Nationwide Population-based Cohort Study Research Articles

Internal mammary node irradiation in node-positive breast cancer patients treated with newer systemic therapies and 3D-based radiotherapy (DBCG IMN2): a prospective, nationwide, population-based cohort study

Internal mammary node irradiation (IMNI) improves overall survival (OS) in node-positive breast cancer patients. However, the effect is not documented in breast cancer patients treated with newer systemic therapies and 3D-based radiotherapy (RT). Therefore, the Danish Breast Cancer Group (DBCG) IMN2 study aimed to investigate the effect of IMNI in node-positive breast cancer patients treated with newer systemic therapies and 3D-based RT. DBCG IMN2 was a nationwide population-based cohort study prospectively allocating node-positive breast cancer patients with right-sided tumours to IMNI and patients with left-sided tumours to no IMNI in six RT centres. Exclusion criteria were prior malignancies, bilateral breast cancer, neoadjuvant systemic therapy, recurrence before RT, or non-standard RT. Systemic treatment included taxane-based chemotherapy, aromatase inhibitors, and trastuzumab. The primary end-point was OS. Secondary endpoints were breast cancer mortality and distant metastasis. Cox regression analyses were used for adjusted hazard ratios (HR). Clinicaltrial.gov ID:NCT06549920. In the period January 2007-May 2014, a total of 4541 patients were included. Patient characteristics were distributed evenly between right- and left-sided patients. Median follow-up was 13.7 years for OS. Survival rates at 15 years were 65.0% in patients with IMNI and 60.8% without leading to an adjusted HR of 0.85 (95% CI, 0.76-0.94; p=0.0016) for OS. Corresponding HRs were 0.84 (95% CI, 0.74-0.95; p=0.0077) for breast cancer mortality and HR 0.87 (95% CI, 0.78-0.98; p=0.026) for distant metastasis. No subgroups were identified for the omission of IMNI. The 15-year cumulative incidence of death from ischemic or valvular heart disease was 0.2% (95% CI, 0.0-0.5) in right-sided and 0.7% (95% CI, 0.4-1.2) in left-sided patients. IMNI reduced distant metastasis and breast cancer mortality and improved OS in node-positive breast cancer patients, despite treatment with newer systemic therapies and 3D-based RT. This work was supported by the Danish Cancer Society and Department of Clinical Medicine, Aarhus University, Denmark.

Risk of Cancers According to the Use of Biological Agents in Patients With Radiographic Axial Spondyloarthritis: A Nationwide Population-Based Cohort Study.

As the duration of use of biological disease-modifying antirheumatic drugs (bDMARDs) in patients with radiographic axial spondyloarthritis (r-axSpA) accumulates over time, long-term real-world safety data on cancer risk are needed. This study assessed the association between tumor necrosis factor inhibitors (TNFis) and interleukin 17 inhibitors (IL-17is) exposures and cancer risk in patients with r-axSpA. From the Korean nationwide database, we assembled 41,889 patients without prior history of cancer who were diagnosed with r-axSpA from 2010 onwards. Patients were followed up through 2021. Multivariable time-varying Cox models were performed to estimate the adjusted hazards ratios (aHRs) and 95% confidence intervals (CIs) of (1) overall cancers and (2) cancer subtypes according to TNFis exposure versus bDMARDs nonexposure, IL-17is exposure versus bDMARDs nonexposure, and IL-17is exposure versus TNFis exposure. The incident rates of overall cancers during bDMARDs nonexposure, TNFis exposure, and IL-17is exposure were 53.8, 37.6, and 67.3 per 10,000 person-years, respectively. TNFis exposure versus bDMARDs nonexposure was not associated with an increased risk of overall cancers (aHR = 0.9, 95% CI = 0.8-1.1). IL-17is exposure was not associated with an increased risk of overall cancers compared with bDMARDs nonexposure (aHR = 1.2, 95% CI = 0.5-3.0) or TNFis exposure (aHR = 1.3, 95% CI = 0.6-3.3). Similarly, no significant associations were observed between bDMARDs exposures and the risk of cancer subtypes. In patients with r-axSpA, there was no evidence of increased cancer risk with TNFis and IL-17is exposures compared with bDMARDs nonexposure, suggesting that the use of bDMARDs is safe with respect to cancer risk in patients with r-axSpA.

Metabolic Dysfunction-Associated Steatotic Liver Disease and Pancreatic Disease-A Population-Based Nationwide Cohort and Sibling-Controlled Study.

Metabolic dysfunction-associated steatotic liver disease (MASLD) has been linked to pancreatic diseases, but evidence from population-based studies with liver histology is lacking. In this population-based cohort including all Swedish adults (n=8563) with biopsy-proven MASLD, we aimed to investigate incidences of pancreatic diseases compared with matched reference individuals from the general population (n=38,858) and full siblings (n=6696). Using Cox proportional hazard models, we calculated multivariable adjusted hazard ratios (aHRs) and confidence intervals (CIs). We documented 359 incidents of pancreatic diseases in MASLD patients and 880 events in matched reference individuals, resulting in an incidence rate difference of 1.54 (95% CI, 1.25-1.84). The relative risk of pancreatic disease was highest in the first two years after MASLD diagnosis (aHR, 2.19 [95% CI, 1.92-2.50), but remained statistically significant increased even up to ten years [aHR, 1.60 (95% CI, 1.38-1.85)]. The most common pancreatic disease in individuals with MASLD was acute non-biliary pancreatitis (1.44 vs. 0.44 events/1000 PY), followed by chronic pancreatitis (0.54 vs. 0.12/1000 PY) and pancreatic cancer (0.88 vs. 0.47/1000 PY). We documented 130 versus 344 pancreas-related deaths among individuals with MASLD and their matched comparators, yielding an absolute risk difference of 0.51/1000 PY and an aHR of 2.41 (95%CI=1.95-2.97). The findings were consistent in sibling-controlled analyses with an aHR of 2.21 (95%CI=1.69-2.90). MASLD was associated with significantly higher rates of acute and chronic pancreatitis of predominantly non-biliary origin, as well as an increased risk of pancreatic cancer and pancreas-related mortality.

Risk factors for disease progression and clinical outcomes in patients with COVID-19 in Taiwan: a nationwide population-based cohort study

BackgroundSince 2021, COVID-19 has had a substantial impact on global health and continues to contribute to serious health outcomes. In Taiwan, most research has focused on hospitalized patients or mortality cases, leaving important gaps in understanding the broader effects of the disease and identifying individuals at high risk. This study aims to investigate the risk factors for disease progression through a nationwide population-based cohort study on COVID-19 in Taiwan.MethodsThis study included 15,056 patients diagnosed with COVID-19 between January 1, 2021, and December 31, 2021, using the Taiwan National Health Insurance Research Database. Baseline and clinical characteristics were collected to verify the association with progression to severity outcomes, including hospital admission, intensive care unit (ICU) admission, invasive ventilatory support, fatal outcome, and the composite outcome of these four events. Patients were observed for 30 days for disease progression. Multivariable logistic regression models were used to calculate odd ratios and 95% confidence intervals (CIs) for each outcome, adjusting for age, sex, region, risk factors, and vaccination status.ResultsOverall, 8,169 patients diagnosed during outpatient visits and 6,887 patients diagnosed during hospitalization were analyzed. Adjusting for age, sex, region, risk factors, and vaccination status, elderly patients had higher risks of hospital admission, ICU admission, invasive ventilatory support, fatal outcome, and composite outcome. Specifically, the risk of the fatal outcome was significantly higher for patients aged 75–84 (odds ratio: 6.11, 95% CI: 4.75–7.87) and those aged 85 years and older (12.70, 9.48–17.02). Patients with cardiovascular disease exhibited higher risks of hospital admission (1.60, 1.31–1.96), ICU admission (1.52, 1.31–1.78), invasive ventilatory support (1.57, 1.26–1.96), and fatal outcomes (1.26, 1.03–1.54) and the composite outcome (1.66, 1.20–1.54). Diabetes mellitus was identified as a significant risk factor for all clinical outcomes (hospital admission: 1.89, 1.53–2.35; ICU admission: 1.53, 1.30–1.79; invasive ventilatory support: 1.27, 1.01–1.60; the composite outcome: 1.45, 1.28–1.66), except for the fatal outcome.ConclusionsThis study indicated the impact of sex, age, and risk factors on the clinical outcomes of COVID-19 patients in Taiwan. Elderly patients and those with cardiovascular disease or diabetes mellitus had higher risks for severe outcomes, including hospitalization, ICU admission, invasive ventilatory support, and mortality. These findings can provide evidence for a better understanding of risk factors for disease progression and inform targeted intervention.

Proteinuria and the risk of Incident atrial fibrillation according to glycemic stages: a nationwide population-based cohort study

BackgroundDiabetes mellitus (DM) and proteinuria each independently raise the risk of atrial fibrillation (AF). We aimed to investigate the relationship between proteinuria and the risk of incident AF across glycemic stages.MethodsA cohort of 4,044,524 individuals without prior AF and type 1 DM was selected from the 2009 Korean National Health Insurance Service health checkup data. The individuals were categorized into five glycemic stages: normal, prediabetes, new-onset DM, early DM (< 5 years), and late DM (≥ 5 years). Proteinuria was graded using a urine dipstick test. The development of incident AF was tracked until 2023.ResultsOverall, the cohort (mean age 47 ± 14 years, 44.8% female) showed increasing annual AF incidence rates from 2.05 to 7.22 per 1000 person-years from normal to late DM (p < 0.001). Incidence rates increased from 2.46 to 8.18 per 1000 person-years with increasing proteinuria (p < 0.001). Adjusted Cox regression models revealed a heightened AF risk with higher proteinuria across all glycemic stages (adjusted hazard ratios for urine dipstick 3+/4+: 1.58, 1.64, 2.39, 2.12, and 2.53 for normal, prediabetes, new-onset DM, early DM, and late DM, respectively). The proteinuria-AF association was more pronounced in individuals with DM than in those without DM but was similar among the new-onset and established DM groups.ConclusionsProteinuria is an independent and significant risk factor for incident AF at all glycemic stages. The risk of incident AF in patients with DM can be stratified by measuring the level of proteinuria rather than comparing the duration of DM. Tailoring clinical strategies to proteinuria level could potentially mitigate this risk, improving patient outcomes.Graphical abstract

Skin cancer risk in over 200.000 patients with haematologic malignancies in 30 years; a nationwide population-based study in the Netherlands.

Patients with haematologic malignancies are at increased risk of developing skin cancer and often experience worse skin cancer-related outcomes. However, there is a lack of nationwide, population-based data with long-term follow-up on the incidence and risks of different skin cancer types across all haematologic malignancies. To assess population-based risk estimates for cutaneous squamous cell carcinoma (CSCC), malignant melanoma (MM), Merkel cell carcinoma (MCC), and basal cell carcinoma (BCC) among patients with haematologic malignancies, stratified by skin cancer type and haematologic malignancy subgroup. These estimates can serve as a base for surveillance guidelines and patient education. This nationwide population-based epidemiologic cohort study used data on 210,794 patients diagnosed with a haematologic malignancy between 1989 and 2020 from the Netherlands Cancer Registry (NCR). In addition, data on each type of histopathologically confirmed skin cancer per patient after haematologic malignancy diagnosis was retrieved from the NCR. Patients with a history of skin cancer prior to their haematologic malignancy were excluded. Cumulative incidences, standardized incidence ratio's (SIRs), and absolute excess risks for each of the four skin cancers were calculated and stratified by haematologic malignancy subgroup, age, sex, follow-up, and primary treatment. The overall 10-year cumulative incidence of developing a first skin cancer was 2.6% for CSCC, 0.5% for MM, 0.05% for MCC, and 4.8% for BCC. Compared to the general population, nearly all haematologic malignancy subgroups showed more than a twofold increased risk of CSCC, MM, MCC and BCC. Patients with chronic lymphocytic leukemia (CLL) showed the highest risks for each of the four skin cancers, with SIRs of 4.4 for CSCC, 2.7 for MM, 9.3 for MCC, and 2.6 for BCC. These elevated risks persisted for more than 30 years after haematologic malignancy diagnosis. Patients with all types of haematologic malignancies, and especially those with CLL, have a lifetime increased risk of developing different types of skin cancer. These findings highlight the importance of creating awareness among patients and care providers about this increased risk and promoting sun-protective measures and regular skin self-examinations in this high-risk population.

Risk of Lymph Node Metastasis in T2 Colon Cancer: A Nationwide Population-Based Cohort Study.

Similar to T1 colon cancer (CC), risk stratification may guide T2 CC treatment and reduce unnecessary major surgery. In this study, prediction models were developed that could identify T2 CC patients with a lower risk of lymph node metastasis (LNM) for whom (intensive) follow-up after local treatment could be considered. A nationwide cohort study was performed involving pT2 CC patients who underwent surgery between 2012 and 2020, using data from the Dutch ColoRectal Audit, which were linked to the Nationwide Pathology Databank. Four machine learning models were evaluated to predict LNM. LNMs were found in 1877/9803 patients (19.1%). Independent risk factors included (younger) age (odds ratio [OR] 0.98, 95% confidence interval [CI] 0.979-0.990), left-sided CC (OR 1.5, 95% CI 1.4-1.7), poor differentiation (OR 1.7, 95% CI 1.4-2.2), and lymphovascular invasion (LVI; OR 4.1, 95% CI 3.6-4.7). A deficient mismatch repair (MMR) status significantly lowered the risk of LNM (OR 0.3, 95% CI 0.2-0.5). The general linear model demonstrated the highest prediction accuracy, achieving area under the receiver operating characteristic curves of 0.67 and 0.68, with good calibration. In the absence of risk factors, elderly patients (≥74years of age) had a predicted risk of LNM of 10.7%, yet up to 30% experienced postoperative complications, with mortality rates reaching up to 3.5%. Patients with a deficient MMR status had a predicted risk of LNM of 6.1% if LVI was absent and the tumor was well-differentiated. The risk of LNM should be weighed against surgical risks. The findings of this study will enable clinicians to make more deliberate considerations about these competing risks before making a shared decision.

Job loss and reemployment of newly diagnosed people with epilepsy: A nationwide cohort study.

Epilepsy has negative socioeconomic impacts on those affected, resulting not only from actual disability but also from social stigma. However, longitudinal studies examining occupational consequences following an epilepsy diagnosis are limited. We aimed to investigate the occupational outcomes of newly diagnosed epilepsy among Korean employees. We conducted a nationwide population-based retrospective cohort study using the Korean National Health Insurance Service database. We included newly diagnosed people with epilepsy (PWE) aged 25 to 54 years, identified by diagnostic codes and antiseizure medication (ASM) prescriptions, who were employed at diagnosis between 2004 and 2018. The employment status of PWE was determined based on their enrollment in the employer-provided health insurance scheme. We analyzed the rates of job loss and reemployment, associated factors, and income changes following diagnosis. Among the 13 122 newly diagnosed PWE, the overall first-year job loss rate across the study period was 21.7%, which was 1.62-2.54 times higher than that of the general population for each year. The excesses of job loss among PWE in safe occupations were comparable to those in safety-sensitive occupations. Central nervous system illness (adjusted hazard ratio [aHR] = 1.12), psychiatric disease (aHR = 1.19), ≥2 emergency room visits or hospitalizations (aHR = 3.00), and ≥4 ASM attempts (aHR = 1.26) increased the risk of job loss. Among individuals who lost their job during the first year, 22.4% were reemployed within 1 year, with similar risk factors hindering reemployment. The income distribution of regained jobs showed a downward shift compared to previous jobs. Newly diagnosed PWE were at risk of job loss, irrespective of the occupational hazards related to seizures. Poor disease control and comorbidities partially contributed to unemployment. Alongside active seizure management, guidance for suitable occupations and the implementation of tailored restrictions based on occupational risk stratification are imperative to improve the job security of PWE.

Carbon monoxide poisoning is associated with increased risk of migraine in the long term: a nationwide population-based cohort study

ObjectiveCarbon monoxide poisoning can cause migraine-like attacks. However, the association between carbon monoxide poisoning and the risk of migraine has not been thoroughly studied. This study aimed to investigate the long-term risk of migraine in patients with carbon monoxide poisoning.MethodsThis nationwide, population-based cohort study was conducted using the administrative database of the National Health Insurance Service of Korea from 2002 to 2021. Patients with carbon monoxide poisoning with at least one visit documented according to the International Classification of Diseases, 10th Revision code T58 were included. Patients were only included if they had the same diagnostic code at two or more outpatient clinic visits. The primary outcome of this study was the incidence of migraine after carbon monoxide poisoning.ResultsThe overall risk of migraine was higher in the carbon monoxide poisoning group regardless of age, sex, or use of hyperbaric oxygen therapy (adjusted hazard ratio, 1.37; 95% confidence interval, 1.28–1.48). The carbon monoxide poisoning group had a persistently higher cumulative incidence of migraine during the observation period than the control group.ConclusionCarbon monoxide poisoning was associated with an increased overall risk of developing migraine during long-term follow-up.

DOP013 Risk of immune mediated inflammatory diseases associated with anti-TNFs and ustekinumab in Crohn’s disease: a nationwide population-based cohort study

Abstract Background Biologics have been variously associated with an increased risk of paradoxical immune mediated inflammatory diseases (IMIDs) in patients with Crohn’s disease (CD). While this risk has been assessed in cohort studies for tumor necrosis factor inhibitors (anti-TNF), only case reports have reported the paradoxical occurrence of IMIDs in patients treated with ustekinumab. The aim of this study was to assess the risk of an incident second IMID in patients with CD treated with anti-TNF and ustekinumab. Methods We identified individuals with CD and no other IMIDs switching after a first anti-TNF to either a second anti-TNF or ustekinumab based on the French administrative healthcare databases 2008-2022. The primary outcome was the occurrence of a second IMID, including inflammatory rheumatic diseases (rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, and polymyalgia rheumatica), skin diseases (psoriasis, hidradenitis suppurativa, and vitiligo), neurologic diseases (multiple sclerosis, myasthenia gravis), thyroiditis, connective tissue diseases, and vasculitis. Follow-up started from treatment switch until occurrence of a second IMID, treatment withdrawal, or December 31, 2022. A lag period of 3 months was considered to minimize protopathic bias. Hazard ratios for the risk of second IMID were calculated, following 1:1 propensity score (PS) weighting, in order to control for confounders including demographics, previous and baseline IBD disease activity, co-treatment exposure, and comorbidities. Results Among 13,994 CD patients included, 10,712 (76.5%) and 3,282 (23.5%) patients were exposed to a second anti-TNF and ustekinumab, respectively. The overall proportion of women was 59.6%. Mean age at cohort entry was 38.0 (SD, 13.8) and 41.6 years (SD, 14.8) in the anti-TNF and ustekinumab groups, respectively. The median follow-up was 5.7 years (IQR, 3.3-9.1). Overall, 578 incident second IMID occurred (incidence rates: 23.2 per 1000 PY, person-years), mainly consisting in psoriasis (350, 60.6%) and ankylosing spondylitis (117, 20.2%). The cumulative incidence of second IMID after 10 years of follow-up was 9.85% (confidence interval 95% [8.84-10.85]). All covariates included in the PS model were balanced with an absolute standardized difference lower than 0.1. The risk of second IMID was lower in patients exposed to ustekinumab compared to those exposed to a second anti-TNF (HR=0.63 CI 95%[0.48-0.81], p-value&amp;lt;0.001). Conclusion Based on a population-based and propensity score weighted cohort of 13,994 CD patients, exposure to ustekinumab was associated with a lower risk of second IMID compared to anti-TNF.

P0586 Nationwide population-based cohort study on the use and persistence of infliximab (IV and SC) in France: the Riposte IBD study

Abstract Background Subcutaneous infliximab (IFX-SC) is available in France since 2021. Beyond the pivotal trials, real-life data is needed. The aim of the RIPOSTE study is to evaluate the real-life use of IFX-SC in France at a nationwide level. Methods Patients affiliated to the French national health insurance with at least one IFX-SC or intravenous (IV) delivery between February 1, 2021, and December 31, 2022, were included, regardless of therapeutic indication. Three patient groups were defined: patients treated solely with IFX-IV (control group); patients who had received less than 3 infusions of IFX-IV before initiating IFX-SC (initiation group); patients who had received at least 3 infusions of IFX-IV before initiating IFX-SC (switch group). Patients were followed from the first IFX infusion until IFX discontinuation, initiation of another advanced therapy, death, or December 31, 2022. Discontinuation of infliximab was defined by a period of at least 3 months after the last day of estimated exposure without any new treatment delivery. Persistence of IFX-SC was assessed by the Kaplan-Meier method. Concomitant exposure of immunosuppressant (IS) and the occurrence of serious adverse events were also assessed. Results A total of 45664 patients received at least one IFX delivery (fig.1), 30842 treated solely with IFX-IV and 12480 patients treated with IFX-SC. Overall, 7467 (59.8%) and 2982 (23.9%) were diagnosed with Crohn’s disease (CD) and ulcerative colitis (UC), including 1449 (19%) and 664 (22%) in the initiation group, respectively. In the initiation group, 129 (8.9%) and 59 patients (9.2%) with CD and UC had not received IFX-IV at induction. The mean age at cohort entry was 40 years (SD, 14.49) in CD and 43 years (SD, 15.73) in UC, with 49% and 53% of men respectively. At 6 months, an IS was associated with IFX-SC in 39% of CD and 34% of UC patients in the initiation group compared to 16% and 17% of CD and UC patients in the switch group. Median patient follow-up for both diseases was 0.92 years, (Q1-Q3; 0.50-1.25). At 6 months, 84% of CD patients (CI [0.82-0.86]) and 80% (CI [0.76-0.83]) of UC patients were still on IFX-SC in the initiation group. Among patients in the switch group, persistence was 90% (CI [0.9-0.91]) for both CD and UC (CI [0.89-0.91]). Switch-back to IFX-IV in patients exposed to IFX-SC during follow-up occurred in 33 CD (2.3%) and 13 UC patients (2.0%) in the initiation group compared to 203 CD (3.4%) and 77 UC patients (3.3%) in the switch group. No new safety signals were identified (Table 1). Conclusion Based on a nationwide population-based cohort, over 80% of patients initiating IFX-SC and over 90% in maintenance with IFX-SC remained on treatment at 6 months. These data are consistent with previously published data.

The impact of regular physical activity on vertebral fractures: Korean nationwide population-based cohort study

BackgroundVertebral fractures are a common medical issue. Physical activity helps improve bone health and manage the risk of fractures. However, much controversy exists about the association between physical activity and vertebral fractures. Therefore, we aimed to investigate the association between changes in regular physical activity (RPA) and vertebral fractures.MethodsThis study was a nationwide, observational cohort study based on claim data from the Korean National Health Insurance Service. Physical activity level was obtained from self-reported questionnaires from 2009 to 2012. Participants were divided depending on their levels of physical activity and the occurrence of vertebral fractures from 2013 to 2016 was recorded.ResultsThe group with sufficient RPA, compared to the Insufficient group (incidence rate showed a decrease of 1.93/1,000 PY; adjusted HR (aHR): 0.83; 95% CI: 0.81–0.84), had a reduced risk of vertebral fracture. From the perspective of RPA changes, the Continuous Sufficient group had an aHR of 0.74, 95% CI 0.72–0.76, and the Increased group had an aHR of 0.87, 95% CI 0.85–0.88. The Decreased group had an aHR of 0.94, 95% CI 0.92–0.95.ConclusionThe degree of RPA could reduce the risk of vertebral fracture. Continuous sufficient RPA helped lower the risk of vertebral fracture.

P1199 Early life exposures predict childhood-onset IBD in a population-based cohort

Abstract Background While many early life exposures have been associated with IBD, prediction of risk based on these variables is not yet available. Therefore, we developed and validated a prediction model for IBD based on early life exposures. Methods We conducted a nationwide population-based cohort study leveraging cross-linked Danish registers consisting of all liveborn singleton offspring in the Danish National Birth Cohort with available data on early life exposures based on the first four DNBC interviews (weeks 12 and 30 of pregnancy, 6 months, and 18 months of offspring age), who were alive and residents of Denmark until at least 18 months of age. Follow up was until IBD diagnoses (based on primary and secondary diagnoses codes in the National Patient Register), emigration, death or end of the study period, September 1, 2022. We used elastic net with underlying Cox regression model to predict IBD diagnosis at ≤14 and &amp;gt;14 years of age. Results A total of 50,592 offspring were included in the study for a median (IQR) of 21.8 (20.4, 22.9) years. Of these, 310 (0.6%) persons were diagnosed with IBD during follow-up. Early life risk factors were predictive of IBD risk at ≤14 years of age but not later in life [Harrell’s C statistic (SE) 0.72 (0.018) and 0.52 (0.004), respectively]. All of the 74 variable terms considered for inclusion were included in the final model, with the five most important being parental IBD, number of infection episodes age 6-18 months, household mammal pets (protective), number of infection episodes age 0-6 months, and antibiotics exposure age 6-18 months. The cumulative incidence of IBD at age 14 years of age was 0.66% (95% CI 0.49-0.84) among those in the highest 5% for predicted risk, and 0.09 % (95% CI 0.075-0.01) for those in the lowest 95% (Figure). Conclusion In a nationwide cohort with long-term follow up data, early life exposures were predictive of childhood-onset IBD, but not later in life. This model warrants validation and could potentially be used to determine IBD risk in children towards prevention strategies.

P1204 Childhood EBV infection is protective against IBD, while adulthood EBV infection is not: a population-based cohort study

Abstract Background Emerging data indicate a role of Epstein Barr Virus (EBV) infection in immune-mediated diseases risk. However, its role in inflammatory bowel disease (IBD) risk remains to be elucidated. Methods We conducted a nationwide population-based cohort study leveraging cross-linked Danish registers consisting of individuals with a record of being tested for EBV between January 1, 2008 and August 31, 2020. We determined the impact of previous EBV infection, active IBV infection, and no EBV infection on IBD risk, based on EBV serological tests, using adjusted Cox proportional hazards regression analyses after adjusting for sex, type of test, year of test, and age at test. We also determined the impact of age at infection, categorized as early or late childhood or adulthood (0-12, 13-20, and ≥21 years, respectively). Results Of 20,386 individuals included in the study who were followed from the first EBV test for a median (IQR) of 3.93 (2.18-5.95) years, 250 developed IBD. In the overall analysis, there were null associations between prior or current EBV infection and IBD risk. In analyses stratified by age, EBV infection in early and late childhood were associated with a protective effect against IBD, although not statistically significant in the former group (aHR 0.81, 95% CI 0.40, 1.66 and 0.50, 95% CI 0.26, 0.95, respectively). This association was driven by an increase in the risk of Crohn’s disease (CD), but not ulcerative colitis (aHR 0.36, 95% CI 0.15, 0.87 and aHR 0.82, 95% CI 0.32, 2.11, respectively). Among adults, while EBV infection was not associated with IBD risk (aHR 2.17, 95% CI 0.71, 6.62), the effect estimate was in the opposite direction relative to that in childhood, suggesting a potentially increased risk. Conclusion In a nationwide cohort, childhood EBV infection was protective against CD. Adulthood EBV infection was not protective, and possibly associated with increased IBD risk, although this was not statistically significant. Validation studies will help elucidate further.

Comparison of Clinical Outcomes Between Two Types of Dipeptidyl Peptidase-4 Inhibitors in Posttransplant Diabetes Mellitus in Kidney Transplantation Recipients: A Nationwide Population-Based Cohort Study in Korea.

Dipeptidyl peptidase-4 inhibitors (DPP-4i) are antidiabetic drugs known for their minimal side effects and limited drug interaction witih immunosuppressants, making them suitable for patients with diabetes and kidney transplant recipients. However, there is limited real-world information regarding the use of DPP-4 inhibitors in patients with post transplant diabetes mellitus (PTDM). We performed a retrospective observational cohort study of 13,828 kidney transplant recipients form Janary 1, 2002, through December 21, 2018, using the Korean National Health Information Database. We extracted PTDM patients, and divided the patients into 2 groups baased on whether they received DPP4-inhibitor which needs dose adjustement (group A) or not (Group B) according to estimaged glomerular filtration rate. Out of 3154 patients who developed PTDM after transplantation, 738 patients prescribed DPP-4 inhibitors. Among these, 490 patients prescribed Group B DPP-4 inhibitors and 238 patients prescribed Group A DPP-4 inhibitors. Multivariate-adjusted Cox regression analysis showed that compared Group B, Group A DPP-4 inhibitors was associated with higher incidence rate of genital tract infection (hazard ratio (HR) 1.87, 95% Confidence Interval (CI) 1.18-2.99), and emergency department visit (HR 3.12, 95% CI 1.89-5.16). However, there was no significantly difference in death (any cause), admission, graft failure, infection, or hypoglycemia between the 2 groups. In patients with PTDM, some kinds of DPP-4 inhibitors, which need dose adjustment according to renal function, were associated with an increased rate of emergency department visit and genital tract infection.

The impact of weight change on suicide mortality: a nationwide population-based cohort study of 2 million Koreans

BackgroundPrevious studies have shown that weight change has a reverse J-shape association with all-cause mortality. However, its association with suicide mortality remains undetermined. In this study, we investigated the association between weight change and suicide mortality using a large-scale, population-based cohort from the Korean National Health Insurance Service database.MethodsA total of 2,103,525 subjects aged ≥ 20 years who underwent a general health screening program twice in the 2-year interval between 2007 and 2009 were included. Subjects were categorized into five groups according to the percent weight change during this period: severe weight loss (< − 15.0%), moderate weight loss (− 15.0 to < − 5.0%), weight stable (− 5.0 to < 5.0%), moderate weight gain (5.0 to < 15.0%), and severe weight gain (≥ 15.0%).ResultsDuring a median follow-up of 11.3 years, 6,179 cases (0.3%) of suicide mortality occurred. Weight change was associated with increased suicide mortality in a reverse J-shaped curve, even after adjustment for covariates. In particular, those with severe weight loss or gain showed 1.8-fold or 1.6-fold increased risk of suicide mortality, respectively. This reverse J-shaped association was consistently observed in subgroup analyses considering age, sex, depression, cancer, and BMI category.ConclusionsModerate to severe weight change within a 2-year interval is associated with increased risk of suicide mortality. To better understand the mechanisms through which weight change affects suicide mortality, studies incorporating information on weight change intentions, medications, weight change-related medical conditions are needed.

Periodontitis and the incidence of inflammatory bowel diseases: A nationwide population-based cohort study.

Periodontitis and other oral health indicators are reportedly related to systemic inflammation. Our study aimed to investigate a possible association of oral health status (periodontitis and number of missing teeth) and oral hygiene behaviors (frequency of tooth brushing, dental visit, and dental scaling) with the risk of inflammatory bowel disease (IBD) incidence. Utilizing the Korean National Health Insurance Database, we conducted a nationwide, population-based cohort study involving participants from the 2003 national health screening program. We followed these individuals until December 2020 or the occurrence of censoring events. Crohn's disease (CD) and ulcerative colitis (UC) were defined by disease classification codes from the International Classification of Diseases-10 and national codes for rare intractable disease. The occurrence of IBD was analyzed using the Cox proportional hazard model, with propensity score matching (PSM) performed to balance baseline characteristics between participants with and without periodontitis. Our analysis involved a total of 2,272,012 participants with a median follow-up period of 17.0 years. The incidence rates for CD and UC were 11.6 and 32.4 per 100,000 person-years, respectively. In multivariable analysis after PSM, the presence of periodontitis was associated with an increased risk of both CD (adjusted hazard ratio [aHR], 1.32, 95% confidence interval [CI], 1.14-1.52, p<0.001) and UC (aHR 1.21, 95% CI 1.10-1.32, p<0.001). Conversely, frequent tooth brushing ≥3 times a day was associated with a reduced risk of CD (aHR 0.81, 95% CI 0.65-0.99, p=0.049) but no significant association was observed with UC. Periodontitis may augment the risk of incidence for CD and UC. This association underscores the potential significance of periodontal health in the context of IBD, emphasizing the importance of comprehensive oral hygiene practices and potential preventive strategies to reduce the risk of CD and UC incidence.

Risk of Osteoporotic Fractures among Patients with Thyroid Cancer: A Nationwide Population-Based Cohort Study.

The associations between thyroid cancer and skeletal outcomes have not been thoroughly investigated. We aimed to investigate the risk of osteoporotic fractures in patients with thyroid cancer compared to that in a matched control group. This retrospective cohort study included 2,514 patients with thyroid cancer and 75,420 matched controls from the Korean National Health Insurance Service-National Sample Cohort (NHIS-NSC, 2006-2019). The rates of osteoporotic fractures were analyzed, and associations with the levothyroxine dose were evaluated. Patients with thyroid cancer had a significantly lower risk of fracture than did the control group (hazard ratio [HR], 0.81; 95% confidence interval [CI], 0.69 to 0.94; P=0.006). Patients diagnosed with thyroid cancer after the age of 50 years (older cancer group) had a significantly lower risk of fracture than did those in the control group (HR, 0.72; 95% CI, 0.6 to 0.85; P<0.001), especially those diagnosed with spinal fractures (HR, 0.66; 95% CI, 0.51 to 0.85; P=0.001). Patients in the older cancer group started osteoporosis treatment earlier than did those in the control group (65.5±7.5 years vs. 67.3±7.6 years, P<0.001). Additionally, a lower dose of levothyroxine was associated with a reduced risk of fractures. In the clinical setting, the risk of fracture in women diagnosed with thyroid cancer after the age of 50 years was lower than that in the control group, which was caused by more proactive osteoporosis treatment in postmenopausal women with thyroid cancer.

Impact of Uterine Leiomyomas on Cardiovascular Disease Risk in Young Reproductive-Aged Women: A Nationwide Population-Based Cohort Study.

Background/Objectives: Uterine leiomyomas are the most common benign gynecological tumors in women of reproductive age and are often associated with localized symptoms. However, emerging evidence suggests a link between uterine leiomyomas and systemic conditions such as cardiovascular disease (CVD), particularly myocardial infarction (MI) and ischemic stroke (IS). This study aimed to investigate the relationship between uterine leiomyomas and the risk of CVD events in young women aged 20-39 years using a large, nationwide, population-based cohort. Methods: This retrospective cohort study analyzed data from the National Health Insurance Service database of South Korea of 2,581,700 women aged 20-39 years who underwent health screening between 2009 and 2012. Uterine leiomyomas were identified using International Code of Disease, 10th Edition codes. CVD events (MI and IS) were defined according to hospital claims and radiological data. Multivariate hazard ratios (HRs) were calculated to evaluate the association between leiomyomas and CVD after adjusting for confounders (age, lifestyle factors, comorbidities, and body mass index). Results: In all, 58,812 were diagnosed with uterine leiomyomas, and 25,063 underwent surgical treatment. During the follow-up period, MI occurred in 115 women (0.21%) and IS in 82 women (0.15%) in the leiomyoma group, compared with 3107 cases of MI (0.12%) and 2240 cases of IS (0.09%) in the non-leiomyoma group. The leiomyoma group demonstrated a higher incidence rate of CVD (IR: 0.63 vs. 0.39 per 1000 person-years). After adjusting for confounding factors such as age, lifestyle, comorbidities, and body mass index (BMI), the hazard ratio (HR) for MI was 1.32, indicating a statistically significant increase in cardiovascular risk. The risk of CVD was lower in women who underwent surgical treatment; however, when specifically analyzing the occurrence of MI and IS, no statistically significant differences were observed between the two groups. Conclusions: Uterine leiomyomas are associated with an increased risk of MI and IS in young women. Surgical treatment itself may be associated with additional cardiovascular risks. Further research is needed to develop strategies to mitigate these risks and elucidate the underlying mechanisms.

Age did not affect the rate of subsequent hysterectomy following hysteroscopic surgery: A population-based retrospective cohort study from 2000 to 2020.

Previous studies found younger age was associated with an increased risk of hysterectomy after hysteroscopic surgeries (HS) due to abnormal uterine bleeding (AUB). The present study aimed to evaluate the effect of age on the incidence of hysterectomy after HS for treating AUB in Taiwan. This was a nationwide population-based retrospective cohort study which utilized the Taiwan National Health Insurance Database. The present study involved 4150 participants who underwent HS due to AUB. The study focused on females aged ≥40 years diagnosed with AUB who underwent HS between 2000 and 2020. Hysterectomy outcomes were analyzed using the Cox proportional hazards model, and age was categorized into three groups (40-44, 45-49, and 50-55 years). Statistical significance was set at P < 0.05. This study involved 4150 participants with an average age of 46.1 years, categorized into the following age groups: 40-44 years (39.6%), 45-49 years (38.8%), and 50-55 years (21.6%). Approximately 8.1% of participants required hysterectomy treatment; the highest incidence was observed in the 40-44-year age group (8.6%). The median time from HS to hysterectomy varied across age groups, ranging from 0.25-2.78 years. The presence of uterine myoma (adjusted hazard ration [aHR]: 2.11; 95% CI: 1.70-2.64; P < 0.0001) and adenomyosis (aHR: 10.24; 95% CI: 8.17-12.85; P < 0.0001) significantly increased the risk of hysterectomy. Kaplan-Meier survival curves demonstrated a comparable likelihood of hysterectomy across age groups within 5 years post-HS, with most occurrences occurring in the initial 5 years. Our study found no age effect on subsequent hysterectomy after HS. This study contributes to a significant understanding of HS outcomes, aiding information for patients seeking AUB surgical options.