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Abstract Despite the association between spinal cord injury (SCI) and various neurological diseases, the risk of Parkinson’s disease (PD) in SCI is not elucidated yet. Especially, the role of SCI severity and injury level in the risk of PD development is not investigated. Based on the nation-wide cohort data the Korean National Health Insurance Service between 2010 and 2018, we investigated the incidence of PD in 7,182 patients with SCI compared with 24,844 age- and sex-matched controls. Adjusted hazard ratio and 95% confidence interval (CI) were calculated using Cox proportional hazards regression. We compared the risk of PD based on the degree of disability (without disability, mild, severe) and SCI level (cervical, thoracic, and lumbar). During the mean follow-up duration of 4.31 years, patients with SCI had a higher risk of PD compared with matched controls. The PD risk was greater among patients with SCI with disability than in those without disability, especially those with mild disability. Additionally, cervical-level injury was associated with the highest risk in patients with SCI without disability, while thoracic-level injury was associated with the highest risk in those with disability. Our study found patients with SCI have increased risk of PD, particularly those with disability and thoracic-level injuries.

Abstract Although smoking is an established risk factor for Mycobacterial infection, the association between smoking and nontuberculous mycobacterial pulmonary disease (NTM-PD) remains unclear. We evaluated the association between smoking and NTM-PD and tuberculosis (TB) using a population-based South Korean nationwide cohort. Using the Korean National Health Insurance Database, we screened individuals over 20 years of age who underwent the national health screening program in 2009. Out of 3,774,308 eligible populations, we identified 2,964 and 26,112 cases of newly developed NTM-PD and TB, respectively. We used multivariate Cox proportional hazards models to estimate the adjusted hazard ratios (aHRs) of risk factors for NTM-PD and TB. The incidence rates for developing NTM-PD and TB were 0.08 and 0.68 per 1,000 person-years, respectively. Current smokers (aHR 0.63, 95% confidence interval [CI] 0.56–0.71) and current heavy smokers (≥ 20 pack-years, aHR 0.74, 95% CI 0.63–0.86) were at lower risk for NTM-PD development than never smokers. On the contrary, current smokers (aHR 1.19, 95% CI 1.15–1.23) and current heavy smokers (aHR 1.27, 95% CI 1.22–1.33) had a higher risk for TB development than never smokers. These trends were augmented if individuals started smoking before age 20 years. In subgroup analyses stratified by age, these trends were prominent in the 40–64 years age range. Current smoking was associated with a decreased risk of NTM-PD and increased risk of TB. These risks were augmented by early smoking initiation and in the middle age population.

Abstract Background The association between nonalcoholic fatty liver disease (NAFLD) and atrial fibrillation (AF) has been inconsistent, and the impact of hepatic fibrosis on this relationship remains uncertain. We investigated the association between NAFLD and the risk of new-onset AF across different age groups. Methods A total of 3,179,582 participants from the 2009 Korean National Health Screening Program were divided into five groups based on NAFLD status: no NAFLD (fatty liver index [FLI]

Abstract Previous studies on the association between age-related macular degeneration (AMD) and rheumatoid arthritis (RA) have shown conflicting results. We sought to assess the association between AMD with/without visual disability (VD) and the risk of RA using National Health Insurance data in South Korea. In total, 3,537,293 individuals who underwent health checkups in 2009 were included and followed until 2019. Participants with VD were defined as those with loss of vision or a visual field defect as certified by the Ministry of Health and Welfare of Korea. Using multivariable adjusted Cox regression analysis, RA hazard ratios were estimated for control and AMD with/without VD groups. In total, 43,772 participants (1.24%) were diagnosed with RA. Individuals with AMD were at higher risk of RA compared to controls, regardless of the presence of VD (aHR 1.11; 95% CI 1.02–1.21). Among individuals with AMD, different risk levels of RA were observed between those without VD (aHR 1.13; 95% CI 1.03–1.21) and those with VD (aHR 0.90; 95% CI 0.64–1.27). AMD was associated with a higher risk of RA, which remained significant as a trend even after adjusting for lifestyle factors and comorbidities.

Aronia melanocarpa, known as black chokeberry, is rich in polyphenols, comprising flavonoids, such as anthocyanins, flavanols, and flavonols, and phenolic acids, such as chlorogenic acid. These polyphenols endow Aronia melanocarpa with preventive and therapeutic properties against various human diseases. Aronia melanocarpa has beneficial effects against diseases such as diabetes, inflammation, and hypertension. Considering the diverse functional components of Aronia melanocarpa, its efficacy in disease prevention and treatment can operate through multiple pathways, offering a more robust approach to disease control. This review covers the latest research results on the functional components of Aronia melanocarpa and their effects on human diseases.

Abstract Background The cancer experienced in adolescent and young adult (AYA) could disturb developmental changes and long-term life. The current AYA guidelines and research for survivorship were developed and reported according to the general age range of 15–39 years; however, expected life events vary by diagnosed age. We aimed to examine the social, psychological, and physical well-being of AYA cancer survivors by age at diagnosis using a multinational representative dataset focusing on age at diagnosis. Methods We conducted a cross-sectional study using the US and Korean National Health and Nutrition Examination Surveys from 2007 to 2018. Participants diagnosed with any cancer aged 15–39 years and were aged > 18 years at the survey year were defined as AYA cancer survivors. AYA were classified into three groups based on their diagnosed age: adolescent survivors (diagnosed between the ages of 15 and 19, n = 45), young adult survivors (diagnosed between the ages of 20 and 29, n = 238), and late young adult survivors (diagnosed between the ages of 30 and 39, n = 539). We also selected an age-, sex-, race-, and survey year-matched general population with 1:5 ratio among participants without cancer (N = 4110). Results The average age of the survey was 29.1, 43.7, and 48.7 years for AYA survivors diagnosed during adolescence, young adulthood, and late young adulthood, respectively. Adolescent survivors had more non-couple marital status (adjusted odds ratio (aOR), 1.34; 95% CI, 1.10–1.64) and unemployed (aOR, 1.30; 95% CI, 1.05–1.61) compared to late young adult survivors. Comparing with the matched general, adolescent survivors were more in poor general health (aOR, 4.65; 95% CI, 2.09–10.38) and unemployed (aOR, 2.17; 95% CI, 1.12–4.24) and late young adult survivors were more non-couple (aOR, 1.40; 95% CI, 1.05–1.86). Conclusion This study provides evidence for future studies on long-term health, which may vary according to age at the time of diagnosis among AYA with cancer.

Abstract Background Supervised machine learning models have been widely used to predict and get insight into diseases by classifying patients based on personal health records. However, a class imbalance is an obstacle that disrupts the training of the models. In this study, we aimed to address class imbalance with a conditional normalizing flow model, one of the deep-learning-based semi-supervised models for anomaly detection. It is the first introduction of the normalizing flow algorithm for tabular biomedical data. Methods We collected personal health records from South Korean citizens (n = 706), featuring genetic data obtained from direct-to-customer service (microarray chip), medical health check-ups, and lifestyle log data. Based on the health check-up data, six chronic diseases were labeled (obesity, diabetes, hypertriglyceridemia, dyslipidemia, liver dysfunction, and hypertension). After preprocessing, supervised classification models and semi-supervised anomaly detection models, including conditional normalizing flow, were evaluated for the classification of diabetes, which had extreme target imbalance (about 2%), based on AUROC and AUPRC. In addition, we evaluated their performance under the assumption of insufficient collection for patients with other chronic diseases by undersampling disease-affected samples. Results While LightGBM (the best-performing model among supervised classification models) showed AUPRC 0.16 and AUROC 0.82, conditional normalizing flow achieved AUPRC 0.34 and AUROC 0.83 during fifty evaluations of the classification of diabetes, whose base rate was very low, at 0.02. Moreover, conditional normalizing flow performed better than the supervised model under a few disease-affected data numbers for the other five chronic diseases – obesity, hypertriglyceridemia, dyslipidemia, liver dysfunction, and hypertension. For example, while LightGBM performed AUPRC 0.20 and AUROC 0.75, conditional normalizing flow showed AUPRC 0.30 and AUROC 0.74 when predicting obesity, while undersampling disease-affected samples (positive undersampling) lowered the base rate to 0.02. Conclusions Our research suggests the utility of conditional normalizing flow, particularly when the available cases are limited, for predicting chronic diseases using personal health records. This approach offers an effective solution to deal with sparse data and extreme class imbalances commonly encountered in the biomedical context.

Background Low socioeconomic status is a risk factor for chronic obstructive pulmonary disease (COPD); however, the association between low household income and COPD in young populations remains unclear.Methods We screened individuals aged 20–39 years who underwent the national health examination between 2009 and 2012 using the Korean National Health Information Database, which was searched until December 2019. We identified 5 965 366 eligible individuals, and 13 296 had newly developed COPD based on health insurance claims. We evaluated household income levels based on the health insurance premiums, categorised them into quartiles and ‘Medical aid’ (the lowest 3% income group), and assessed the annual income status from the preceding 4 years. Multivariate Cox proportional hazard models were used to estimate the adjusted HR (aHR) of risk factors for COPD.Results In the Medical aid group, the incidence rate for developing COPD was 0.56/1000 person-years, with an aHR of 2.45 (95% CI 1.91 to 3.13) compared with that of the highest income quartile group. This association was prominent in consecutive recipients of Medical aid (aHR 2.37, 95% CI 1.80 to 3.11) compared with those who had never been Medical aid beneficiaries. Those who experienced a decline in household income between the previous (preceding 4 years) and baseline time points had an increased risk of developing COPD, regardless of previous income status.Conclusion Low household income was associated with an increased risk of developing COPD in the young population. This risk was augmented by sustained low income and declining income status.

Abstract Background The risk of incident atrial fibrillation (AF) among breast cancer survivors, especially for younger women, and cancer treatment effects on the association remain unclear. This study aimed to investigate the risk of AF among breast cancer survivors and evaluate the association by age group, length of follow-up, and cancer treatment. Methods Using data from the Korean Health Insurance Service database (2010–2017), 113,232 women newly diagnosed with breast cancer (aged ≥ 18 years) without prior AF history who underwent breast cancer surgery were individually matched 1:5 by birth year to a sample female population without cancer (n = 566,160) (mean[SD] follow-up, 5.1[2.1] years). Sub-distribution hazard ratios (sHRs) and 95% confidence intervals (CIs) considering death as a competing risk were estimated, adjusting for sociodemographic factors and cardiovascular/non-cardiovascular comorbidities. Results BCS had a slightly increased AF risk compared to their cancer-free counterparts (sHR 1.06; 95% CI 1.00–1.13), but the association disappeared over time. Younger BCS (age 65 years. Use of anthracyclines was associated with increased AF risk among BCS (sHR 1.57; 95% CI 1.28–1.92), which was more robust in younger BCS (sHR 1.94; 95% CI 1.40–2.69 in those aged ≤ 50 years). Conclusions Our findings suggest that younger BCS had an elevated risk of incident AF, regardless of the length of follow-up. Use of anthracyclines may be associated with increased mid-to-long-term AF risk among BCS. Graphical Abstract

Background: Concern has been growing regarding post-tuberculosis (TB) morbidities, including neurologic and vascular comorbidities. However, the association between post-TB status and the risk of dementia has been evaluated in only few studies. Therefore, in the present study, the risk of dementia was investigated in a nationwide population-based cohort. Methods: Using the Korean National Health Insurance Service (KNHIS) database, this study included TB survivors (n = 50,182) and matched controls (n = 50,182) for age, sex, and year of index date. The risk of dementia was estimated using Cox proportional hazards regression, and stratified analyses for related factors were performed. Results: During a mean 3.5 years of follow-up, the incidence of dementia was 9.32 for Alzheimer disease and 1.17 for vascular dementia per 1000 person-years for TB survivors and 7.21 and 0.67, respectively, for matched controls. The overall risk of Alzheimer disease was 1.11 (95% confidence interval (CI) 1.03–1.20)-fold higher in TB survivors than in matched controls. For vascular dementia, 1.48 (95% CI 1.16–1.89)-fold higher risk was found in TB survivors than in matched controls. The strength of the association between TB and dementia was higher in CNS TB (aHR 1.76, 95% CI 1.18 –2.64) than non-CNS TB (aHR 1.11, 95% CI 1.05–1.19) compared to controls, especially for patients with vascular dementia (3.33, 95% CI 1.06–10.49). Conclusion: TB survivors had a significantly higher risk of dementia than the general population.

Prostaglandin D2 (PGD2) levels are high in the balding areas of human scalps, and PGD2 has been found to inhibit hair growth. It is known that the inhibition of the PGD2 receptor can promote hair growth by preventing hair follicles from entering the catagen phase. Thus, we identified an antagonist of DP2, the receptor for PGD2, as a potential treatment for hair loss using an AI-based DeepZema® drug development program. In this study, we identified that the DP2 antagonist (DP2A) could ameliorate alopecia in human follicle dermal papilla cells (HFDPCs) that were stimulated by dihydrotestosterone (DHT), a known molecule related to hair loss. We observed that the DP2A promoted wound healing efficiency and increased alkaline phosphatase levels in the HFDPCs that were damaged with DHT. In addition, we found that the DP2A diminished the reactive oxygen species (ROS) levels generated in the DHT-damaged HFDPCs. We confirmed that the DP2A effectively recovered the membrane potential of mitochondria in these cells. We also demonstrated that the DP2A enhanced the phosphorylation levels of both Akt and ERK in the HFDPCs that were damaged with DHT. Notably, we revealed that the DP2A slightly enlarged the three-dimensional spheroid size in these cells and confirmed that the DP2A improved hair growth in the organ culture of human hair follicles. Taken together, we suggest that DP2A has therapeutic effects on HFDPCs that are damaged by DHT and holds promise as a potential treatment for treating hair loss.

Objectives: Estimating the risk of diabetes mellitus (DM) is important for the proper management of patients with spinal cord injury (SCI). We investigated the short-term and long-term risks of DM among patients with SCI, according to the presence or severity of post-SCI disability and the level of injury. Methods: We conducted a retrospective cohort study using the Korean National Health Insurance Service (2010–2018) database. After matching by age and sex, 6129 SCI patients and 22,979 controls were included. The primary outcome was incident DM, and risk was evaluated for both the short term (within 1 year after SCI) and the long term (after 1 year of SCI diagnosis). Results: The risk of DM was higher among patients with cervical- and thoracic-level SCI accompanied by disability compared to the controls during follow-up (4.6 ± 2.6 years). The short-term risk of DM was higher among patients with SCI (odds ratio [OR] 2.51, 95% confidence interval [CI] 1.91–3.27) than among the controls and it was even higher among patients with severe disability (OR 5.38, 95% CI 2.91–9.27). According to the level of injury, patients with cervical SCI had the highest short-term risk of DM (with disability, OR 4.93, 95% CI 3.07–7.63). There was no significant increase of DM risk in the long term, after 1 year of SCI diagnosis. Conclusions: Patients with SCI accompanied by severe disability and cervical-level injury had higher risks of pronounced DM in the short term. The findings of this study emphasize the need for active surveillance of DM among patients with high-level SCI and disability, especially in the short term, in addition to continuous monitoring and proper management of DM in the long term.

Background Amputation confers disabilities upon patients and is linked to substantial morbidity and death attributed to heart disease. While some studies have focused on traumatic amputees in veterans, few studies have focused on traumatic amputees within the general population. Therefore, the present study aimed to assess the risk of heart disease in patients with traumatic amputation with disability within the general population using a large‐scale nationwide population‐based cohort. Methods and Results We used data from the Korean National Health Insurance System. A total of 22 950 participants with amputation were selected with 1:3 age, sex‐matched controls between 2010 and 2018. We used Cox proportional hazard models to calculate the risk of myocardial infarction, heart failure, and atrial fibrillation among amputees. Participants with amputation had a higher risk of myocardial infarction (adjusted hazard ratio [aHR], 1.30 [95% CI, 1.14–1.47]), heart failure (aHR, 1.27 [95% CI, 1.17–1.38]), and atrial fibrillation (aHR, 1.17 [95% CI, 1.03–1.33]). The risks of myocardial infarction and heart failure were further increased by the presence of disability (aHR, 1.43 [95% CI, 1.04–1.95]; and aHR, 1.38 [95% CI, 1.13–1.67], respectively). Conclusions We demonstrate an increased risk of myocardial infarction, heart failure, and atrial fibrillation among individuals with amputation, and the risk further increased in those with disabilities. Clinicians should pay attention to the increased risk for heart disease in patients with amputation.

Abstract Background There exists a paucity of data regarding whether gamma‐glutamyl transferase is associated with disease‐specific mortality in patients with type 2 diabetes mellitus. This study aimed to investigate the association of serum gamma‐glutamyl transferase levels with all‐cause and disease‐specific mortality in patients with diabetes mellitus using a Korean nationwide health‐screening database. Methods A total of 9 687 066 patients without viral hepatitis or liver cirrhosis who underwent health examination in 2009 were included. These patients were divided into four groups according to sex‐specific quartiles of serum gamma‐glutamyl transferase levels. Results During a median follow‐up period of 8.1 years, 222 242 deaths were identified. The all‐cause mortality rate increased as the serum gamma‐glutamyl transferase levels became higher (highest quartile vs lowest quartile: hazard ratio [HR], 1.57; 95% confidence interval [CI], 1.55–1.59; p for trend

PurposeTuberculosis (TB) is linked to sustained inflammation even after treatment, and fracture risk is higher in TB survivors than in the general population. However, no individualized fracture risk prediction model exists for TB survivors. We aimed to estimate fracture risk, identify fracture-related factors, and develop an individualized risk prediction model for TB survivors.MethodsTB survivors (n = 44,453) between 2010 and 2017 and 1:1 age- and sex-matched controls were enrolled. One year after TB diagnosis, the participants were followed-up until the date of fracture, death, or end of the study period (December 2018). Cox proportional hazard regression analyses were performed to compare the fracture risk between TB survivors and controls and to identify fracture-related factors among TB survivors.ResultsDuring median 3.4 (interquartile range, 1.6–5.3) follow-up years, the incident fracture rate was significantly higher in TB survivors than in the matched controls (19.3 vs. 14.6 per 1,000 person-years, p

The physiological changes and alterations in gait following amputation may increase the risk of fractures. However, there is insufficient research on fracture risk in amputees. Therefore, this study intended to analyze whether the risk of new fractures increases after traumatic amputations. This population-based, retrospective cohort study used data from the Korean National Health Insurance System database. The study included 19,586 participants who had undergone an amputation and 76,645 matched controls. The incidence of any fracture and site-specific fractures (vertebral, hip, and others) according to amputation site(s) and severity of disability due to amputation were evaluated using Cox proportional hazard regression analysis. During the mean follow-up of 4.2 years, amputees had a higher incidence rate (IR) of any fracture (adjusted HR [aHR] 1.47, 95% CI 1.36–1.60), vertebral fracture (aHR 1.63, 95% CI 1.44–1.85), hip fracture (aHR 1.85, 95% CI 1.39–2.46), and other fracture (aHR 1.34, 95% CI 1.20–1.49) compared to that of controls. In the presence of disability, the risks were further increased and were highest among amputees with severe disabilities. All fracture risks were higher in amputees than they were in controls, regardless of lower limb or upper limb amputation. This cohort study demonstrated that traumatic amputees experienced higher incidence of all fractures than did individuals without amputations, and this risk increases with severity of disability. This finding underscores the importance of early screening and lifestyle interventions to address fracture risk in traumatic amputees.

Prostaglandin E2 (PGE2) is known to be effective in regenerating tissues, and bimatoprost, an analog of PGF2α, has been approved by the FDA as an eyelash growth promoter and has been proven effective in human hair follicles. Thus, to enhance PGE2 levels while improving hair loss, we found dihydroisoquinolinone piperidinylcarboxy pyrazolopyridine (DPP), an inhibitor of 15-hydroxyprostaglandin dehydrogenase (15-PGDH), using DeepZema®, an AI-based drug development program. Here, we investigated whether DPP improved hair loss in human follicle dermal papilla cells (HFDPCs) damaged by dihydrotestosterone (DHT), which causes hair loss. We found that DPP enhanced wound healing and the expression level of alkaline phosphatase in DHT-damaged HFDPCs. We observed that DPP significantly down-regulated the generation of reactive oxygen species caused by DHT. DPP recovered the mitochondrial membrane potential in DHT-damaged HFDPCs. We demonstrated that DPP significantly increased the phosphorylation levels of the AKT/ERK and activated Wnt signaling pathways in DHT-damaged HFDPCs. We also revealed that DPP significantly enhanced the size of the three-dimensional spheroid in DHT-damaged HFDPCs and increased hair growth in ex vivo human hair follicle organ culture. These data suggest that DPP exhibits beneficial effects on DHT-damaged HFDPCs and can be utilized as a promising agent for improving hair loss.

Abstract Smoking patients with diabetes mellitus (DM) are at greater risk of developing pneumonia. How smoking behavior changes affect the risk of pneumonia hospitalization, however, remains unclear. Therefore, we investigated the association between smoking behavior change and the risk of pneumonia hospitalization in patients with DM. From January 1, 2009 and December 31, 2018, we investigated the association between smoking behavior change and the risk of pneumonia hospitalization in patients with DM. A total of 332,798 adult patients with DM from the Korean National Health Insurance System database who underwent health screening examination between 2009 and 2012, and were smokers at the first health examination were included. During a mean follow-up of 4.89 years, 14,598 (4.39%) incident pneumonia hospitalization cases were identified. Reducers had a slightly increased risk of pneumonia hospitalization (aHR 1.06, 95% CI 1.01–1.10) compared to sustainers. Quitters did not have a significant association with incidence of pneumonia hospitalization. However, increasers had 13% higher risk of pneumonia hospitalization (aHR 1.13, 95% CI 1.07–1.18), regardless of whether initial smoking was light, moderate, or heavy. Our study showed that an increase in smoking intensity was associated with an increased risk of pneumonia hospitalization in people with DM. However, a protective effect of smoking reduction or cessation on pneumonia risk was not demonstrated.

Abstract Background The current guidelines for survivorship in adolescents and young adults (AYA) cancer are based on studies conducted in the United States and European AYA survivors. However, previous studies have shown that the health-related quality of life in cancer survivors can vary depending on race, yet the long-term health differences among AYA survivors by race/ethnicity have not been fully explored. Therefore, our aim is to compare the psychosocial and physical health of AYA survivors and their matched controls across different racial and ethnic groups. Methods We conducted a cross-sectional study using US National Health and Nutrition Examination Survey (NHANES) and the Korea NHANES from 2007 to 2018. We included AYA cancer survivors who were diagnosed with any type of cancer aged between 15 and 39 years, and who were adult with aged over 18 years old at survey year. We then stratified the study population by race/ethnicity with Non-Hispanic White (NHW, n = 310), African American (AA, n = 42), Hispanic (n = 81) from NHANES, and Asian (n = 389) from the Korea NHANES. We also selected 5 times age-, sex-, race-, and survey year-matched general population among participants who had never been diagnosed with cancer (N = 4110). Variables were defined using questionnaire data, physical exams, and laboratory tests. Results Compared to NHW, Hispanics (aOR 1.15, 95% CI 1.00–1.32) had poor or fair general health, lower education (aOR 1.23, 95% CI 1.07–1.40), and lower household income (aOR 1.16, 95% CI 1.01–1.33). AA survivors were more likely to be non-coupled (aOR 1.35, 95% 1.15–1.60) and have hypertension (aOR 1.18, 95% CI 1.03–1.36). Asians were more former/current drinkers (aOR 1.21, 95% CI 1.05–1.40). NHW are more likely to experience psychological limitation. Compared to matched general, NHW and Asian survivors had poor general health and psychological health. Conclusions This study provides evidence for future studies concerning long-term health after AYA cancer survivorship that may vary according to race.

Abstract Introduction Although an association between metabolic dysfunction‐associated fatty liver disease (MAFLD) and cardiovascular disease or overall mortality has been reported, it is unclear whether there is an association between MAFLD and cancer incidence or mortality. We aimed to investigate the differential risk of all‐ and site‐specific cancer incidence and mortality according to MAFLD subgroups categorized by additional etiologies of liver disease. Methods Using the Korean National Health Insurance Service database, we stratified the participants into three groups: (1) single‐etiology MAFLD (S‐MAFLD) or MAFLD of pure metabolic origin; (2) mixed‐etiology MAFLD (M‐MAFLD) or MAFLD with additional etiological factor(s) (i.e., concomitant liver diseases and/or heavy alcohol consumption); and (3) non‐MAFLD. Hepatic steatosis and fibrosis were defined using the fatty liver index and the BARD score, respectively. Cox proportional hazards regression was performed to estimate the risk of cancer events. Results Among the 9,718,182 participants, the prevalence of S‐MAFLD and M‐MAFLD was 29.2% and 6.7%, respectively. During the median 8.3 years of follow‐up, 510,330 (5.3%) individuals were newly diagnosed with cancer, and 122,774 (1.3%) cancer‐related deaths occurred among the entire cohort. Compared with the non‐MAFLD group, the risk of all‐cancer incidence and mortality was slightly higher among patients in the S‐MAFLD group (incidence, adjusted hazard ratio [aHR] = 1.03; 95% confidence interval [CI]: 1.02−1.04; mortality, aHR = 1.06; 95% CI: 1.04−1.08) and highest among patients with M‐MAFLD group (incidence, aHR = 1.31; 95% CI: 1.29−1.32; mortality, aHR = 1.45; 95% CI: 1.42−1.48, respectively). The M‐MAFLD with fibrosis group (BARD score ≥ 2) showed the highest relative risk of all‐cancer incidence (aHR = 1.38, 95% CI = 1.36–1.39), followed by the M‐MAFLD without fibrosis group (aHR = 1.09, 95% CI = 1.06–1.11). Similar trends were observed for cancer‐related mortality. Conclusions MAFLD classification, by applying additional etiologies other than pure metabolic origin, can be used to identify a subgroup of patients with poor cancer‐related outcomes.

Abstract Background We aimed to examine the association between smoking behavior change and risk of cardiovascular disease (CVD) incidence and mortality in patients with type 2 diabetes mellitus (T2DM). Methods This study used nationwide data from the Korean National Health Insurance System and included 349,137 T2DM patients who smoked. Smoking behavior changes were defined with five groups: quitters, reducers I (≥ 50% reduction), reducers II (20–50% reduction), sustainers (± 20%), and increasers (≥ 20% increase) from the number of cigarettes/day at the baseline. Results During a median follow-up of 5.1 years, 6,514 cases of myocardial infarction (MI) (1.9%), 7,837 cases of ischemic stroke (IS) (2.2%), and 14,932 deaths (4.3%) were identified. Quitters had a significantly decreased risk of MI (adjusted hazard ratio [aHR] 0.80, 95% CI 0.75–0.86) and IS (aHR 0.80, 95% CI 0.75–0.85) compared to sustainers, whereas reducers did not have a significant association with the risk of MI (aHR 1.03, 95% CI 0.94–1.13) and IS (aHR 1.00, 95% CI 0.92–1.08) in reducer I. Quitters also had a lower all-cause and CVD mortality than sustainers. Conclusions Smoking cessation was associated with decreased CVD incidence, and all-cause and CVD mortality among T2DM patients. However, smoking reduction was not associated with decreased risks for these.

BackgroundLung cancer diagnosis affects an individual’s quality of life as well as physical and emotional functioning. Information on survivorship care tends to be introduced at the end of treatment, but early intervention may affect posttreatment adjustment. However, to the best of our knowledge, no study has explored the effect of early information intervention on the return to work, family, and societal roles of lung cancer survivors. ObjectiveWe report the study protocol of a comprehensive care prehabilitation intervention designed to facilitate lung cancer survivors’ psychological adjustment after treatment. MethodsA comprehensive care program was developed based on a literature review and a qualitative study of patients with lung cancer and health professionals. The Lung Cancer Comprehensive Care Program consists of educational videos and follow-up visits by a family medicine physician. To prevent contamination, the control group received routine education, whereas the intervention group received routine care and intervention. Both groups completed questionnaires before surgery (T0) and at 1-month (T1), 6-month (T2), and 1-year (T3) follow-up visits after surgery. The primary outcome was survivors’ psychological adjustment to cancer 6 months after pulmonary resection. ResultsThe historical control group (n=441) was recruited from September 8, 2021, to April 20, 2022, and the intervention group (n=350) was recruited from April 22, 2022, to October 17, 2022. All statistical analyses will be performed upon completion of the study. ConclusionsThis study examined the effectiveness of an intervention that provided general and tailored informational support to lung cancer survivors, ranging from before to the end of treatment. Trial RegistrationClinicalTrials.gov NCT05078918; https://clinicaltrials.gov/ct2/show/NCT05078918 International Registered Report Identifier (IRRID)DERR1-10.2196/54707

BackgroundHeart failure (HF) is one of the most common initial manifestations of cardiovascular disease in patients with type 2 diabetes. Although smoking is an independent risk factor for HF, there is a lack of data for the incidence of HF according to changes in smoking behaviors in patients with type 2 diabetes. ObjectiveWe aimed to examine the association between interval changes in smoking behavior and the risk of HF among patients with type 2 diabetes. MethodsWe conducted a retrospective cohort study using the National Health Insurance Service database. We identified 365,352 current smokers with type 2 diabetes who had 2 consecutive health screenings (2009-2012) and followed them until December 31, 2018, for the incident HF. Based on smoking behavior changes between 2 consecutive health screenings, participants were categorized into quitter, reducer I (≥50% reduction) and II (

Abstract Background Colorectal cancer survivors often experience decline in physical performance and poor quality of life after surgery and during adjuvant therapies. In these patients, preserving skeletal muscle mass and high-quality nourishment are essential to reduce postoperative complications and improve quality of life and cancer-specific survival. Digital therapeutics have emerged as an encouraging tool for cancer survivors. However, to the best of our knowledge, randomized clinical trials applying personalized mobile application and smart bands as a supportive tool to several colorectal patients remain to be conducted, intervening immediately after the surgical treatment. Methods This study is a prospective, multi-center, single-blinded, two-armed, randomized controlled trial. The study aims to recruit 324 patients from three hospitals. Patients will be randomly allocated to two groups for one year of rehabilitation, starting immediately after the operation: a digital healthcare system rehabilitation (intervention) group and a conventional education-based rehabilitation (control) group. The primary objective of this protocol is to clarify the effect of digital healthcare system rehabilitation on skeletal muscle mass increment in patients with colorectal cancer. The secondary outcomes would be the improvement in quality of life measured by EORTC QLQ C30 and CR29, enhanced physical fitness level measured by grip strength test, 30-sec chair stand test and 2-min walk test, increased physical activity measured by IPAQ-SF, alleviated pain intensity, decreased severity of the LARS, weight, and fat mass. These measurements will be held on enrollment and at 1, 3, 6 and 12 months thereafter. Discussion This study will compare the effect of personalized treatment stage-adjusted digital health interventions on immediate postoperative rehabilitation with that of conventional education-based rehabilitation in patients with colorectal cancer. This will be the first randomized clinical trial performing immediate postoperative rehabilitation in a large number of patients with colorectal cancer with a tailored digital health intervention, modified according to the treatment phase and patient condition. The study will add foundations for the application of comprehensive digital healthcare programs focusing on individuality in postoperative rehabilitation of patients with cancer. Trial registration NCT05046756. Registered on 11 May 2021.

Abstract Background Midlife hypertension has been recognized as a modifiable risk factor for dementia, but association between blood pressure (BP) in late life and dementia has been inconclusive. In addition, few studies have investigated effects of BP control on dementia incidence in the frail elderly. Thus, this study aimed to investigate the association of BP and dementia incidence with concomitant consideration of physical frailty in the young elderly population. Methods Using the Korean National Health Information Database, we identified 804,024 subjects without history of dementia at age 66. Dementia diagnosis was defined with prescription records of anti-dementia drugs and dementia-related diagnostic codes. Physical frailty was measured using the Timed Up and Go test. Association of BP and dementia incidence with concomitant consideration of physical frailty was investigated using Cox hazards analyses. Results The risks of Alzheimer’s and vascular dementia increased from systolic BP ≥ 160 and 130–139 mmHg, respectively; a significant association of dementia incidence with low BP was not observed. In the analyses stratified by the physical frailty status, low BP was not associated with increased risks of dementia within the groups both with and without physical frailty. Conclusions High BP was associated with increased risks of dementia, especially for vascular dementia, while low BP was not associated with increased risks of any type of dementia in young elderly people, even in those with physical frailty. This study suggests the need for tight BP control in young elderly people, irrespective of frailty status, to prevent dementia and supports the current clinical guidelines of hypertension treatment.

OBJECTIVES We examined the associations of socioeconomic factors, health behaviors, and comorbidities with early-onset lung cancer. METHODS The study included 6,794,287 individuals aged 20–39 years who participated in a Korean national health check-up program from 2009 to 2012. During the follow-up period, 4,684 participants developed lung cancer. Multivariable Cox regression analysis was used to estimate the independent associations of potential risk factors with incident lung cancer. RESULTS Older age (multivariable hazard ratio [mHR], 1.13; 95% confidence interval [CI], 1.12 to 1.14) and female sex (mHR, 1.62; 95% CI, 1.49 to 1.75) were associated with increased lung cancer risk. Current smoking was also associated with elevated risk (

ObjectiveThere have been no studies on the association between changes in smoking and alcohol consumption or combined changes in smoking and alcohol consumption frequencies and PD risk. To assess the influence of changes in smoking and alcohol consumption on the risk of Parkinson’s disease (PD).MethodsNational Health Insurance Service (NHIS) database between January 2009 to December 2011 was analyzed. A total of 3,931,741 patients were included. Study participants were followed up for the incidence of PD until December 2017.ResultsCompared to the sustained non-smokers, sustained light smokers (adjusted hazard ratio [aHR] 0.80, 95% confidence interval [CI] 0.75–0.85), sustained moderate smokers (aHR 0.54, 95% CI 0.47–0.61), and sustained heavy smokers (aHR 0.49, 95% CI 0.44–0.55) had a lower risk of PD. Compared to those who sustained non-drinking, sustained light drinkers (aHR 0.85 95% CI 0.89–0.91), sustained moderate drinkers (aHR 0.68, 95% CI 0.60–0.78), and sustained heavy drinkers (aHR 0.77, 95% CI 0.68–0.87) showed decreased risk of PD. Among non-drinkers, those who started drinking to a light level were at decreased risk of PD (aHR 0.84, 95% CI 0.77–0.91). Among non-smoking and non-drinking participants, those who initiated smoking only (aHR 0.78, 95% CI 0.70–0.86), drinking only (aHR 0.77, 95% CI 0.68–0.87), and both smoking and drinking (aHR 0.69, 95% CI 0.58–0.82) showed decreased risk of PD.ConclusionSmoking is associated with decreased risk of PD with a dose–response relationship. Alcohol consumption at a light level may also be associated with decreased risk of PD. Further studies are warranted to find the possible mechanisms for the protective effects of smoking and drinking on PD, which may present insights into the etiology of PD.

Abstract Background To assess the association between the reproductive factors of age at menarche, age at menopause, and reproductive span and the incidence of myocardial infarction (MI) and ischemic stroke (IS). Methods We used a population-based retrospective cohort study from the National Health Insurance Service database of Korea including a total of 1,224,547 postmenopausal women. Associations between age at menarche (≤ 12, 13–14 [reference], 15, 16, and ≥ 17 years), age at menopause (

Abstract Population-based data regarding the prognostic implication of gamma-glutamyl transferase (GGT) have been inconsistent. We examined the association of GGT with all-cause and disease-specific mortality. Using the Korean nationwide database, we included 9,687,066 subjects without viral hepatitis or cirrhosis who underwent a health examination in 2009. Subjects were classified into three groups by sex-specific tertile of serum GGT levels. The underlying causes of death were classified by 10th Revision of the International Classification of Diseases codes. During the median follow-up period of 8.3 years, 460,699 deaths were identified. All-cause mortality increased as serum GGT levels became higher (hazard ratio [HR], 95% confidence interval [CI] 1.05, 1.04–1.05 in the middle tertile, and 1.33, 1.32–1.34 in the high tertile) compared to the low tertile of serum GGT levels. Similar trends were observed for cardiovascular disease (CVD) (HR, 95% CI 1.07, 1.05–1.09 in the middle tertile, 1.29, 1.26–1.31 in the high tertile), cancer (HR, 95% CI 1.08, 1.07–1.10 in the middle tertile, 1.38, 1.36–1.39 in the high tertile), respiratory disease (HR, 95% CI 1.10, 1.08–1.13 in the middle tertile, 1.39, 1.35–1.43 in the high tertile), and liver disease mortality (HR, 95% CI 1.74, 1.66–1.83 in the middle tertile, 6.73, 6.46–7.01 in the high tertile). Regardless of smoking, alcohol consumption and history of previous CVD and cancer, a higher serum GGT levels were associated with a higher risk of mortality. Serum GGT levels may be useful for risk assessment of all-cause and disease-specific mortality in general population.

Abstract Common etiologies between age-related macular degeneration (AMD) and kidney disease advocate a close link between AMD and end-stage renal disease (ESRD). However, the risk of ESRD in people with AMD was not reported. Here, we investigated the association between AMD and the risk of ESRD by using a nationwide, population-based cohort data in Korea. 4,206,862 participants aged 50 years or older were categorized by presence of AMD and visual disability. Risk of ESRD was the primary outcome. Cox regression hazard model was used to examine the hazard ratios (HRs) with adjustment for potential confounders. Stratified analyses by age, sex, baseline kidney function, and cardiometabolic comorbidities were performed. During the mean 9.95 years of follow-up, there were 21,759 incident ESRD events (0.52%). AMD was associated with 33% increased risk of ESRD (adjusted HR [aHR] 1.33, 95% confidence interval [CI] 1.24–1.44), and the risk was even higher when accompanied by visual disability (aHR 2.05, 95% CI 1.68–2.50) than when not (aHR 1.26, 95% CI 1.17–1.37). Age, baseline kidney function, and cardiometabolic comorbidities significantly interact between AMD and the risk of ESRD. Our findings have clinical implications on disease prevention and risk factor management of ESRD in patients with AMD.

Abstract Background Metabolic-associated fatty liver disease (MAFLD) encompasses diverse disease groups with potentially heterogeneous clinical outcomes. We investigated the risk of all-cause and disease-specific mortality in MAFLD subgroups. Methods Using the Korean National Health Insurance Service database, participants were divided into four subgroups: no MAFLD, MAFLD-diabetes, MAFLD-overweight/obese, and MAFLD-lean. Hazard ratios (HRs) and 95% confidence interval (CI) values for all-cause and disease-specific mortality according to MAFLD subgroups were analyzed using Cox proportional hazards models. Results Among 9,935,314 participants, those with MAFLD-diabetes showed the highest risk of all-cause and disease-specific mortality. The HRs (95% CI) for all-cause mortality were 1.61 (1.59–1.63), 1.36 (1.34–1.38), and 1.19 (1.18–1.20) in the MAFLD-diabetes, MAFLD-lean, and MAFLD-overweight/obese groups, respectively. The magnitude of cardiovascular disease and cancer-related risk showed the same pattern. The risk of liver-related mortality in the MAFLD-lean group (HR: 2.84, 95% CI: 2.72–2.97) was comparable with that in the MAFLD-diabetes group (HR: 2.85, 95% CI: 2.75–2.95). When stratified by body mass index, liver-related mortality was the highest in MAFLD-lean individuals in the underweight group (HR, 5.03, 95% CI: 4.23–5.97). Conclusions The MAFLD-lean and MAFLD-diabetes groups had a higher risk of all-cause and disease-specific mortality than did the MAFLD-overweight/obese group. Classifying MAFLD subgroups based on metabolic phenotypes might help risk stratification of patients with MAFLD.

Abstract This nationwide population-based cohort study searched for demographic, comorbid, behavioral, and reproductive risk factors for idiopathic macular hole (MH) development using data provided by the Korean National Health Insurance Service. A total of 4,496,867 individuals aged 50–79 years who participated in the Korean National Health Screening Program in 2013 or 2014 were included. Participants were followed up until December 2018, and incident cases of idiopathic MH were identified. Prospective associations between incident idiopathic MH and various covariates were investigated using multivariable-adjusted Cox proportional hazard models. During an average follow-up period of 4.91 years, 3054 patients were newly diagnosed with idiopathic MHs. Women showed greater risk (hazard ratio of 1.71) and earlier presentation of idiopathic MH than men. Compared to the normal body mass index group, the obese group (≥ 25 kg/m2) showed a significantly lower risk of idiopathic MH. Among postmenopausal women, those with two or more children showed a greater risk of idiopathic MH than those who had not been pregnant, with a hazard ratio of 1.80. In conclusion, idiopathic MH occurred earlier and greater in women. Childbirth were associated with an increased risk of MH development, and obesity was associated with a lower risk of MH.

Abstract Background Type 2 diabetes and non-alcoholic fatty liver disease (NAFLD) commonly coexist. However, NAFLD’s effect on mortality in Asian patients with type 2 diabetes awaits full elucidation. Therefore, we examined NAFLD-related all-cause and cause-specific mortality in a nationwide Asian population with type 2 diabetes. Methods We included patients who had undergone general health checkups between 2009 and 2012 using the National Health Insurance Service database linked to death-certificate data. Hepatic steatosis was defined as a fatty liver index (FLI) ≥ 60, and advanced hepatic fibrosis was determined using the BARD score. Findings During the follow-up period of 8.1 years, 222,242 deaths occurred, with a mortality rate of 14.3/1000 person-years. An FLI ≥ 60 was significantly associated with increased risks of all-cause and cause-specific mortality including cardiovascular disease (CVD)-, cancer-, and liver disease (FLI ≥ 60: hazard ratio [HR] = 1.02, 95% confidence interval [CI] 1.01–1.03 for all-cause; 1.07, 1.04–1.10 for CVD; 1.12, 1.09–1.14 for cancer; and 2.63, 2.50–2.77 for liver disease). Those with an FLI ≥ 60 and fibrosis (BARD ≥ 2) exhibited increased risks of all-cause (HR, 95% CI 1.11, 1.10–1.12), CVD- (HR, 95% CI 1.11, 1.09–1.14), cancer- (HR, 95% CI 1.17, 1.15–1.19), and liver disease-related (HR, 95% CI 2.38, 2.29–2.49) mortality. Conclusion Hepatic steatosis and advanced fibrosis were significantly associated with risks of overall and cause-specific mortality in patients with type 2 diabetes. Our results provide evidence that determining the presence of hepatic steatosis and/or fibrosis potentially plays a role in risk stratification of mortality outcomes in patients with type 2 diabetes mellitus.

Abstract This nationwide population-based cohort study evaluated the association between lipid profiles and the future risk of exudative age-related macular degeneration (AMD) using authorized clinical data provided by the Korean National Health Insurance Service. A total of 6,129,616 subjects over 50 years of age who participated in the Korean National Health Screening Program in 2013 or 2014 were included. Data on risk factors, including age, sex, comorbidities, behavioral factors, and baseline lipid profiles, including total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, and triglyceride (TG) levels were collected. Patients were followed-up patients until December 2018, and incident cases of exudative AMD were identified using registered diagnostic codes. During an average follow-up period of 4.91 years, 18,803 patients were newly diagnosed with exudative AMD. Compared to the lowest HDL cholesterol quartile group, the highest HDL cholesterol quartile group had a greater risk of future exudative AMD development with a hazard ratio (95% confidence interval) of 1.13 (1.08–1.18) in the fully adjusted model. The highest TG quartile group had a lower risk of exudative AMD than the lowest TG quartile group, with a hazard ratio (95% confidence interval) of 0.84 (0.81–0.88). High HDL cholesterol and low TG levels were prospectively associated with exudative AMD incidence.

Abstract In studies evaluating the association between body mass index (BMI) and risk of tuberculosis (TB), the data for the underweight population has been limited and results were conflicting. Our study aimed to evaluate whether being underweight increases the risk of TB using a nationwide representative sample from the Republic of Korea. A large population-based cohort study of over ten million subjects who participated in the health screening in 2010 was performed using the Korean National Health Insurance database 2010–2017. We evaluated the incidence and risk of TB by BMI category (kg/m2) for Asians using a multivariable Cox regression model, adjusting for age, sex, smoking, alcohol consumption, regular exercise, low-income state, and underlying hypertension, diabetes mellitus, and dyslipidemia. To evaluate the association between BMI and TB risk, the underweight population was further subdivided according to the degree of thinness. During 70,063,154.3 person-years of follow-up, 52,615 of 11,135,332 individuals developed active TB with an incidence of 0.75 per 1000 person-years. Overall, there was a log-linear inverse relationship between TB incidence and BMI, within the BMI range of 15–30 kg/m2 (R2 = 0.95). The estimated adjusted hazard ratio (HR) for incident TB in the underweight population (BMI

BackgroundCigarette smoking is an important risk factor for developing chronic obstructive pulmonary disease (COPD). However, the effect of smoking on the development of COPD in young individuals remains unclear. We aimed to evaluate the effect of smoking on COPD development in young individuals.MethodsUsing the Korean National Health Information Database, we screened individuals aged 20–39 years who participated in the national health check-up between 2009 and 2012. We defined physician-diagnosed COPD based on health insurance claims and searched the database until December 2019. We identified 6,307,576 eligible individuals, and 13,789 had newly developed COPD. We used multivariate Cox proportional hazards models to estimate the adjusted hazard ratio (aHR) of risk factors for COPD.ResultsThe incidence rate for developing COPD was 0.26/1000 person-year. The risk of developing COPD was significantly higher in current smokers [aHR 1.46, 95% confidence interval (CI) 1.39–1.53] and former smokers (aHR 1.21, 95% CI 1.14–1.29) than in non-smokers. Furthermore, the risk increased with increasing smoking amounts (≥20 pack-years, aHR 2.24; 10–20 pack-years, aHR 1.55;

BackgroundAlcohol and diabetes are known risk factors for hepatocellular carcinoma (HCC); however, it is unclear whether the association between alcohol consumption and HCC risk differs by fasting serum glucose level and diabetes. We investigated the dose-response relationship between alcohol consumption and the risk of HCC according to glycemic status.Methods and findingsThis population-based observational cohort study included patients who underwent general health checkups in 2009 using the Korean National Health Insurance Service Database. The primary outcome was HCC incidence, and Cox proportional hazard regression analysis was performed to estimate the relationship between alcohol consumption and HCC risk according to glycemic status. A total of 34,321 patients newly diagnosed with HCC were observed in the median follow-up period of 8.3 years. In the multivariable model, we adjusted for age, sex, smoking, regular exercise, income, hypertension, dyslipidemia, and body mass index. Mild-to-moderate alcohol consumption increased the risk of HCC in all glycemic statuses (normoglycemia: hazard ratio [HR], 1.06; 95% confidence interval [CI], 1.02 to 1.10; prediabetes: HR, 1.19; 95% CI, 1.14 to 1.24; and diabetes: HR, 2.02; 95% CI, 1.93 to 2.11) compared to normoglycemic nondrinking. Heavy alcohol consumption also increased the risk of HCC in all glycemic statuses (normoglycemia: HR, 1.39; 95% CI, 1.32 to 1.46; prediabetes: HR, 1.67; 95% CI, 1.58 to 1.77; and diabetes: HR, 3.29; 95% CI, 3.11 to 3.49) compared to normoglycemic nondrinking. Since alcohol consumption information in this study was based on a self-administered questionnaire, there may be a possibility of underestimation. Although we excluded patients with a history of viral hepatitis using diagnosis codes, we could not obtain information on hepatitis B or hepatitis C serum markers.ConclusionsBoth mild-to-moderate and heavy alcohol consumption was associated with an increased risk of HCC in all glycemic statuses. The increased risk of HCC according to alcohol consumption was the highest in the diabetes group, suggesting that more intensive alcohol abstinence is required for patients with diabetes.

IntroductionCognitive impairment is a common feature of multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD). However, there is a lack of population-based study of dementia risk in these disorders. In the present study, the risk of dementia in MS and NMOSD patients in Republic of Korea was estimated.MethodsData analyzed in this study were obtained from the Korean National Health Insurance Service (KNHIS) database between January 2010 and December 2017. The study included 1,347 MS patients and 1,460 NMOSD patients ≥40 years of age who had not been diagnosed with dementia within 1 year prior to the index date. Matched controls were selected based on age, sex, and the presence of hypertension, diabetes mellitus, or dyslipidemia.ResultsIn MS and NMOSD patients, the risk of developing any dementia [adjusted hazard ratio (aHR) = 2.34; 95% confidence interval (CI) = 1.84–2.96 and aHR = 2.19; 95% CI = 1.61–3.00, respectively], Alzheimer’s disease [AD; aHR = 2.23; 95% confidence interval (CI) = 1.70–2.91 and aHR = 1.99; 95% CI = 1.38–2.88, respectively], and vascular dementia (aHR = 3.75; 95% CI = 1.91–7.35 and aHR = 3.21; 95% CI = 1.47–7.02, respectively) was higher compared with the matched controls. NMOSD patients had a lower risk of any dementia and AD compared with MS patients after adjusting for age, sex, income, hypertension, diabetes, and dyslipidemia (aHR = 0.67 and 0.62).ConclusionThe risk of dementia increased in MS and NMOSD patients and dementia risk was higher in MS than in NMOSD.

The objective of this study is to investigate the correlation between the neighborhood deprivation index and survival rates of cancer patients in Korea. In this study, 5-year age-standardized survival rates of patients with cancer were determined using the National Cancer Cohort from 2014 to 2018 in Korea. The primary cancer sites were the stomach, colorectum, liver, lung, breast, cervix, prostate, and thyroid. Disparities were measured, and their impact on the overall survival rates was assessed using the Korean version of the Neighborhood Deprivation Index. Pearson’s correlation coefficient was calculated to determine the strength of the correlation. The study cohort comprised 726,665 patients with cancer, of whom 50.7% were male. The predominant primary cancer sites were the stomach (n = 138,462), colorectum (n = 125,156), and thyroid gland (n = 120,886). Urban residents showed better survival outcomes than those situated in rural areas. The most deprived quartile had the lowest survival rate, while the least deprived quartile had the highest (p < 0.001). Most cancer types revealed significant correlations between neighborhood deprivation and 5-year age-standardized overall survival, with lung cancer showing the most substantial negative correlation (r = −0.510), followed by prostate cancer (r = −0.438). However, thyroid cancer showed only a marginal correlation (p = 0.069). The results of this study suggested that neighborhood deprivation is closely linked to disparities in overall survival across various types of cancer. A substantial negative correlation between the neighborhood deprivation index and all-cause mortality for lung and prostate cancer, as compared to breast and cervical cancers covered by the National Cancer Screening Program, may reinforce the need to address healthcare access and improve the early detection of cancer in socioeconomically deprived neighborhoods.

The Korea National Disability Registration System (KNDRS) was established in 1989 to provide social welfare benefits based on predefined criteria for disability registration and an objective medical assessment using a disability grading system. Disability registration requires (1) a medical examination by a qualified specialist physician and (2) a medical advisory meeting to review the degree of disability. Medical institutions and specialists for the diagnosis of disabilities are legally stipulated, and medical records for a specified period are required to support the diagnosis. The number of disability types has gradually expanded, and 15 disability types have been legally defined. As of 2021, 2.645 million people were registered as disabled, accounting for approximately 5.1% of the total population. Among the 15 disability types, disabilities of the extremities account for the largest proportion (45.1%). Previous studies have investigated the epidemiology of disabilities using data from the KNDRS, combined predominantly with data from the National Health Insurance Research Database (NHIRD). Korea has a mandatory public health insurance system that covers the entire Korean population, and the National Health Insurance Services manages all eligibility information, including disability types and severity ratings. In short, the KNDRS-NHIRD is a significant data resource for research on the epidemiology of disabilities.

Background and purposeThe association between fatty liver and fracture risk has not been firmly established. In this study, we investigated the relationship between the fatty liver index (FLI) and the incidence of fractures among individuals ≥50 years of age, using a nationwide population-based cohort.MethodsData from the Korean National Health Insurance System between January 2009 and December 2019 were analyzed using the Cox proportional hazards model. Fatty liver status was defined using FLI. Newly diagnosed fractures were identified based on insurance claim data.ResultsAmong the 3,384,457 individuals who met our inclusion criteria over the study period, 444,203 cases of incident fractures were identified over a median follow-up of 10.3 years. On multivariate analysis, the risk of fracture was significantly higher among individuals with a higher FLI score compared to those with an FLI

Background Age‐related macular degeneration (AMD) is the leading cause of visual disability. AMD shares some risk factors with the pathogenesis of cardiovascular disease (CVD). However, previous studies examining the association between AMD and the risk of CVD provide conflicting results. Hence, we investigated the association between AMD, visual disability, and the risk of CVD. Methods and Results This is a nationwide cohort study using data from the Korean National Health Insurance System database (2009–2019) on subjects who underwent a national health screening program in 2009. A total of 3 789 963 subjects were categorized by the presence of AMD and visual disability. Visual disability was defined as a best‐corrected visual acuity of ≤20/100 by validated documentation from a specialist physician. Cox regression hazard model was used to examine the hazard ratios (HRs) of CVD, including myocardial infarction and ischemic stroke, after adjusting for potential confounders. During a mean 9.77 years of follow‐up, AMD was associated with a 5% higher risk of myocardial infarction (adjusted HR [aHR], 1.05 [95% CI, 1.01–1.10]) but not associated with increased risk of overall CVD (aHR, 1.02 [95% CI, 1.00–1.05]) or ischemic stroke (aHR, 1.02 [95% CI, 0.98–1.06]). However, when AMD was accompanied by visual disability, there was increased risk of CVD (aHR, 1.17 [95% CI, 1.06–1.29]), myocardial infarction (aHR, 1.18 [95% CI, 1.01–1.37]), and ischemic stroke (aHR, 1.20 [95% CI, 1.06–1.35]). These trends were more evident in women and subjects with cardiometabolic comorbidities. Conclusions AMD with visual disability, but not all AMD, was associated with an increased risk of CVD. Patients with AMD who have visual disability should be targeted for CVD prevention.

Abstract This nationwide population-based cohort study evaluated the association between female reproductive factors and the incidence of retinal vein occlusion (RVO) and retinal artery occlusion (RAO) using data provided by the Korea National Health Insurance Service. A total of 2,289,347 postmenopausal women over 50 years of age who participated in both national health screening and cancer screening in 2013 or 2014 were included. Data on female reproductive factors, including age at menarche, age at menopause, parity, history of hormone replacement therapy, and oral contraceptive pill usage, were collected. Patients were followed up until December 2018, and incident cases of RVO and RAO were identified using registered diagnostic codes from claim data. During an average follow-up period of 4.90 years, 7461 and 1603 patients were newly diagnosed with RVO and RAO, respectively. In the multivariable-adjusted Cox proportional hazard model, patients who experienced menopause after 55 years of age had a lower risk of RVO and RAO development compared to those who had menopause before 45 years of age, with a hazard ratio (95% confidence interval) of 0.83 (0.76–0.95) for RVO and 0.80 (0.66‒0.98) for RAO. In conclusion, early menopause was an independent risk factor for future development of RVO and RAO.

Abstract Background Stomach cancer is one the most common neoplasms with high mortality. However, fear of cancer recurrence (FCR) in stomach cancer survivors has been scarcely evaluated. Thus, the aim of this study was to evaluate FCR and factors related to FCR in Korean stomach cancer survivors. Methods A total of 363 stomach cancer survivors who had completed primary treatment and had no metastasis or recurrence were recruited between September 2014 and March 2017 regardless of time lapse after the initial diagnosis. FCR was assessed using the Korean version of the FCR Inventory (FCRI). Participants were divided into two groups; clinical FCRI group (score of severity subscale of FCRI ≥ 13) and non-clinical FCRI group (the scores

Background Hyperthyroidism is associated with an increased glomerular filtration rate (GFR) in the hyperdynamic state, which is reversible after restoring euthyroidism. However, long-term follow-up of renal dysfunction in patients with hyperthyroidism has not been performed. Methods This was a retrospective cohort study using the Korean National Health Insurance database and biannual health checkup data. We included 41,778 Graves’ disease (GD) patients and 41,778 healthy controls, matched by age and sex. The incidences of end-stage renal disease (ESRD) were calculated in GD patients and controls. The cumulative dose and duration of antithyroid drugs (ATDs) were calculated for each patient and categorized into the highest, middle, and lowest tertiles. Results Among 41,778 GD patients, 55 ESRD cases occurred during 268,552 person-years of follow-up. Relative to the controls, regardless of smoking, drinking, or comorbidities, including chronic kidney disease, GD patients had a 47% lower risk of developing ESRD (hazard ratio [HR], 0.53; 95% confidence interval [CI], 0.37 to 0.76). In particular, GD patients with a higher baseline GFR (≥90 mL/min/1.73 m2; HR, 0.33; 95% CI, 0.11 to 0.99), longer treatment duration (>33 months; HR, 0.31; 95% CI, 0.17 to 0.58) or higher cumulative dose (>16,463 mg; HR, 0.29; 95% CI, 0.15 to 0.57) of ATDs had a significantly reduced risk of ESRD. Conclusion This was the first epidemiological study on the effect of GD on ESRD, and we demonstrated that GD population had a reduced risk for developing ESRD.

Abstract We conducted a retrospective cohort study to evaluate the temporal pattern of incidence of chronic conditions after developing breast cancer using a population-based national registry. We selected 84,969 women with newly diagnosed breast cancer between 2002 and 2016 and a 1:10 sample of age-matched non-breast cancer controls (N = 1,057,674). The main study exposure was incident breast cancer, considered as a time-varying exposure. The outcomes were incident cases of leukemia, endometrial cancer, myeloma, cardiomyopathy, osteoporosis, end stage renal disease (ESRD), pulmonary fibrosis, hypothyroidism, type 2 diabetes, hypertension and hyperlipidemia. The development of breast cancer was associated with a significantly increased risk of all outcomes analyzed except for ESRD and hypertension. The fully-adjusted risks of leukemia (HR 3.09; 95% CI 2.11–4.51), cardiomyopathy (HR 2.65; 95% CI 1.90–3.68), endometrial cancer (HR 3.53; 95% CI 2.76–4.53), hypothyroidism (HR 1.29; 95% CI 1.19–1.40), pulmonary fibrosis (HR 1.84; 95% CI 1.12–3.02), and hyperlipidemia (HR 1.24; 95% CI 1.20–1.28) remained significantly elevated after more than 5 years since diagnosis. Optimal care for breast cancer survivors requires close collaboration between oncologists and allied health care professionals to identify and manage the long-term morbidity and mortality associated with these chronic conditions.

Purpose: The factors associated with the dietary supplement (DS) use of Asian breast cancer survivors in consideration of the duration of use and types of DS have not been well established. Methods: We recruited 693 Korean female breast cancer survivors at two university-affiliated hospitals and collected study data through a self-administered questionnaire and a review of medical records. A multiple logistic regression analysis was conducted to evaluate the multivariable-adjusted association between DS use and study variables. Results: The prevalence of any (≥2 weeks) and long-term (≥6 months) DS use among study participants was 48.2% and 12.0%, respectively. Education level, alcohol use, adequate physical activity (≥150 min/week), and time lapse after cancer diagnosis were positively associated with any DS use. Among DS users, as compared with short-term (≥2 weeks and

Health screening is an important component of health promotion programs, and countries have promoted general health screening targeting the prevention and early management of common chronic diseases. In Korea, a General Health Screening Program (GHSP) began with workers in the 1950s and continuously expanded its target population, and currently includes the adult population. The main target diseases are cerebroand cardiovascular diseases, including hypertension, diabetes mellitus, dyslipidemia, obesity, and related health behaviors. Other target conditions include other diseases (e.g., anemia, liver disease, visual/auditory impairment), mental health (e.g., depression), and geriatric disease and function (osteoporosis, dementia, risk of fall, etc.). The National Health Information Database, including GHSP information, is now extensively used in clinical and public health research. The participation rate is currently 70% to 80%, but varies according to age, disability, and the socioeconomic status. There is a need for a more systematic evaluation of the screening items, reducing disparity gaps in participation, and linking GHSP to actual health promotion.

Background: A small number of studies have suggested an association between systemic lupus erythematosus (SLE) and Parkinson’s disease (PD). Objectives: This study aimed to determine the risk of incident PD among Korean patients with SLE. Design: A nationwide retrospective cohort study using the claims database of the National Health Insurance Service of Korea was conducted. Methods: Patients above 40 years of age diagnosed with SLE between 2010 and 2015 were included in the study. The primary outcome of the study was incident PD, defined by registration in the rare intractable diseases program for PD and an ICD-10 code of G20. Subjects were followed until PD diagnosis or the end of 2017. We estimated the cumulative incidence of PD among the SLE cohort and compared this to that in a 1:5 age- and sex-matched control group. Results: Totals of 11,615 SLE cases and 58,075 matched controls were identified. The cumulative incidence rate of PD was 0.7 per 1000 person-years in the SLE cohort. The crude hazard ratio (HR) of incident PD was 1.71 (95% CI: 1.25–2.36) among the SLE cohort compared to the control group. The HR was 1.59 (95% CI: 1.15–2.20) after adjustment for age, sex, income, and baseline comorbidities. Conclusion: This study demonstrated that patients with SLE had an increased risk of incident PD compared to non-SLE controls. Further research is required to determine the mechanism underlying this and to elucidate the precise role of systemic inflammation in the development of PD in patients with SLE.

Abstract Background Previous studies have shown that the incidence and risk factors of gout differs according to sex. However, little research has been done on the association between reproductive factors and gout. We conducted an analysis of a large nationwide population-based cohort of postmenopausal women to determine whether there is an association between reproductive factors and the incidence of gout. Methods A total of 1,076,378 postmenopausal women aged 40–69 years who participated in national health screenings in 2009 were included in the study. The outcome was the occurrence of incident gout, which was defined using the ICD-10 code of gout (M10) in the claim database. Cox proportional hazard models were used for the analyses and stratified analyses according to body mass index (BMI) and the presence/absence of chronic kidney disease (CKD) were performed. Results The mean follow-up duration was 8.1 years, and incident cases of gout were 64,052 (incidence rate 7.31 per 1000 person-years). Later menarche, earlier menopause, and a shorter reproductive span were associated with a high risk of gout. No association between parity and gout incidence was observed. Use of oral contraceptives (OC) and hormone replacement therapy (HRT) were associated with an increased risk of gout. The association between reproductive factors and gout was not statistical significant in the high BMI group. The effects of OC and HRT usage on gout were not significant in the CKD group. Conclusion Shorter exposure to endogenous estrogen was associated with a high risk of gout. Conversely, exposure to exogenous estrogen such as OC and HRT was associated with an increased risk of gout.