± 1.2 in 2013 to 1.2 ± 1.0 in 2018. After the first STR (EVG/c/TDF/FTC) was approved in 2014, prescription transitions from MTR to STR were observed among more than 38% of patients. In 2018, most treatment-naïve patients were prescribed STRs (91.2%). There was a time lag for STR prescription trends in non-metropolitan hospitals compared with those in metropolitan cities. Our data provide a valuable perspective for evaluating ART regimen prescription patterns on a national scale.

Clinical Effect of Hepatitis B Virus on COVID-19 Infected Patients: A Nationwide Population-Based Study Using the Health Insurance Review & Assessment Service Database.

BACKGROUND: Several studies have recently suggested that liver disease and cirrhosis were risk factors for poor outcomes in patients with coronavirus disease 2019 (COVID-19) infections. However, no large data study has reported the clinical course of COVID-19 patients with chronic hepatitis B virus (HBV) infections. This study investigated whether HBV infection had negative impacts on the clinical outcomes of COVID-19 patients. METHODS: We performed a nationwide population-based cohort study with 19,160 COVID-19-infected patients in 2020 from the Korean Health Insurance Review and Assessment database. The clinical outcomes of COVID-19 patients with chronic HBV infections were assessed and compared to those of non-HBV-infected patients. RESULTS: Of the 19,160 patients diagnosed with COVID-19, 675 (3.5%) patients had chronic HBV infections. The HBV-infected patients were older and had more commodities than the non-HBV infected COVID-19 patients. During the observation period, COVID-19-related mortality was seen in 1,524 (8.2%) of the non-HBV-infected 18,485 patients, whereas 91 (13.5%) in HBV-infected 675 patients died of COVID-19 infection. Compared to patients without HBV infections, a higher proportion of patients with chronic HBV infections required intensive care unit (ICU) admission and had organ failures. However, odds ratios for mortality, ICU admission, and organ failure were comparable between the two groups after adjusting for age, sex, and comorbid diseases including liver cirrhosis and hepatocellular carcinoma. CONCLUSION: COVID-19-infected patients with HBV infections showed worse clinical courses than non-HBV-infected COVID-19 patients. However, after adjustment, chronic HBV infection itself does not seem to affect the clinical outcomes in COVID-19 patients.

Pregnancy-associated risk factors and incidence of systemic sclerosis in primiparous women: A nationwide population-based cohort study.

OBJECTIVES: To evaluate the pregnancy-related risk factors and incidence rate (IR) of systemic sclerosis (SSc) in primipara using the Health Insurance Review and Assessment database, covering all medical claims in South Korea. METHODS: From the database, 2,260,952 primipara aged 18-49 years from 2008 to 2018 were identified. The patients were followed up after their index delivery until December 2019. A Cox proportional hazard analysis was performed to identify the association of pregnancy-related factors with SSc development. RESULTS: The SSc IR was 0.62 cases per 100,000 patient-years. Primipara had a higher risk of developing SSc after 3 years postpartum than in the first 3 years of delivery (OR = 1.98, 95% CI: 1.36-2.78, p < .001). A multivariate analysis showed that older age (35-49 years) (HR = 2.14, 95% CI: 1.05-4.35, p = .037) and a Caesarean section (CS) (HR = 1.86, 95% CI: 1.10-3.15, p = .021) are risk factors for SSc. At 3 years postpartum, CS (HR = 2.97, 95% CI: 1.39-6.32, p = .005) and a female infant (HR = 2.28, 95% CI: 1.11-4.71, p = .026) were associated with SSc development. CONCLUSION: Having a CS, late childbirth, and a female infant are the risk factors for SSc in primipara. This study establishes the IR of SSc in primipara.

Risk of All-Cause Mortality in Levothyroxine-Treated Hypothyroid Patients: A Nationwide Korean Cohort Study.

Background: Although hypothyroidism is associated with various comorbidities, its relationship with increased all-cause mortality remains controversial. The aim of this nationwide retrospective cohort study was to investigate whether hypothyroid patients treated with levothyroxine had increased mortality compared to controls. Methods: Hypothyroid subjects were identified through the Korean National Health Insurance Service Claims database between 2008 and 2017. Hypothyroidism in this study was defined as overt hypothyroidism treated with long-term prescription of levothyroxine (>6 months). After 1:3 age-, sex- and index year-matching, 501,882 patients with newly diagnosed hypothyroidism and 1,505,646 controls without hypothyroidism were included. Results: During a mean follow-up of 6 years, 25,954 (5.2%) hypothyroid patients and 59,105 (3.9%) controls died. Hypothyroidism was significantly associated with increased all-cause mortality (adjusted hazard ratio [HR], 1.14; 95% confidence interval [CI] 1.12-1.16) even with levothyroxine treatment. When stratified by age, sex, and cardiovascular disease risk, independent associations between hypothyroidism and mortality remained significant in all subgroups. The risk of mortality was higher in the < 65 age group (HR: 1.25, 95% CI: 1.22-1.29), men (HR: 1.28, 95% CI: 1.25-1.31), and the high cardiovascular disease risk group (HR: 1.31, 95% CI: 1.29-1.34). The mortality rate of hypothyroid patients was highest within 1 year of treatment and decreased with time. Conclusion: This nationwide, population-based cohort study showed that all-cause mortality was significantly higher in levothyroxine-treated hypothyroid patients than in non-hypothyroid controls. This association remained significant regardless of age, sex, and cardiovascular disease risk.

Entecavir versus Tenofovir for the Prevention of Hepatocellular Carcinoma in Treatment-naïve Chronic Hepatitis B Patients in Korea.

BACKGROUND: The occurrence of hepatocellular carcinoma (HCC) is a major concern during antiviral therapy for chronic hepatitis B. There are conflicting opinions regarding the effects of entecavir (ETV) and tenofovir disoproxil fumarate (TDF) on HCC prevention. We assessed these two antiviral medications for preventing HCC in treatment-naïve patients with chronic hepatitis B. METHODS: We conducted a retrospective cohort study using nationwide claims data from the Korea Health Insurance Review and Assessment Service. We included 55,473 treatment-naïve adult cases where ETV or TDF treatment was started between 2013 and 2017 (cohort 1). The ETV and TDF groups were matched 1:2 based on age, sex, comorbidities, hospital type, and index date year. Patients were followed up until December 2018. The outcome was the development of HCC. Subgroup analyses were conducted according to sex, age, hospital type and the presence of cirrhosis. We also compared the outcomes of patients who had started antiviral therapy during the 2012-2014 period (cohort 2). RESULTS: The matched participants (18,491 in the ETV and 36,982 in the TDF groups) were a part of the study for, on average, 41.2 months. The incidence of HCC did not differ significantly between the ETV (1.46 per 100 patient-years) and the TDF (1.36 per 100 patient-years) treatments (hazard ratio, 0.93; 95% confidence interval, 0.86-1.01; P = 0.081). By contrast, HCC incidence was significantly higher in the ETV group than tenofovir group of cohort 2. CONCLUSION: In patients with chronic hepatitis B, the ETV treatment did not result in a higher rate of HCC than the TDF treatment.