Association between exercise habits and incident type 2 diabetes mellitus in patients with thyroid cancer: nationwide population-based study.

BACKGROUND: We investigated the association between exercise habits before or after thyroidectomy and incident type 2 diabetes mellitus (T2DM) in patients with thyroid cancer. METHODS: An observational cohort study of 69,526 thyroid cancer patients who underwent thyroidectomy for the treatment of thyroid cancer between 2010 and 2016 was performed using the Korean National Health Information Database. Regular exercise was defined as mid-term or vigorous exercise at least 1 day in a week based on a self-reported questionnaire. Patients were divided into four groups according to exercise habits before and after thyroidectomy: persistent non-exercisers, new exercisers, exercise dropouts, and exercise maintainers. RESULTS: During a median follow-up of 4.5 years, 2,720 (3.91%) patients developed T2DM. The incidence of T2DM per 1,000 person years was lower in patients who performed regular exercise before or after thyroidectomy than in persistent non-exercisers (10.77 in persistent non-exerciser group, 8.28 in new exerciser group, 8.59 in exercise dropout group, and 7.61 in exercise maintainer group). Compared with the persistent non-exerciser group, the new exerciser group (hazard ratio [HR] 0.87, 95% confidence interval [CI] 0.78-0.97), the exercise dropout group (HR 0.81, 95% CI 0.72-0.91), and the exercise maintainer group (HR 0.84, 95% CI 0.76-0.93) had lower risks of incident T2DM. Exercising < 1,500 MET-minutes/week in the exercise maintainer group was associated with a lower risk of incident T2DM compared with persistent non-exercisers (< 500: HR 0.80, 95% CI 0.67-0.96, P = 0.002; 500 to < 1,000: HR 0.81, 95% CI 0.71-0.93, P < 0.001; 1,000 to < 1,500: HR 0.81, 95% CI 0.69-0.94, P < 0.001). CONCLUSIONS: Regular exercise before or after thyroidectomy was associated with a lower risk of incident T2DM in patients with thyroid cancer.

Early-Onset Ocular Motor Cranial Neuropathy Is a Strong Predictor of Dementia: A Nationwide, Population-Based Cohort Study.

PURPOSE: To assess the risk of dementia in individuals with newly diagnosed ocular motor cranial neuropathy (OMCN). DESIGN: A nationwide, population-based cohort study using authenticated data from the Korean National Health Insurance Service (KNHIS). PARTICIPANTS: This study included 60 781 patients with OMCN who received a diagnosis between 2010 and 2017 and were followed up through 2018, with an average follow-up of 3.37 ± 2.21 years with a 1-year lag. After excluding patients with disease related to oculomotor dysfunction preceding the OMCN diagnosis, a total of 52 076 patients with OMCN were established. Of these, 23 642 patients who had participated in the National Health Screening Program (NHSP) within 2 years before the OMCN diagnosis were included. After applying the exclusion criteria, the final cohort comprised 19 243 patients and 96 215 age and sex-matched control participants without OMCN. METHODS: We identified patients with newly diagnosed OMCN in the KNHIS database and collected participant characteristics from the health checkup records of the NHSP. The study end point was determined by the first claim with a dementia diagnostic code and antidementia medications. The association of OMCN with dementia risk was examined using Cox proportional hazards regression analysis, adjusting for potential confounding factors. MAIN OUTCOME MEASURES: The main outcome measures were hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause dementia (ACD), Alzheimer's disease (AD), and vascular dementia (VaD) development in patients with OMCN relative to those without OMCN. RESULTS: Patients with newly diagnosed OMCN demonstrated higher metabolic comorbidities than those without OMCN. New OMCN was associated with an elevated risk of ACD (HR, 1.203; 95% CI, 1.113-1.300), AD (HR, 1.137; 95% CI, 1.041-1.243), and VaD (HR, 1.583; 95% CI, 1.286-1.948), independent of potential confounding factors. The younger age groups exhibited a stronger association between OMCN and ACD (HR, 8.690 [< 50 years] vs. 1.192 [≥ 50 years]; P = 0.0004; HR, 2.517 [< 65 years] vs. 1.099 [≥ 65 years]; P < 0.0001). CONCLUSIONS: This nationwide population-based study assessed the association between OMCN and dementia risk. Our results demonstrated a robust relationship between OMCN and the risk of dementia, particularly in the younger population. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Weight change in people with depression and the risk of dementia: a nationwide cohort study.

BACKGROUND: Depression is a risk factor for dementia and weight change can appear as a symptom of depression. However, the association between weight change after the diagnosis of depression and the risk of dementia is poorly established. This study aimed to investigate the association between weight change before and after a diagnosis of depression with the subsequent risk of dementia. METHODS: The National Health Insurance Sharing Service database was used. 1 308 730 patients aged ⩾40 years diagnosed with depression were identified to be eligible. Weight changes after their depression diagnosis were categorized and subsequent incidence of dementia was followed up. RESULTS: During an average follow-up period of 5.2 years (s.d., 2.0 years), 69 373 subjects were newly diagnosed with all-cause dementia (56 351 were Alzheimer's disease and 6877 were vascular dementia). Regarding all outcomes, compared to those with a minimal weight change (-5 to 5%), all groups with weight gain or loss showed increased risks of dementia after adjusting potential risk factors for dementia, in all analysis models with a dose-response relationship, showing a U-shaped association. CONCLUSIONS: Weight change as a symptom of depression could be a predictor for the future development of dementia.

Risk of depression and anxiety in multiple sclerosis and neuromyelitis optica spectrum disorder: A nationwide cohort study in South Korea.

BACKGROUND: We investigated the risks of depression/anxiety in patients with multiple sclerosis (pwMS) or patients with neuromyelitis optica spectrum disorder (pwNMOSD). OBJECTIVES: MS/NMOSD cohorts were collected from Korean National Health Insurance Service, using the International Classification of Diseases-10th and information on Rare Intractable Disease program. Patients who were younger than 20 years, had a previous depression/anxiety, or died in the index year were excluded. METHODS: Hazard ratios (HRs) of depression/anxiety in pwMS and pwNMOSD from controls matched 1:5 for age, sex, hypertension, diabetes, and dyslipidemia were calculated using Cox regressions with a 1-year lag period and estimated over time. RESULTS: During a mean follow-up of 4.1 years, adjusted hazard ratios (aHR) for depression were 3.25 (95% confidence interval (CI) = 2.59-4.07) in MS and 2.17 (1.70-2.76) in NMOSD, and aHRs for anxiety were 1.83 (1.49-2.23) in MS and 1.56 (1.26-1.91) in NMOSD. The risks of anxiety/depression did not differ between MS and NMOSD and were highest in the second year after diagnosis of MS/NMOSD. The relative risk of depression was higher in younger pwMS/pwNMOSD, and the relative risk of anxiety was higher in pwMS who was male, had low income, or lived in a non-urban area. CONCLUSION: The risk of depression and anxiety was increased in pwMS/pwNMOSD.

Migraine Risk in Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorder: A Nationwide Cohort Study in South Korea.

INTRODUCTION: Although the relationship between migraine and multiple sclerosis (MS) has been reported, the risk of migraine in MS and neuromyelitis optica spectrum disorder (NMOSD) is unclear. Therefore, this study investigated the risk of migraine in the Korean MS and NMOSD populations. METHODS: This study analyzed claims data from 1492 patients with MS and 1551 patients with NMOSD based on diagnostic codes in the Korean National Health Insurance Service. Migraine risk was compared with a control group (matched 1:5 for age, sex, and comorbidities) using Cox proportional hazards analysis. Patients aged <20 years and with previous migraine were excluded. RESULTS: Migraine risk was higher in patients with MS (adjusted hazard ratio [aHR] 1.37; 95% confidence interval [CI]: 1.15-1.62) but did not differ significantly in patients with NMOSD (aHR 1.05; 95%CI: 0.87-1.27) compared to controls. No significant sex-based differences in migraine risk were observed. Patients with NMOSD showed decreasing risk with age (p for interaction=0.040). Comorbidities like hypertension, diabetes, or dyslipidemia did not significantly alter migraine risk in either group. CONCLUSION: The study results revealed an increased risk of migraines in patients with MS but not in patients with NMSOD compared with matched controls.

Association of physical activity with fractures in kidney transplant recipients: A Korean nationwide cohort study.

Kidney transplant recipients are at high risk for fractures, primarily due to post-transplant bone disease. This retrospective cohort study analyzed data from the Korean National Health Insurance Service, including 10 083 kidney transplant recipients examined from 2009 to 2017. We assessed fracture incidence, emphasizing vertebral and hip fractures, and the association of physical activity and traditional risk factors with fracture risk. Kidney transplant recipients were categorized into three groups according to physical activity levels: non-activity, metabolic equivalent of task (MET) 1-499, and MET ≥500. Physical activity was associated with a decreased risk of all types of fractures: any (MET 1-499: adjusted hazard ratio (aHR) .75; 95% confidence interval (CI) .62-.92, MET ≥500: aHR .84; 95% CI .70-1.00), vertebral (MET 1-499: aHR .69; 95% CI .49-.98, MET ≥500: aHR .67; 95% CI .49-.91), and hip (MET 1-499: aHR .43; 95% CI .23-.81) fractures. Additionally, older age, female sex, and diabetes were associated with an increased fracture risk. The assessment of physical activity and traditional risk factors could improve fracture risk prediction. Our findings emphasize the need for further research to establish optimal physical activity recommendations for fracture prevention in kidney transplant recipients.

Increased Risk of Incident Chronic Obstructive Pulmonary Disease and Related Hospitalizations in Tuberculosis Survivors: A Population-Based Matched Cohort Study.

BACKGROUND: Tuberculosis (TB) survivors have an increased risk of developing chronic obstructive pulmonary disease (COPD). This study assessed the risk of COPD development and COPD-related hospitalization in TB survivors compared to controls. METHODS: We conducted a population-based cohort study of TB survivors and 1:1 age- and sex-matched controls using data from the Korean National Health Insurance Service database collected from 2010 to 2017. We compared the risk of COPD development and COPD-related hospitalization between TB survivors and controls. RESULTS: Of the subjects, 9.6% developed COPD, and 2.8% experienced COPD-related hospitalization. TB survivors had significantly higher COPD incidence rates (36.7/1,000 vs. 18.8/1,000 person-years, P < 0.001) and COPD-related hospitalization (10.7/1,000 vs. 4.3/1,000 person-years, P < 0.001) than controls. Multivariable Cox regression analyses revealed higher risks of COPD development (adjusted hazard ratio [aHR], 1.63; 95% confidence interval [CI], 1.54-1.73) and COPD-related hospitalization (aHR, 2.03; 95% CI, 1.81-2.27) in TB survivors. Among those who developed COPD, the hospitalization rate was higher in individuals with post-TB COPD compared to those with non-TB COPD (10.7/1,000 vs. 4.9/1,000 person-years, P < 0.001), showing an increased risk of COPD-related hospitalization (aHR, 1.84; 95% CI, 1.17-2.92). CONCLUSION: TB survivors had higher risks of incident COPD and COPD-related hospitalization compared to controls. These results suggest that previous TB is an important COPD etiology associated with COPD-related hospitalization.

Incidentally found parotid gland lesion in 18F-FDG PET/CT for staging evaluation of patients with hepatocellular carcinoma: remote possibility of metastatic tumor or second primary salivary gland malignancy.

OBJECTIVES: We primarily aimed to evaluate whether parotid incidental lesion (PIL) in 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) for staging evaluation of patients with hepatocellular carcinoma (HCC) would represent a possibility of extrahepatic metastasis or second primary malignancy (SPM). Additionally, we explored the incidence of PIL in HCC patients and examined any associated risk factors. METHODS: We retrospectively analyzed patients with HCC who underwent 18F-FDG PET/CT at our institution from 2010 to 2022. The pathological findings of PILs in HCC patients were investigated for confirmatory identification of the risk of HCC metastasis or SPM in parotid gland. Healthy controls received 18F-FDG PET/CT for health screening were also enrolled to compare the incidence of PILs with HCC patients. Various parameters associated with patient demographics and characteristics of HCC were analyzed to find the related factors of PILs. RESULTS: A total of 17,674 patients with HCC and 2,090 healthy individuals who had undergone 18F-FDG PET/CT scans were enrolled in the analyses. Among the 54 HCC patients who underwent pathological confirmation for PILs, benign primary parotid tumor was most commonly observed (n = 43 [79.6%]); however, no malignant lesions were detected, including HCC metastasis. The incidence of PILs was higher in patients diagnosed with HCC compared with the control group (485 [2.7%] vs. 23 [1.1%], p = 0.002). Analysis for the risk factors for PILs revealed that patient age, sex, and positive viral markers were significantly associated with the incidence of PILs in patients with HCC (all p < 0.001). CONCLUSIONS: Our study demonstrates that PILs are more frequently identified in patients with HCC on 18F-FDG PET/CT. However, no malignant PIL, including extrahepatic metastasis of HCC, was identified. Therefore, the presence of PIL should not impede or delay the treatment process for patients with HCC. Additionally, we suggested that for future swift and straightforward differential diagnoses of PIL, the development of additional protocols within the PET/CT imaging could be beneficial.

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.

Long-Term Mortality of Tuberculosis Survivors in Korea: A Population-based Longitudinal Study.

BACKGROUND: When assessing long-term tuberculosis (TB) mortality, few studies addressed the impact of behavior habits and socioeconomic status. Therefore, we aimed to evaluate long-term TB mortality and risk factors while accounting for potential confounders. METHODS: This cohort study included TB survivors (n = 82 098) aged ≥20 years between 2010 and 2017, and 1:1 age- and sex-matched controls (n = 82 098). The participants were followed up for death 1 year after study enrollment until December 2018. Long-term mortality was adjusted for behavior habits (smoking, alcohol consumption, or exercise), income level, body mass index (BMI), and comorbidities. RESULTS: During a median of 3.7 years of follow-up, the incidence rate of mortality was significantly higher in TB survivors than those in the matched controls (18.2 vs. 8.8 per 1000 person-years, P < .001). Even after adjusting for potential confounders, the mortality risk was 1.62-fold (95% confidence interval [CI], 1.54-1.70) higher in TB survivors than those in the matched controls. In addition, the hazard of mortality in TB survivors relative to matched controls significantly increased in participants aged ≥30 years, with the highest risk in those in their 40s. Male sex (adjusted hazard ratio [HR]: 2.31; 95% CI, 2.16-2.47), smoking pack-years (HR: 1.005; 95% CI, 1.004-1.006), heavy alcohol consumption (HR: 1.12; 95% CI, 1.01-1.23), and lowest income (HR: 1.27; 95% CI, 1.18-1.37) were positively associated with increased hazards for mortality, whereas higher BMI (HR: 0.91; 95% CI, .90-.92) and regular exercise (HR: 0.82; 95% CI, .76-.88) reduced the hazards of long-term mortality in TB survivors. CONCLUSIONS: The long-term mortality risk was significantly higher in TB survivors than those in the matched controls, even after adjusting for potential confounders.

Increased Lung Cancer Risk and Associated Risk Factors in Tuberculosis Survivors: A Korean Population-Based Study.

BACKGROUND: Few studies have comprehensively evaluated the risk of lung cancer in tuberculosis survivors with consideration of smoking status and chronic obstructive pulmonary disease (COPD). Furthermore, little is known about lung cancer risk factors in tuberculosis survivors. METHODS: This population-based cohort study enrolled tuberculosis survivors (n = 75 467) between 2010 and 2017 and 1:1 age- and sex-matched controls. Subjects were followed up for 1 year from the date of tuberculosis diagnosis to the date of the incident lung cancer, death, or December 2018, whichever came first. The risk of lung cancer was evaluated according to smoking and COPD status. We also evaluated the risk factors for lung cancer and developed an individualized lung cancer prediction model for tuberculosis survivors. RESULTS: During a median follow-up duration of 4.8 years, the incident lung cancer risk was 1.72-fold higher in tuberculosis survivors than in the controls. Among tuberculosis survivors, those who were current smokers with ≥20 pack-years showed the highest risk of lung cancer (adjusted hazard ratio, 6.78) compared with never-smoker, non-tuberculosis-infected controls. tuberculosis survivors with COPD had a higher risk (2.43) than non-COPD, non-tuberculosis-infected controls. Risk factors for lung cancer in tuberculosis survivors were pulmonary tuberculosis, age >60 years, smoking, and the presence of COPD or asthma. The individualized lung cancer risk model showed good discrimination (concordance statistic = 0.827). CONCLUSIONS: Previous tuberculosis infection is an independent risk factor regardless of smoking status or amount and COPD. Closer monitoring of tuberculosis survivors, especially heavy smokers or those with COPD, is needed for early lung cancer diagnosis.

Risk of fracture in neuromyelitis optica spectrum disorder and multiple sclerosis: a nationwide cohort study in South Korea.

PURPOSE: Interest in fractures in patients with multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) has considerably increased in the last decade. However, few studies have compared the incidence of fractures between patients with MS and NMOSD using a nationwide database. This study aimed to evaluate the differences in the risk of fracture between patients with NMOSD and MS compared to that in healthy controls using cohort data from a Korean nationwide database. METHODS: In this retrospective cohort study, data from the National Health Insurance Service (NHIS) database from January 2010 to December 2017 were analyzed. A total of 1,217/1,329 patients with MS/NMOSD free of fractures at the index date were included. Matched controls were selected based on age, sex, and the presence of hypertension, diabetes mellitus, and dyslipidemia. The mean follow-up durations after the index date were 4.40/4.08 years for patients with MS/NMOSD and 4.73/4.28 for their matched controls. RESULTS: The adjusted hazard ratios (aHRs) with 95% confidence intervals of any, hip, and vertebral fractures were 1.81 (1.43-2.28), 3.36 (1.81-6.24), and 2.01 (1.42-2.99) times higher for patients with MS than for controls, respectively, and they were 1.85 (1.47-2.34), 3.82 (2.05-7.11), and 2.84 (1.92-4.21) times higher for patients with NMOSD than for controls, respectively. No significant differences were observed in the incidence of fractures between the MS and NMOSD groups. Patients with MS/NMOSD had a 1.8-fold higher risk of fracture than matched controls, and the risk of hip fracture was especially high (3- to 4-fold higher). CONCLUSIONS: Clinicians need to regularly assess patients with MS/NMOSD for the risk of fractures and take preventative measures to reduce it.

Bone Mineral Density and the Risk of Parkinson's Disease in Postmenopausal Women.

BACKGROUND: Whether bone mineral density (BMD) is related to the risk of Parkinson's disease (PD) is unclear. OBJECTIVES: The objective of this study was to examine the association between BMD status and incident PD in postmenopausal women. METHODS: We retrospectively examined a nationwide cohort of 272,604 women aged 66 years who participated in the 2009-2012 Korean national health screening for transitional ages. BMD was evaluated using dual-energy X-ray absorptiometry of the central bones. The use of antiosteoporosis medications (AOMs) was assessed. We performed multivariable Cox proportional hazards regression to evaluate the association between BMD and PD risk by calculating hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: During the median follow-up of 7.7 years, 2,884 (1.1%) incident PD cases developed. After adjusting for confounding factors, lower BMD was associated with an increased risk of PD (P for trend <0.001). Individuals with osteoporosis had a 1.40-fold higher HR (1.40, 95% CI: 1.25-1.56) than those with a normal BMD. Sensitivity analyses suggested the associations robust to longer lag periods and further adjustment. These associations were prominent in individuals without AOM use before or after enrollment (P for interaction = 0.031 and 0.014). Increased risks of PD in individuals with osteopenia and osteoporosis who did not use AOMs were attenuated by the medication use during the follow-up period, regardless of previous AOM use. CONCLUSIONS: Lower postmenopausal BMD and osteoporosis were associated with an increased risk of PD. In addition, this association could be mitigated using AOMs. Proper management of BMD in postmenopausal women may help prevent PD. © 2023 International Parkinson and Movement Disorder Society.

Histamine-2 Receptor Antagonists and Proton Pump Inhibitors Are Associated With Reduced Risk of SARS-CoV-2 Infection Without Comorbidities Including Diabetes, Hypertension, and Dyslipidemia: A Propensity Score-Matched Nationwide Cohort Study.

BACKGROUND: This study aimed to identify the effect of histamine-2 receptor antagonist (H2RA) and proton pump inhibitor (PPI) use on the positivity rate and clinical outcomes of coronavirus disease 2019 (COVID-19). METHODS: We performed a nationwide cohort study with propensity score matching using medical claims data and general health examination results from the Korean National Health Insurance Service. Individuals aged ≥ 20 years who were tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) between 1 January and 4 June 2020 were included. Patients who were prescribed H2RA or PPI within 1 year of the test date were defined as H2RA and PPI users, respectively. The primary outcome was SARS-CoV-2 test positivity, and the secondary outcome was the instance of severe clinical outcomes of COVID-19, including death, intensive care unit admission, and mechanical ventilation administration. RESULTS: Among 59,094 patients tested for SARS-CoV-2, 21,711 were H2RA users, 12,426 were PPI users, and 24,957 were non-users. After propensity score matching, risk of SARS-CoV-2 infection was significantly lower in H2RA users (odds ratio [OR], 0.85; 95% confidence interval [CI], 0.74-0.98) and PPI users (OR, 0.62; 95% CI, 0.52-0.74) compared to non-users. In patients with comorbidities including diabetes, dyslipidemia, and hypertension, the effect of H2RA and PPI against SARS-CoV-2 infection was not significant, whereas the protective effect was maintained in patients without such comorbidities. Risk of severe clinical outcomes in COVID-19 patients showed no difference between users and non-users after propensity score matching either in H2RA users (OR, 0.89; 95% CI, 0.52-1.54) or PPI users (OR, 1.22; 95% CI, 0.60-2.51). CONCLUSION: H2RA and PPI use is associated with a decreased risk for SARS-CoV-2 infection but does not affect clinical outcome. Comorbidities including diabetes, hypertension, and dyslipidemia seem to offset the protective effect of H2RA and PPI.

Age at menopause and risk of heart failure and atrial fibrillation: a nationwide cohort study.

AIMS: This study aimed to examine the association of premature menopause and age at menopause with the risk of heart failure (HF) and atrial fibrillation (AF). METHODS AND RESULTS: A total of 1 401 175 postmenopausal women, who had undergone health examination provided by the Korean National Health Insurance Service, were included, and their reproductive histories were collected. Multivariable Cox proportional hazard models were performed to determine the hazard ratios (HRs) and 95% confidence intervals (CIs) of incident HF and AF, according to the history of premature menopause and age at menopause. At a mean follow-up of 9.1 years, there were 42 699 (3.0%) and 44 834 (3.2%) new cases of HF and AF, respectively. Women with history of premature menopause had an increased risk of HF (HR: 1.33, 95% CI: 1.26-1.40) and AF (HR: 1.09, 95% CI: 1.02-1.16), compared to women without the history. Compared with women aged ≥50 years at menopause, those aged 45-49, 40-44, and <40 years at menopause showed a significantly increased trend in HRs for the incident risk of both HF and AF (P for trend <0.001). The robustness of the results of a series of sensitivity analyses further strengthens the main findings. CONCLUSION: Our findings suggest that postmenopausal women with a history of premature menopause or early menopausal age may have an increased risk of HF and AF. These reproductive factors need to be considered for preventing the future risk of HF and AF.

Tuberculosis and Risk of Ischemic Stroke: A Nationwide Cohort Study.

BACKGROUND: Conflicting results exist regarding the risk of ischemic stroke in tuberculosis survivors. We aimed to estimate the risk of ischemic stroke using a nationwide population-based retrospective cohort. METHODS: We gathered data from the Korean National Health Insurance Service on tuberculosis survivors and 1:1 age- and sex-matched non-tuberculosis cases. Eligible participants were followed up from 1 year after tuberculosis diagnosis to the date of ischemic stroke event, date of death, or until the end of the study period (December 31, 2018), whichever came first. Cox proportional hazard regression and stratified analyses were performed to identify any related factors. RESULTS: During follow-up periods of 3.8 years for patients with tuberculosis and matched non-tuberculosis cases, 1.3% of patients with tuberculosis (941/72 863) and 1.0% of matched non-tuberculosis cases (707/72 863) developed ischemic stroke. The overall risk of ischemic stroke was higher in tuberculosis patients (adjusted hazard ratio: 1.22 [95% CI, 1.10-1.36]) compared with the matched non-tuberculosis cases. A stratified analysis showed that patients with tuberculosis had increased risk of ischemic stroke regardless of age, sex, smoking status, alcohol consumption, physical activity, body mass index, and Charlson Comorbidity Index score. CONCLUSIONS: Tuberculosis survivors had a higher risk of ischemic stroke than their matched non-tuberculosis cases. The results of this study suggest that tuberculosis is a crucial infectious factor associated with increased incidence of ischemic stroke.

Risk of stroke in multiple sclerosis and neuromyelitis optic spectrum disorder: a Nationwide cohort study in South Korea.

BACKGROUND: People with multiple sclerosis (MS) are more likely to develop stroke than those without. However, little is known about the association between neuromyelitis optica spectrum disorder (NMOSD) and the risk of stroke. We aimed to estimate the risk of stroke in patients with MS and NMOSD in South Korea. METHODS: Data from the Korean National Health Insurance between January 2010 and December 2017 were analysed. A total of 1541/1687 adult patients with MS/NMOSD, who were free of stroke were included. Matched controls were selected based on age, sex and the presence of hypertension, diabetes mellitus and dyslipidaemia. RESULTS: The risk of developing stroke was 2.78 times higher (adjusted HR (aHR), 95% CI 1.91 to 4.05) in patients with MS compared with controls matched by age, sex, hypertension, diabetes mellitus and dyslipidaemia. The risk of stroke in NMOSD was also higher than that in matched controls (aHR=1.69, 95% CI 1.10 to 2.61) and not statistically different from that of MS (p=0.216). The patients with MS had a higher risk for either of ischaemic or haemorrhagic stroke (HR=2.63 and 2.93, respectively), whereas those with NMOSD had a higher risk for ischaemic stroke (HR=1.60) with marginal statistical significance. CONCLUSIONS: The risk of stroke is increased in patients with MS and NMOSD and seemed comparable between the two conditions. This is the first study that estimates the risk of stroke in patients with MS and NMOSD within the same population.

Risk of Parkinson's disease in multiple sclerosis and neuromyelitis optica spectrum disorder: a nationwide cohort study in South Korea.

BACKGROUND: Neurodegeneration is associated with pathogenesis of both multiple sclerosis (MS) and neuromyelitis optica (NMOSD). Parkinson's disease (PD) is a representative neurodegenerative disease, however, whether MS or NMOSD is associated with risk of PD is not known. METHODS: MS and NMOSD cohorts were collected from the Korean National Health Insurance Service between 1 January 2010 and 31 December 2017, using International Classification of Diseases 10th revision diagnosis codes and information in the Rare Intractable Disease management programme. The PD incidence rate that occurred after a 1-year lag period was calculated and compared with that of a control cohort matched for age, sex, hypertension, diabetes and dyslipidaemia in a 1:5 ratio. RESULTS: The incidence rates of PD in patients with MS and NMOSD were 3.38 and 1.27 per 1000 person-years, respectively, and were higher than that of their matched control groups. The adjusted HR of PD was 7.73 (95% CI, 3.87 to 15.47) in patients with MS and 2.61 (95% CI, 1.13 to 6.02) in patients with NMOSD compared with matched controls. In both patients with MS and NMOSD, there were no significant differences in relative risk when stratified by sex, age, diabetes, hypertension and dyslipidaemia. CONCLUSION: The PD risk was higher in patients with MS and NMOSD compared with healthy controls and was particularly high in patients with MS. Further investigations should be performed to determine the pathophysiology and occurrence of PD in patients with MS and NMOSD.

Acute myocardial infarction risk in multiple sclerosis and neuromyelitis optica spectrum disorder: A nationwide cohort study in South Korea.

BACKGROUND: The link between neuromyelitis optica spectrum disorder (NMOSD) and cardiovascular disease is currently unclear. OBJECTIVE: To determine the acute myocardial infarction (MI) risk in patients with MS and NMOSD. METHODS: This study analyzed the Korean National Health Insurance Service database between January 2010 and December 2017. The included patients comprised 1503/1675 adults with MS/NMOSD who had not experienced ischemic heart disease or ischemic stroke at the index date. Matched controls were selected based on age, sex, and the presence of hypertension, diabetes mellitus (DM), and dyslipidemia. RESULTS: The risks of developing MI were 2.61 (hazard ratio (HR), 95% confidence interval (CI) 1.73-3.95) and 1.95 (95% CI = 1.18-3.22) times higher in MS and NMOSD compared with the control populations. Patients with NMOSD had a similar MI risk compared with patients with MS, after adjusting for age, sex, income, hypertension, DM, and dyslipidemia (HR = 0.59, 95% CI = 0.34-1.02, p = 0.059). Among each patient group, the MI risk did not differ significantly with age (20-39, 40-64 or ⩾65 years), sex, or the presence of hypertension, DM, or dyslipidemia. CONCLUSION: The MI risk increased in MS and NMOSD and seemed to be comparable between NMOSD and MS.

Proton Pump Inhibitor Co-Therapy in Patients with Atrial Fibrillation Treated with Oral Anticoagulants and a Prior History of Upper Gastrointestinal Tract Bleeding.

PURPOSE: The risk of gastrointestinal bleeding (GIB) can be mitigated by proton pump inhibitor (PPI) co-therapy in patients with atrial fibrillation (AF) treated with anticoagulants. We aimed to evaluate the effect of PPIs on the risk of GIB in Asian patients with AF, treated with oral anticoagulants (OACs), and with a prior history of upper GIB. METHODS: Using a nationwide claims database, OAC-naïve patients with AF and a history of upper GIB before initiating OAC treatment between January 2010 and April 2018 were included. Patients were categorized into 10 groups according to the index OAC (warfarin, rivaroxaban, dabigatran, apixaban, and edoxaban) and whether or not they received PPI co-therapy, and were followed up for incidence of major GIB. RESULTS: Among a total of 42,048 patients, 40% were prescribed PPIs as co-therapy with OACs. Over a median 0.6 years (interquartile ranges 0.2-1.7 years) of follow-up, rivaroxaban use without PPIs showed the highest crude incidence of major GIB (2.62 per 100 person-years), followed by the use of warfarin without a PPI (2.20 per 100 person-years). Compared to the patients without PPI use, PPI co-therapy was associated with a significantly lower risk of major GIB, by 40% and 36%, in the rivaroxaban and warfarin groups, respectively. In dabigatran, apixaban, and edoxaban users, PPI co-therapy did not show a significant reduction in the risk of major GIB. CONCLUSION: Among patients with AF receiving anticoagulant treatment and with a prior history of upper GIB, PPI co-therapy was associated with a significant reduction in the risk of major GIB in patients treated with rivaroxaban and warfarin.