Antihypertensive Medication Adherence and Cardiovascular Outcomes in Patients With Cancer: A Nationwide Population-Based Cohort Study.

Background Hypertension is an important cause of morbidity, which predisposes patients to major cardiovascular events and mortality. The aim of this study was to explore the association between adherence to antihypertensive medication and clinical outcomes in adult patients with cancer. Methods and Results Using the 2002 to 2013 Korean National Health Insurance Service-National Sample Cohort, we extracted adult patients with cancer treated with antihypertensive medications. Based on the medication possession ratio value, participants were divided into 3 groups: good (medication possession ratio ≥0.8), moderate (0.5≤ medication possession ratio <0.8), and poor (medication possession ratio <0.5) adherence groups. The primary outcomes were overall and cardiovascular mortality. The secondary outcome was cardiovascular events requiring hospitalization due to major cardiovascular diseases. Among 19 246 patients with cancer with concomitant hypertension, 66.4% were in the nonadherence group (26.3% were moderate and 40.0% were poor adherence group). Over a median of 8.4 years of follow-up, 2752 deaths and 6057 cardiovascular events occurred. Compared with the good adherence group, the moderate and poor adherence groups had a 1.85-fold and 2.19-fold increased risk for overall mortality, and 1.72-fold and 1.71-fold elevated risk for cardiovascular mortality, respectively, after adjustment for possible confounders. Furthermore, the moderate and poor adherence groups had a 1.33-fold and 1.34-fold elevated risk of new-onset cardiovascular events, respectively. These trends were consistent across cardiovascular event subtypes. Conclusions Nonadherence to antihypertensive medication was common in patients with cancer and was associated with worse clinical outcomes in adult patients with cancer with hypertension. More attention should be paid to improving adherence to antihypertensive medication among patients with cancer.

Gemcitabine-cisplatin versus MVAC chemotherapy for urothelial carcinoma: a nationwide cohort study.

This study assessed the trends in methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) and gemcitabine-cisplatin (GC) regimens in Korean patients with metastatic urothelial carcinoma (UC) and compared the side effects and overall survival (OS) rates of the two regimens using nationwide population-based data. The data of patients diagnosed with UC between 2004 and 2016 were collected using the National Health Insurance Service database. The overall treatment trends were assessed according to the chemotherapy regimens. The MVAC and GC groups were matched by propensity scores. Cox proportional hazard analysis and Kaplan-Meier analysis were performed to assess survival. Of 3108 patients with UC, 2,880 patients were treated with GC and 228 (7.3%) were treated with MVAC. The transfusion rate and volume were similar in both the groups, but the granulocyte colony-stimulating factor (G-CSF) usage rate and number were higher in the MVAC group than in the GC group. Both groups had similar OS. Multivariate analysis revealed that the chemotherapy regimen was not a significant factor for OS. Subgroup analysis revealed that a period of ≥ 3 months from diagnosis to systemic therapy enhanced the prognostic effects of the GC regimen. The GC regimen was widely used as the first-line chemotherapy in more than 90% of our study population with metastatic UC. The MVAC regimen showed similar OS to the GC regimen but needed greater use of G-CSF. The GC regimen could be a suitable treatment option for metastatic UC after ≥ 3 months from diagnosis.

Incidence of Retinal Artery Occlusion and Related Mortality in Korea, 2005 to 2018.

Importance: It remains unclear whether comorbidities in patients with retinal artery occlusion (RAO), a rare retinal vascular disorder, differ by subtype and whether mortality is higher. Objective: To examine the nationwide incidence of clinically diagnosed, nonarteritic RAO, causes of death, and mortality rate in patients with RAO compared with that in the general population in Korea. Design, Setting, and Participants: This retrospective, population-based cohort study examined National Health Insurance Service claims data from 2002 to 2018. The population of South Korea was 49 705 663, according to the 2015 census. Data were analyzed from February 9, 2021, to July 30, 2022. Main Outcomes and Measures: The nationwide incidence of any RAO, including central RAO (CRAO; International Statistical Classification of Diseases and Related Health Problems, Tenth Revision [ICD-10] code, H34.1) and noncentral RAO (other RAO; ICD-10 code, H34.2) was estimated using National Health Insurance Service claims data from 2002 to 2018, with 2002 to 2004 as the washout period. Furthermore, the causes of death were evaluated and the standardized mortality ratio was estimated. The primary outcomes were the incidence of RAO per 100 000 person-years and the standardized mortality ratio (SMR). Results: A total of 51 326 patients with RAO were identified (28 857 [56.2%] men; mean [SD] age at index date: 63.6 [14.1] years). The nationwide incidence of any RAO was 7.38 (95% CI, 7.32-7.44) per 100 000 person-years. The incidence rate of noncentral RAO was 5.12 (95% CI, 5.07-5.18), more than twice that of CRAO (2.25 [95% CI, 2.22-2.29]). Mortality was higher in patients with any RAO than in the general population (SMR, 7.33 [95% CI, 7.15-7.50]). The SMR for CRAO (9.95 [95% CI, 9.61-10.29]) and for noncentral RAO (5.97 [95% CI, 5.78-6.16]) showed a tendency toward a gradual decrease with increasing age. The top 3 causes of death in patients with RAO were diseases of the circulatory system (28.8%), neoplasms (25.1%), and diseases of the respiratory system (10.2%). Conclusions and Relevance: This cohort study found that the incidence rate of noncentral RAO was higher than that of CRAO, whereas SMR was higher for CRAO than noncentral RAO. Patients with RAO show higher mortality than the general population, with circulatory system disease as the leading cause of death. These findings suggest that it is necessary to investigate the risk of cardiovascular or cerebrovascular disease in patients newly diagnosed with RAO.

Neoadjuvant versus adjuvant chemotherapy in upper tract urothelial carcinoma: A nationwide cohort study.

PURPOSE: This study aimed to evaluate the trend of adjuvant chemotherapy (AC) and neoadjuvant chemotherapy (NAC) in patients who underwent radical nephroureterectomy with bladder cuff excision (NUx) for upper tract urothelial carcinoma (UTUC) to compare the perioperative outcomes and overall survival (OS) between AC and NAC using nationwide population-based data. MATERIALS AND METHODS: We collected data on patients diagnosed with UTUC and treated with NUx between 2004 and 2016 using the National Health Insurance Service database, and evaluated the overall treatment trends. The AC and NAC groups were propensity score-matched. Cox proportional hazard and Kaplan-Meier analyses were used to assess survival. RESULTS: Of the 8,705 enrolled patients, 6,627 underwent NUx only, 94 underwent NAC, and 1,984 underwent AC. The rate of NUx without perioperative chemotherapy increased from 70.8 to 78.2% (R2 = 0.632; p < 0.001). The rates of dialysis (p = 0.398), TUR-BT (p = 1.000), and radiotherapy (p = 0.497) after NUx were similar. In the Kaplan-Meier curve, the NAC and AC groups showed no significant difference (p = 0.480). In multivariate analysis, treatment with AC or NAC was not associated with OS (hazard ratio 0.83, 95% confidence interval 0.49-1.40, p = 0.477). CONCLUSION: The use of NUx without perioperative chemotherapy has tended to increase in South Korea. Dialysis, TUR-BT, and radiotherapy rates after NUx were similar between the NAC and AC groups. There was no significant difference in OS between the NAC and AC groups. Proper perioperative chemotherapy according to patient and tumor conditions should be determined by obtaining more evidence of UTUC.

Incidence and predictors of intracranial bleeding after coronary artery bypass graft surgery.

Background: There is a paucity of direct data on the incidence and predictors of intracranial bleeding (ICB) after coronary artery bypass graft surgery (CABG). Methods: The Korean National Health Insurance database was used to identify patients without prior ICB who underwent CABG. The outcomes of interest were the time-dependent incidence rates of ICB and the associated mortality. Results: Among 35,021 patients who underwent CABG between 2007 and 2018, 895 (2.6%) experienced an ICB during a median follow-up of 6.0 years. The 1-year cumulative incidence of ICB was 0.76%, with a relatively high incidence rate (9.93 cases per 1,000 person-years) within the first 1-30 days. Subsequent incidence rates showed a sharp decline until 3 years, followed by a steady decrease up to 10 years. The 1-year mortality rate after ICB was 38.1%, with most deaths occurring within 30 days (23.6%). The predictors of ICB after CABG were age ≥ 75 years, hypertension, pre-existing dementia, history of ischemic stroke or transient ischemic attack, and end-stage renal disease. Conclusions: In an unselected nationwide population undergoing CABG, the incidence of ICB was non-negligible and showed a relatively high incidence rate during the early postoperative period. Post-CABG ICB was associated with a high risk of premature death. Further research is needed to stratify high-risk patients and personalize therapeutic decisions for preventing ICB after CABG.

Understanding and Utilizing Claim Data from the Korean National Health Insurance Service (NHIS) and Health Insurance Review & Assessment (HIRA) Database for Research.

Almost every Korean (97%) is enrolled in the National Health Insurance program, and most receive medical treatment at least once a year. Data are collected by the Health Insurance Review and Assessment Service (HIRA), and the results of the review are sent to the National Health Insurance Service (NHIS). The data handled by NHIS and HIRA cover almost the entire population and can be used for various research purposes. NHIS and HIRA support research by making these data available to researchers. The greatest advantage of these data is that they are the only data which include virtually the entire population. Both HIRA and NHIS data are provided in the form of sample data and all (customized) data. NHIS and HIRA data are similar but exhibit minor differences. HIRA data consists of five tables, including general specification details, in-hospital treatment details, disease details, out-of-hospital prescription details, and nursing institution information. NHIS data include death records (including cause of death), some medical examination records, and the socio-economic variables of the subject, such as income, in addition to all the HIRA data. Clinical results of treatments are not recorded in NHIS or HIRA. However, because public data are used for billing purposes, actual research has thus far been limited. Therefore, researchers must develop a study design that can minimize the errors or bias occurring during the course of the study. Therefore, it is necessary to clearly understand the structure and characteristics of NHIS and HIRA data when initiating research.

Anaerobe coverage is important for the prognosis of pyogenic liver abscess: A population-based study in Korea.

BACKGROUND: Gram-negative bacteria such as Klebsiella pneumoniae and Escherichia coli are the most common cause of pyogenic liver abscess (PLA). We investigated whether the use of anaerobic-covering antibiotics is essential for the treatment of pyogenic liver abscess. METHODS: We analyzed the Health Insurance Review and Assessment Service data in Korea between 2007 and 2017. We classified PLA into two groups: a group using antibiotics that inhibited only aerobic strains (anaerobe (-) group) and a group using antibiotics that inhibited both aerobic and anaerobic strains (anaerobe (+) group). The primary outcome was the difference in in-hospital mortality between the two groups. RESULTS: During this period, a total of 30,690 PLA patients were obtained. There were 6733 patients in the anaerobe (-) group and 23,957 patients in the anaerobe (+) group. In-hospital mortality was significantly lower in the anaerobe (+) group than the anaerobe (-) group (7.9% vs. 15.6%, p < 0.001). In multivariate analysis, the use of anaerobic antibiotics reduced the in-hospital mortality by 42% (odds ratio 0.42, 95% confidence interval 0.38-0.46, p < 0.001) after adjusting for age and comorbidities. Furthermore, the improvement of in-hospital mortality was present regardless of the presence of cancer or diabetes. CONCLUSION: The use of broad-spectrum empirical antibiotics covering anaerobic strains is important for the treatment of pyogenic liver abscess.

Comparative Effects of Sodium-Glucose Cotransporter 2 Inhibitor and Thiazolidinedione Treatment on Risk of Stroke among Patients with Type 2 Diabetes Mellitus.

BACKGROUND: Although cardiovascular outcome trials using sodium-glucose cotransporter-2 inhibitors (SGLT-2i) showed a reduction in risk of 3-point major adverse cardiovascular events (MACE), they did not demonstrate beneficial effects on stroke risk. Additionally, meta-analysis showed SGLT-2i potentially had an adverse effect on stroke risk. Contrarily, pioglitazone, a type of thiazolidinedione (TZD), has been shown to reduce recurrent stroke risk. Thus, we aimed to compare the effect of SGLT-2i and TZD on the risk of stroke in type 2 diabetes mellitus (T2DM) patients. METHODS: Using the Korean National Health Insurance Service data, we compared a 1:1 propensity score-matched cohort of patients who used SGLT-2i or TZD from January 2014 to December 2018. The primary outcome was stroke. The secondary outcomes were myocardial infarction (MI), cardiovascular death, 3-point MACE, and heart failure (HF). RESULTS: After propensity-matching, each group included 56,794 patients. Baseline characteristics were well balanced. During the follow-up, 862 patients were newly hospitalized for stroke. The incidence rate of stroke was 4.11 and 4.22 per 1,000 person-years for the TZD and SGLT-2i groups respectively. The hazard ratio (HR) of stroke was 1.054 (95% confidence interval [CI], 0.904 to 1.229) in the SGLT-2i group compared to the TZD group. There was no difference in the risk of MI, cardiovascular death, 3-point MACE between groups. Hospitalization for HF was significantly decreased in SGLT-2i-treated patients (HR, 0.645; 95% CI, 0.466 to 0.893). Results were consistent regardless of prior cardiovascular disease. CONCLUSION: In this real-world data, the risk of stroke was comparable in T2DM patients treated with SGLT-2i or TZD.

Neoadjuvant versus adjuvant chemotherapy in bladder cancer: a nationwide cohort study.

PURPOSE: Radical cystectomy is the standard of care for muscle-invasive bladder cancer. However, the 5-year survival rate is only about 50%. Therefore, additional treatments are needed. We compared the perioperative outcomes, overall survival, and treatment trends in patients with bladder cancer who underwent radical cystectomy and either neoadjuvant or adjuvant chemotherapy using nationwide population-based data. MATERIALS AND METHODS: We collected the data of patients diagnosed with bladder cancer treated with radical cystectomy between 2004 and 2016 using the National Health Insurance Service database. We evaluated overall treatment trends. The neoadjuvant chemotherapy and adjuvant chemotherapy groups were matched by propensity score. Cox proportional hazard analysis and Kaplan-Meier analysis were used to assess survival. RESULTS: Of 6134 patients, 1379 underwent adjuvant chemotherapy and 389 underwent neoadjuvant chemotherapy. The utilization rate of neoadjuvant chemotherapy increased from 6.4 to 12.2% from 2004 to 2016 (p = 0.018). The administration rate and number of granulocyte colony-stimulating factor cycles were lower in the neoadjuvant chemotherapy group than in the adjuvant chemotherapy group (p < 0.001 and p = 0.027, respectively). After propensity score matching, the neoadjuvant chemotherapy group had significantly better overall survival than the adjuvant chemotherapy group (p = 0.004). In multivariate analysis, neoadjuvant chemotherapy was associated with better overall survival (hazard ratio 0.77, 95% confidence interval 0.65-0.92, p = 0.003). CONCLUSIONS: Neoadjuvant chemotherapy was associated with lower granulocyte colony-stimulating factor administration and better overall survival than adjuvant chemotherapy. Neoadjuvant chemotherapy should be considered for patients with bladder cancer who undergo radical cystectomy.

A population-based study of pyogenic liver abscess in Korea: Incidence, mortality and temporal trends during 2007-2017.

BACKGROUND/AIMS: Although the epidemiology of pyogenic liver abscess (PLA) continues to change, only a few population-based studies have been conducted in Korea. This study investigated the epidemiology and clinical outcomes of PLA patients during a period of 10 years. METHODS: We analysed the Health Insurance Review and Assessment Service data between 2007 and 2017. The data included annual incidence rates, demographic data, underlying diseases, complications and mortality of PLA patients. RESULTS: The annual incidence of PLA for all age groups was 10.9 per 100 000 population. The incidence was gradually increased from 5.7 per 100 000 in 2007 to 14.4 per 100 000 in 2017. In patients with liver abscess, the prevalence of diabetes and malignancy were 37.24% and 26.5% respectively. Metastatic infection was reported in 1.74% of the patients, and endophthalmitis was most common. The mean in-hospital mortality was 9.6%, and there was no significant difference in mortality by year during the observation period. Mortality increased with age and was greatly affected by the underlying diseases, especially cancer. Based on the multivariate analysis results, the mortality of PLA patients was associated with older age, female sex, diabetes, malignancy and chronic kidney disease. CONCLUSION: The PLA incidence is rapidly increasing in Korea, especially in people with comorbidities. In addition, the causes and risk factors of PLA infections are changing and thus further research on epidemiology, different diagnosis and management approaches is required.

Fenofibrate Use Is Associated With Lower Mortality and Fewer Cardiovascular Events in Patients With Diabetes: Results of 10,114 Patients From the Korean National Health Insurance Service Cohort.

OBJECTIVE: We investigated the long-term clinical efficacy of fenofibrate use with regard to mortality and cardiovascular outcomes in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: We performed a population-based cohort study using data of the South Korean National Health Insurance Service from 2003 to 2014. Of 63,727 participants with diabetes aged 40-79 years, 5,057 users of fenofibrate only were compared with 5,057 nonusers of fenofibrate and/or omega-3 fatty acid with 1:1 propensity matching. The primary end point was a composite of myocardial infarction, stroke, percutaneous coronary revascularization, and cardiac death for a median of 3 years. RESULTS: The primary end point was significantly lower in fenofibrate users compared with those using neither fenofibrate nor omega-3 fatty acid (13.4 vs. 15.5 per 1,000 person-years; hazard ratio [HR] 0.76; 95% CI 0.62-0.94; P = 0.010). Cardiac death (1.8 vs. 3.1 per 1,000 person-years; HR 0.59; 95% CI 0.352-0.987; P = 0.0446), all-cause death (7.6 vs. 15.3 per 1,000 person-years; HR 0.437; 95% CI 0.340-0.562; P < 0.0001), and stroke (6.5 vs. 8.6 per 1,000 person-years; HR 0.621; 95% CI 0.463-0.833; P = 0.0015) were significantly lower in the fenofibrate group. When the duration of fenofibrate use was stratified by quartile, the risk decreased in quartile 4, with an HR of 0.347 (95% CI 0.226-0.532; P < 0.0001). In subgroup analysis, the favorable effect of fenofibrate was sustained consistently across all subsets of patients, including those classified by LDL cholesterol, HDL cholesterol, and triglyceride levels. CONCLUSIONS: Use of fenofibrate was associated with a lower rate of total and cardiac mortality and cardiovascular events in patients with type 2 diabetes during a 3-year follow-up in real-world large populations.

Adverse outcomes after surgeries in patients with liver cirrhosis among Korean population: A population-based study.

BACKGROUND: Patients with liver cirrhosis have an increased risk of in-hospital mortality or postoperative complication after surgery. However, large-scale studies on the prognosis of these patients after surgery are lacking. The aim of the study was to investigate the adverse outcomes of patients with liver cirrhosis after surgery over five years. METHODS AND FINDINGS: We used the Health Insurance Review and Assessment Service-National Inpatient Samples (HIRA-NIS) between 2012 and 2016. In-hospital mortality and hospital stay were analyzed using the data. Mortality rates according to the surgical department were also analyzed. Of the 1,662,887 patients who underwent surgery, 16,174 (1.0%) patients had cirrhosis. The in-hospital mortality (8.0% vs. 1.0%) and postoperative complications such as respiratory (6.0% vs. 5.3%) or infections (2.8% vs. 2.4%) was significantly higher in patients with cirrhosis than in those without cirrhosis. In addition, the total hospitalization period and use of the intensive care unit were significantly higher in patients with liver cirrhosis. In propensity score matching analysis, liver cirrhosis increased the risk of adverse outcome significantly [adjusted OR (aOR) 1.67, 95% CI 1.56-1.79, P<0.001], especially in-hospital mortality. In liver cirrhosis group, presence of decompensation or varices showed significantly increased postoperative complication or mortality. Adverse outcomes in patients with cirrhosis was the highest in patients who underwent otorhinolaryngology surgery (aOR 1.86), followed by neurosurgery (aOR 1.72), thoracic and cardiovascular surgery (aOR 1.56), and plastic surgery (aOR 1.36). CONCLUSION: The adverse outcomes of patients with cirrhosis is significantly high after surgery, despite advances in cirrhosis treatment.

Effects of a DPP-4 Inhibitor and RAS Blockade on Clinical Outcomes of Patients with Diabetes and COVID-19.

BACKGROUND: Dipeptidyl peptidase-4 inhibitor (DPP-4i) and renin-angiotensin system (RAS) blockade are reported to affect the clinical course of coronavirus disease 2019 (COVID-19) in patients with diabetes mellitus (DM). METHODS: As of May 2020, analysis was conducted on all subjects who could confirm their history of claims related to COVID-19 in the National Health Insurance Review and Assessment Service (HIRA) database in Korea. Using this dataset, we compared the short-term prognosis of COVID-19 infection according to the use of DPP-4i and RAS blockade. Additionally, we validated the results using the National Health Insurance Service (NHIS) of Korea dataset. RESULTS: Totally, data of 67,850 subjects were accessible in the HIRA dataset. Of these, 5,080 were confirmed COVID-19. Among these, 832 subjects with DM were selected for analysis in this study. Among the subjects, 263 (31.6%) and 327 (39.3%) were DPP4i and RAS blockade users, respectively. Thirty-four subjects (4.09%) received intensive care or died. The adjusted odds ratio for severe treatment among DPP-4i users was 0.362 (95% confidence interval [CI], 0.135 to 0.971), and that for RAS blockade users was 0.599 (95% CI, 0.251 to 1.431). These findings were consistent with the analysis based on the NHIS data using 704 final subjects. The adjusted odds ratio for severe treatment among DPP-4i users was 0.303 (95% CI, 0.135 to 0.682), and that for RAS blockade users was 0.811 (95% CI, 0.391 to 1.682). CONCLUSION: This study suggests that DPP-4i is significantly associated with a better clinical outcome of patients with COVID-19.

Cardiovascular disease burden in adult patients with cancer: An 11-year nationwide population-based cohort study.

BACKGROUND: Cardiovascular disease (CVD) is an important cause of morbidity and mortality in patients with cancer. However, the real-world CVD burden of adult cancer patients has not been well established. This study aimed to evaluate the prevalence and mortality of pre-existing and new-onset CVD in patients with cancers. METHODS: We analysed the prevalence and mortality of pre-existing and new-onset CVD in 41,034 adult patients with ten common solid cancers in a single payer system using data from the Korean National Health Insurance Service-National Sample Cohort from 2002 to 2013. RESULTS: When all types of cancer were included, 11.3% (n = 4647) of patients had pre-existing CVD when they were diagnosed with cancer. After excluding patients with pre-existing CVD, 15.7% of cancer patients (n = 5703) were newly diagnosed with CVD during the follow-up period (median 68 months). Both pre-existing and new-onset CVD were associated with increased risk of overall mortality and 5-year mortality. Multivariate analysis to predict all-cause mortality indicated both pre-existing and new-onset CVD, male sex, old age, prior history of diabetes or chronic kidney disease, suburban residential area, and low-income status as significant factors. CONCLUSIONS: Eleven percent of cancer patients had pre-existing CVD at the time of cancer diagnosis, and about 16% of cancer patients without pre-existing CVD were newly diagnosed with CVD, mostly within 5 years after the cancer diagnosis. Proper management of pre-existing CVD is necessary and pre-emptive prevention of new-onset CVD may alter treatment options and outcomes.