Risk of secondary primary malignancies in survivors of upper tract urothelial carcinoma: A nationwide population-based analysis.

BACKGROUND: To investigate the cancer types and risk factors of secondary primary malignancy (SPM) in patients with upper tract urothelial carcinoma (UTUC) in Taiwan. METHODS: Using National Health Insurance Research Dataset and catastrophic illness registry, we enrolled newly diagnosed UTUC patients from 2000 to 2013. Those without catastrophic illness registration were excluded from the study. The cancer types and hazard ratios (HRs) of subsequent SPMs were calculated according to the antecedent malignancy. We analyzed the risk factors for developing SPMs using multivariate Cox proportional hazard models. RESULTS: A total of 9050 UTUC patients were registered and 2187 (24.2%) patients developed SPMs during the study period. As compared with primary UTUC, the relative risk ratios of SPM was 2.5 folds and 18% higher in those with antecedent non-UC malignancy and with bladder cancer history, respectively. Totally, 387 (37.8%) of 1022 UTUC patients with antecedent non-UC malignancy developed subsequent SPM after UTUC diagnosis. The antecedent and subsequent cancer types are similar and kidney cancer is most common, followed by hepatoma. Multivariate analysis showed that a history of antecedent non-UC malignancy is the most unfavorable factor for SPM development (HR, 2.50; 95% CI, 2.23-2.81), followed by liver disease, male gender, antecedent bladder cancer history, age ≥ 75 years, and chronic kidney disease. CONCLUSIONS: Our study, conducted in Taiwan and involving 9050 UTUC patients, meticulously examined the types of SPM and the associated risk factors. Our research unearthed several pivotal discoveries: a preceding history of non-UC malignancies emerged as the single most influential factor contributing to the occurrence of subsequent cancers, followed by liver disease, male gender, antecedent bladder cancer history, age ≥75 years, and chronic kidney disease. Futhermore, kidney cancer emerged as the predominant subsequent malignancy, closely trailed by hepatoma..

Vesicoureteral reflux is associated with increased risk of chronic kidney disease: A nationwide cohort study.

The association between vesicoureteral reflux (VUR) and chronic kidney disease (CKD) risk remains unestablished. We investigated the incidence of CKD in children with VUR in Taiwan and evaluated whether they had a higher risk of CKD than the general population. A nationwide population-based cohort study was conducted among children with VUR identified using Taiwan's National Health Insurance Research Database from 2000 to 2013. VUR was defined according to the International Classification of Diseases, Ninth Revision, Clinical Modification codes. We identified the children with VUR and randomly selected comparison children according to a 1:1 ratio, matching them by age, gender, index year and comorbidity using data from the National Health Insurance Research Database. In total, 8648 children with VUR and 8648 comparison children were included. All children were followed from the study date until a diagnosis of CKD, termination of insurance, or the end of 2013. Cox proportional hazards regressions were performed to compare the hazard ratios for CKD between the 2 cohorts. Incident cases of CKD were identified. After adjustment for potential confounders, the study cohort was independently associated with a higher risk of CKD (adjusted hazard ratio, 3.78; 95% confidence interval, 2.10-7.18). This population-based cohort study indicated that children with VUR have a higher risk of CKD than those without VUR.

The Impact of Psychological Distress on Cervical Cancer.

OBJECTIVE: Psychological distress is considered a factor for cancer development. However, the impact of mood disorders (depression and bipolar) on the development of cervical cancer remains uncertain. We conducted a nationwide population-based retrospective cohort study to investigate the association between mood disorders and the subsequent risk of developing cervical cancer. METHODS: A total of 138,130 participants' profiles between 2000 and 2012 were extracted from the National Health Insurance Research Database and subdivided into a mood-disorder cohort (27,626 participants) and a non-mood-disorder cohort (110,504 participants). Cohorts were propensity-matched for a 1:4 ratio according to age and index year. The Cox proportional hazards regression model was utilized for assessing cervical cancer risk between cohorts. RESULTS: Kaplan-Meier analysis revealed that the mood-disorder cohort had a higher cumulative incidence of cervical cancer. The mood-disorder cohort was also associated with an increased risk of cervical cancer after adjustments for potential confounders. Subgroup analysis revealed a negative impact of mood disorders on cervical cancer, especially in the 30-50 years and white-collar groups. CONCLUSIONS: Our findings demonstrated that mood disorders were associated with an increased risk of cervical cancer development, which provide helpful information for clinical strategies to reduce the incidence of cervical cancer in this vulnerable population.

The trends in the incidence and thrombosis-related comorbidities of antiphospholipid syndrome: a 14-year nationwide population-based study.

BACKGROUND: This study aims to provide 14-year nationwide epidemiology data to evaluate the incidence ratio of APS in Taiwan and the condition of comorbidities by analyzing the National Health Insurance Research Database. METHODS: Nineteen thousand one hundred sixty-three patients newly diagnosed as having APS during the 2000-2013 period and 76,652 controls (with similar distributions of age and sex) were analyzed. RESULTS: The incidence of APS increased from 4.87 to 6.49 per 10,000 person-years in the Taiwan population during 2000-2013. The incidence of APS increased with age after 20 years old, especially in the female population, and it rose rapidly after age over 60 years old. In addition, APS cohorts presented a higher proportion of diabetes mellitus, hypertension, hyperlipidemia, stroke, heart failure, atrial fibrillation, myocardial infarction, PAOD, chronic kidney disease, COPD, deep vein thrombosis, pulmonary embolism, SLE, rheumatoid arthritis, Sjogren's syndrome, and polymyositis. CONCLUSIONS: Our study indicated an increasing trend in APS incidence among the Taiwanese population and a relationship between APS and potential comorbidities. This large national study found that the APS risk is heavily influenced by sex and age. Thus, the distinctive sex and age patterns might be constructive given exploring potential causal mechanisms. Furthermore, our findings indicate that clinicians should have a heightened awareness of the probability of APS, especially in women in certain age groups presenting with symptoms of APS.

Cardiovascular outcomes of metformin use in patients with type 2 diabetes and chronic obstructive pulmonary disease.

Aim: To know whether metformin use has different influence on cardiovascular risks in patients with type 2 diabetes mellitus (T2DM) and chronic obstructive pulmonary disease (COPD) as compared with metformin no-use. Methods: This study employed a retrospective cohort study design. Using propensity score matching, we recruited 55 ,224 pairs of metformin users and nonusers from Taiwan's National Health Insurance Research Database between 1 January 2000, and 31 December 2017. Cox proportional-hazards models with robust standard error estimates were used to compare the risks of cardiovascular outcomes. Results: The mean study period of metformin users and nonusers was 11.04 (5.46) and 12.30 (4.85) years, respectively. Compared with the nonuse of metformin, the adjusted hazard ratios (95% CI) of metformin use for composited cardiovascular events, stroke, coronary artery disease, and heart failure were 0.51 (0.48-0.53), 0.62 (0.59-0.64), 0.48 (0.46-0.50), and 0.61 (0.57-0.65), respectively. The longer cumulative duration of metformin use had even lower adjusted hazard ratios compared with metformin nonuse. Conclusion: In patients with coexisting T2DM and COPD, metformin use was associated with significantly lower risks of CVD; moreover, longer duration of metformin use was associated with a lower risk of CVD. A well-designed prospective study is required to verify the results.

First-in-human pilot trial of combined intracoronary and intravenous mesenchymal stem cell therapy in acute myocardial infarction.

Background: Acute ST-elevation myocardial infarction (STEMI) elicits a robust cardiomyocyte death and inflammatory responses despite timely revascularization. Objectives: This phase 1, open-label, single-arm, first-in-human study aimed to assess the safety and efficacy of combined intracoronary (IC) and intravenous (IV) transplantation of umbilical cord-derived mesenchymal stem cells (UMSC01) for heart repair in STEMI patients with impaired left ventricular ejection fraction (LVEF 30-49%) following successful reperfusion by percutaneous coronary intervention. Methods: Consenting patients received the first dose of UMSC01 through IC injection 4-5 days after STEMI followed by the second dose of UMSC01 via IV infusion 2 days later. The primary endpoint was occurrence of any treatment-related adverse events and the secondary endpoint was changes of serum biomarkers and heart function by cardiac magnetic resonance imaging during a 12-month follow-up period. Results: Eight patients gave informed consents, of whom six completed the study. None of the subjects experienced treatment-related serious adverse events or major adverse cardiovascular events during IC or IV infusion of UMSC01 and during the follow-up period. The NT-proBNP level decreased (1362 ± 1801 vs. 109 ± 115 pg/mL, p = 0.0313), the LVEF increased (52.67 ± 12.75% vs. 62.47 ± 17.35%, p = 0.0246), and the wall motion score decreased (26.33 ± 5.57 vs. 22.33 ± 5.85, p = 0.0180) at the 12-month follow-up compared to the baseline values. The serial changes of LVEF were 0.67 ± 3.98, 8.09 ± 6.18, 9.04 ± 10.91, and 9.80 ± 7.56 at 1, 3, 6, and 12 months, respectively as compared to the baseline. Conclusion: This pilot study shows that combined IC and IV transplantation of UMSC01 in STEMI patients with impaired LVEF appears to be safe, feasible, and potentially beneficial in improving heart function. Further phase 2 studies are required to explore the effectiveness of dual-route transplantation of UMSC01 in STEMI patients.

Breast-conserving surgery with whole breast radiation therapy has a subsequent lower mood disorder incidence rate than total mastectomy in early-stage breast cancer patients: a nationwide population-based longitudinal study.

PURPOSE: Breast-conserving surgery (BCS) followed by whole breast radiation therapy (BCS-WBRT) or total mastectomy without WBRT (TM-no-WBRT) is the primary treatment for early stage breast cancer patients. Our study aimed to identify which early stage breast cancer treatment strategies had a subsequent lower incidence rate of mood disorder over a period of 10 years after the primary treatment. METHODS: This retrospective cohort study consisted of newly diagnosed early stage breast cancer patients in Taiwan from 2000 to 2013 using the National Health Insurance Research Database in Taiwan. We used a 1:1 propensity score matching by age to enrol patients into the BCS-WBRT and TM-no-WBRT groups. Statistical analyses were performed to calculate the hazard ratio and cumulative incidence rate. RESULTS: Our study consisted of 876 BCS-WBRT patients and 1949 TM-no-WBRT patients. After propensity score matching, each study group included 876 patients. The results showed that the mood disorder incidence rate was lower in the BCS-WBRT group than in the TM-no-WBRT group. Multivariate Cox regression analysis revealed that the BCS-WBRT group had a decreased risk of developing mood disorder (adjusted hazard ratio 0.69, 95% CI 0.53-0.90, p < 0.01). Furthermore, the Kaplan-Meier analysis showed that the BCS-WBRT group had a lower cumulative incidence rate of mood disorder, especially depression, after undergoing 10 years of primary treatment (p = 0.004). CONCLUSION: Our results indicated that BCS-WBRT was associated with a lower risk of development of mood disorder over a 10-year period compared to TM-no-WBRT in early stage breast cancer patients. Our findings may provide helpful information, along with other clinical data, for breast cancer patients as they choose the type of appropriate surgery for treatment.

Corrigendum: Decreased Risk of Anxiety in Diabetic Patients Receiving Glucagon-Like Peptide-1 Receptor Agonist: A Nationwide, Population-Based Cohort Study.

[This corrects the article DOI: 10.3389/fphar.2022.765446.].

Decreased Risk of Anxiety in Diabetic Patients Receiving Glucagon-like Peptide-1 Receptor Agonist: A Nationwide, Population-Based Cohort Study.

Background: Previous findings on using Glucagon-like peptide-1 receptor agonist (GLP1-RA) as an antidepressant were conflicting, lacking large-scale studies. We used population-based data to investigate depression and anxiety risk in diabetic patients receiving the medication. Methods: From claims records of the National Health Insurance Research Database (NHIRD) of Taiwan, we identified cohorts of 10,690 GLP1-RA users and 42,766 propensity score-matched patients without GLP1-RA use from patients with diabetes mellitus (DM) diagnosed in 2011-2017, matched by age, gender, index year, occupation, urbanization, comorbidities, and medications. Incidence, hazard ratios (HR) and 95% confidence interval (CI) of depression and/or anxiety were estimated by the end of 2017. Results: The overall combined incidence of anxiety and/or depression was lower in GLP1-RA users than in non-users (6.80 versus 9.36 per 1,000 person-years), with an adjusted HR adjusted hazard ratio (aHR) of 0.8 (95% CI: 0.67-0.95) after controlling for covariates. The absolute incidence reduction was greater in anxiety (2.13 per 1,000 person-years) than in depression (0.41 per 1,000 person-years). The treatment effectiveness was significant for women. Patients taking GLP1-RA for longer than 180 days had the incidence of anxiety reduced to 2.93 per 1,000 person-years, with an aHR of 0.41 (95%CI: 0.27-0.61), compared to non-users. Dulaglutide could significantly decrease risks of both anxiety and depression. Conclusion: Patients with DM receiving GLP1-RA therapy have a greater reduction of the risk of anxiety than that of depression. Our findings strengthen previous research that advocated possible anti-depressant or anxiolytic effects of GLP1-RA and may lead to improved treatment adherence among patients with DM.

Scabies Infestation and Risk of Acute Myocardial Infarction: A Population-Based Cohort Study.

BACKGROUND: Scabies is an infectious inflammatory skin disease. Cytokine-mediated inflammatory responses may be one of the pathological mechanisms underlying myocardial infarction. OBJECTIVE: We explore the association between scabies and subsequent acute myocardial infarction (AMI) and all-cause mortality; Methods: We conducted a nationwide population-based study using data from the National Health Insurance Research Database (NHIRD) in Taiwan. Patients with scabies (n = 30,184) and 120,739 controls without scabies were included. The primary outcomes were incidental AMI and all-cause mortality. Using Cox proportional-hazards regression analysis, we estimated the risk of acute myocardial infarction for the study cohort; Results: The mean age of the study cohort was 51.81 ± 19.89 years. The adjusted sub-distribution hazard ratios (aSHRs) of AMI were 1.214 (95% CI, 1.068-1.381) after adjusting for demographic characteristics, income, OPD utility frequency, days in hospital, co-morbidities, and medication. The adjusted hazard ratio (aHR) of all-cause mortality after adjusting for age, gender, income, OPD utility frequency, days in hospital, co-morbidities, co-medication, and urbanization was 1.612 (95% CI, 1.557-1.669). CONCLUSIONS: Our study showed that patients with scabies infestations were at higher risk for subsequent AMI and all-cause mortality.

Diabetes, hypertension, and cardiovascular disease development.

BACKGROUND: We aimed to compare cardiovascular risks among participants with T2DM with and without subsequent HTN and participants with HTN with and without subsequent T2DM. METHODS: From January 1, 2000, to December 31, 2018, we identified 16,236 matched pairs of T2DM participants with and without HTN (T2DM cohorts), 53,509 pairs of HTN participants with and without T2DM (HTN cohorts), and 21,158 pairs of comorbid HTN and T2DM participants with T2DM history or HTN history (comorbid cohorts) from Taiwan's National Health Insurance Research Database. Cox proportional-hazard models were used to calculate the risk of cardiovascular disease. RESULTS: The mean follow-up time of this study was 6.75 years. Mean incident rates of coronary artery disease for T2DM cohorts, HTN cohorts, and comorbid cohorts were 16.80, 23.18, and 31.53 per 1000 person-years, respectively. The adjusted hazard ratios (HRs) (95% confidence intervals [95% CIs]) for incident coronary artery disease, stroke, and heart failure in T2DM participants with versus without HTN were 2.22 (2.07-2.37), 1.19 (1.16-1.23), and 0.92 (0.82-1.02), respectively; the adjusted HRs for HTN participants with versus without T2DM were 1.69 (1.55-1.84), 1.25 (1.21-1.30), and 0.98 (0.93-1.05), respectively; the adjusted HRs for comorbid T2DM and HTN participants with previous T2DM versus previous HTN were 2.78 (2.37-3.27), 1.20 (1.13-1.28), and 0.95 (0.88-1.03), respectively. CONCLUSIONS: This nationwide cohort study demonstrated that both T2DM with subsequent HTN and HTN with subsequent diabetes were associated with higher cardiovascular disease risks.

Fibromyalgia and periodontitis: Bidirectional associations in population-based 15-year retrospective cohorts.

BACKGROUND: To determine the bidirectional link between periodontitis and fibromyalgia. METHODS: In this cohort study, 196,428 periodontitis patients and 196,428 propensity score-matched non-periodontitis controls were enrolled. A Cox proportional hazard model was utilized to estimate the risk of fibromyalgia and survival analysis was adopted to assess the time-dependent effect of periodontitis on fibromyalgia. Subgroup analyses stratified by age, sex, and tracking period were conducted to identify susceptible populations. A parallel and symmetrical cohort that recruited 141,439 fibromyalgia patients and 141,439 propensity score-matched non-fibromyalgia controls ascertained the inverse effect of fibromyalgia on incident periodontitis. RESULTS: Patients with periodontitis were more likely to develop fibromyalgia than non-periodontitis controls (HR = 1.42, 95% CI = 1.39-1.44, P < 0.001), which persisted in the survival analysis (log-rank test P < 0.0001). This effect was significant in both sexes and all age subgroups, and was particularly evident in males (HR = 1.52, 95% CI = 1.48-1.56, P < 0.001) and younger periodontitis patients (HR = 1.55, 95% CI = 1.50-1.60, P < 0.001). Fibromyalgia patients who never had periodontitis presented with greater risk for periodontitis over time (HR = 1.43, 95% CI = 1.40 - 1.45, P < 0.001; log-rank test P < 0.0001). CONCLUSIONS: Patients of both sexes and all age subgroups with periodontitis presented with a greater risk of fibromyalgia. Subgroups that were the most susceptible to periodontitis-associated fibromyalgia were periodontitis patients that were males and below 30 years old. Risks of periodontitis were also greater in fibromyalgia patients who never had periodontitis.

Protein energy wasting-based nutritional assessment predicts outcomes of acute ischemic stroke and solves the epidemiologic paradox.

OBJECTIVE: Overweight and hyperlipidemia, the two established risk factors for acute ischemic stroke, are paradoxically associated with favorable outcomes. The paradox may be resolved by the concept of protein energy wasting (PEW), in which total cholesterol level and body mass index are used as nutritional indexes for predicting outcomes of chronic kidney disease. METHODS: Among 12 271 people with acute ischemic stroke and chronic kidney disease, 2086 were defined as being at risk of PEW-with a body mass index <22 kg/m2 plus either a serum albumin level <38 g/L or a total cholesterol level <4.14 mmol/L (160 mg/dL) without the use of lipid-lowering drugs-and all the others were a control group. The hazards of PEW for mortality and functional outcomes were evaluated using propensity score matching and multivariate Cox regression analysis. RESULTS: Based on the propensity score, 2081 PEW participants were matched to the same number of non-PEW control participants. PEW was associated with a higher mortality risk at 3 mo (adjusted hazard ratio, 1.19; 95% confidence interval [CI], 1.02-1.42) and 1 y (adjusted hazard ratio, 1.33; 95% CI1.13-1.52). PEW was also associated with poor functional outcomes (modified Rankin Scale score >2) at 1 mo (adjusted odds ratio, 1.32; 95% CI, 1.08-1.61) and 3 mo (adjusted odds ratio, 1.27; 95% CI, 1.03-1.56). CONCLUSIONS: According to the PEW-based assessment system, a modest decrease in body mass index and total cholesterol levels suggests malnutrition and is associated with adverse outcomes of acute ischemic stroke.

Omega-3 fatty acids and blood-based biomarkers in Alzheimer's disease and mild cognitive impairment: A randomized placebo-controlled trial.

BACKGROUND: Increased serum levels of pro-inflammatory biomarkers are consistently associated with cognitive decline. The omega-3 unsaturated fatty acids (n-3 PUFAs) had been linked to slowing cognitive decline due to their potential anti-inflammatory effects. To our knowledge, the different regiments of pure DHA, pure EPA, and their combination on various associated symptoms of dementia, including a mild form of cognitive impairment (MCI) and Alzheimer's disease (AD), have never been studied. METHODS: This multisite, randomized, double-blind, placebo-controlled trial was conducted at two veteran's retirement centers and one medical center in central Taiwan between 2013 and 2015. 163 MCI or AD patients were randomly assigned to placebo (n = 40), docosahexaenoic acid (DHA, 0.7 g/day, n = 41), eicosapentaenoic acid (EPA, 1.6 g/day, n = 40), or EPA (0.8 g/day) + DHA (0.35 g/day) (n = 42) group for 24 months. The results were measured as the cognitive and functional abilities, biochemical, and inflammatory cytokines profiles. Chi-square tests, two-sample t-test, ANOVA, and linear mixedeffects models were conducted with p < 0.05. RESULTS: 131 (80%) participants had completed the trial with all cognitive, functional, and mood status assessments. The statistically significant difference between the placebo and treatment groups was not determined, concerning the changes in cognitive, functional, and mood status scores, the biochemical profiles, and inflammatory cytokines levels. However, EPA was found to reduce the C-C motif ligands 4 (CCL4) level (p < 0.001). Additionally, EPA could reduce the constructional praxis (p < 0.05) and spoken language ability scores (p < 0.01), and DHA also reduced the spoken language ability score (p < 0.05). CONCLUSION: Overall, n-3 PUFAs supplements did not reduce cognitive, functional, and depressive symptom outcomes, but spoken language ability and constructional praxis subitems of ADAS-cog. These findings show that attention to clinical heterogeneity in dementia is crucial when studying nutrients interventions, such as n-3 PUFAs. In addition, with small effect size CCL4 is a better indicator than other inflammatory cytokines for EPA treatment response.

Epidemiology of Meckel's diverticulum: A nationwide population-based study in Taiwan: Characteristics of the cases from surgery between 1996 and 2013.

ABSTRACT: The diverse presentation of Meckel's diverticulum (MD) is a diagnostic challenge for clinicians and most previous studies consist of single institutional case series. The aim of this study was to review the related diagnoses of MD and to investigate the epidemiological characteristics using Taiwan's National Health Insurance Research Database.We conducted an observational study using a population-based database. Patients diagnosed with MD who concurrently received intestinal surgery were identified. We analyzed the patients' demographic characteristics and relevant diagnoses using χ2 test and 2-sample t test.We identified 2453 newly diagnosed MD patients from 1996 to 2013 and 1227 patients (50%) with intestinal obstruction, gastrointestinal bleeding, and acute appendicitis (acute abdominal pain) were defined as symptomatic. The male to female ratio was 2.4:1 with half of the patients experiencing symptomatic MD before the age of 20 years' old. The age-specific and annual incidence were calculated for all MD and symptomatic MD. Among the symptomatic MD patients, intestinal obstruction was present in 583 (48%), acute appendicitis was present in 464 (38%), and gastrointestinal bleeding was present in 283 (23%) patients. Intestinal obstruction was the most common preoperative diagnosis in the 0 to 10 years and >20 years' age groups, and acute appendicitis (acute abdominal pain) was the most common diagnosis in the 11 to 20 years' age group.This population-based 18 years' epidemiologic study described the distributions of MD symptoms among different age groups, which may help clinicians gain a better understanding of this diagnostically challenging gastrointestinal anomaly.

Increased risk of Parkinson's disease among patients with age-related macular degeneration.

BACKGROUND: This study aimed to investigate the risk of Parkinson's disease (PD) among patients with age-related macular degeneration (AMD) and its association with confounding comorbidities. METHODS: A population-based retrospective cohort study was conducted using Longitudinal Health Insurance Database 2000 (LHID2000). We established AMD and non-AMD cohorts from January 1, 2000 to December 31, 2012 to determine the diagnosis of PD. A total of 20,848 patients were enrolled, with 10,424 AMD patients and 10,424 controls matched for age, sex, and index year at a 1:1 ratio. The follow-up period was from the index date of AMD diagnosis to the diagnosis of PD, death, withdrawal from the insurance program, or end of 2013. Multivariable Cox regression analysis was performed to examine the hazard ratio (HR) and 95% confidence interval (CI) for the risk of PD between the AMD and non-AMD cohorts. RESULT: After adjusting for potential confounders, there was a higher risk of developing PD in the AMD cohort than in the non-AMD cohort (adjusted HR = 1.35, 95% CI = 1.16-1.58). A significant association could be observed in both female (aHR = 1.42, 95% CI = 1.13-1.80) and male (aHR = 1.28, 95% CI = 1.05-1.57) patients, aged more than 60 years (60-69: aHR = 1.51, 95% CI = 1.09-2.09, 70-79: aHR = 1.30, 95% CI = 1.05-1.60; 80-100: aHR = 1.40, 95% CI = 1.01-1.95), and with more than one comorbidity (aHR = 1.40, 95% CI = 1.20-1.64). A significant association between increased risk of PD and AMD was observed among patients with comorbidities of osteoporosis (aHR = 1.68, 95% CI = 1.22-2.33), diabetes (aHR = 1.41, 95% CI = 1.12-1.78) and hypertension (aHR = 1.36, 95% CI = 1.15-1.62) and medications of statin (aHR = 1.42, 95% CI = 1.19-1.69) and calcium channel blocker (CCB) (aHR = 1.32, 95% CI = 1.11-1.58). The cumulative incidence of PD was significantly higher over the 12-year follow-up period in AMD cohort (log-rank test, p < 0.001). CONCLUSIONS: Patients with AMD may exhibit a higher risk of PD than those without AMD.

Association Between Severity of Leptospirosis and Subsequent Major Autoimmune Diseases: A Nationwide Observational Cohort Study.

Introduction: Infections play a role in autoimmune diseases (AD). Leptospirosis has been linked to the trigger of systemic lupus erythematosus. Objective: To investigate subsequent risk of major AD in hospitalized Taiwanese for Leptospirosis. Methods: Retrospective observational cohort study was employed. The enrolled period was from 2000 to 2012. In the main model, we extracted 4026 inpatients with leptospirosis from the Taiwan National Health Insurance Research Database (NHIRD) and 16,104 participants without leptospirosis at a 1:4 ratio propensity-score matched (PSM) by age, gender, index year, and comorbidities. The follow-up period was defined as the time from the initial diagnosis of leptospirosis to major AD occurrence or 2013. This study was re-analyzed by frequency-matching as a sensitivity analysis for cross-validation. Univariable and multivariable Cox proportional hazards regression models were applied to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Results: The adjusted HR (95% CI) of major ADs for the leptospirosis group was 4.45 (3.25-6.79) (p < 0.001) compared to the controls after full adjustment. The risk of major ADs was 5.52-fold (95% CI, 3.82-7.99) higher in leptospirosis patients hospitalized for seven days and above than the controls, while 2.80-fold (95% CI, 1.68-5.61) in those hospitalized less than seven days. The sensitivity analysis yields consistent findings. Stratified analysis revealed that the association between leptospirosis and major ADs was generalized in both genders, and all age groups. Conclusions: Symptomatic leptospirosis is associated with increased rate of subsequent major ADs, and the risk seems to be higher in severe cases.

Renal dysfunction is associated with lower odds of home discharge for patients with stroke.

OBJECTIVES: Studies on the association of estimated glomerular filtration rate (eGFR) levels with hospital discharge disposition after stroke are limited with inconsistent results. This study investigated the odds of home discharge with eGFR levels at admission for patients with stroke using the Taiwan Stroke Registry (TSR) data. METHODS: From the TSR database, a total of 51,338 stroke patients from 2006 to 2015 were categorized into five groups based on eGFR levels at admission. The proportion of home discharge by the eGFR levels was calculated and logistic regression analysis was used to estimate the related odds ratio (OR) and 95% confidence interval. RESULTS: Near 85% of stroke patients were discharged to home. The proportion of home discharges decreased as the eGFR level declined. Compared to patients with eGFR ≥90 mL/min/1.73 m2, the adjusted ORs of home discharge were 0.91, 0.85, 0.63, 0.56 for patients with eGFR 60-89, eGFR 30-59, eGFR 15-29, and eGFR < 15 mL/min/1.73 m2 or on dialysis, respectively, in a graded relationship. The trends were consistent in the ischemic stroke and hemorrhagic stroke patients. The areas under the receiver operating characteristic curve for all stroke patients, ischemic stroke patients, and hemorrhagic stroke patients were 0.801, 0799, 0.815, respectively. CONCLUSION: The odds of home discharge for stroke patients decreased with a significant independent graded association with declining eGFR levels. Renal function could predict home discharge after stroke.

Non-Typhoidal Salmonella and the Risk of Kawasaki Disease: A Nationwide Population-Based Cohort Study.

Objective: The aim of this study was to investigate the relationship between non-typhoidal Salmonella (NTS) infection and the risk of Kawasaki disease (KD) by using a nationwide population-based data set in Taiwan. Methods: In this retrospective cohort study, we enrolled 69,116 patients under 18 years of age, with NTS from January 1st, 2000, to December 31st, 2013, using the population-based National Health Insurance Research Database of Taiwan. A comparison group without NTS was matched (at a 1:4 ratio) by propensity score. The two cohorts were followed from the initial diagnosis of NTS until the date of KD development or December 31st, 2013. Cox proportional hazard regression analysis was conducted to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) after adjusting for covariates. Also, we conducted sensitivity analyses to examine our findings. Results: After adjusting for covariates, the risk of KD for the children with NTS was significantly higher than that of the comparison group (hazard ratio = 1.31; 95% confidence interval = 1.03-1.66; p < 0.01). Stratified analysis showed that the associated risk of the investigated outcome was significant in children aged ≤2 years (aHR= 1.31, 95% C.I. 1.02-1.69), in female patients (aHR= 1.46, 95% C.I. 1.03-2.08), and in those without allergic diseases. Conclusions: NTS is associated with an increased risk of KD in Taiwanese children.

Evaluation of the efficacy of traditional Chinese medicine for the reproductive and pregnancy outcomes in women with endometriosis: A nationwide population-based study.

OBJECTIVE: Patients with endometriosis may seek traditional Chinese medicine (TCM) to help them conceive. The present study aims to evaluate the effects of TCM on reproductive and pregnancy outcomes in patients with endometriosis. MATERIALS AND METHODS: The patients with endometriosis taken from the National Health Insurance (NHI) research database between 2000 and 2012 were divided into two cohorts based on the use of TCM treatment. The two cohorts were matched by age and comorbidities and followed up until a new diagnosis of infertility, ectopic pregnancy, or miscarriage. Multivariable Cox proportional hazards models were used to evaluate the hazard ratio (HR) of reproductive and pregnancy outcomes. RESULTS: A total of 5244 patients with endometriosis were analyzed, including 1748 TCM users and 3496 matched control subjects. The proportion of infertility was higher in TCM users than in non-TCM users (adjusted hazard ratio [HR]: 1.34, 95% confidence interval [CI]: 1.13-1.60). However, there was no significant difference in the proportion of ectopic pregnancies between TCM users and non-TCM users (adjusted HR: 0.82, 95% CI: 0.60-1.13). There was no significant difference in the proportion of miscarriages between TCM users and non-TCM users (adjusted HR: 1.23, 95% CI: 0.95-1.61). CONCLUSION: TCM treatment showed insignificant efficacy in decreasing the risk of ectopic pregnancy and miscarriage in patients with endometriosis.