Nationwide Population-based Study Research Articles

Continuing or stopping 5-aminosalicylates in patients with inflammatory bowel disease on anti-TNF therapy: A nationwide population-based study.

The impact of continuing or stopping 5-aminosalicylates (5-ASA) after commencing anti-tumour necrosis factor (anti-TNF) therapy in patients with inflammatory bowel disease (IBD) remains unclear. To compare the outcomes of patients with IBD who stopped or continued 5-ASA after starting anti-TNF therapy. We analysed data from the Korean National Health Insurance claims database between 2007 and 2020. We compared the clinical outcomes of patients who stopped or continued 5-ASA within 90 days of anti-TNF initiation. The primary outcome was any adverse clinical event defined as a composite of new corticosteroid use, IBD-related hospitalisation, or intestinal surgery. Among 7442 patients included for analysis (4479 [60.2%] with Crohn's disease [CD] and 2963 [39.8%] with ulcerative colitis [UC]), 1037 (13.9%) discontinued 5-ASA within 90 days of starting anti-TNF therapy. During a median 4.3-year follow-up, discontinuation of 5-ASA was not associated with an increased risk of adverse clinical events (adjusted hazard ratio 1.01, 95% confidence interval 0.93-1.10). The cumulative incidence of each adverse clinical event and the composite outcome were not significantly different between groups (all, p > 0.05). Additionally, separate analyses in CD and UC cohorts revealed no differences in adverse clinical outcomes between the 5-ASA continuation and discontinuation groups. Subgroup analyses by presumed risk factors for disease relapse showed no significant differences in the risk of adverse events between groups. In this nationwide population-based study, discontinuing 5-ASA after starting anti-TNF therapy was not associated with an increased risk of adverse events in patients with IBD.

Survival among people with HIV and their families in Denmark 1995–2021: a nationwide population-based cohort study

Survival among people with HIV (PWH) has vastly improved globally over the last few decades but remains lower than among the general population. We aimed to estimate time trends of survival among PWH and their families from 1995 to2021. We conducted a registry-based, nationwide, population-based, matched cohort study. We included all Danish-born PWH from 1995 to 2021 who had been on antiretroviral therapy for 90 days, did not report intravenous drug use, and were not co-infected with hepatitis C (n=4168). We matched population controls from the general population 10:1 to PWH by date of birth and sex (n=41,680). For family cohorts, we identified siblings, mothers, and fathers of PWH and population controls. From Kaplan-Meier tables with age as time scale, we estimated survival from age 25. We compared PWH with population controls and families of PWH with families of population controls to calculate mortality rate ratios adjusted for sex, age, comorbidities, and education (aMRR). The median age of death among PWH increased from 27.5 years in 1995-1997 to 73.9 years (2010-2014), but thereafter survival increased only marginally. From 2015 to 2021, mortality was increased among PWH (aMRR 1.87 (95% CI: 1.65-2.11)) and siblings (aMRR: 1.25 (95% CI: 1.07-1.47)), mothers (aMRR: 1.30 (95% CI: 1.17-1.43)), and fathers (aMRR: 1.15 (95% CI: 1.03-1.29)) of PWH compared to their respective control cohorts. Mortality among siblings of PWH who reported heterosexual route of HIV transmission (aMRR: 1.51 (95% CI: 1.16-1.96)) was higher than for siblings of PWH who reported men who have sex with men as route of HIV transmission (aMRR 1.19 (95% CI: 0.98-1.46)). Survival among PWH improved substantially until 2010, after which it increased only marginally. This may partly be due to social and behavioural factors as PWH families also had higher mortality. Preben and Anna Simonsen's Foundation and Independent Research Fund Denmark.

Optimal Systolic Blood Pressure for the Prevention of All-Cause and Cardiovascular Disease Mortality in Older Adults With Hypertension: Nationwide Population-Based Cohort Study.

Target systolic blood pressure (SBP) levels for older adults with hypertension vary across countries, leading to challenges in determining the appropriate SBP level. This study aims to identify the optimal SBP level for minimizing all-cause and cardiovascular disease (CVD) mortality in older Korean adults with hypertension. This retrospective cohort study used data from the National Health Insurance Service database. We included older adults aged 65 years or older who were newly diagnosed with hypertension and underwent a National Health Insurance Service health checkup in 2003-2004. We excluded patients who had a history of hypertension or CVD, were not prescribed medication for hypertension, had missing blood pressure or any other covariate values, and had fewer than 2 health checkups during the follow-up period until 2020. We categorized the average SBP levels into 6 categories in 10 mm Hg increments, from <120 mm Hg to ≥160 mm Hg; 130-139 mm Hg was the reference range. Cox proportional hazards models were used to examine the relationship between SBP and all-cause and CVD mortalities, and subgroup analysis was conducted by age group (65-74 years and 75 years or older). A total of 68,901 older adults newly diagnosed with hypertension were included in this study. During the follow-up period, 32,588 (47.3%) participants had all-cause mortality and 4273 (6.2%) had CVD mortality. Compared to older adults with SBP within the range of 130-139 mm Hg, individuals who fell into the other SBP categories, excluding those with SBP 120-129 mm Hg, showed significantly higher all-cause and CVD mortality. Subgroup analysis showed that older adults aged 65-74 years had higher all-cause and CVD mortality rates according to SBP categories than those aged 75 years or older. The SBP levels within the range of 120-139 mm Hg were associated with the lowest all-cause and CVD mortality rates among older Korean adults with hypertension. It is recommended to reduce SBP to <140 mm Hg, with 120 mm Hg as the minimum value for SBP, for older Korean adults with hypertension. Additionally, stricter SBP management is required for adults aged 65-74 years.

The influence of factors associated with past reproductive histories on migraines in middle-aged premenopausal women: a nationwide population-based study in Republic of Korea.

Women can experience various reproductive events, such as pregnancy, childbirth, lactation, and contraception, which cause long-term changes in female hormones. In middle-aged women, the prevalence of migraine is high, and a clear gender difference is evident. This study investigated the effects of factors associated with past reproductive events on the risk of new migraine in middle-aged premenopausal women. The influence of reproductive factors on migraine in middle-aged women was investigated using the Korean National Health Insurance Service (KNHIS) and Korean Health Examination (KHE) databases. The reproductive factors of interest were parity, breastfeeding, and oral contraceptive (OC) use. The study included 949,704 middle-aged premenopausal women 40-60 years of age. The study population was divided into two groups based on new diagnosis of migraine during the follow-up period (2009-2018). The risk of new migraine tended to increase in the primiparous (hazard ratio, HR: 1.179; 95% confidence interval, CI: 1.137-1.221) and multiparous groups (HR: 1.181; 95% CI: 1.142-1.221) compared with the nulliparous group. The breastfeeding ≥12 months group (HR: 1.071; 95% CI: 1.052-1.091) showed a significantly increased risk of new migraine compared with the non-breastfeeding group. All women in the OC groups (< 1 year, HR: 1.048; 95% CI: 1.028-1.069 and ≥ 1 year, HR: 1.100; 95% CI: 1.067-1.134) showed a higher risk of new migraine than those in the non-OC group. The results of the current study indicate that childbirth, longer breastfeeding, and OC use may be associated with a higher risk of new migraine in middle-aged premenopausal women.

Demographic Characteristics and Economic Burden of Clostridioides difficile Infection in Korea: A Nationwide Population-Based Study after Propensity Score Matching.

Clostridioides difficile infection (CDI) poses a considerable threat to global public health. However, there have been insufficient propensity score-matched data on its demographic characteristics and economic burden. Using nationwide claims data, we assessed longitudinal changes in the demographic characteristics and economic burden of CDI between 2011 and 2019 after propensity score matching. We performed a regression analysis to compare the differences in the length of hospital stay and medical costs between patients with CDI and controls (gastroenteritis and colitis). The CDI hospitalization rate increased 2.9-fold between 2011 and 2019. The CDI group had higher comorbidity index scores and was more frequently diagnosed at tertiary hospitals and in the Seoul region than the control group (all p < 0.001). The annual incidence rate of CDI/10,000 persons significantly increased in both sexes and all age groups. The length of hospital stay and medical costs were 3.3-fold and 5.0-fold greater, respectively, in the CDI than in the control group (both p < 0.001). Although the length of hospital stay decreased, total medical costs increased in all age groups and both sexes between 2011 and 2019 (all p < 0.001). When compared with the control group, the CDI-attributable length of hospital stay and medical cost were greater by 15.3 days and KRW 3413 (×103), respectively, after matching. In conclusion, CDI incidence, particularly among the elderly population with comorbidities, has been increasing. In addition, the length of hospital stay and total medical costs of the CDI group were greater than those of the control group.

Inhaled Corticosteroids and the Risk of Nontuberculous Mycobacterial Infection in Chronic Airway Disease: A Nationwide Population-Based Study.

Chronic airway diseases, such as asthma and chronic obstructive pulmonary disease (COPD), are increasingly being treated with inhaled corticosteroids (ICS). However, ICSs carry potential infection risks, particularly nontuberculous mycobacteria (NTM). This study investigated the association between ICS use and NTM infection risk using national insurance data, particularly for individuals with chronic airway diseases. We conducted a nationwide population-based study using data from the National Health Insurance Service-National Sample Cohort in South Korea from 2002 to 2019. The cohort included 57,553 patients diagnosed with COPD or asthma. To assess the risk of NTM infection, we used Cox proportional hazards models and propensity score-based inverse probability treatment weighting (IPTW) to ensure a balanced analysis of covariates. Of the 57,553 patients (mean age: 56.0 years, 43.2% male), 16.5% used ICS and 83.5% did not. We identified 63 NTM infection cases, including 9 among ICS users and 54 among non-users. Before and after IPTW, ICS use was associated with a higher risk of NTM infection (adjusted hazard ratio [HR], 4.01; 95% confidence interval [CI]: 7.48-15.58). Higher risks were significant for patients ≥65 years (adjusted HR: 6.40, 95% CI: 1.28-31.94), females (adjusted HR: 10.91, 95% CI: 2.24-53.20), never-smokers (adjusted HR: 6.31, 95% CI: 1.49-26.64), systemic steroid users (adjusted HR: 50.19, 95% CI: 8.07-312.19), and those with higher comorbidity scores (adjusted HR: 6.64, 95% CI: 1.19-37.03). ICS use in patients with chronic airway diseases might increase the risk of NTM infection, particularly in older females, never-smokers, and systemic steroid users.

Ten-year incidence of keratoconus in relation to sex, age, and thyroid gland dysfunction: a nationwide population-based cohort study (2009-2018).

Keratoconus is a corneal ectatic disorder that often leads to visual impairment and may require corneal transplantation. However, its age and gender-based incidence and potential association with thyroid gland dysfunction (TGD) remain poorly understood. This study aims to clarify these aspects and investigate the possible connection between keratoconus and TGD. We conducted a nationwide population-based cohort study using data from the Korean National Health Insurance Service database. A retrospective chart review was conducted on 4,059,021 patients aged over 20 without underlying corneal diseases in 2009. The end of the review period was at ten years, or until the onset of keratoconus. To evaluate the association with TGD, multivariate Cox regression analysis was used with adjustment of confounding variables such as sex and age. During the review period, 2,334 patients developed keratoconus before the 10-year mark. Females exhibited a higher keratoconus incidence (7.101 per 100,000 person-years) compared to males (5.559) (P<0.001). After adjusting for age, the hazard ratio (HR) for keratoconus was 1.295 times higher [95% confidence interval (CI): 1.193-1.406] in females compared to males. Age groups were stratified in 10-year intervals. The highest incidence of keratoconus was observed in the 20 to 29-year age group (10.695 per 100,000 person-years). All other age groups had significantly lower HR values, with the lowest at 50-59 years (0.508, 95% CI: 0.447-0.577). Keratoconus incidence per 100,000 person-years was 6.227 in subjects without TGD, 6.019 in the hypothyroidism group and 8.287 in the hyperthyroidism group, respectively. Although not statistically significant, individuals with hyperthyroidism showed a higher HR (1.290, 95% CI: 0.939-1.771) for keratoconus when compared to those without TGD, after adjusting for age and sex. This study emphasizes a female predominance in keratoconus incidence and suggests a possible connection between hyperthyroidism and keratoconus. Furthermore, it affirms a higher incidence of keratoconus among young individuals.

Risk of Cardiovascular Events Associated with Chronic Obstructive Pulmonary Disease and/or Metabolic Syndrome: A Large-Scale Nationwide Population-Based Cohort Study.

Chronic obstructive pulmonary disease (COPD) and metabolic syndrome (MetS) are among the most prevalent conditions that might predispose individuals to life-threatening events. We aimed to examine their associations with cardiovascular (CV) events and mortality using a large-scale population dataset from the National Health Information Database in Korea. This population-based cohort study enrolled adults aged ≥40 years who had undergone more than two health examinations between 2009 and 2011. They were divided into four groups based on the presence of COPD and MetS. Analysis of the outcomes and CV events or deaths was performed from 2014 to 2019. We compared CV event incidence and mortality rates using a multivariate Cox proportional hazards model and Kaplan-Meier curves. Totally, 5,101,810 individuals were included, among whom 3,738,458 (73.3%) had neither COPD nor MetS, 1,193,014 (23.4%) had only MetS, 125,976 (2.5%) had only COPD, and 44,362 (0.9%) had both. The risk of CV events was significantly higher in individuals with both COPD and MetS than in those with either COPD or MetS alone (HRs: 2.4 vs 1.6 and 1.8, respectively; all P <0.001). Similarly, among those with both COPD and MetS, all-cause and CV mortality risks were also elevated (HRs, 2.9 and 3.0, respectively) compared to the risks in those with either COPD (HRs, 2.6 and 2.1, respectively) or MetS (HRs, 1.7 and 2.1, respectively; all P <0.001). The comorbidity of MetS in patients with COPD increases the incidence of CV events and all-cause and cardiovascular mortality rates.

Six-year trend of subsequent allergic diseases following Kawasaki disease and its clinical implications: A population-based matched cohort study of 34,712 patients.

It has been suggested that allergic diseases may increase after Kawasaki disease (KD). We aimed to analyze the temporal patterns of allergic disease incidence after KD. A nationwide population-based matched cohort study was conducted using data from the Korean National Health Insurance claims database. Patients aged <5 years diagnosed with KD and their 1:3 propensity score-matched controls were included. Three cohorts were established: Cohort A, patients with allergies; Cohort B, patients without allergies; and Cohort C, patients without allergies, but excluding patients with birth history and underlying medical conditions. Cumulative incidence rates (%) and associated hospital visits for allergic rhinitis, atopic dermatitis, urticaria, and asthma were compared between the cases and controls during the 6-year follow-up period. The study population comprised 8678 patients diagnosed with KD and 26,034 controls. In Cohort A, although initially, there were intergroup differences in the number of hospital visits for certain allergic diseases, these differences were inconsistent and varied depending on the type of allergic disease. Over time, the differences narrowed, and by the sixth year, the gap had decreased significantly. In Cohorts B and C, the initial incidence rates of the four allergic diseases and associated hospital visits were lower in patients with KD as compared to controls. However, with a faster rate of increase, the incidence rates and number of hospital visits eventually surpassed those of the controls. The pattern of delayed increase in cumulative incidence rates and hospital visits for allergic diseases after KD suggests the possibility of a shared genetic or immunologic susceptibility between KD and allergic diseases, which becomes evident over time, rather than a direct influence of KD resulting in allergic diseases.

New-onset atrial fibrillation, cardiovascular outcomes and all-cause mortality in patients with newly diagnosed cancer: A large population-based matched cohort study.

11184 Background: Studies have shown an association between atrial fibrillation (AF) and cancer, but the relationship is incompletely studied. there is also a paucity of data regarding the specific association between cancer type and AF risk . Notably, the longitudinal associations of new-onset AF with adverse cardiovascular (ACV) outcomes in Newly Diagnosed Cancer Patients remain unclear. Thus, through a comprehensive nationwide population-based study, we assessed the associations between new-onset AF and subsequent risks of ACV events and all-cause mortality. Methods: This large retrospective cohort study was conducted using the TriNetX database and included adults (&gt;18 years) with any new cancer diagnoses. We performed 1:1 propensity score matching (PSM) for demographics, BMI, nicotine dependence, comorbidities, cancer type, and medications to similar controls as cancer patients without AF. The primary outcome was new ACV events like heart failure (HF), major adverse cardiovascular events (MACE; coronary artery intervention myocardial infarction, or unstable angina), ischemic heart disease (IHD), and cerebrovascular events (CVE; cerebral infarction, carotid intervention, stroke, transient ischemic attack. The secondary outcome was all-cause mortality. Sensitivity analysis assessed statistical robustness. Hazard ratios (HR) were calculated to compare group outcomes. Results: Among the new diagnoses, 52,606 developed AF, and 374,959 remained AF free during the follow-up. After PSM, both cohorts (51,567 each) were well-matched. The mean follow-up duration was 4.8 (± 2.7) years. Among newly diagnosed cancer patients, those with incident AF had higher risk of MACE (HR 1.56; 95% CI 1.49–2.16), HF (HR 3.10; 95% CI 2.76–4.36), IHD (HR 1.68; 95% CI 1.41–2.01), CVE (HR 2.93; 95% CI 2.13–4.04), and all-cause mortality (HR 2.56; 95% CI 1.89–3.78) compared with those without incident AF. We noted a higher incidence rate during the initial months after the diagnosis of AF for both sexes. During the first year, the association with any ACV events (men: HR 2.78, 95% CI, 1.85–3.20; women: HR 1.81, 95% CI, 1.31–2.67) was more substantial than that following AF diagnosis for both sexes. New ‐onset AF was strongly associated with metastatic cancer. In sensitivity analysis, we excluded individuals with &lt;1 year of follow-up results were consistent, and all statistically significant associations remained unchanged. Conclusions: cancer patients who developed AF had significantly higher risks of subsequent adverse cardiovascular events and greater all-cause mortality. AF was strongly associated with metastatic disease. Our findings highlight the importance of strategies for AF prevention to mitigate macrovascular complications in all newly diagnosed cancer patients.

The effect of inhaler prescription on the development of lung cancer in COPD: a nationwide population-based study

BackgroundCOPD is associated with the development of lung cancer. A protective effect of inhaled corticosteroids (ICS) on lung cancer is still controversial. Hence, this study investigated the development of lung cancer according to inhaler prescription and comorbidties in COPD.MethodsA retrospective cohort study was conducted based on the Korean Health Insurance Review and Assessment Service database. The development of lung cancer was investigated from the index date to December 31, 2020. This cohort included COPD patients (≥ 40 years) with new prescription of inhalers. Patients with a previous history of any cancer during screening period or a switch of inhaler after the index date were excluded.ResultsOf the 63,442 eligible patients, 39,588 patients (62.4%) were in the long-acting muscarinic antagonist (LAMA) and long-acting β2-agonist (LABA) group, 22,718 (35.8%) in the ICS/LABA group, and 1,136 (1.8%) in the LABA group. Multivariate analysis showed no significant difference in the development of lung cancer according to inhaler prescription. Multivariate analysis, adjusted for age, sex, and significant factors in the univariate analysis, demonstrated that diffuse interstitial lung disease (DILD) (HR = 2.68; 95%CI = 1.86–3.85), a higher Charlson Comorbidity Index score (HR = 1.05; 95%CI = 1.01–1.08), and two or more hospitalizations during screening period (HR = 1.19; 95%CI = 1.01–1.39), along with older age and male sex, were independently associated with the development of lung cancer.ConclusionOur data suggest that the development of lung cancer is not independently associated with inhaler prescription, but with coexisting DILD, a higher Charlson Comorbidity Index score, and frequent hospitalization.

Cranial Nerve Palsy and Risk of Kidney Cancer: A Nationwide Population-Based Study.

Background and Objective: Understanding whether cranial nerve palsy (CNP) acts as an independent risk factor for kidney cancer could have important implications for patient care, early detection, and potentially the development of preventive strategies for this type of cancer in individuals with CNP. This study aimed to examine the risk of kidney cancer following the onset of ocular motor CNP and assess whether CNP could be considered an independent risk factor for kidney cancer. Materials and Methods: A population-based cohort study was conducted using data from the National Sample Cohort (NSC) database of Korea's National Health Insurance Service which was collected from 2010 to 2017. Follow-up was until kidney cancer development, death, or 31 December 2018. Cox proportional hazard regression analysis was performed to determine hazard ratios (HRs) for kidney cancer according to CNP status. Participants aged 20 years or more diagnosed with CNP from 2010 to 2017 were included. Exclusions comprised individuals with specific pre-existing conditions, inability to match a control group, and missing data, among others. CNP patients were age-sex matched in a 1:5 ratio with control cases. The primary outcome was incidence of kidney cancer during the follow-up period. Results: This study comprised 118,686 participants: 19,781 in the CNP group, and 98,905 in the control group. Compared to the control group, participants with CNP had a higher risk of kidney cancer (adjusted HR in model 4, 1.599 [95% CI, 1.116-2.29]). After a 3-year lag period, the CNP group had a significantly higher risk (adjusted HR in model 4, 1.987 [95% CI, 1.252-3.154]). Conclusions: Ocular motor CNP may be an independent risk factor for kidney cancer, as indicated by a higher incidence of kidney cancer in CNP patients. Further research is needed to elucidate the underlying mechanisms and explore potential preventive measures for kidney cancer in patients with ocular motor CNP.

Risk of Gastrointestinal Perforation in Patients With Rheumatic Diseases Exposed to Janus Kinase Inhibitors Versus Adalimumab: A Nationwide Cohort Study.

To compare the risk of gastrointestinal perforation (GIP), a rare but serious adverse event, in patients who a JAK inhibitor (JAKi; tofacitinib, baricitinib, upadacitinib, or filgotinib) versus adalimumab (tumor necrosis factor inhibitor) among a comprehensive real-world population of patients with rheumatic diseases. We conducted a nationwide population-based cohort study of the French national health data system, the exposed group that received a JAKi and the comparison group adalimumab. We included all individuals with a rheumatic disease who had their first dispensation of these treatments from July 2017 to December 2021. The primary endpoint was the occurrence of GIP (end of follow-up May 2022). Weighted hazard ratios (wHRs) were estimated with the inverse probability of treatment weighting method to account for confounding factors. Concomitant administration of systemic glucocorticoids, nonsteroidal anti-inflammatory drugs, and proton-pump inhibitors were time-varying variables. The cohort included 39,758 patients: 12,335 and 27,423 in the groups that received a JAKi and adalimumab (mean age 58.2 and 47.3 years; female 76% and 58%; rheumatoid arthritis 85.3% and 27.3%, and psoriatic arthritis/axial spondyloarthritis 14.7% and 72.7%), respectively. During follow-up, 38 and 42 GIPs occurred in the groups that received a JAKi and adalimumab groups; incidence rates were 2.1 (95% confidence interval [CI] 1.5-2.8) and 1.1 (95% CI 0.8-1.5) per 1,000 person-years, respectively. Rates of GIP did not differ between the groups that received a JAKi and adalimumab: wHR 1.1 (95% CI 0.7-1.9; P = 0.65). Despite the lack of power in some subgroup analyses, results were consistent whatever the subgroup of a type of JAKi received or subgroup with a type of rheumatic disease. In this nationwide cohort study, the rates of GIPs did not differ between groups of patients who received JAKi and adalimumab treatment. These results need to be confirmed in other observational studies.

Diabetes and further risk of cancer: a nationwide population-based study

BackgroundIndividuals with diabetes have a significantly higher risk of developing various forms of cancer, and the potential biological links between these two diseases are not completely understood.MethodsThis was a longitudinal retrospective nationwide cohort study, a study design that allows us to examine the natural course of cancer development over an extended period of time with a large sample size. Initially, 3,111,975 and 22,208,395 eligible patients aged ≥ 20 years with and without diabetes, respectively, were matched by age, sex, and the Charlson comorbidity index. Ultimately, 1,751,457 patients were selected from each group. Stratified populations for diabetic retinopathy (DR) (n = 380,822) and without DR (n = 380,822) as well as proliferative DR (PDR) (n = 141,150) and non-proliferative DR (NPDR) (n = 141,150) were analyzed in this study. The main outcome measure was the first-time diagnosis of cancer during the follow-up period.ResultsWe observed a 20% higher risk of total cancer incidence [hazard ratios (HR), 1.20; p < 0.001] in the diabetes cohort compared to the non-diabetes cohort. The highest HR was observed for liver and pancreas cancers. Moderately increased risks were observed for oral, colon, gallbladder, reproductive (female), kidney, and brain cancer. Furthermore, there was a borderline significantly increased risk of stomach, skin, soft tissue, female breast, and urinary tract (except kidney) cancers and lymphatic and hematopoietic malignancies. The stratified analysis revealed that the total cancer incidence was significantly higher in the DR cohort compared to the non-DR cohort (HR, 1.31; p < 0.001), and there was a borderline increased risk in the PDR cohort compared to the NPDR cohort (HR, 1.13; p = 0.001).ConclusionsThis study provides large-scale, nationwide, population-based evidence that diabetes is independently associated with an increased risk of subsequent development of total cancer and cancer at specific sites. Notably, this risk may further increase when DR develops.

Proteinuria and risk of ocular motor cranial nerve palsy: a nationwide population-based study

Understanding the association between dipstick-detected proteinuria and oculomotor cranial nerve palsy (CNP) could have significant implications for understanding the mechanism of CNP development and for developing preventive strategies against CNP development in patients with proteinuria. This study aimed to determine the relationship between dipstick-determined proteinuria and ocular motor CNP using National Sample Cohort (NSC) database from Korea’s National Health Insurance Service (NHIS). A nationwide population-based cohort study was conducted using data from the NSC database of Korea’s NHIS. These data were collected from 2009 to 2018. A one-year time lag was established to prevent a situation in which the causal link was inverted. Participants aged 20 years or more who were diagnosed with proteinuria in 2009 were included. Individuals with specific pre-existing CNP, missing data, and those who were newly diagnosed with CNP or who died within one year of being tested were excluded. The study population was classified into six groups according to the degree of proteinuria (negative, trace, or between 1 + and 4 +) based on the urine dipstick test. A Cox proportional hazard regression analysis was performed to determine the linkage between the degree of proteinuria and ocular motor CNP. A total of 5,807 (0.14% of subjects) with ocular motor CNP were assigned to the ocular motor CNP group and 4,047,205 subjects were assigned to the control group. After full adjustment of comorbidities, hazard ratios (HRs) for 1 + , 2 + , 3 + and 4 + proteinuria groups were 1.449 (95% confidence interval [CI] 1.244–1.687), 2.081 (1.707–2.538), 1.96 (1.322–2.904), and 3.011 (1.507–6.014), respectively, for developing ocular motor CNP compared to the proteinuria-negative group. In subgroup analysis, the HR of patients with proteinuria for the development of ocular motor CNP was higher in the younger age group (less than 40 years) (P = 0.0242) and the group with DM (P = 0.04). Our population-based cohort study demonstrated a significant association between proteinuria and the incidence of CNP, suggesting that urine protein level could be a new clinical marker for predicting the development of CNP.

Association between sodium–glucose cotransporter-2 (SGLT2) inhibitors and macular degeneration in patients with diabetes: a nationwide population-based study in Taiwan

AimsEvidence showed that SGLT2 inhibitors have greater protective effects against retinal diseases compared to other hypoglycemic agents. Thus, we explore the association between SGLT2 inhibitor usage and macular degeneration (MD) in Taiwanese patients with diabetes.MethodsThe National Health Insurance (NHI) program's claim data are released as the National Health Insurance Research Database (NHIRD). This database covers more than 99% of the residents in Taiwan. We included data on patients who were newly diagnosed with type 2 diabetes mellitus (ICD-9-CM: 250, exclude 250.1x; ICD-10-CM: E11), with an age at diagnosis of over 20 years as our study population. Patients who received (sodium-glucose cotransporter 2 inhibitor) SGLT2i (ATC code: A10BK) over 90 days in 2016–2019 were defined as the SGLT2i cohort. Conversely, patients who did never received SGLT2i were defined as the non-SGLT2i cohort. The exclusion criteria were having MD before the index date, receiving SGLT2i within 1–89 days, and missing data on sex, age, or days of SGLT2i usage. Two cohorts were matched by 1:1 propensity score matching, which was based on age, sex, payroll bracket grade, urbanization, comorbidities, and medications.ResultsCompared to non-SGLT2i cohort, patients who received SGLT2i had a significantly lower risk of MD (adjusted hazard ratio = 0.70, 95%CI = 0.66–0.75).ConclusionsWe found that SGLT2is has a strong protective effect against MD in patients with diabetes. SGLT2is may have benefits beyond glycemic control in patients with DR. However, additional clinical and experimental studies are required.

Surgical treatment for obstructive sleep apnea prevents arrhythmic events: a nationwide population-based study

Abstract Background/Introduction Obstructive sleep apnoea (OSA) is a well-established risk factor for the development and exacerbation of cardiac arrhythmias. Continuous positive airway pressure therapy is recommended as the primary non-invasive treatment for OSA. However, suboptimal patient compliance remains a common challenge. Purpose This study explores the benefits of surgery in reducing the occurrence of arrhythmias associated with OSA. The study aims to investigate the impact of surgery in managing OSA-associated arrhythmias. Methods Data from the Korean Health Insurance, from January 2009 to December 2020, were retrospectively compiled and analysed to investigate the clinical outcomes of 359,851 individuals with OSA. Propensity score matching (PSM) at a 1:4 ratio was employed to compare patients who underwent surgery with those who did not. A final cohort of 117,665 participants (85.4% men, aged 60 years old or younger: 94.2%) was established, with 23,533 having undergone surgery for OSA and 94,132 receiving non-surgical management. Over a five-year follow-up period, the occurrence rates of atrial fibrillation (AF), premature beats (premature atrial contractions or premature ventricular contractions), ventricular arrhythmias, sudden cardiac arrest, atrioventricular block, and sinus node dysfunction were evaluated. Results Across the six types of arrhythmias, the cohort that underwent surgery for OSA consistently exhibited a lower incidence of arrhythmias than the non-surgical cohort. In the PSM analysis, a statistically significant reduction in the incidence of AF, premature beats, and sudden cardiac arrest was observed in groups of patients who underwent surgery for OSA. Among those who developed AF, the group that underwent surgery for OSA had a fivefold higher incidence than the non-surgical group (hazard ratio [HR] 5.384, 95% confidence interval [CI] 3.459-8.381). The incidence of premature beats was more than four times higher in the non-surgical group (HR 4.284, 95% CI 2.96-6.177, p&amp;lt;0.0001), and sudden arrest was more than 24x higher in the non-surgical group (HR 24.089, 95% CI 3.348-173.312). Conclusion This study suggests a potential causative relationship between OSA and arrhythmias. Additionally, surgical intervention for OSA may be considered an effective strategy for preventing arrhythmias in young patients. Further clinical research is warranted to validate and refine these observations.Figure 1Figure 2

Secondhand tobacco smoke and risk of atrial fibrillation: an observational epidemiologic and gene-environment interaction analysis

Abstract Background Second-hand tobacco smoke (SHS) is related to coronary artery disease and increases susceptibility to arrhythmia inducibility including atrial fibrillation (AF). However, epidemiologic evidence on the relationship between SHS and the risk of incident AF remains controversial. Purpose To evaluate the effect of SHS exposure on the long-term risk of AF and assess whether gene-environment interaction (synergism) exists by utilising the population-based data from the UK biobank. Methods We performed a nationwide population-based cohort study using the UK Biobank database. Participants with previous AF or current smokers were excluded. Participants were categorised into SHS-exposure and non-exposure groups. The risk of incident AF was assessed using the multivariable Cox proportional hazards model. We also evaluated the synergistic effect of SHS exposure and the polygenic risk score (PRS) of AF. Results Out of 400,493 participants, AF occurred in 23,471 (5.9%) during a median follow-up of 12.5 years. The SHS-exposure group (mean exposure 2.2 ± 5.2 hours/week) had a higher proportion of male participants with a younger age. The risk of incident AF was significantly increased in the SHS-exposure group (multivariable-adjusted hazard ratio [aHR] 1.06, 95% confidence interval 1.03-1.10, P &amp;lt;0.001) compared to the non-exposure group, suggesting a dose-dependent manner (aHR of severe SHS-exposure group, 1.11 [1.03-1.20], P = 0.005). The risk of AF increases regardless of the exposure location (home, outside, or workplace). When SHS-exposure was combined with the high genetic risk of AF, significant additive interaction was observed on the risk AF (Synergy Index of SHS-exposure with 3rdtertile of AF PRS, 1.13 [1.02-1.25], P = 0.024). Conclusion Exposure to SHS is a significant predictor for an increased risk of AF, with a synergistic effect when combined with genetic predisposition. Minimising SHS exposure, especially in individuals with a heightened genetic susceptibility to AF, may hold potential benefits for reducing the future risk of AF.

#209 Relation between exercise pattern changes and renal outcome in new-onset diabetes: a nationwide population-based study

Abstract Background and Aims Exercise reduced risk of diabetes and obesity. However, it remains unclear whether the pattern changes of exercise are increased risk of end-stage renal disease in new-onset diabetes mellitus (DM) patients. Method We assessed diabetes development in 2015 in 21,122,422 non-diabetic Koreans enrolled in Korean National Health Screening (KNHS) from 2009 to 2012 using International Classification of Diseases 10th (ICD-10) code and anti-diabetic medication prescription. Renal outcome (End-stage renal disease) was defined using V-code. The risk of ESRD evaluated in never exercise (none), after new-onset DM (post only), before new-onset DM and no exercise after new-onset DM (pre-only) and persistent exercise group (persistent group). Results During median 4.8-year follow-up, 275 (0.21%) of ESRD was occurred. After fully adjusted, the hazard ratio (HR) for ESRD was lowest in persistent exercise group 0.521 [0.302 to 0.899]. Post only exercise 0.674 [0.461 to 0.985] group showed better renal outcome compared to pre only exercise group 0.791 [0.535 to 1.169] or never exercise group [reference, 1.0]. Subgroup analysis for age, sex, history of chronic kidney disease, hypertension showed similar results. Even light exercise such as walking tended to reduce the risk of renal outcome 0.817 [0.634 to 1.037]. The higher 0.627 [0.441 to 0.892] or moderate 0.7 [0.514 to 0.953] strength of exercise type showed the lower risk of renal outcome in new-onset DM patients. Conclusion This study provides compelling evidence that exercise, particularly when maintained over time, is associated with a substantial reduction in the risk of ESRD in individuals with new-onset DM. These findings underscore the importance of incorporating regular physical activity as a crucial component of comprehensive health management strategies for individuals with diabetes, offering both clinicians and patients valuable insights for optimizing renal outcomes.

Socioeconomic inequalities in the uptake of postpartum care at home across Dutch neighbourhoods.

Postpartum care focuses on prevention of health problems by performing medical check-ups and through enhancing maternal empowerment, the parent-infant interaction and knowledge about mother's own health and that of her newborn. We aimed to investigate whether there was significant clustering within neighbourhoods regarding the uptake of postpartum care and to what extent neighbourhood-level differences are explained by individual socio-demographic factors, pregnancy-related factors and neighbourhood-level determinants (i.e. deprivation and urbanization). A nationwide population-based observational study was carried out using linked routinely collected healthcare data from appropriate-for-gestational-age weight live-born term singleton deliveries (2015-18) in the Netherlands. We performed two-level multivariable logistic regression analyses, using three different models. Model 1 contained no explanatory variables and was used to assess clustering of postpartum care uptake within neighbourhoods. In model 2, individual-level determinants were added one by one and in model 3, neighbourhood-level determinants were added. About 520818 births were included. Multilevel modelling showed that 11% of the total variance in postpartum care uptake could be attributed to the neighbourhood of residence. Individual characteristics explained 38% of the neighbourhood variance, of which income and migration background were the most important contributors. An additional 6% of the variation could be explained by neighbourhood-level determinants. We found substantial neighbourhood differences in postpartum care uptake. These differences are influenced by a complex interplay between individual-level and neighbourhood-level determinants, highlighting the importance of addressing both individual and neighbourhood-level determinants to improve the uptake of postpartum care and therewith overall community health.