Clozapine-induced Myocarditis in Korea: Analysis of a Nationwide Database and Comparison to Other Countries.

BackgroundLong-term growth data of very low birth weight (VLBW) infants are currently collected in the Korean Neonatal Network (KNN) and National Health Insurance Service (NHIS) database. However, variance in the number of infants, check-up time, and check-up parameters led to decreased credibility of cumulated data. We aimed to compare the data on serial growth outcomes by major morbidities from birth to 5 years in VLBW infants between the KNN and NHIS databases.MethodsWe combined the NHIS and KNN data of VLBW infants born between 2013 and 2015. The check-up times in the NHIS database were at 4–6, 9–12, 18–24, 30–36, 42–48, and 54–60 months of age, whereas in the KNN were at 18–24 months of corrected age and at 36 months of age.ResultAmong 8,864 VLBW infants enrolled based on the birth certificates from the Statistics Korea, 6,086 infants (69%) were enrolled in the KNN, and 5,086 infants (57%) participated in the NHIS health check-up. Among 6,068 infants, 3,428 infants (56%) were enrolled at a corrected age of 18–24 months and 2,572 infants (42%) were enrolled at a chronological age of 33–36 months according to the KNN follow-up registry. However, based on the national birth statistics data, the overall follow-up rate of the KNN at 36 months of age was as low as 29%. The NHIS screening rate was lower at first (23%); however, it increased over time to exceed the KNN follow-up rate. Growth failure (weight under 10th percentile) at corrected ages of 18–24 months and 36 months were more common in the NHIS than KNN (42% vs. 20%, 37% vs. 34.5%). Infants with bronchopulmonary dysplasia and periventricular leukomalacia showed similar rates of growth failure at 2 years but varying rates at 3 years between the KNN and NHIS.ConclusionBy integrating the KNN and NHIS data indirectly at continuous time points according to morbidities, we found that there are discontinuities and discrepancies between the two databases among VLBW infants. Establishing an integrated system by patient level linking the KNN and NHIS databases can lead to better understanding and improved neonatal outcomes in VLBW infants in Korea.

Dear Editor, Antibiotics are considered indispensable in numerous treatments against infectious diseases. However, their over-prescription and widespread use are emerging as important global issues, as they lead to resistant bacteria, reducing the efficacy of antibiotics[1]. The defined daily doses per 1,000 habitants per day for antibiotics in South Korea is 28, which is much higher than the average of Organization for Economic Co-operation and Development countries[1]. In animal studies, antibiotic tigecycline was found to inhibit the proliferation and induce apoptosis of hepatocellular carcinoma (HCC) cells[2]. In addition, isoprenoid antibiotic was found to suppress the growth and invasion of HCC by targeting the signal transducer and activator of the transcription 3 signaling cascade[3]. Despite evidence of the beneficial effects of antibiotics against HCC, evidence regarding their effects on the long-term development of HCC is limited. Introduction regarding the incidence of HCC is provided in the Supplementary file. This nationwide population-based retrospective cohort study used data from the Korean National Health Insurance Service (NHIS)[4], comprising demographic information, health screening results, medical records related to inpatient and outpatient visits, and pharmaceutical prescriptions (Supplementary file). We identified 12,163,324 individuals aged ≥ 20 years who underwent health screening between 2005 and 2006 from the NHIS database for the adjusted analyses. Individuals were excluded if (1) died (n = 23,940), (2) had any cancer (n = 1,871,500), or (3) had missing values for covariates (n = 462,857) before the first day of follow-up. A total of 9,805,027 individuals were included (Supplementary Figure S1). They were followed up with a median of 15.0 years (mean, 14.2 years) from January 1, 2007, until the date of cancer event, death, or December 31, 2021, whichever came earliest. Antibiotics were defined based on the World Health Organization Anatomical Therapeutic Chemical classification of drugs (Supplementary Table S1). The primary exposure was defined as cumulative days of antibiotic prescriptions within the first five years. Antibiotic cumulative days were categorized into none, 1-14, 15-59, 60-179, 180-364, and ≥365 days. The secondary exposure was the number of antibiotic classes, which were classified as none, 1, 2, 3, 4, and 5 or more. The outcome was newly diagnosed HCC. HCC was identified using the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision code of C220 combined with the critical condition codes for cancer (V193-V194) of the NHIS. Baseline characteristics and infection rates of the study population who underwent health screening between 2005 and 2006 are depicted in Supplementary Tables S2-S3. Long-term antibiotic users were likely to be older, never smokers, with a higher body mass index and Charlson comorbidity index. Increasing the cumulative days of antibiotic exposure was associated with a lower risk of HCC after the adjustments (Ptrend < 0.001; Table 1). The long-term antibiotic use (≥ 365 days) group was associated with a lower risk of HCC (adjusted hazard ratio [aHR]: 0.64; 95% confidence interval [CI]: 0.61-0.67) in model 5 when compared to the antibiotic non-user group. HCC risk by cumulative days of antibiotics as a continuous variable is shown in Supplementary Table S4. These results were consistent regardless of men (Supplementary Table S5) and women (Supplementary Table S6). As compared with individuals who were not prescribed antibiotics, men (aHR: 0.62, 95% CI: 0.59-0.65) and women (aHR: 0.73, 95% CI: 0.63-0.83) who were prescribed antibiotics for ≥ 365 days had a significantly reduced risk of HCC in model 4, respectively. In several sensitivity analyses, the findings were consistent with those of the primary analyses (Supplementary Table S7). First, when we washed out HCC events after the follow-up during the first 1, 3, or 5 years, overall trends remained unchanged. Second, after excluding the individuals who were diagnosed with chronic liver disease, hepatitis B virus infection (HBV), hepatitis C virus infection, and type 2 diabetes before the index date, the aHR of individuals who used antibiotics for ≥ 365 days was lower (aHR: 0.70) compared to antibiotic non-users. The risk of HCC was also lower after prolonging antibiotic exposure from 5 to 7 years compared to antibiotic non-users (aHR: 0.64, 95% CI: 0.60-0.68). The antibiotic use as the cumulative days during the last year of exposure period also showed that antibiotic use is associated with a lower risk of HCC (Ptrend < 0.001). Stratified analyses were performed to evaluate differences in HCC risk by covariates (Supplementary Table S8). The aHR of ≥ 365 days of antibiotic use was lower in participants with HBV infection (aHR: 0.59) compared to participants without HBV infection (aHR: 0.64). In the antibiotic user group with ≥ 365 days, patients with hepatitis B virus infection who did not receive antiviral treatment had an aHR of 0.57 (95% CI: 0.51-0.64), and patients with HBV infection who received antiviral treatment had an aHR of 0.83 (95% CI: 0.63-1.09; Supplementary Table S9). In addition, a greater number of antibiotic classes prescribed was associated with a reduced risk of HCC (Supplementary Table S10). Individuals who have been prescribed 5 or more classes of antibiotics were associated with a reduced risk of HCC compared to those who did not prescribe antibiotics (aHR: 0.65, 95% CI: 0.62-0.69, Ptrend < 0.001). When we evaluated the association of any use of the category-specific antibiotics with the risk of HCC, no significant difference was found between never use versus any use of the category-specific antibiotics (Supplementary Table S11). In this nationwide cohort study, we identified a dose-dependent association between cumulative days of antibiotics prescription and the risk of HCC. This association remained significant after adjusting for potential confounding factors. The results are noteworthy as previous studies have found that antibiotics may be linked to a higher risk of certain diseases, such as cardiovascular disease, and the effects of antibiotics on the gut microbe-related metabolites are considered a major contributing factor[5, 6]. Since antibiotics may disrupt intestinal dysbiosis, which has been found to affect antitumor immune surveillance and contribute to the progression of liver disease toward cancer, antibiotics may be considered an unfavorable condition regarding the risk of HCC[7]. However, interestingly, gentamicin and amikacin antibiotics have been identified to decrease the deoxycholic acid concentration in liver tissues in a mouse model[8]. Deoxycholic acid, part of the enterohepatic circulation, has been shown to induce senescence-associated secretory phenotype in hepatic stellate cells, leading to the secretion of tumor-promoting and inflammatory factors in the liver and facilitating the development of HCC in mice[9]. Another possible explanation for the protective effects of antibiotics against HCC could be their anti-inflammatory properties, which are considered beneficial against non-bacterial infections[10]. Further rationale behind the proposed hypothesis is provided in the Supplementary file. There are some underlying limitations that need to be considered when interpreting our results. First, cumulative days of antibiotics may not represent the actual doses of antibiotics. Second, the study could not account for other potential confounding factors, such as dietary habits, environmental factors, and genetic factors, which might influence the observed associations. Additionally, since gut microbiota and microorganisms within the liver may differ in different ethnicities, future studies from other regions are needed to generalize our results. In conclusion, antibiotics were associated with a lower risk of HCC, and a negative relationship was observed between the cumulative days of antibiotics or the number of classes of antibiotics and the risk of HCC. Understanding the beneficial effects of antibiotics against HCC and exploring actionable approaches may provide novel insights to lower the incidence of HCC. The authors declare no competing interests. This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korean government (2021R1F1A1063346) and the research program of the Korea Medical Institute. Sun Jae Park received a scholarship from the BK21 FOUR education program from the National Research Foundation of Korea (NRF). The institutional review board of Seoul National University Hospital approved this study (No. E-2108-136-1246). Informed consents were exempted because the NHIS database is strictly anonymized according to the Personal Data Protection Act. Not applicable. Not applicable. Not applicable. The data that support the findings of this study are available from the Korean National Health Insurance Service, but restrictions apply to the availability of these data, which were used under license for the current study and are thus not publicly available. Data are, however, available from the Korean National Health Insurance Service (https://nhiss.nhis.or.kr) upon reasonable research proposal and with permission of the Korean National Health Insurance Service. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

BackgroundThe burden of rare diseases on society and patients’ families has increased in Korea. However, because of the infrequency of rare diseases, there is a lack of resources and information to address these cases and inadequate funding for the management of these patients. We investigated the average annual cumulative incidence of rare diseases and the trends in annual cumulative incidence from 2011 to 2015 in Korea by using nationwide administrative data from the Korean National Health Insurance Service (NHIS) database for patients registered with the co-payment assistance policy for rare and incurable diseases. Annual cumulative incidence per 10,000,000 was calculated as the total number of newly enrolled patients with the Korean Standard Classification of Diseases (KCD)-7 code in the register, divided by the number of residents with health insurance coverage during each year. We employed simple linear regression analysis to evaluate the trends in annual cumulative incidence/10,000,000 population per year for each rare disease.ResultsOverall, national support was provided for patients with 415 KCD codes listed among the targeted rare diseases. The total number of newly enrolled patients with rare diseases was 53,831 in 2011, 52,658 in 2012, 52,955 in 2013, 71,530 in 2014, and 70,559 in 2015. The number of rare diseases with an average annual cumulative incidence of 100/10,000,000 and above was 22 (5.30%), while there were 227 (54.70%) and 148 (35.66%) with an average cumulative incidence between 1/10,000,000 and 100/10,000,000 and less than 1/10,000,000, respectively. The trends in the annual cumulative incidence for 43 rare diseases were statistically significant (p-value < 0.05). The rare diseases for which the incremental trend per year was statistically significant were sarcoidosis (D86, D86.0, D86.1, D86.2, D86.3, D86.8, D86.9), Parkinson’s disease (G20), Guillain-Barré syndrome (G61.0), primary biliary cirrhosis (K74.3) and Sjogren’s syndrome (M35.0).ConclusionsThe number of rare diseases showing an increasing trend in annual cumulative incidence was higher than the number of diseases showing a decreasing trend in annual cumulative incidence. Given that the definition and diagnosis vary based on country and that there is difficulty in identifying valid cases, further detection strategies are needed to establish the incidence of each rare disease considering the importance of establishing a health policy based on the actual incidence of the targeted diseases.

Background & aimsChronic rhinosinusitis (CRS) is one of the most prevalent upper respiratory tract diseases. However, little is known the effect of CRS on the cardiovascular aspects of patients. This study aimed to investigate the incidence of acute myocardial infarction (AMI) in patients with CRS compared with that in the general population.MethodsThis retrospective cohort study was performed using the Korean National Health Insurance Service (NHIS) database. To minimize confounding, age, sex, and cardiovascular risk profiles were adjusted. The primary endpoint was newly diagnosed AMI in patients between January 2005 and December 2018. The relative risk of AMI in patients with CRS was compared with that in controls. Kaplan–Meier survival curves and Cox proportional regression tests were used for statistical analyses.ResultsAmong 5,179,981 patients from the NHIS database, 996,679 patients with CRS were selected. The control group was 10 times (n = 9,966,790) the number of individuals in the CRS group. The CRS group had better cardiovascular profiles than those of the control group and had an adjusted hazard ratio of 0.99 (95% confidence interval, 0.97–1.02) for AMI.ConclusionThere was no significant association between the two groups regardless of the presence of nasal polyps. This is the first study adjusting cardiovascular risk profiles and analyzing the relationship between CRS and AMI. CRS was not associated with a high incidence of AMI after adjusting for cardiovascular risk factors.

To investigate the population-based incidence of uveitis and the differences between anterior and non-anterior uveitis using the comprehensive Korean National Health Insurance Service (NHIS) database. We extracted data of patients who visited the clinic and were diagnosed with uveitis (based on Korean Classification of Diseases) from 2010 to 2021. The incidence of uveitis, differences between the demographics, and the underlying co-morbidities of anterior uveitis, non-anterior uveitis, and control groups were investigated. We identified 919,370 cases with uveitis (anterior: 800,132; non-anterior: 119,238). The average incidences (per 10,000 persons) of anterior and non-anterior uveitis were 13.0 (95% confidence interval [CI], 12.9-13.0), and 1.9 (95% CI, 1.9-1.9), respectively. The incidence increased (2010: 13.0; 2019: 16.5) but decreased during the coronavirus disease (COVID-19) pandemic (2020: 15.5; 2021: 15.4). The non-anterior group was significantly associated with sex (female, odds ratio [OR]: 1.09, p < 0.0001), specific age range (40-69 years, p < 0.0001), high Charlson Comorbidity Index (p < 0.0001), high household income (p < 0.0001), and various immunologic diseases (antiphospholipid antibody syndrome, OR: 1.79, p < 0.0001; systemic lupus erythematosus, OR: 1.22, p < 0.0001; psoriasis, OR: 1.13, p < 0.0001; ulcerative colitis, OR: 1.11, p = 0.0013; tuberculosis, OR: 1.09, p < 0.0001; rheumatoid arthritis, OR: 1.05, p < 0.0001) compared with the anterior group. Using the NHIS database, we conducted the largest population-based epidemiological study on uveitis in South Korea to estimate its increasing incidence in the past decade (including changes during COVID-19 pandemic) as well as its anatomical distribution. Our results may be beneficial for estimating the national burden of uveitis.

BackgroundAn increased incidence of hair loss disorders has been noted among patients with coronavirus disease 2019 (COVID-19) and individuals vaccinated against COVID-19. However, research involving large populations on this topic is lacking.ObjectiveTo investigate the risks associated with developing hair loss disorders in patients with COVID-19 and individuals vaccinated against COVID-19.MethodsThis nationwide, population-based, cross-sectional study included patients diagnosed with COVID-19 and healthy individuals without a history of COVID-19 infection registered in the Korean National Health Insurance Service (NHIS) database between January 1, 2021, and December 31, 2021. COVID-19 infection and vaccine databases were integrated using this NHIS database. The odds ratios of hair loss disorders were compared using multivariate logistic regression models.ResultsCOVID-19 infection was associated with an increased risk of total alopecia (adjusted odds ratio [aOR], 1.076; 95% confidence interval [CI], 1.002–1.156), although this association was not significant after propensity score matching. No significant associations were found between COVID-19 infection and alopecia areata or telogen effluvium. However, COVID-19 vaccination was positively correlated with total alopecia (aOR, 1.266; 95% CI, 1.191–1.346), alopecia areata (aOR, 1.243; 95% CI, 1.154–1.339), and telogen effluvium (aOR, 1.495; 95% CI, 1.133–1.974).ConclusionCOVID-19 vaccination was positively correlated with hair loss disorders but not COVID-19 infection. However, given the advantages of vaccines in reducing COVID-19 mortality and morbidity, alopecia may be relatively reversible and less severe. Physicians need to understand the benefits and possible side effects of the COVID-19 vaccine.

Background & aimsNasal obstruction caused by nasal septal deviation is very bothersome and, therefore, can affect the patient’s emotional state. However, little is known about the effect of nasal septal deviation (NSD) on the neuropsychiatric aspects of patients. Therefore, this study aims to verify the higher incidence of anxiety, depression, and migraine in patients diagnosed with NSD compared to general populations using big data.MethodsThis retrospective cohort study collected subjects from the Korean National Health Insurance Service (NHIS) database. Adjustments were made to minimize the confounding of variables for age, sex, residence type, income levels, hypertension, diabetes, dyslipidemia, rhinitis, and chronic rhinosinusitis between the two groups. The primary endpoint of this study was newly diagnosed anxiety, depression, and migraine between January 2009 and December 2018. Kaplan-Meier survival curves, logarithmic rank test, and Cox proportional regression test were used for statistical analysis.ResultsAmong a total of 135,769 subjects in the NHIS database, 48,495 patients with NSD (NSD group) and 54,475 control subjects (control group) were selected. Patients with NSD had an increased risk of anxiety, depression, and migraine compared to the control group. In the NSD group, the adjusted hazard ratios (HR) were 1.236 (95% CI, 1.198–1.276) for anxiety, 1.289 (95% CI, 1.238–1.343) for depression, and 1.251 (95% CI, 1.214–1.290) for migraine.ConclusionNSD is associated with a higher incidence of anxiety, depression, and migraine. Therefore, it is suggested that physicians carefully consider psychoneurological distress and employ therapeutic strategies to minimize these conditions.

Background:Limited data exist on idiopathic pulmonary fibrosis (IPF) incidence and risk factors in elderly populations, making early intervention and preventive strategies challenging. Further research is needed to address this gap and improve outcomes.Objectives:This study used the Korean National Health Insurance Service (NHIS) database to investigate factors associated with the development of IPF in elderly people.Design:A retrospective cohort study was conducted to evaluate risk factors for IPF in an elderly population.Methods:This study evaluated 1,250,901 participants aged 75 years and older with health screening examination records in the NHIS database from 2012 to 2015. Cox proportional hazards regression models were used to assess the associations between IPF risk and demographics, lifestyle factors, and comorbidities, and subgroup analyses were used to explore multifactor interactions.Results:During a median follow-up of 7.4 years, 3955 participants developed IPF, for an incidence rate of 0.38 per 1000 person-years. Elderly participants (aged 75–85 years) exhibited higher IPF incidence than extremely elderly participants (⩾85 years) (0.40 vs 0.17 per 1,000 person-years, p < 0.01), though the difference was not significant in the multivariable analysis. The factors independently associated with increased IPF risk were male sex (adjusted hazard ratio [aHR] = 2.56, 95% confidence interval [CI] = 2.35–2.78), high body mass index (BMI) (aHR=1.45, 95% CI = 1.34–1.56 ), smoking (aHR = 1.24, 95% CI = 1.13–1.37 for ever-smokers < 20 pack-years [PYs]; aHR = 1.28, 95% CI = 1.17–1.39 for ever-smokers ⩾ 20 PYs), dyslipidemia (aHR = 1.17, 95% CI = 1.08–1.26), chronic kidney disease (aHR = 1.08, 95% CI = 1.01–1.16), and chronic obstructive pulmonary disease (COPD) (aHR = 1.49, 95% CI = 1.37–1.63). Additive or synergistic effects were observed among sex, BMI, smoking, and dyslipidemia, notably among males, and interactions between COPD and smoking status modulated IPF risk.Conclusion:Male sex, high BMI, smoking, and dyslipidemia might additively or synergistically increase the IPF risk among elderly people, highlighting the need for targeted prevention strategies in those populations.

P3429A novel prediction model for mortality after cardiac surgery using institutional case volume

Dear Editor, As the overall survival rate of cancer patients has been increasing, an increasing number of patients are experiencing septic shock, and the corresponding mortality rate is becoming unacceptably high [1]. Among cases of organ failure caused by septic shock, the development of acute kidney injury (AKI) is known to be common and correlated with poor outcomes [2]. Moreover, a large Danish cohort study revealed that critically ill patients with cancer had a greater risk of AKI and requirement of renal replacement therapy (RRT) compared to patients without cancer [3]. Adverse outcomes dramatically increase in patients with severe AKI who received RRT, and a recent survey in China reported that the hospital mortality rate for this population was up to 80% [4]. Although the association between septic AKI and mortality has been widely investigated, knowledge about whether patients with recovered renal function have increased long-term risk of end-stage renal disease compared with patients who have not recovered renal function had been scarce, especially in the cancer population [5]. Few studies have tried to reveal the clinical impact of AKI in patients with malignancy, and they included a relatively small sample size or included only certain types of conditions, such as hematologic malignancy [6]. In this study, we tried to determine the relationship between renal function recovery and long-term dialysis dependency among patients with cancer. We conducted a nationwide population-based study of adult cancer patients who presented to the emergency department with septic shock in South Korea between 2009 and 2017 using data from the Korean National Health Insurance Service (NHIS). The NHIS database contains all of the claim data, including demographics, drug prescriptions, diagnostic codes for the disease coding, the International Classification of Disease 10th edition (ICD-10), insurers’ payment coverage, and claimed treatment details [7]. Detailed information about our protocol to select the study population was provided in Supplementary Methods. In brief, we selected all patients admitted to a hospital via the emergency department and who fulfilled the clinical surveillance definition of septic shock according to Sepsis-3, based on concurrent vasopressors, antibiotics, and blood cultures [8]. To identify patients with cancer, we used the cancer diagnosis codes C00-C97 according to ICD-10 (n = 42,477) (Figure 1). Among these patients, we included those who required RRT owing to AKI during admission and excluded those who were already diagnosed with end-stage renal disease and received RRT within 1 year (n = 5,449). Data on demographics, insurance type, religion, underlying disease, chemotherapy, radiotherapy, presence of neutropenia, and cancer type were collected. Renal recovery was defined as discharge from the hospital without further need for RRT within 1 month. We also collected follow-up data of 1 year from the date of hospitalization, including survival and dialysis dependency. In cases where patients had more than one visit because of septic shock, data collected at the first admission was used. All statistical analyses were performed using the Statistical Package for the Social Sciences (SPSS) software for Windows, version 26 (IBM Corp., Armonk, NY, USA). Descriptive statistics were stratified by survival within 1 year (i.e., survivor and non-survivor). Univariate logistic regression model was used to compare recovery (within 1 month) and non-recovery groups. Furthermore, the Cox proportional hazard model with multivariable adjustment was used to compare septic shock survivors within 1-year and death. A P value < 0.05 was considered statistically significant. Renal recovery, re-dialysis rates, and long-term prognosis of cancer patients with septic shock who received dialysis. AKI, acute kidney injury; RRT, renal replacement therapy Of the 5,449 patients receiving dialysis, 1,060 survived at 30 days. Of these, 826 patients were successfully weaned from dialysis after diagnosis of septic shock, and 234 had a continuous need for dialysis within 1 month after discharge (Supplementary Table S1). There were no differences in age, gender, insurance type, and underlying illness between the recovery and non-recovery groups. Moreover, the proportions of cancer types, including gastric, colorectal, gall bladder, pancreatic, liver, lung cancers, leukemia, and multiple myeloma, were similar between the recovery and non-recovery groups. Meanwhile, receiving chemotherapy was more frequent in patients with renal recovery than in those without recovery (19.6% vs. 12.0%, P = 0.008). Among 826 patients who did not require RRT within 1 month, 233 (28.2%) restarted RRT within 1 year (Figure 1). To compare the potential clinical impacts of each variable, we conducted a multivariate Cox-proportional hazard model. There were no significant differences between 1-year survivors and non-survivors in terms of demographics, underlying disease, presence of neutropenia, chemotherapy, and radiotherapy (Supplementary Table S2). Most types of malignancies, such as gastric, pancreatic, liver, lung cancers, and leukemia showed similar proportions between survivors and non-survivors except colorectal cancer and multiple myeloma. Failure in weaning of dialysis was an independent risk factor for 1-year mortality in the multivariate Cox-proportional hazard model (hazard ratio = 1.713, 95% confidence interval = 1.457–2.014, P < 0.01). Among the 826 cancer patients with successful weaning of dialysis, 233 (28.2%) showed dialysis dependency within 1 year. To our best knowledge, this is the largest study regarding AKI on long-term clinical impact in pooled cancer patients using a nationwide database with high coverage of the Korean population (97%). Our findings could help to give a more comprehensive knowledge of long-term outcomes of septic AKI in cancer patients. However, the Korean NIHS data did not include detailed laboratory data, the cancer stage, performance status, severity of the septic shock, and severity of acute kidney injury. Therefore, it was also not possible to know the cancer stage, baseline performance status, and severity of septic shock. Furthermore, we defined renal recovery by using a 1-month dialysis code, and the recovery rate could have been underestimated because renal function could improve slower than that period. We found that the non-recovery of renal function was correlated with increased mortality in the cancer cohort with septic shock. Even after recovery from AKI and successful weaning of dialysis at discharge, one-fourth of the patients needed RRT within 1 year. One previous report announced that 82% of critically ill cancer patients with AKI had their renal function recovered and only 6% of patients required long-term RRT [9]. Another study reported chronic RRT dependence in 12.9% of patients with hematologic malignancies [10]. The different occurrences and outcomes were largely due to the differences in the study population and the proportion of the disease severity. In conclusion, these findings suggest that physicians should focus on the recovery of renal function during admission, and patients should be followed up carefully even after recovery of AKI. This study used data from the NHIS customized health information data (NHIS-2019-1-510), which was provided by the Korean NHIS. The authors alone are responsible for the content and writing of this manuscript. Not applicable. WYK had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. JSK analyzed the data, wrote and revised the manuscript. YJK collected and analyzed the data. The authors declare that no competing interests exist. Not applicable. This study was supported by a grant from the Korean Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI) funded by the Ministry of Health & Welfare, Republic of Korea (grant no. HI18C2383). This study was approved by the Institutional Review Board of Asan Medical Center and waived informed consent because of the retrospective study design. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

IntroductionStatins are the cornerstone of secondary prevention in atherosclerotic cardiovascular disease (ASCVD), but their association with new-onset diabetes mellitus (NODM) remains incompletely defined. Whether the risk of NODM differs among individual statins within the same intensity class has not been well established.MethodsUsing the Korean National Health Insurance Service (NHIS) database, we identified 29,826 patients with established ASCVD who initiated statin therapy between 2009 and 2012 and were followed for up to five years. The primary endpoint was incident NODM, defined by new diagnostic coding plus antidiabetic medication use after a three-year window period. The secondary endpoint was major adverse cardiac and cerebrovascular events (MACCE).ResultsOverall, 11,918 patients (40.0%) developed NODM. The incidence of NODM was comparable between high- and moderate-intensity statins (42.9% vs. 41.1%). In the moderate-intensity group, rosuvastatin (adjusted HR 1.07, 95% CI 1.01–1.14), pravastatin (HR 1.19, 95% CI 1.02–1.38), and simvastatin (HR 1.15, 95% CI 1.06–1.20) were associated with higher NODM risk compared with atorvastatin, while fluvastatin and pitavastatin showed no significant differences. MACCE incidence was similar across statins.DiscussionIn this nationwide secondary prevention cohort, the risk of NODM differed across individual statins despite comparable cardiovascular outcomes. These findings suggest that the diabetogenic effect of statins may be agent-specific rather than a uniform class effect, highlighting the importance of individualized statin selection balancing metabolic and cardiovascular benefits.

ObjectiveTemporomandibular disorders (TMD) significantly impact quality of life, and insomnia has emerged as a potential contributing factor. This study aimed to evaluate the association between clinically diagnosed insomnia and the risk of developing TMD using nationwide data from the Korean National Health Insurance Service (NHIS).MethodsWe collected baseline data from 2011 to 2014 using the NHIS database and followed participants until 2019. A total of 358,475 adults without previous insomnia or TMD were analyzed, and propensity score matching (1:3) was performed to create balanced insomnia (n = 20,813) and non-insomnia (n = 62,439) cohorts. Insomnia was defined using diagnostic codes combined with prescription records. Cox proportional hazards models and Kaplan-Meier estimates were employed to evaluate the TMD incidence over a follow-up period ending in 2019.ResultsIndividuals with insomnia exhibited a significantly higher incidence of TMD (6.46 vs. 4.48 per 1,000 person-years). Even after adjusting for demographic, lifestyle, and clinical variables, insomnia remained a significant independent predictor of TMD, with a 36% increased risk (HR = 1.36; 95% CI: 1.25–1.49). Kaplan-Meier analysis confirmed a consistently higher cumulative incidence of TMD among insomnia patients (p < 0.001).ConclusionClinically diagnosed insomnia was found to be associated with an increased risk of developing TMD. However, as this study was based on the NHIS database, causality cannot be definitively established. Nonetheless, these findings suggest that incorporating sleep disturbances assessments into the evaluation and management of TMD may be beneficial. Further prospective studies are warranted to clarify this association and assess the potential benefits of integrated care strategies.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12903-025-06967-3.

We analyzed data from the Korean National Health Insurance Service (NHIS) to investigate whether smoking increases the risk of end-stage kidney disease (ESKD). This retrospective nationwide population-based cohort study included the data of 23,232,091 participants who underwent at least one health examination between 2009 and 2012. Smoking status was recorded at baseline. The incidence of ESKD was identified via ICD-10 codes and special medical aid codes from the Korean National Health Insurance Service database till December 2016. A Cox proportional-hazards model with multivariable adjustment was used to evaluate the association between smoking and ESKD incidence. Overall, 24.6% of participants were current smokers; 13.5% and 61.9%, were ex- and non-smokers, respectively. Overall, 45,143 cases of ESKD developed during the follow-up period. Current smokers (hazard ratio [HR], 1.39; 95% confidence interval [CI], 1.35–1.43) and ex-smokers (HR, 1.09; 95% CI, 1.06–1.12) demonstrated a significant increase in the adjusted risk of ESKD compared to non-smokers. The risk of ESKD was directly proportional to the smoking duration, number of cigarettes smoked daily, and pack-years. In conclusion, smoking is associated with a greater risk of ESKD in the general Korean population; the risk increases with an increase in the smoking duration, number of cigarettes smoked daily, and pack-years.

Background The incidence of inflammatory bowel disease (IBD) is increasing in Asia. Numerous risk factors associated with IBD development have been investigated. This study aimed to demonstrate the risk factors of Crohn’s disease (CD) diagnosed in persons aged &amp;gt;40 years in South Korea and to specify any differences between age groups by using the National Health Insurance Service (NHIS) database. Methods Using the National Health Insurance Service (NHIS) database, a total of 14,060,821 persons aged &amp;gt;40 years who underwent national health screening in 2009 were followed up until December 2017. Patients with newly diagnosed CD were enrolled and compared with non-CD cohort. CD was identified according to the International Classification of Diseases 10th revision and the rare/intractable disease registration programme codes from the NHIS database. The mean follow-up periods were 7.39 years. Age and sex were adjusted for in the multivariate analysis model. Results During the follow-up, 1337 (1.33/100,000) patients developed CD. Men in the middle-aged group (40–64 years) had a higher risk than women (adjusted HR [aHR] 1.46, 95% CI 1.29–1.66); however, this difference tended to disappear as the age of onset increases. In the middle-aged group, patients with a history of smoking (adjusted hazard ratio [aHR] 1.29, 95% confidence interval [CI] 1.06–1.58) and anemia (aHR 1.99, 95% CI 1.67–2.36) had a significantly higher CD risk. In the elderly group (age, ³65 years), ex-smoking and anemia also increased the CD risk (aHR 1.58 [95% CI 1.16–2.18] and 1.91 [95% CI 1.53–2.38], respectively). Especially in the middle-aged group, those with chronic kidney disease (CKD) had a statistically elevated CD risk (aHR 1.38, 95% CI 1.06–1.79). Alcohol consumption and higher body mass index showed negative association trend with CD incidence in both of the age groups. (Middle-aged: aHR 0.76 [95%CI 0.65–0.87] and aHR 0.38 [95%CI 0.27–0.53], respectively) (elderly-group: aHR 0.57 [95%CI 0.42–0.77] and aHR 0.52 [95%CI 0.32-.83], respectively) For regular physical activity and dyslipidemia, negative correlation between CD incidences was proved only in the middle-aged group (aHR 0.85 [95%CI 0.74–0.96] and aHR 0. [95%CI 0.75 [95% CI 0.63–0.89], respectively). Conclusion This study demonstrated four risk factors (ex-smoking, anemia, CKD, and lower BMI) and three possible protective factors (alcohol consumption, physical activity, and dyslipidemia) for CD in Asians age &amp;gt;40 years. Individuals with potential risk factors need more cautious monitoring for CD.

Background and objectivesThe Korean National Health Insurance Service (NHIS) database has been widely used for cardiovascular research. We validated the primary diagnostic codes of major clinical outcomes, including acute myocardial infarction (AMI), gastrointestinal bleeding (GIB), stroke, and intracranial hemorrhage (ICH) used for Korea NHIS claims.Subjects and methodsFrom 2016 to 2017, 800 patients with primary diagnostic codes of AMI, GIB, stroke, or ICH at discharge were randomly selected from a single tertiary medical center in Korea (200 patients per each diagnosis). The positive predictive value (PPV), sensitivity, and specificity of the primary diagnostic codes were calculated using hospital medical record review as the gold standard. Further improvement in the diagnostic validity of the codes was assessed by combining clinical information such as duration of hospitalization, blood transfusion, brain imaging studies, or prescription records of antithrombotic agents.ResultsAmong 200 patients with AMI as the primary discharge diagnosis, 184 patients were clinically confirmed (PPV of 92.0%). For GIB, 184 (92.0%) patients with the primary discharge diagnosis were verified to have true GIB events, showing PPV of 92%. For stroke, 181 (90.5%) patients were clinically confirmed with true stroke events. For ICH, 143 (71.5%) patients were verified to be true ICH events. In stroke and ICH, the PPV and specificity improved after combining with the hospitalization duration, imaging studies, and prescription of antithrombotic agents.ConclusionsFor major clinical outcomes in the NHIS database, the primary diagnostic codes showed favorable reliability. For stroke and ICH, considerations of relevant clinical information could improve the accuracy of diagnosis.