Nationwide Population-based Cohort Study Research Articles

Social characteristics and social benefit use among premenopausal breast cancer survivors in Denmark: a population-based cohort study.

In 2020, one million women aged < 55years were diagnosed with breast cancer globally. The impact of breast cancer and its treatments on these women's ability to work and need for social benefits may differ by social characteristics. We evaluated social benefit use following breast cancer by education and cohabitation. We conducted a nationwide population-based cohort study, including women aged 18-55years diagnosed with stage I-III breast cancer in Denmark during 2002-2011. Statistics Denmark provided information on cohabitation, education, and social benefit use from 1year pre-diagnosis to 10years post-diagnosis. We calculated weekly proportions ofself-support, unemployment, disability pension, flexi jobs, and sick leave according to education and cohabitation. Of 5345 women, 81.8% were self-supporting, 4.5% received disability pensions, 1.6% had flexi jobs, 3.6% were on sick leave, and 5.5% were unemployed 1 yearpre-diagnosis. Ten years post-diagnosis, the proportions were 69.0%, 13.0%, 10.5%, 3.4%, and 2.0% of 3663 survivors. Disability pensions and flexi jobs increased from 12.1 to 26.4% and 2.8 to 13.5% in women with short education, from 4.1 to 12.8% and 1.8 to 12.2% in women with medium education, and from 0.8 to 6.0% and 0.9 to 6.9% in longer educated. Disability pensions increased more in women living alone (7.8 to 19.9%), than in cohabiting women (3.6 to 11.3%). Use of social benefits reflecting lost ability to work was highest in less educated women and in women living alone. Awareness of these groups is crucial when tailoring efforts to support work participation in cancer survivors.

Reactivation of Varicella-Zoster Virus in Patients with Lung Cancer Receiving Immune Checkpoint Inhibitors: Retrospective Nationwide Population-Based Cohort Study from South Korea.

This study aimed to determine the association between immune checkpoint inhibitors (ICIs) and the risk of herpes zoster (HZ) incidence in patients with lung cancer. We obtained national claims data of 51,021 patients from South Korea with lung cancer between August 2017 and December 2021. The study population was classified into ICI and non-ICI groups based on the prescription of ICIs at least once during the study period. To estimate the effects of ICIs treatment compared with those without ICIs treatment on HZ incidence, we used the Cox proportional hazards model adjusted for sex, age, comorbidities, and concomitant use of immunosuppressive drugs. Stratified analyses based on sex, age, and comorbidities were conducted to identify corresponding risk factors. Of the 51,021 study participants, 897 (1.8%) were prescribed ICIs and 2262 (4.4%) were diagnosed with HZ. Approximately 75.6% of the patients receiving ICIs were male, and the prevalence of diabetes, cardiovascular disease, and chronic lung disease in the ICI group was significantly lower than that in the non-ICIs group. The Kaplan-Meier plot showed that the probability of incidence of HZ in the ICIs group was lower than that in the non-ICIs group. Additionally, treatment with ICIs was associated with a 31% lower incidence of developing HZ when compared to that seen without ICIs treatment (95% confidence interval [CI], 0.48-1.00). This association was stronger in females (hazard ratio [HR], 0.42; 95% CI, 0.19-0.94) and those less than 68 years of age (HR, 0.58; 95% CI, 0.34-0.99). In these real-world data from an Asian population with lung cancer, ICIs treatment might be associated with a reduced risk of HZ compared to that without ICIs treatment.

Farming activities and risk of inflammatory bowel disease: a French nationwide population-based cohort study.

Epidemiological data regarding inflammatory bowel disease (IBD) are lacking, in particular for occupationally exposed populations. We investigated whether, among the entire French farm manager (FM) workforce, certain agricultural activities are more strongly associated with IBD than others. Nationwide population-based insurance claims and electronic health records from all FMs that worked at least once over the period 2002-2016 were used (n=1088561, 69% males). The outcome measure was the association between 26 farming activities and the risk of IBD, Crohn's disease (CD), and ulcerative colitis (UC), measured as hazard ratios (HRs), after adjusting for age, sex, pre-existing medical comorbidities, and farm location. The time to first chronic disease declaration was used as the underlying timescale. A model was generated for every activity and disease, utilizing a reference group comprising all FMs who abstained from the specified activity from 2002 to 2016. There were 1752 IBD cases, with 704 CD (40.2%) and 1048 UC (59.8%) cases, respectively. Elevated HRs were observed for fruit arboriculture (HR from 1.17 to 1.52) and dairy farming (HR from 1.22 to 1.46) for all IBD, in crop farming for CD only (HR=1.26 [95CI%: 1.06-1.49]), and in shellfish farming (HR from 2.12 to 2.51) for both CD and IBD. Further research regarding specific farming activities and exposures likely to modify the microbiota (e.g., pesticides, pathogens) is required to identify potential occupational risk factors (agricultural exposome) for IBD. Exposure to Mycobacterium avium subspecies paratuberculosis, cryptosporidium, environmental toxins, micro/nanoplastics, and pesticides represents promising research avenues.

Increased risk of psychiatric disorder in patients with hearing loss: a nationwide population-based cohort study

BackgroundHearing loss has been shown to be a risk factor for psychiatric disorders. In addition, long-term hearing loss is associated with increased hospitalization and mortality rates; however, the increased risk and duration of effect of hearing loss in combination with other chronic diseases on each psychiatric disorder are still not clearly defined. The purpose of this article is to clarify the risk of hearing loss for each disorder over time.MethodsThis was a retrospective cohort study, and a national health insurance research database in Taiwan was utilized. All (n = 1,949,101) Taiwanese residents who had a medical visit between 2000 and 2015 were included. Patients with hearing loss and a comparative retrospective cohort were analyzed. Every subject was tracked individually from their index date to identify the subjects who later received a diagnosis of a psychiatric disorder. The Kaplan‒Meier method was used to analyze the cumulative incidence of psychiatric disorders. Cox regression analysis was performed to identify the risk of psychiatric disorders.ResultsA total of 13,341 (15.42%) and 31,250 (9.03%) patients with and without hearing loss, respectively, were diagnosed with psychiatric disorders (P < 0.001). Multivariate analysis indicated that hearing loss significantly elevated the risk of psychiatric disorders (adjusted HR = 2.587, 95% CI 1.723–3.346, p < 0.001).ConclusionOur findings indicate that patients with hearing loss are more likely to develop psychiatric disorders. Furthermore, the various psychiatric disorders are more likely to occur at different times. Our findings have important clinical implications, including a need for clinicians to implement early intervention for hearing loss and to pay close attention to patients’ psychological status.Trial registration TSGHIRB No. E202216036.

Atrial fibrillation: age at diagnosis, incident cardiovascular events, and mortality.

Patients with atrial fibrillation (AF) are at increased risks of cardiovascular diseases and mortality, but risks according to age at diagnosis have not been reported. This study investigated age-specific risks of outcomes among patients with AF and the background population. This nationwide population-based cohort study included patients with AF and controls without outcomes by the application of exposure density matching on the basis of sex, year of birth, and index date. The absolute risks and hazard rates were stratified by age groups and assessed using competing risk survival analyses and Cox regression models, respectively. The expected differences in residual life years among participants were estimated. The study included 216 579 AF patients from year 2000 to 2020 and 866 316 controls. The mean follow-up time was 7.9 years. Comparing AF patients with matched controls, the hazard ratios among individuals ≤50 years was 8.90 [95% confidence interval (CI), 7.17-11.0] for cardiomyopathy, 8.64 (95% CI, 7.74-9.64) for heart failure, 2.18 (95% CI, 1.89-2.52) for ischaemic stroke, and 2.74 (95% CI, 2.53-2.96) for mortality. The expected average loss of life years among individuals ≤50 years was 9.2 years (95% CI, 9.0-9.3) years. The estimates decreased with older age. The findings show that earlier diagnosis of AF is associated with a higher hazard ratio of subsequent myocardial disease and shorter life expectancy. Further studies are needed to determine causality and whether AF could be used as a risk marker among particularly younger patients.

Thiazide-associated hyponatremia in arterial hypertension patients: A nationwide population-based cohort study.

Thiazides are the first-line treatment for hypertension, however, they have been associated with hospitalizations for thiazide-associated hyponatremia (TAH). The aim of this study was to evaluate the risk of TAH and other drug-associated hyponatremia in a Korean population. The study used big data from the National Health Insurance Sharing Service of 1,943,345 adults treated for hypertension from January 2014 to December 2016. The participants were divided into two groups based on the use of thiazides. Cox proportional hazard models were used to identify independent risk factors for the occurrence of hyponatremia. The study found that hyponatremia-related hospitalizations were significantly higher in the thiazide group than the control group (2.19%vs. 1.45%). The risk increased further with concurrent use of other diuretics or desmopressin, and thiazide+spironolactone+desmopressin and hospitalization risk further increased (4.0 and 6.9 times). Multivariate analysis showed that hyponatremia occurrence increased with age, diabetes mellitus, depression, and thiazide use (hazard ratio=1.436, p<0.001). The thiazide group had better 6-year overall survival than the control group but had more fractures and hyponatremia. Thiazide use is associated with an increased risk of hyponatremia and related complications. However, the mortality rate decreased in those who received thiazides, suggesting that thiazide use itself is not harmful and may help decrease complications and improve prognosis with proper, cautious use in high-risk patients.

Prior Appendectomy Is Associated With a Milder Clinical Course in Crohn's Disease: A Nationwide Population-based Cohort Study.

Appendectomy may affect the clinical course of Crohn's disease (CD), but rigorous evidence is sparse and contradicting. The aim of this study was to examine the association between appendectomy and the clinical course of CD. All patients diagnosed with CD in Denmark in the period from 1977 to 2017 were identified from the Danish National Patient Registry. Patients with appendectomy were matched with up to 10 comparators with CD and no appendectomy; and rates of CD-related hospital admissions were compared between CD patients with and without appendectomy using incidence rate ratios (IRRs). We used stratified Cox regression analysis to calculate adjusted hazard ratios (aHRs) of initiating treatment with biologics or undergoing intestinal resections. In all, 21 189 CD patients (1936 with appendectomy and 19 253 without) were identified and followed for a median of 13.6 years. Crohn'sdisease patients who had undergone appendectomy experienced a lower rate of CD-related hospital admissions (appendectomy before CD: IRR = 0.83; 95% confidence interval [CI], 0.81-0.85; appendectomy after CD:IRR = 0.85; 95% CI, 0.81-0.88) compared with CD patients without appendectomy. For patients with appendectomy before CD diagnosis, the rate of initiating biologics was lower compared with CD patients with no appendectomy (aHR1-<5 years = 0.61; 95% CI, 0.46-0.81; aHR5-<10 years 0.47; 95% CI, 0.33-0.66; aHR10-20 years = 0.61; 95% CI, 0.47-0.79), as was the risk of undergoing colorectal resections (aHR1-<5 years = 0.94; 95% CI, 0.77-1.15; aHR5-<10 years 0.63; 95% CI, 0.47-0.85; aHR10-20 years = 0.75; 95% CI, 0.54-1.04). Rates of small bowel resections were comparable for CD patients with or without appendectomy prior to CD. Appendectomy performed after CD did not influence the rate of initiating treatment with biologics or undergoing intestinal resections. The clinical course of CD is milder for those who have previously undergone appendectomy.

Maternal human papillomavirus infection and the risk of congenital malformations: A nationwide population-based cohort study.

Previous research has explored theories regarding the vertical transmission of human papillomavirus (HPV) infection and its association with adverse pregnancy and perinatal outcomes. However, the impact of maternal HPV infection on congenital anomalies (CAs) in offspring remains relatively understudied. We conducted a population-based cohort study linking the Taiwan Birth Registry, Taiwan Death Registry, and National Health Insurance Research Database, in which newborns born in Taiwan between 2009 and 2015 were included. We established a maternal HPV infection cohort comprising 37 807 newborns and matched them with a comparison group of 151 228 newborns at a 1:4 ratio based on index year, age, and sex. The study examined a composite outcome and subgroups of different types of congenital malformations. Differences in cumulative incidence of CAs were assessed using Kaplan-Meier curves and log-rank tests. Adjusted hazard ratios (aHRs) were estimated using Cox proportional hazard regressions. No significant association was found between HPV infection and the broad spectrum of CAs (aHR: 1.04, 95% confidence interval [CI]: 0.98-1.10; log-rank test p = 0.14). However, we observed a 19% increased risk of musculoskeletal CAs in the maternal HPV infection group (aHR: 1.19; 95% CI: 1.05-1.34) compared to those without maternal HPV exposure. Other factors, including the type of HPV (aHR: 0.65; 95% CI: 0.16-2.63), the timing of exposure (during or before pregnancy), and maternal age (aHR for <30 years: 1.02, 95% CI: 0.94-1.1; aHR for 30-39 years: 1.05, 95% CI: 0.99-1.11; aHR for ≥40 years: 0.88, 95% CI: 0.67-1.17), did not significantly affect the risk for any CA. In conclusion, gestation detection of HPV infection was associated with musculoskeletal CAs but not other major CAs. Prospective studies are warranted to elucidate the necessity of prenatal screening in populations at risk.

Iron Metabolic Biomarkers and the Mortality Risk in the General Population: A Nationwide Population-Based Cohort Study.

Iron is an essential element in the human body and plays a critical role in many physiological and cellular processes. However, the association between iron status and the risk of all-cause or cause-specific mortality has not been well-investigated. And it is unclear whether the association between iron metabolic biomarkers and the risk of mortality differs between people with and without diabetes mellitus (DM). This work aimed to investigate associations between iron metabolic biomarkers and all-cause and cause-specific mortality risk in the general population, and heterogeneities in the associations among population with and without DM.. A total of 29 166 adults from the National Health and Nutrition Examination Survey (NHANES) III and NHANES 1999 to 2010 were included, with linkage to the National Death Index to December 31, 2019. Cox proportional-hazard models and Fine-Gray subdistribution hazard models were used to estimate associations between iron metabolic biomarkers and outcomes. During a median follow-up of 18.83 years, 9378 deaths were observed, including 3420 cardiovascular disease (CVD) deaths and 1969 cancer deaths. A significant linear association between serum ferritin (SF) and all-cause mortality was observed among the overall population and those without DM. J-shaped associations between transferrin saturation (TSAT) and all-cause and CVD mortality were observed among all populations. In the overall population, compared to the first quartile (Q1) group, the adjusted hazard ratio (HR) (95% CI) for all-cause mortality was 1.07 (1.00-1.15), 1.05 (0.98-1.12), 1.13 (1.05-1.21) in Q2, Q3, and Q4 groups for SF, while the HR was 0.94 (0.88-0.99), 0.92 (0.86-0.97), and 0.93 (0.88-0.99) for TSAT. In individuals without DM, the adjusted HR of the Q4 of SF were 1.19 (1.03-1.37) for CVD mortality and 1.25 (1.05-1.48) for cancer mortality. In individuals with DM, the adjusted HRs of the Q4 of TSAT were 0.76 (0.62-0.93) for CVD mortality and 1.47 (1.07-2.03) for cancer mortality. Iron metabolism abnormalities increase mortality risk in the general population. The associations of iron status with mortality were significantly different between individuals with and without DM, which indicated tailored strategies for iron homeostasis are needed.

Longitudinal BMI change and outcomes in Chronic Obstructive Pulmonary Disease: a nationwide population-based cohort study

BackgroundThe association between longitudinal body mass index (BMI) change and clinical outcomes in patients with chronic obstructive pulmonary disease (COPD) has not fully investigated.MethodsThis retrospective cohort study included 116,463 COPD patients aged ≥ 40, with at least two health examinations, one within 2 years before and another within 3 years after COPD diagnosis (January 1, 2014, to December 31, 2019). Associations between BMI percentage change with all-cause mortality, primary endpoint, and initial severe exacerbation were assessed.ResultsBMI decreased > 5% in 14,728 (12.6%), while maintained in 80,689 (69.2%), and increased > 5% in 21,046 (18.1%) after COPD diagnosis. Compared to maintenance group, adjusted hazard ratio (aHR) for all-cause mortality was 1.70 in BMI decrease group (95% CI:1.61, 1.79) and 1.13 in BMI increase group (95% CI:1.07, 1.20). In subgroup analysis, decrease in BMI showed a stronger effect on mortality as baseline BMI was lower, while an increase in BMI was related to an increase in mortality only in obese COPD patients with aHRs of 1.18 (95% CI: 1.03, 1.36). The aHRs for the risk of severe exacerbation (BMI decrease group and increase group vs. maintenance group) were 1.30 (95% CI:1.24, 1.35) and 1.12 (95% CI:1.07, 1.16), respectively.ConclusionsA decrease in BMI was associated with an increased risk of all-cause mortality in a dose-dependent manner in patients with COPD. This was most significant in underweight patients. Regular monitoring for weight loss might be an important component for COPD management.

Mitral Valve Repair vs. Replacement by Different Etiologies - A Nationwide Population-Based Cohort Study.

When mitral valve (MV) surgery is indicated, repair is preferred over replacement; however, this preference is not supported by evidence from clinical trials. Furthermore, the benefits of MV repair may not be universal for all etiologies of MV disease.Methods and Results: This study identified a total of 18,428 patients who underwent MV repair (n=4,817) or MV replacement (n=13,611) during 2001-2018 from Taiwan's National Health Insurance Research Database. These patients were classified into 4 etiologies: infective endocarditis (IE, n=2,678), rheumatic heart disease (RHD, n=4,524), ischemic mitral regurgitation (IMR, n=3,893), and degenerative mitral regurgitation (DMR, n=7,333). After propensity matching, all-cause mortality during follow-up was lower among patients receiving MV repair than among patients receiving MV replacement in the IE, IMR, and DMR groups (hazard ratio [HR]=0.72, 95% confidence interval [CI]: 0.55-0.93; HR=0.82, 95% CI: 0.73-0.92; and HR 0.73, 95% CI: 0.64-0.84, respectively). However, in the RHD group, the MV reoperation rate was higher after MV repair than after MV replacement (subdistribution HR=1.91, 95% CI: 1.02-3.55). In comparison with MV replacement, MV repair was associated with a lower late mortality in patients with IE, IMR, and DMR, and a higher risk of reoperation in patients with RHD.

Abstract 4865: Income dynamics and the risk of hepatocellular carcinoma in individuals with type 2 diabetes: A nationwide population-based cohort study

Abstract Introduction: Type 2 diabetes (T2D) is associated with over 2 times increased risk of hepatocellular carcinoma (HCC). Low-income status is associated with a higher risk of developing HCC, more advanced stage, and mortality. Evidence is limited on whether income dynamics are associated with the risk of developing HCC in individuals with T2D who are susceptible to income changes. We examined whether income levels and income changes are associated with HCC risk. Methods: Using representative data from the Korean National Health Insurance Service (NHIS), 2,227,893 adults with T2D (aged ≥ 20 years) without a cancer history were included between 2015-2016. Income levels were measured based on health insurance premiums and categorized into 4 levels (quartiles [Q], 1 [low income], to 4 [high income]). These quartiles excluded the very low-income individuals who qualified as Medical Aids beneficiaries (MAB), which comprised a 5th income category. To identify income change, income levels were collected annually from the baseline year backward 4 years. The incident HCC, defined based on ICD-10 codes and special reimbursement codes, was identified until December 2020. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated to assess the association between income parameters and HCC after adjusting for sociodemographic factors, comorbidities, and diabetes duration and treatment. Income parameters included 1) the baseline income status, 2) the cumulative number of years being in each income level, and 3) changes in income level between the two time points (4 years ago vs. baseline). Results: During follow-up (median, 3.9 years), 9,887 HCC cases developed. Individuals who had experienced at least one episode of MAB during the five years showed a significantly higher HCC risk than those who had never qualified as MAB (HRs ranging from 1.52 to 2.01). In contrast, individuals who had experienced high-income status (Q4) during the five years had a lower HCC risk than those who had never experienced (HRs ranging from 0.79 to 0.92; HRn=5 years vs. n=0 years 0.79, 95% CI 0.75-0.83; P for trend &amp;lt;0.05). Individuals in the low-income status (MAB-Q1) at the first assessment (4 years ago) but experienced increased income had a reduced risk of HCC, which linearly declined with increasing income rise. Also, those who experienced a substantial increase in income up to the top quartile (Q4) had the lowest HCC risk (HR 0.73, 95% CI 0.60-0.88; P for trend&amp;lt;0.05) than those who maintained the low-income status. Conclusions: Experiencing any very low- or high-income state was independently associated with increased or decreased HCC risk. Improved income levels among those in the low-income status had an inverse linear association with reduced HCC risk. Our findings underline the need for increased public policy awareness of the impact of income dynamics on HCC risk in adults with T2D. Citation Format: Jongha Baek, Benjamin C. Amick III, Clare C. Brown, Mario Schootman, Marie-Rachelle Narcisse, Seung-Hyun Ko, Pearl A. McElfish, Michael R. Thomsen, Seong-Su Lee, Kyungdo Han, Yong-Moon Mark Park. Income dynamics and the risk of hepatocellular carcinoma in individuals with type 2 diabetes: A nationwide population-based cohort study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4865.

Spondyloarthritis in first-degree relatives and spouses of patients with inflammatory bowel disease: A nationwide population-based cohort study from Sweden.

Register-based research suggests a shared pathophysiology between inflammatory bowel disease [IBD] and spondyloarthritis [SpA], but the role of familial [genetic and environmental] factors in this shared susceptibility is largely unknown. We compared the risk of SpA in first-degree relatives [FDRs] and spouses of IBD patients with FDRs and spouses of matched population-based reference individuals. We identified 147,080 FDRs and 25,945 spouses of patients with incident IBD [N=39,203] during 2006-2016 and 1,453,429 FDRs and 258,098 spouses of matched reference individuals [N=390,490], by linking nationwide Swedish registers and gastrointestinal biopsy data. Study participants were followed 1987-2017. Cox regression was used to estimate hazard ratios [HRs] of SpA. During follow-up, 2,430 FDRs of IBD patients [6.5/10,000 person-years] and 17,761 FDRs of reference individuals [4.8/10,000 person-years] were diagnosed with SpA, corresponding to an HR of 1.35 [95%CI:1.29,1.41]. In subgroup analyses, the increased risk of SpA was most pronounced in FDRs of Crohn's disease patients [HR=1.44; 95%CI:1.34,1.56] and of IBD patients aged <18 years at diagnosis [HR=1.46; 95%CI: 1.27,1.68]. IBD patient's spouses also had a higher SpA rate than reference individuals' spouses, but the difference was less pronounced [4.3 vs. 3.5/10,000 person-years; HR=1.22; 95%CI:1.09,1.37]. No subgroup-specific risk pattern was identified among spouses. The observed shared familial risks between IBD and SpA support shared genetic factors in their pathogenesis. However, spouses of IBD patients were also at increased risk for SpA, reflecting the influence of environmental exposures or similarities in health-seeking patterns.

Osteoporosis Is Associated with an Increased Risk of Colorectal Neoplasms Regardless of Sex: Nationwide Population-Based Cohort Study.

Vitamin D may have anticancer effects against colorectal cancer (CRC). Bone mineral density (BMD) reflects the long-term vitamin D status. This study investigated the association between osteoporosis and colorectal neoplasms (CRN). The data were obtained from the National Health Insurance Service sample cohort, which included 60,386 osteoporosis patients and 8224 controls who underwent BMD in 2002-2019. The logistic regression models included age, sex, income level, and comorbidity. Sensitivity tests were performed using the data from the National Health Screening Program. In total, 7706 (11.2%) patients were diagnosed with CRN, and the proportion was significantly higher in osteoporosis patients than in controls (11.7% vs. 8.1%). In the multivariate analysis, osteoporosis was associated with an increased risk of CRN (odds ratio (OR) = 1.91, 95% confidence interval = 1.75-2.09, p < 0.0001), which was significant for both colorectal adenomas and CRC (OR = 1.88 and 1.83, respectively). A subgroup analysis by sex revealed a significant association between osteoporosis and CRN in both women and men (OR = 2.06 and 1.66, respectively). The sensitivity tests revealed results similar to those of the original dataset. In conclusion, osteoporosis is significantly associated with CRN risk in both sexes. In high-risk patients with low BMD, appropriate screening for CRN and vitamin D supplementation are required, regardless of sex.

Antibiotic exposure during pregnancy increases risk for childhood atopic diseases: a nationwide cohort study

PurposeThe prevalence of atopic diseases has increased in recent decades. A possible link between antibiotic use during pregnancy and childhood atopic disease has been proposed. The aim of this study is to explore the association of antibiotic exposure during pregnancy with childhood atopic diseases from a nationwide, population-based perspective.MethodsThis was a nationwide population-based cohort study. Taiwan’s National Health Insurance Research Database was the main source of data. The pairing of mothers and children was achieved by linking the NHIRD with the Taiwan Maternal and Child Health Database. This study enrolled the first-time pregnancies from 2004 to 2010. Infants of multiple delivery, preterm delivery, and death before 5 years old were excluded. All participants were followed up at least for 5 years. Antenatal antibiotics prescribed to mothers during the pregnancy period were reviewed. Children with more than two outpatient visits, or one admission, with a main diagnosis of asthma, allergic rhinitis, or atopic dermatitis were regarded as having an atopic disease.ResultsA total of 900,584 children were enrolled in this study. The adjusted hazard ratios of antibiotic exposure during pregnancy to childhood atopic diseases were 1.12 for atopic dermatitis, 1.06 for asthma, and 1.08 for allergic rhinitis, all of which reached statistical significance. The trimester effect was not significant. There was a trend showing the higher the number of times a child was prenatally exposed to antibiotics, the higher the hazard ratio was for childhood atopic diseases.ConclusionsPrenatal antibiotic exposure might increase the risk of childhood atopic diseases in a dose-dependent manner.

Impact of smoking reduction on lung cancer risk in patients with COPD who smoked fewer than 30 pack-years: a nationwide population-based cohort study

BackgroundThe effects of smoking reduction on the incidence of lung cancer in patients with chronic obstructive pulmonary disease (COPD) are not well known. This study aimed to investigate the effects of changes in smoking habits after COPD diagnosis on lung cancer development in patients who smoked less than 30 pack-years.MethodsThis nationwide retrospective cohort study included 16,832 patients with COPD who smoked less than 30 pack-years at the time of COPD diagnosis. Based on changes in smoking habits in the health screening examination data, smokers were categorized into three groups: quitters, reducers, and sustainers. The primary outcome was the risk of lung cancer development, which was estimated using the Cox proportional hazards model. We also modelled the amount of smoking reduction as a continuous variable.ResultsDuring a median follow-up of 4 years, the cumulative incidence of lung cancer was the highest among sustainers, followed by reducers and quitters. Compared with sustainers, reducers (adjusted HR 0.74, 95% CI:0.56–0.98) and quitters (adjusted HR 0.78, 95% CI:0.64–0.96) had a significantly lower risk of lung cancer. Incidence of lung cancer showed a decreasing trend with a decreasing amount of smoking (P for linearity < 0.01).ConclusionsIn patients with COPD who smoked less than 30 pack-years, smoking reduction and cessation lowered the risk of lung cancer.

Postoperative Bisphosphonates Use is Associated with Reduced Adverse Outcomes After Primary Total Joint Arthroplasty of Hip and Knee: A Nationwide Population-Based Cohort Study.

Bisphosphonates have been associated with a decreased risk of revision surgery after total joint arthroplasty of the hip or knee (TJA) because of their effects on decreased periprosthetic bone loss and prosthetic migration. However, the results in the early literature are inconsistent, and the influence of bisphosphonates on associated complications and subsequent TJA remains unknown. This study investigated the association between the use of bisphosphonates and the risk of adverse outcomes after primary TJA. This matched cohort study utilized the National Health Insurance Research Database in Taiwan to identify patients who underwent primary TJA over a 15-year period (January 2000-December 2015 inclusive). Study participants were further categorized into two groups, bisphosphonate users and nonusers, using propensity score matching. The Kaplan-Meier curve analysis and adjusted hazard ratios (aHRs) of revision surgery, adverse outcomes of primary surgery and subsequent TJA were calculated using Cox regression analysis. This study analyzed data from 6485 patients who underwent total hip arthroplasty (THA) and 20,920 patients who underwent total knee arthroplasty (TKA). The risk of revision hip and knee arthroplasty was significantly lower in the bisphosphonate users than in the nonusers (aHR, 0.54 and 0.53, respectively). Furthermore, the risk of a subsequent total joint arthroplasty, adverse events and all-cause mortality were also significantly reduced in the bisphosphonate users. This study, involving a large cohort of patients who underwent primary arthroplasties, revealed that bisphosphonate treatment may potentially reduce the risk of revision surgery and associated adverse outcomes. Furthermore, the use of bisphosphonates after TJA is also associated with a reduced need for subsequent arthroplasty.Research Registration Unique Identifying Number (UIN): ClinicalTrials.gov Identifier-NCT05623540 ( https://clinicaltrials.gov/show/NCT05623540 ).

Relationship between menopausal hormone therapy and breast cancer: A nationwide population-based cohort study.

To explore the risk of breast cancer associated with menopausal hormone therapy (MHT), including the various progestogens used today. The study included postmenopausal women over 40 years from the National Health Insurance Database in South Korea (2011-2014) who either used MHT for over 6 months (MHT group) or never used MHT (non-MHT group) and were matched 1:1 based on several variables using propensity score matching. Both groups were followed until 2020. The non-MHT and MHT groups comprised 153 736 women each. In Cox proportional hazard analysis with time-dependent covariates, MHT was associated with an increased risk of breast cancer (hazard ratio [HR] 1.22, 95% confidence interval [CI] 1.15-1.3). Tibolone, estradiol valerate (EV)/medroxyprogesterone acetate (MPA), EV/norethisterone acetate (NETA), conjugated equine estrogen (CEE), EV, estradiol hemihydrate (EH), CEE/micronized progesterone (MP), CEE/MPA, EV/MP, EV/MPA, and EH/MP did not increase the risk of breast cancer compared with the non-MHT group. However, EH/drospirenone (DRSP) (HR 1.51, 95% CI 1.38-1.66), EH/NETA (HR 1.66, 95% CI 1.34-2.06), EH/dydrogesterone (DYD) (HR 1.37, 95% CI 1.12-1.68), and EV/cyproterone acetate (CPA) (HR 1.74, 95% CI 1.54-1.96) increased the risk of breast cancer compared with the non-MHT group. MHT was linked to increased breast cancer risk, but not all MHTs. Specific combined therapies (EH/DRSP, EH/DYD, EH/NETA, and EV/CPA) were associated with higher risk, whereas estrogen alone and tibolone were not.

Birth cohort effects on diagnosed atrial fibrillation incidence: nationwide cohort study from 1980 to 2018

BackgroundThe incidence of atrial fibrillation (AF) shows substantial temporal trends, but the contribution of birth cohort effects is unknown. These effects refer to the relationship between birth year and the...

Inhibition of sodium-glucose cotransporter-2 and liver-related complications in individuals with diabetes: a Mendelian randomization and population-based cohort study.

No medication has been found to reduce liver-related events. We evaluated the effect of sodium-glucose cotransporter-2 inhibitor (SGLT2i) on liver-related outcomes. Single nucleotide polymorphisms associated with SGLT2 inhibition were identified, and a genetic risk score (GRS) was computed using the UK Biobank data (n=337,138). Two-sample Mendelian randomization (MR) was conducted using the FinnGen (n=218,792) database and the UK Biobank data. In parallel, a nationwide population-based study using the Korean National Health Insurance Service (NHIS) database was conducted. The development of liver-related complications (ie, hepatic decompensation, HCC, liver transplantation, and death) was compared between individuals with type 2 diabetes mellitus and steatotic liver diseases treated with SGLT2i (n=13,208) and propensity score-matched individuals treated with dipeptidyl peptidase-4 inhibitor (n=70,342). After computing GRS with 6 single nucleotide polymorphisms (rs4488457, rs80577326, rs11865835, rs9930811, rs34497199, and rs35445454), GRS-based MR showed that SGLT2 inhibition (per 1 SD increase of GRS, 0.1% lowering of HbA1c) was negatively associated with cirrhosis development (adjusted odds ratio=0.83, 95% CI=0.70-0.98, p =0.03) and this was consistent in the 2-sample MR (OR=0.73, 95% CI=0.60-0.90, p =0.003). In the Korean NHIS database, the risk of liver-related complications was significantly lower in the SGLT2i group than in the dipeptidyl peptidase-4 inhibitor group (adjusted hazard ratio=0.88, 95% CI=0.79-0.97, p =0.01), and this difference remained significant (adjusted hazard ratio=0.72-0.89, all p <0.05) across various sensitivity analyses. Both MRs using 2 European cohorts and a Korean nationwide population-based cohort study suggest that SGLT2 inhibition is associated with a lower risk of liver-related events.