Data Resource Profile: The Cancer Public Library Database in South Korea.

This paper provides a comprehensive overview of the Cancer Public Library Database (CPLD), established under the Korean Clinical Data Utilization for Research Excellence project (K-CURE). The CPLD links data from four major population-based public sources: the Korea National Cancer Incidence Database in the Korea Central Cancer Registry, cause-of-death data in Statistics Korea, the National Health Information Database in the National Health Insurance Service, and the National Health Insurance Research Database in the Health Insurance Review & Assessment Service. These databases are linked using an encrypted resident registration number. The CPLD, established in 2022 and updated annually, comprises 1,983,499 men and women newly diagnosed with cancer between 2012 and 2019. It contains data on cancer registration and death, demographics, medical claims, general health checkups, and national cancer screening. The most common cancers among men in the CPLD were stomach (16.1%), lung (14.0%), colorectal (13.3%), prostate (9.6%), and liver (9.3%) cancers. The most common cancers among women were thyroid (20.4%), breast (16.6%), colorectal (9.0%), stomach (7.8%), and lung (6.2%) cancers. Among them, 571,285 died between 2012 and 2020 owing to cancer (89.2%) or other causes (10.8%). Upon approval, the CPLD is accessible to researchers through the K-CURE portal. The CPLD is a unique resource for diverse cancer research to investigate medical use before a cancer diagnosis, during initial diagnosis and treatment, and long-term follow-up. This offers expanded insight into healthcare delivery across the cancer continuum, from screening to end-of-life care.

What is the relationship between the local population change and cancer incidence in patients with dyslipidemia: Evidence of the impact of local extinction in Korea.

BACKGROUND: Changes in the local population are intricately linked to healthcare infrastructure, which subsequently impacts the healthcare sector. A decreasing local population can result in lagging health infrastructure, potentially leading to adverse health outcomes as patients may be at risk of not receiving optimal care and treatment. While some studies have explored the relationship between chronic diseases and local population decline, evidence regarding cancer is insufficient. In this study, we focused on how deteriorating management of chronic diseases such as dyslipidemia could influence the risk of cancer. We investigated the relationship between changes in the local population and cancer incidence among patients with dyslipidemia. METHODS: This cohort study was conducted using claims data. Data from adult patients with dyslipidemia from the National Health Insurance Service-National Sample Cohort conducted between 2002 and 2015 were included. Population changes in each region were obtained from the Korean Statistical Information Service and were used to link each individual's regional code. Cancer risk was the dependent variable, and Cox proportional hazards regression was used to estimate the target associations. RESULTS: Data from 336,883 patients with dyslipidemia were analyzed. Individuals who resided in areas with a decreasing population had a higher risk of cancer than those living in areas with an increasing population (decrease: hazard ratio (HR) = 1.06, 95% CI = 1.03-1.10; normal: HR = 1.05, 95% CI = 1.02-1.09). Participants living in regions with a low number of hospitals had a higher risk of cancer than those in regions with a higher number of hospitals (HR = 1.20, 95% CI = 1.12-1.29). CONCLUSION: Patients in regions where the population has declined are at a higher risk of cancer, highlighting the importance of managing medical problems caused by regional extinction. This could provide evidence for and useful insights into official policies on population decline and cancer risk.

Relationship between patient outcomes and patterns of fragmented cancer care in older adults with gastric cancer: A nationwide cohort study in South Korea.

INTRODUCTION: Fragmented cancer care, defined as receipt of care from multiple hospitals, has been shown to be associated with poor patient outcomes and high expense. However, evidence regarding the effects of hospital choice by patients with cancer on overall survival are lacking. Thus, we investigated the relationship between patterns of fragmented care and five-year mortality in patients with gastric cancer. MATERIALS AND METHODS: Using the Korean National Health Insurance senior cohort of adults aged ≥60 years, we identified patients with gastric cancer who underwent gastrectomy during 2007-2014. We examined the distribution of the study population by five-year mortality, and used Kaplan-Meier survival curves/log-rank test and Cox proportional hazard model to compare five-year mortality with fragmented cancer care. RESULTS: Among the participants, 19.5% died within five years. There were more deaths among patients who received fragmented care, especially those who transferred to smaller hospitals (46.6%) than to larger ones (40.0%). The likelihood of five-year mortality was higher in patients who received fragmented cancer care upon moving from large to small hospitals than those who did not transfer hospitals (hazard ratio, 1.28; 95% confidence interval, 1.10-1.48, P = .001). Moreover, mortality was higher among patients treated in large hospitals or in the capital area for initial treatment, and this association was greater for patients from rural areas. DISCUSSION: Fragmentation of cancer care was associated with reduced survival, and the risk of mortality was higher among patients who moved from large to small hospitals.

Combination therapy with moderate-intensity atorvastatin and ezetimibe versus high-intensity atorvastatin monotherapy in patients treated with percutaneous coronary intervention in practice: assessing RACING generalizability.

AIMS: Using rosuvastatin, the RACING (randomized comparison of efficacy and safety of lipid-lowering with statin monotherapy versus statin/ezetimibe combination for high-risk cardiovascular diseases) trial showed the beneficial effects of combining moderate-intensity statin with ezetimibe compared with high-intensity statin monotherapy in patients with atherosclerotic cardiovascular disease. This study investigated whether the beneficial effects of combination lipid-lowering therapy extend to patients treated with atorvastatin, not rosuvastatin, in daily clinical practice. METHODS AND RESULTS: Using stabilized inverse probability of treatment weighting, a total of 31 993 patients who were prescribed atorvastatin after drug-eluting stent (DES) implantation were identified from a nationwide cohort database: 6 215 patients with atorvastatin 20 mg plus ezetimibe 10 mg (combination lipid-lowering therapy) and 25 778 patients with atorvastatin 40-80 mg monotherapy. The primary endpoint was the 3-year composite of cardiovascular death, myocardial infarction, coronary artery revascularization, hospitalization for heart failure treatment, or non-fatal stroke in accordance with the RACING trial design. Combination lipid-lowering therapy was associated with a lower incidence of the primary endpoint (12.9% vs. 15.1% in high-intensity atorvastatin monotherapy; hazard ratio [HR] 0.81, 95% confidence interval [CI] 0.74-0.88, p < 0.001). Compared with high-intensity atorvastatin monotherapy, combination lipid-lowering therapy was also significantly associated with lower rates of statin discontinuation (10.0% vs. 8.4%, HR 0.81, 95% CI 0.73-0.90, p < 0.001) and new-onset diabetes requiring medication (8.8% vs. 7.0%, HR 0.80, 95% CI 0.70-0.92, p = 0.002). CONCLUSIONS: In clinical practice, a combined lipid-lowering approach utilizing ezetimibe and moderate-intensity atorvastatin was correlated with favorable clinical outcomes, drug compliance, and a reduced incidence of new-onset diabetes requiring medications in patients treated with DES implantation. Trial registration: ClinicalTrial.gov (NCT04715594).

Synthetic Tabular Data Based on Generative Adversarial Networks in Health Care: Generation and Validation Using the Divide-and-Conquer Strategy.

BACKGROUND: Synthetic data generation (SDG) based on generative adversarial networks (GANs) is used in health care, but research on preserving data with logical relationships with synthetic tabular data (STD) remains challenging. Filtering methods for SDG can lead to the loss of important information. OBJECTIVE: This study proposed a divide-and-conquer (DC) method to generate STD based on the GAN algorithm, while preserving data with logical relationships. METHODS: The proposed method was evaluated on data from the Korea Association for Lung Cancer Registry (KALC-R) and 2 benchmark data sets (breast cancer and diabetes). The DC-based SDG strategy comprises 3 steps: (1) We used 2 different partitioning methods (the class-specific criterion distinguished between survival and death groups, while the Cramer V criterion identified the highest correlation between columns in the original data); (2) the entire data set was divided into a number of subsets, which were then used as input for the conditional tabular generative adversarial network and the copula generative adversarial network to generate synthetic data; and (3) the generated synthetic data were consolidated into a single entity. For validation, we compared DC-based SDG and conditional sampling (CS)-based SDG through the performances of machine learning models. In addition, we generated imbalanced and balanced synthetic data for each of the 3 data sets and compared their performance using 4 classifiers: decision tree (DT), random forest (RF), Extreme Gradient Boosting (XGBoost), and light gradient-boosting machine (LGBM) models. RESULTS: The synthetic data of the 3 diseases (non-small cell lung cancer [NSCLC], breast cancer, and diabetes) generated by our proposed model outperformed the 4 classifiers (DT, RF, XGBoost, and LGBM). The CS- versus DC-based model performances were compared using the mean area under the curve (SD) values: 74.87 (SD 0.77) versus 63.87 (SD 2.02) for NSCLC, 73.31 (SD 1.11) versus 67.96 (SD 2.15) for breast cancer, and 61.57 (SD 0.09) versus 60.08 (SD 0.17) for diabetes (DT); 85.61 (SD 0.29) versus 79.01 (SD 1.20) for NSCLC, 78.05 (SD 1.59) versus 73.48 (SD 4.73) for breast cancer, and 59.98 (SD 0.24) versus 58.55 (SD 0.17) for diabetes (RF); 85.20 (SD 0.82) versus 76.42 (SD 0.93) for NSCLC, 77.86 (SD 2.27) versus 68.32 (SD 2.37) for breast cancer, and 60.18 (SD 0.20) versus 58.98 (SD 0.29) for diabetes (XGBoost); and 85.14 (SD 0.77) versus 77.62 (SD 1.85) for NSCLC, 78.16 (SD 1.52) versus 70.02 (SD 2.17) for breast cancer, and 61.75 (SD 0.13) versus 61.12 (SD 0.23) for diabetes (LGBM). In addition, we found that balanced synthetic data performed better. CONCLUSIONS: This study is the first attempt to generate and validate STD based on a DC approach and shows improved performance using STD. The necessity for balanced SDG was also demonstrated.

Risk of depression and anxiety disorders according to long-term glycemic variability.

BACKGROUND: Poor glycemic control has been linked to psychiatric symptoms. However, studies investigating the relationship between glycemic variability (GV) and depression and anxiety disorders are limited. We investigated the association of GV with depression and anxiety disorders. In addition, the relationship between trends in fasting plasma glucose (FPG) levels and these disorders were explored. METHODS: We analyzed the National Health Insurance Service-National Sample Cohort database (2002-2013) with 151,814 participants who had at least three health screenings between 2002 and 2010. Visit-to-visit FPG variability was measured as variability independent of the mean (VIM). Depression and anxiety disorders were diagnosed using ICD-10 codes (F41 for anxiety and F32 or F33 for depression) after index date. We analyzed the association between GV and incidences of these disorders using Kaplan-Meier and Cox proportional hazards methods. Trajectory analysis was conducted to explore the relationship between FPG trends and these disorders. RESULTS: During follow-up, 7166 and 14,149 patients were newly diagnosed with depression and anxiety disorders, respectively. The highest quartile group of FPG-VIM had a greater incidence of depression and anxiety than the lowest quartile group, with adjusted hazard ratios of 1.09 (95 % confidence interval [CI]: 1.02-1.17) and 1.08 (95 % CI: 1.03-1.14). Group with persistent hyperglycemia, identified through trajectory clustering of FPG levels, had a 1.43-fold increased risk of depression compared to those with consistently low FPG levels. LIMITATIONS: Potential selection bias by including participants with at least three health screenings. CONCLUSIONS: High GV and persistent hyperglycemia are associated with increased incidence of depression and anxiety disorders.

Effects of ranitidine and nizatidine on the risk of gastrointestinal cancer.

Purpose: Gastrointestinal (GI) cancer occurs in digestive organs such as the stomach, colon, liver, esophagus, and pancreas. About 83,034 cases occurred in Korea alone in 2020. Dietary factors, alcohol consumption, Helicobacter pylori (H. pylori), and lifestyle factors increase the incidence of diseases such as gastritis, peptic ulcer, pancreatitis, and gastroesophageal reflux disease (GERD), which can develop into GI cancer. However, in 2019, the US Food and Drug Administration announced that the drugs ranitidine and nizatidine, which are used for digestive disorders, contain carcinogens. In this study, we investigated the effects of ranitidine and nizatidine on the development of GI cancer. Materials and methods: In this study, using National Health Insurance Service-National Sample Cohort (NHIS-NSC) version 2.5 (updated from 2002 to 2019), subjects who developed GI cancer were enrolled in the case group, and those who were at risk of, but did not develop, cancer were enrolled in the control group. Thereafter, risk-set matching was performed (1:3 ratio) by sex and age at the time of diagnosis of cancer in the case group. Through this procedure, 22,931 cases and 68,793 controls were identified. The associations of ranitidine and/or nizatidine with GI cancer were confirmed by adjusted odds ratios (aORs) and 95% confidence intervals (CIs) calculated through conditional logistic regression analysis. Results: The aORs of ranitidine and/or nizatidine users were lower than those of nonusers in all average prescription days groups (< 30 days/year: aOR [95% CI] = 0.79 [0.75-0.82]; 30-59 days/year: aOR [95% CI] = 0.66 [0.59-0.73]; 60-89 days/year: aOR [95% CI] = 0.69 [0.59-0.81]; ≥ 90 days/year: aOR [95% CI] = 0.69 [0.59-0.79]). Sensitivity analyses were conducted with different lag periods for the onset of GI cancer after drug administration, and these analyses yielded consistent results. Additional analyses were also performed by dividing subjects into groups based on cancer types and CCI scores, and these analyses produced the same results. Conclusion: Our study, using nationwide retrospective cohort data, did not find evidence suggesting that ranitidine and nizatidine increase the risk of GI cancer. In fact, we observed that the incidence of GI cancer was lower in individuals who used the drugs compared to nonusers. These findings suggest a potential beneficial effect of these drugs on cancer risk, likely attributed to their ability to improve digestive function.

The effects of hospice care on healthcare expenditure among cancer patients.

PURPOSE: It is necessary to estimate the hospice usage and hospice-related cost for entire cancer patients using nationwide cohort data to establish a suitable ethical and cultural infrastructure. This study aims to show the effects of hospital hospice care on healthcare expenditure among South Korean cancer patients. METHODS: This study is a retrospective cohort study using customized health information data provided by the National Health Insurance Service. Individuals who were diagnosed with stomach, colorectal, or lung cancer between 2003 and 2012 were defined as new cancer patients, which included 7,176 subjects. Patients who died under hospital-based hospice care during the follow-up period from January 2016 to December 2018 comprised the treatment group. Healthcare expenditure was the dependent variable. Generalized estimating equations was used. RESULTS: Among the subjects, 2,219 (30.9%) had used hospice care at an average total cost of 948,771 (± 3,417,384) won. Individuals who had used hospice care had a lower odds ratio (EXP(ß)) of healthcare expenditure than those who did not (Total cost: EXP(ß) = 0.27, 95% confidence intervals (CI) = 0.25-0.30; Hospitalization cost: EXP(ß) = 0.32, 95% CI = 0.29-0.35; Outpatient cost: EXP(ß) = 0.02, 95% CI = 0.02-0.02). CONCLUSION: Healthcare expenditure was reduced among those cancer patients in South Korea who used hospice care compared with among those who did not. This emphasizes the importance of using hospice care and encourages those hesitant to use hospice care. The results provide useful insights into both official policy and the existing practices of healthcare systems.

Combination Lipid-Lowering Therapy in Patients Undergoing Percutaneous Coronary Intervention.

BACKGROUND: The RACING (randomized comparison of efficacy and safety of lipid-lowering with statin monotherapy versus statin/ezetimibe combination for high-risk cardiovascular diseases) trial examined the effects of combination therapy with moderate-intensity statin and ezetimibe in patients with atherosclerotic cardiovascular disease compared with high-intensity statin monotherapy. OBJECTIVES: This observational study was conducted to evaluate the impact of 2 treatment strategies used in the RACING trial in clinical practice. METHODS: After stabilized inverse probability of treatment weighting, a total of 72,050 patients who were prescribed rosuvastatin after drug-eluting stent implantation were identified from a nationwide cohort database: 10,794 patients with rosuvastatin 10 mg plus ezetimibe 10 mg (combination lipid-lowering therapy) and 61,256 patients with rosuvastatin 20 mg monotherapy. The primary endpoint was the 3-year composite event of cardiovascular death, myocardial infarction, coronary artery revascularization, hospitalization for heart failure treatment, or nonfatal stroke in accordance with the RACING trial. RESULTS: Combination lipid-lowering therapy was associated with a lower occurrence of the primary endpoint (11.6% vs 15.2% for those with high-intensity statin monotherapy; HR: 0.75; 95% CI: 0.70-0.79; P < 0.001). Compared with high-intensity statin monotherapy, combination lipid-lowering therapy was associated with fewer discontinuations of statin (6.5% vs 7.6%; HR: 0.85; 95% CI: 0.78-0.94: P < 0.001) and a lower occurrence of new-onset diabetes requiring medication (7.7% vs 9.6%; HR: 0.80; 95% CI: 0.72-0.88; P < 0.001). CONCLUSIONS: In clinical practice, combination lipid-lowering therapy with ezetimibe and moderate-intensity statin was associated with favorable clinical outcomes and drug compliance in patients treated with drug-eluting stent implantation. (CONNECT DES Registry; NCT04715594).

Cancer care patterns in South Korea: Types of hospital where patients receive care and outcomes using national health insurance claims data.

BACKGROUND: Although strengthening coverage has improved cancer care, there are concerns related to medical distortion. Previous studies have only examined whether patients visit a specific hospital, and not the continuum of patients with cancer, resulting in a lack of evidence in South Korea. This study aimed to investigate the patterns in hospital type for cancer care and analyze their association with outcomes. METHODS: The data for this study were obtained from the National Health Insurance Services Sampled Cohort database. This study included patients with four types of cancer (top four cancer incidence in 2020): gastric (3353), colorectal (2915), lung (1351), and thyroid (5158) cancer. The latent class mixed model was used to investigate cancer care patterns, and multiple regression or survival analysis was performed to examine medical cost, length of stay (LOS), and mortality. RESULTS: The patterns in each cancer type were classified into two to four classes, namely, mainly visited clinics or hospitals, mainly visited general hospitals, mainly visited tertiary hospitals (MT), and tertiary to general hospitals through trajectory modeling based on the utilization of cancer care. Compared to the MT pattern, other patterns were generally associated with higher cost, LOS, and mortality. CONCLUSION: The patterns found in this study may be a more realistic way of defining patients with cancer in South Korea compared to previous studies, and its association-related outcomes may be used as a basis to address problems in the healthcare system and prepare alternatives for patients with cancer. Future studies should review cancer care patterns related to other factors such as regional distribution.

Association of polypharmacy with all-cause mortality and adverse events among elderly colorectal cancer survivors.

BACKGROUND: The risk of inappropriate drug exposure in elderly colorectal cancer (CRC) survivors after the initial cancer treatment has not been well studied. This study investigated the association of polypharmacy (PP) with overall survival, hospitalization, and emergency room (ER) visits among older CRC survivors. METHODS: A retrospective cohort study was conducted using the Korean National Health Insurance claims data follow-up from 2002 to 2017. Participants comprised those aged ≥65 years who were hospitalized with a diagnosis of CRC received cancer treatment and survived at least 2 years from the initial CRC diagnosis between 2003 and 2012. PP was defined based on the number of individual drugs during the third year, after 2 years of survival since the initial cancer treatment. PP was categorized as follows: non-PP (zero to four prescribed drugs); PP (five to nine drugs), and excessive PP (≥10 drugs). Main outcomes are all-cause mortality, hospitalization, and ER visits. RESULTS: Of the 55,228 participants, 44.5% died, 83.1% were hospitalized, and 46.1% visited the ER. The PP and excess PP groups showed increased risk of all-cause mortality, hospitalization, and ER visit compared with the low PP group, and was highly associated among groups including patients aged 65 to 74 years and those in low-level frailty groups. CONCLUSIONS: These risks can be minimized by increasing awareness and enhancing behaviors among health care professionals, especially clinician and pharmacists, to be aware of potential drug interactions, review, and ongoing monitoring. PLAIN LANGUAGE SUMMARY: The risk of inappropriate drug exposure in older colorectal cancer (CRC) survivors after the initial cancer treatment has not been well studied. Polypharmacy was associated with adverse outcomes, including all-cause mortality, hospitalization, and emergency room visits among older CRC survivors and it was particularly associated with those who were 65 to 75 years and those with low risk of frailty. When prescribing drugs, physicians should be mindful of finding a balance between adequate treatment of diseases and avoiding adverse drug effects in survivors of CRC.

Pioglitazone Use and Reduced Risk of Dementia in Patients With Diabetes Mellitus With a History of Ischemic Stroke.

BACKGROUND AND OBJECTIVES: Previous studies have reported the protective effect of pioglitazone on dementia in patients with type 2 diabetes mellitus (DM). Recent studies have shown that pioglitazone also lowers the risk of primary and recurrent stroke. Understanding the characteristics of patients particularly associated with the benefits of pioglitazone would facilitate its personalized use by specifying subpopulations during routine clinical care. The aim of this study was to examine the effects of pioglitazone use on dementia in consideration of stroke occurrence. METHODS: Using nationwide longitudinal data of patients with DM from the Korean National Health Insurance Service DM cohort (2002-2017), we investigated the association of pioglitazone use with incident dementia in patients with new-onset type 2 DM. The heterogeneity of the treatment effect was examined using exploratory analyses. Using a multistate model, we assessed the extent to which incident stroke affects the association between pioglitazone use and dementia. RESULTS: Pioglitazone use was associated with a reduced risk of dementia, compared with nonuse (adjusted hazard ratio [aHR] = 0.84, 95% CI 0.75-0.95); the risk reduction in dementia was greater among patients with a history of ischemic heart disease or stroke before DM onset (aHR = 0.46, 95% CI 0.24-0.90; aHR = 0.57, 95% CI 0.38-0.86, respectively). The incidence of stroke was also reduced by pioglitazone use (aHR = 0.81, 95% CI 0.66-1.00). However, when the stroke developed during the observation period of pioglitazone use, such lowered risk of dementia was not observed (aHR = 1.27, 95% CI 0.80-2.04). DISCUSSION: Pioglitazone use is associated with a lower risk of dementia in patients with DM, particularly in those with a history of stroke or ischemic heart disease, suggesting the possibility of applying a personalized approach when choosing pioglitazone to suppress dementia in patients with DM.

Does fragmented cancer care affect survival? Analysis of gastric cancer patients using national insurance claim data.

BACKGROUND: We aimed to investigate the association between fragmented cancer care in the early phase after cancer diagnosis and patient outcomes using national insurance claim data. METHODS: From a nationwide sampled cohort database, we identified National Health Insurance beneficiaries diagnosed with gastric cancer (ICD-10: C16) in South Korea during 2005-2013. We analyzed the results of a multiple logistic regression analysis using the generalized estimated equation model to investigate which patient and institution characteristics affected fragmented cancer care during the first year after diagnosis. Then, survival analysis using the Cox proportional hazard model was conducted to investigate the association between fragmented cancer care and five-year mortality. RESULTS: Of 2879 gastric cancer patients, 11.9% received fragmented cancer care by changing their most visited medical institution during the first year after diagnosis. We found that patients with fragmented cancer care had a higher risk of five-year mortality (HR: 1.310, 95% CI: 1.023-1.677). This association was evident among patients who only received chemotherapy or radiotherapy (HR: 1.633, 95% CI: 1.005-2.654). CONCLUSIONS: Fragmented cancer care was associated with increased risk of five-year mortality. Additionally, changes in the most visited medical institution occurred more frequently in either patients with severe conditions or patients who mainly visited smaller medical institutions. Further study is warranted to confirm these findings and examine a causal relationship between fragmented cancer care and survival.

The effect of continuity of care of dyslipidaemia patients on preventable hospitalisation and healthcare expenditures.

Although continuous treatment leads to better patient outcomes, evidence regarding the effect of the continuity of care (COC) on preventable hospitalisation and medical expenses in Korea for patients with dyslipidaemia is insufficient. We evaluated the effect of COC on preventable hospitalisation and medical expenses for patients with dyslipidaemia. This study used National Health Insurance Sampling cohort data (2008-2015). We measured COC with the Bice-Boxerman index based on the outpatient visits of patients diagnosed with dyslipidaemia for the first time. Preventable hospitalisation included admission for cardiovascular disease (CVD) and all costs for outpatient visits. We evaluated the association of COC with preventable hospitalisation and medical expenses using a generalised estimating equation model. Patients (N = 53,372) with newly diagnosed dyslipidaemia participated. Compared to non-hospitalised patients, hospitalised patients had higher fragmentation scores for CVD, met more healthcare providers, had higher total outpatient visits and had a lower proportion of primary healthcare providers served. A higher fragmentation score was associated with an increased risk of hospitalisation (rate ratio [RR]: 1.873, 95% confidence interval [CI]: 1.520-2.309) and healthcare expenditure (RR: 1.381, 95% CI: 1.322-1.442). The magnitude of the effect of COC on hospitalisation differed according to patients' drug intake and residence location. Fragmentation of care was associated with preventable hospitalisation and increased healthcare costs, especially for patients taking medications/living in rural areas. It is necessary to promote a more effective COC.

Multifarious Translational Regulation during Replicative Aging in Yeast.

Protein synthesis is strictly regulated during replicative aging in yeast, but global translational regulation during replicative aging is poorly characterized. To conduct ribosome profiling during replicative aging, we collected a large number of dividing aged cells using a miniature chemostat aging device. Translational efficiency, defined as the number of ribosome footprints normalized to transcript abundance, was compared between young and aged cells for each gene. We identified more than 700 genes with changes greater than twofold during replicative aging. Increased translational efficiency was observed in genes involved in DNA repair and chromosome organization. Decreased translational efficiency was observed in genes encoding ribosome components, transposon Ty1 and Ty2 genes, transcription factor HAC1 gene associated with the unfolded protein response, genes involved in cell wall synthesis and assembly, and ammonium permease genes. Our results provide a global view of translational regulation during replicative aging, in which the pathways involved in various cell functions are translationally regulated and cause diverse phenotypic changes.

Prolonged dual antiplatelet therapy after drug-eluting stent implantation in patients with diabetes mellitus: A nationwide retrospective cohort study.

Background: Optimal duration of dual antiplatelet therapy (DAPT) in patients with diabetes mellitus (DM) who have undergone drug-eluting stent (DES) implantation is not clearly established. This study sought to impact of DAPT duration on real-world clinical outcome in patients with or without DM. Methods: Using a nationwide cohort database, we investigate the association between DAPT duration and clinical outcome between 1 and 3 years after percutaneous coronary intervention (PCI). Primary outcome was all-cause death. Secondary outcomes were cardiovascular death, myocardial infarction, and composite bleeding events. After weighting, 90,100 DES-treated patients were included; 29,544 patients with DM and 60,556 without DM; 31,233 patients with standard DAPT (6-12 months) and 58,867 with prolonged DAPT (12-24 months). Results: The incidence of all-cause death was significantly lower in patients with prolonged DAPT [8.3% vs. 10.5% in those with standard DAPT, hazard ratio (HR) 0.78, 95% confidence interval (CI) 0.72-0.84] in diabetic patients and non-diabetic patients (4.5% vs. 5.0% in those with standard DAPT, HR 0.89, 95% CI 0.83-0.96). The incidence of composite bleeding events was 5.7% vs. 5.4%, respectively, (HR 1.07, 95% CI 0.96-1.18) in diabetic patients and 5.6% vs. 5.0%, respectively, in non-diabetic patients (HR 1.13, 95% CI 1.05-1.21). There was a significant interaction between the presence of DM and DAPT duration for all-cause death (p for interaction, pint = 0.01) that further favored prolonged DAPT in diabetic patients. However, there was no significant interaction between the presence of DM and DAPT duration for composite bleeding events (pint = 0.38). Conclusions: This study showed that prolonged rather than standard DAPT might be clinically beneficial in diabetic patients with DES implantation. Trial registration: ClinicalTrial.gov (NCT04715594).

Long-Term Beta-Blocker Therapy in Patients With Stable Coronary Artery Disease After Percutaneous Coronary Intervention.

Background: It is unclear whether beta-blocker treatment is advantageous in patients with stable coronary artery disease (CAD) who underwent percutaneous coronary intervention (PCI). We evaluated the clinical impact of long-term beta-blocker maintenance in patients with stable CAD after PCI with drug-eluting stent (DES). Methods: From a nationwide cohort database, we identified the stable CAD patients without current or prior history of myocardial infarction or heart failure who underwent DES implantation. An intention-to-treat principle was used to analyze the impact of beta-blocker treatment on long-term outcomes of major adverse cardiovascular events (MACE) composed of cardiovascular death, myocardial infarction, and hospitalization with heart failure. Results: After stabilized inverse probability of treatment weighting, a total of 78,380 patients with stable CAD was enrolled; 45,746 patients with and 32,634 without beta-blocker treatment. At 5 years after PCI with a 6-month quarantine period, the adjusted incidence of MACE was significantly higher in patients treated with beta-blockers [10.0 vs. 9.1%; hazard ratio (HR) 1.11, 95% CI 1.06-1.16, p < 0.001] in an intention-to-treat analysis. There was no significant difference in all-cause death between patients treated with and without beta-blockers (8.1 vs. 8.2%; HR 0.99, 95% CI 0.94-1.04, p = 0.62). Statistical analysis with a time-varying Cox regression and rank-preserving structure failure time model revealed similar results to the intention-to-treat analysis. Conclusions: Among patients with stable CAD undergoing DES implantation, long-term maintenance with beta-blocker treatment might not be associated with clinical outcome improvement. Trial Registration: ClinicalTrial.gov (NCT04715594).

Benefit and risk of prolonged dual antiplatelet therapy after drug-eluting stent implantation in patients with chronic kidney disease: A nationwide cohort study.

BACKGROUND AND AIMS: The optimal duration of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) with drug-eluting stent in patients with chronic kidney disease (CKD) is not clearly established. This study purposed to compare clinical outcomes of patients with 6-12 (standard) versus 12-24 months (prolonged) DAPT according to CKD. METHODS: Using a nationwide, claim-based database, we retrospectively evaluated association between DAPT duration and clinical outcomes including death, composite ischemic event, and composite bleeding event between 1 and 3 years after PCI. CKD was defined as estimated glomerular filtration rate <60 mL/min/1.73 m2. Of 73,941 eligible patients, 13,425 (18.2%) had CKD and 49,019 (66%) were prescribed prolonged DAPT. Prolonged DAPT had no significant impact on the risk of clinical outcomes in patients with normal renal function. RESULTS: In patients with CKD, prolonged DAPT was associated with a lower risk of all-cause death (HR 0.85, 95% CI 0.76-0.95) and composite ischemic events (HR 0.87, 95% CI 0.78-0.96) and a higher risk of composite bleeding events (HR 1.18, 95% CI 1.02-1.37). Benefit of prolonged DAPT on reducing composite ischemic event increased significantly in patients with worsened renal dysfunction (pinteraction = 0.02) while there was no significant interaction between its bleeding risk and renal dysfunction (pinteraction = 0.22). CONCLUSIONS: While standard DAPT would be recommended in patients with normal renal function, tailored decision for DAPT duration would be considered in those with CKD to balance between ischemic and bleeding risks.

Long-Term Clinical Outcomes Between Biodegradable and Durable Polymer Drug-Eluting Stents: A Nationwide Cohort Study.

Background: Despite the theoretical benefits of biodegradable polymer drug-eluting stents (BP-DES), clinical benefits of BP-DES over durable polymer DES (DP-DES) have not been clearly demonstrated. Using data from a large-volume nationwide cohort, we compared long-term clinical outcomes between BP-DES- and DP-DES-treated patients. Methods: A retrospective cohort study that enrolled all patients who underwent percutaneous coronary intervention (PCI) with new-generation DES between 2010 and 2016 in Korea was conducted by using the National Health Insurance Service database. The outcomes of interest were all-cause death, cardiovascular death, and myocardial infarction (MI). Results: A total of 127,731 patients treated with new-generation DES with thin struts (<90 µm) were enrolled for this analysis. After stabilized inverse probability of treatment weighting, the incidence of all-cause death was significantly lower in patients treated with BP-DES (n = 19,521) at 5 years after PCI (11.3 vs. 13.0% in those treated with DP-DES [n = 108,067], hazard ratio [HR] 0.92, 95% confidence interval [CI], 0.88-0.96, p < 0.001), while showing no statistically significant difference at 2 years after PCI (5.7 vs. 6.0%, respectively, HR 0.95, 95% CI, 0.89-1.01, p = 0.238). Similarly, use of BP-DES was associated with a lower incidence of cardiovascular death (7.4 vs. 9.6% in those treated with DP-DES, HR 0.82, 95% CI, 0.77-0.87, p < 0.001), and MI (7.4 vs. 8.7%, respectively, HR 0.90, 95% CI, 0.86-0.94, p = 0.006) at 5 years after PCI. There was no statistically significant difference of cardiovascular death (4.6 vs. 4.9%, respectively, HR 0.93, 95% CI, 0.85-1.01, p = 0.120) and MI (5.0 vs. 5.1%, respectively, HR 0.98, 95% CI, 0.92-1.05, p = 0.461) at 2 years after PCI. Conclusions: Implantation of BP-DES was associated with a lower risk of all-cause death, cardiovascular death, and MI compared with DP-DES implantation. This difference was clearly apparent at 5 years after DES implantation. Clinical Trial Registration: ClinicalTrial.gov, NCT04715594.

Fragmentation of care and colorectal cancer survival in South Korea: comparisons according to treatment at multiple hospitals.

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