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To evaluate birth outcomes in women with hypertensive disorders of pregnancy (HDP) and gestational diabetes mellitus (GDM), we used insurance data of Taiwan to evaluate 11 adverse neonatal outcomes of infants born to women with HDP (N = 7775) and with both HDP and GDM (HDP/GDM) (N = 1946), comparing to women with neither disorder (N = 19,442), matched by age. The impacts of preeclampsia/eclampsia were also evaluated. Results showed that Caesarean section delivery was near 1.7-fold greater in the HDP/GDM and HDP groups than in comparisons. The preterm delivery rates were more than threefold greater in HDP/GDM group and HDP group than in comparisons with adjusted odds ratios (aORs) of 4.84 (95% confidence interval (CI) 4.34–5.40) and 3.92 (95% CI 3.65–4.21), respectively, followed by jaundice (aORs 2.95 (95% CI 2.63–3.33) and 1.90 (95% CI 1.76–2.06)), and small gestation age (SGA) (aORs 6.57 (95% CI 5.56–7.75) and 5.81 (95% CI 5.15–6.55)). Incidence rates of birth trauma, patent ductus arteriosus, atrial septal defect, respiratory distress syndrome, and neonatal hypoglycemia were also higher in the HDP/GDM and HDP groups than in the comparison group. Most adverse outcomes increased further in women with preeclampsia or eclampsia. In conclusion, women with HDP are at elevated risks of adverse neonatal outcomes. Risks of most adverse outcomes increase further for women with both HDP and GDM. Preeclampsia or eclampsia may also contribute to these outcomes to higher risk levels. Every pregnant woman with these conditions deserves specialized prenatal care.

Background Restless legs syndrome (RLS) is prevalent in patients with chronic obstructive pulmonary disease (COPD). No large population-based cohort study has assessed the relationship. We evaluated the incidence of RLS among COPD patients by sociodemographic status (SES) and comorbidity using insurance claims data of Taiwan. Methods From the database, we established a cohort consisting of 77,831 individuals aged ≥ 20 years newly diagnosed with COPD from 2000 to 2013. We also identified same number of individuals without COPD as the comparison cohort, frequency matched by sex, age and index year. Both cohorts were followed up to the end of 2013 to estimate the incidence and hazard ratio (HR) of developing RLS. Results The incidence of RLS was 2.2-fold higher in COPD patients than in those free of COPD (6.67 and 3.08 per 10,000 person-years), with an adjusted HR (aHR) 1.68 (95% CI 1.41–2.01) after controlling for covariates. The incidence rates in both cohorts increased with age and higher in low socioeconomic group. The risk of RLS increased further among COPD patients with additional comorbidities. Compared to those without COPD and comorbidity, the aHR was 7.93 (95% CI 1.11–57.8) for those with iron deficiency, 3.95 (96% CI 1.92–8.13) with Parkinson's disease, 2.85 (95% CI 1.05–7.72) with polyneuropathy, or 1.81 (95% CI 1.14–2.87) with diabetes. Conclusion Patients with COPD are at an increased risk of developing RLS regardless of gender, age and occupation. The COPD patients with comorbidities should be particularly cautious about the RLS risk.

Background: Inflammation plays a crucial role in both type 2 diabetes mellitus (T2DM) and psoriasis pathogenesis; thus, a bidirectional association between them is likely suspected. Aims: We investigated the possible bidirectional association between T2DM and psoriasis. Methods: Using the Taiwan National Health Insurance Research Database, we conducted two retrospective cohort studies. The analysis of psoriasis onset in relation to T2DM status included 31,697 patients with diabetes and 126,788 nondiabetic control subjects (Analysis 1). The analysis of T2DM onset in relation to psoriasis status included 1,947 psoriatic patients and 7,788 nonpsoriatic control subjects (Analysis 2). The follow-up period was from 2000 to the date of the outcome of interest, date of death, or December 31, 2013. Cox proportional models were used to estimate the relative hazards. Results: In Analysis 1, Kaplan–Meier (KM)-based cumulative incidence of psoriasis was higher in the T2DM cohort than that in the non-T2DM cohort (1.2% vs. 0.7%). The covariate-adjusted hazard ratio (HR) was 1.40 [95% confidence interval (CI), 1.20–1.63] for patients with T2DM. Analysis 2 revealed KM-based cumulative T2DM incidences of 18.7% and 13.1% in psoriatic and nonpsoriatic subjects, respectively. The adjusted HR for incident T2DM was higher in patients with psoriasis (1.38; 95% CI, 1.20–1.58). Limitation: This article may not represent the population worldwide and patient selection bias may exist. Conclusion: Our results provide evidence for a bidirectional T2DM–psoriasis association. T2DM and psoriasis are common worldwide; thus, our findings have public health implications for the early identification and management of these comorbid diseases.

BackgroundFew investigations have evaluated the influences on peripheral arterial disease (PAD) risk of statin treatment in hemodialysis (HD) subjects with hyperlipidemia (HL).MethodsFrom the National Health Insurance Research Dataset, we identified 3658 HD patients with statin therapy for HL as the statin cohort, and then selected, by 1:1 propensity score matching, 3658 HD patients with HL but without statin use as the nonstatin cohort in 2000–07. The cohorts were followed through until the end of 2011. We used Cox proportional hazards regression analysis to assess the hazard ratio (HR) of PAD development.ResultsThe average follow-up period was 4.18 years; the incident PAD risk was 1.35-fold greater in statin users than in nonusers (16.87 versus 12.46/1000 person-years), with an adjusted HR (aHR) of 1.34 for PAD [95% confidence interval (CI) 1.12–1.62]. The PAD risk increases were significant for patients receiving fluvastatin (aHR 1.88; 95% CI 1.12–3.14) and atorvastatin (aHR 1.60; 95% CI 1.24–2.08). The risk increased with higher annual average statin dosage (P for trend ConclusionsHD patients with HL on statin medication were at increased PAD risk, which increased with cumulative statin dosage. Thorough considerations are needed before prescribing statins to HD patients.

Purpose: This retrospective cohort study was conducted to determine the glaucoma risk associated with metabolic disease (MetD) using insurance claims data of Taiwan. Methods: From the database, we identified patients with newly diagnosed hypertension, diabetes and/or hyperlipidemia from the years 2000 to 2002 as the MetD cohort (N = 42,036) and an age-gender-diagnosis-date matched control cohort without MetD with a two-fold sample size than that of the MetD cohort. Both cohorts were followed until the development of glaucoma, death, or withdrawal, until 31 December 2013. The incidence of glaucoma, and the Cox method estimated hazard ratio (HR) of glaucoma were calculated. Results showed that the incidence of glaucoma was two-fold higher in the MetD cohort than in the controls (1.99 versus 0.99 per 1000 person-years), with an adjusted HR of 1.66 (95% CI: 1.50–1.85). The glaucoma incidence was higher in patients with diabetes than those with hypertension and hyperlipidemia (2.38 versus 1.95 and 1.72 per 1000 person-years, respectively). The incidence increased to 5.67 per 1000 person-years in patients with all three comorbidities, with an aHR of 4.95 (95% CI: 2.35–10.40). We also found higher incidence rates of primary open-angle glaucoma and primary angle-closure glaucoma with aHRs of 2.03 and 1.44, respectively. It was concluded that glaucoma risk increased with the number of MetD. Health providers need to monitor patients with MetD to prevent glaucoma.

Background Evidences have shown that the stroke risk associated with long-term exposure to particulate matter with an aerodynamic diameter of ≤2.5 μm (PM2.5) varies among people in North America, Europe and Asia, but studies in Asia rarely evaluated the association by stroke type. We examined whether long-term exposure to PM2.5 is associated with developing all strokes, ischemic stroke and hemorrhagic stroke. Methods The retrospective cohort study consisted of 1,362,284 adults identified from beneficiaries of a universal health insurance program in 2011. We obtained data on air pollutants and meteorological measurements from air quality monitoring stations across Taiwan in 2010–2015. Annual mean levels of all environmental measurements in residing areas were calculated and assigned to cohort members. We used Cox proportional hazards models to estimate hazard ratio (HR) and 95% confidence interval (CI) of developing stroke associated with 1-year mean levels of PM2.5 at baseline in 2010, and yearly mean levels from 2010 to 2015 as the time-varying exposure, adjusting for age, sex, income and urbanization level. Results During a median follow-up time of 6.0 years, 12,942 persons developed strokes, 9919 (76.6%) were ischemic. The adjusted HRs (95% CIs) per interquartile range increase in baseline 1-year mean PM2.5 were 1.03 (1.00–1.06) for all stroke, 1.06 (1.02–1.09) for ischemic stroke, and 0.95 (0.89–1.10) for hemorrhagic stroke. The concentration-response curves estimated in the models with and without additional adjustments for other environmental measurements showed a positively linear association between baseline 1-year mean PM2.5 and ischemic stroke at concentrations greater than 30 μg/m3, under which no evidence of association was observed. There was an indication of an inverse association between PM2.5 and hemorrhagic stroke, but the association no longer existed after controlling for nitrogen dioxide or ozone. We found similar shape of the concentration-response association in the Cox regression models with time-varying PM2.5 exposures. Conclusion Long-term exposure to PM2.5 might be associated with increased risk of developing ischemic stroke. The association with high PM2.5 concentrations remained significant after adjustment for other environmental factors.

(1) Background: In previous research, higher levels of urine heavy metals, especially lead and cadmium, have been associated with increased cardiovascular risk. However, there is no information linking exposure to heavy metal to endothelial and platelet microparticles (EMPs and PMPs), particularly in the younger population, which are novel biomarkers of endothelial dysfunction. (2) Methods: From a nationwide database, which was incepted in 1992–2000, screening for renal health among Taiwanese school children, a total of 789 subjects were recruited. Cross-sectional analysis was performed to evaluate the association between serum EMPs/PMPs and urine iron, nickel, copper, cadmium, lead, chromium, manganese, and zinc levels in the adolescent and young adult population. (3) Results: After we adjusted the conventional cardiovascular risk factors, CD31+/CD42a− and CD31+/CD42a+ counts, in subjects’ serum, respective markers of EMP and PMP displayed a significant positive dose-response relationship with urinary lead and cadmium levels. Higher quartiles of urine lead and cadmium levels were associated with an increased risk of higher EMPs/PMPs (≥75th percentile) in a multivariate logistic regression model. (4) Conclusion: Higher urinary lead and cadmium concentrations are strongly associated with endothelium–platelet microparticles in this adolescent and young adult population, which could help explain, in part, the mechanism through which heavy metal exposure results in cardiotoxicity.

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.

Studies evaluating the association between age-related macular degeneration (AMD) risk and HCV infection are scant. In this population-based cohort study, 13,300 patients newly diagnosed as having HCV (HCV cohort) and 26,600 propensity score-matched patients without HCV (non-HCV cohort) were identified from the Taiwan National Health Insurance Research Database between 2000 and 2013. Furthermore, 1,983 patients with HCV who received pegylated interferon and ribavirin treatment (HCV-treated cohort) and propensity score-matched patients with HCV (matched at a ratio of 1:2) who did not receive this treatment (HCV-untreated cohort) were selected from the HCV cohort. Cox proportional hazards regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) associated with the risk of AMD in the HCV and non-HCV cohorts. The adjusted HR (aHR) for AMD in the HCV cohort was 1.22 (95% CI = 1.09–1.35). This significant association was observed only for nonexudative AMD (aHR = 1.22, 95% CI = 1.09–1.37). Compared with the HCV-untreated cohort, the HCV-treated cohort showed no significant association with any type of AMD (aHR = 1.07, 95% CI = 0.81–1.43). Age and sex did not modify AMD development after the exposure and treatment of chronic HCV infection. Our findings revealed that patients with chronic HCV infection had an increased risk of AMD.

Erythropoietic medications such as including erythropoietin (EPO) are known to be neuroprotective and to correlate with improved cognitive functions. However, it is not known whether supplementation with EPO reduces the risk of dementia in end-stage renal disease (ESRD) patients receiving hemodialysis (HD). Here, we determined whether EPO levels correlate with the incidence of different dementia subtypes, including Alzheimer's disease (AD), vascular dementia (VaD), and unspecified dementia (UnD), and whether such associations vary with annual cumulatively defined daily doses (DDDs) of EPO for ESRD patients receiving HD. This retrospective study included data from 43,906 adult ESRD patients who received HD between 1999 and 2010. Using hazard ratios and Cox regression models, we found that patients receiving EPO had a 39% lower risk of general dementia than those in the non-EPO group. Similarly, the risks of VaD and UnD was lower for patients in the EPO cohort. The risk of dementia was further reduced in HD patients treated with EPO in combination with iron. Our results suggest that the use of EPO medications in HD patients is associated with a reduced risk of VaD and UnD, but not AD, regardless of whether EPO is used alone or in combination with iron.

In the family of alkylphenolic compounds, 4-tertiary-Octylphenol (4-t-OP) is extensively used in many products. In animal and in vitro studies, 4-t-OP exposure has been linked to cardiovascular disease (CVD) risk factors; however, there are no previous human epidemiological studies. In this study, 886 subjects were recruited from a cohort of Taiwanese adolescents and young adults to study the relationship between serum levels of 4-t-OP, CVD risk factors, and common carotid artery intima-media thickness (CIMT). The geometric mean (SD) 4-t-OP concentration was 32.52 (1.71) ng/mL. We found that serum levels of 4-t-OP were negatively associated with markers of glucose homeostasis (insulin, homeostasis model assessment of insulin resistance (HOMA-IR) and homeostasis model assessment of β-cell function (HOMA-β)), z score of body mass index (BMI z score) and CIMT but were positively associated with lipid profiles (high density lipoprotein cholesterol (HDL-C), Apolipoprotein A1). A one-unit elevation in natural log-transformed 4-t-OP (ng/mL) was negatively correlated with CIMT (mm) (β = -0.029, SE = 0.003, P < 0.001) in multiple linear regression analyses. The relationship between 4-t-OP and CIMT remained the same in all subgroups or if bisphenol A (BPA) was considered a covariate. In this study, we observed that higher levels of 4-t-OP levels were negatively correlated with markers of glucose homeostasis, BMI z score, and CIMT; positively correlated with lipid profiles (HDL-C and apolipoprotein A) in this cohort. Future research on exposure to 4-t-OP and CVD risk factors is warranted.

This study investigated whether people with chronic kidney disease (CKD) are at the risk of new-onset type 2 diabetes. A cohort comprising 16,624 people with CKD, and an age- and sex-matched control cohort of 66,496 persons without any clinical kidney disease were identified from the Taiwan National Health Insurance Database during the period of 2000–2010. Both cohorts were followed up to 2011 to evaluate the incidence and hazard ratio (HR) of developing new-onset type 2 diabetes. Diseases were identified based on diagnosis coding. The incidence of type 2 diabetes was 1.51-fold higher in the CKD cohort than in the control cohort (16.9 versus 11.2 per 1,000 person-years) with an adjusted hazard ratio of 1.17 (95% confidence interval, (CI)1.10–1.24). In the multivariate Cox regression model considering the competing-risk death, the adjusted subhazard ratio of type 2 diabetes was 1.30 (95% CI1.22–1.38) for the CKD cohort compared to the control cohort. People with CKD patients are at an increased risk of developing new-onset type 2 diabetes. Close surveillance for diabetes should be considered for these people.

Background and aims This study investigated risks of short-term (1 and 3 months) and long-term (1-year) recurrent stroke associated with glomerular filtration rate (eGFR) in patients with acute ischemic stroke. Methods From the Taiwan Stroke Registry data, we identified 45,876 acute ischemic stroke patients from April 2006 to April 2014 and classified them into 4 groups based on the eGFR at admission: ≥ 90, 60–89, 30–59, and Results Both the risks of short-term and long-term recurrent stroke increased as the eGFR levels declined. The 1-month recurrent incidence rates increased steadily from 0.54 to 0.59, 0.84 and 0.89 per 1000 person-days, as the eGFR declined from ≥90 to 60–89, 30–59, and Conclusions There is an independent graded association between an increased risk of recurrent stroke and declining eGFR levels in patients with acute ischemic stroke.

Using the claims data of one million insured residents in Taiwan from 1996&ndash, 2013, this study identified 12,126 women in an urban city (Taichung) and 7229 women in a rural county (Yunlin), aged 20 and above. We compared Papanicolaou (Pap) test uses and cervical cancer detection rates between urban and rural women. Results showed that the Pap screening rate was slightly higher in rural women than in urban women (86.1 vs. 81.3 percent). The cervical cancer incidence was much greater for women without Pap test than women with the test (35.8 vs. 9.00 per 1000 in rural women and 20.3 vs. 7.00 per 1000 in urban women). Nested case-control analysis showed that Pap test receivers had an adjusted odds ratio (OR) of 0.35 (95% CI = 0.25&ndash, 0.51) to be diagnosed with cervical cancer as compared to those who did not receive the test. The rural women had an adjusted OR of 1.46 (95% CI = 1.03&ndash, 2.06) to be diagnosed with cervical cancer as compared to urban women. In conclusion, women in rural area are at higher cancer risk than city women. Women who do not undergo Pap tests deserve timely intervention of Pap test to prevent the onset of cancer, particularly in rural women with low income.

Background Patients with functional dyspepsia (FD) are more likely to have persistent depression, yet whether depression and antidepressant treatments are associated with subsequent risk of FD remain unclear. Methods Using population-based insurance administrative data of Taiwan, an 11-year historic cohort study was assembled, comparing cases aged 18 and above with the diagnosis of depressive disorder, to a propensity score-matched sample of adults without depression. Incident FD as a primary diagnosis was ascertained. Hazard ratios of FD were calculated using Cox regression models by age, gender, other comorbidities, nonsteroidal anti-inflammatory medications, antidepressants and antidiabetic agents. Results A total of 20,197 people with depressive disorder and 20,197 propensity score-matched comparisons without depression were followed up. The incidence of FD was 1.7-fold greater in the depressive cohort than in comparisons (12.9 versus 7.57 per 1000 person-years), with an adjusted hazard ratio (aHR) of 2.16 (95% confidence interval (CI) 1.93~2.41). Increased risks were significant regardless of comorbidities or medication uses, the highest in the untreated depression group compared to the group without depression, with an aHR of 2.51(95% CI 2.15~2.93). Conclusions This population-based study showed that patients with depressive disorder are at elevated risk of FD. Antidepressant treatment could reduce the risk of FD.

Studies on the thyroid disease risk in patients with rheumatoid arthritis (RA) associated with comorbidities are limited. This population-based retrospective cohort study investigated the hypothyroidism risk in patients with RA and the role of comorbidities. We used Taiwan National Health Insurance Research Database to identify 16,714 RA patients newly diagnosed in 2000 to 2008 and 66,856 control persons without RA, frequency matched by sex, age, and index year. Incidence and the RA group to controls hazard ratio of hypothyroidism were estimated. The hypothyroidism incidence was 1.74-fold higher in the RA group than in controls (16.6 vs 9.52 per 10,000 person–years), with the Cox method estimated adjusted hazard ratio of 1.67 (95% confidence interval = 1.39–2.00) after controlling for covariates. Near 75% of the study population were women, with the incidence 3.6-time higher than men in both groups. The hypothyroidism incidence increased with age, from 12.1 per 1000 person–years in 20 to 39 years to 20.0 per 1000 person–years in 60+ years in RA patients, higher than that in controls (7.17 vs 10.0 per 1000 person–years, respectively by age). Each comorbidity was related to an increased incidence and higher in the RA group than in controls. Among all comorbidities, stroke exerted the greatest impact in the RA group with an adjusted hazard ratio of 3.85 (95% confidence interval = 1.24–12.0). RA patients have an increased risk of developing hypothyroidism; this risk was pronounced in women and the elderly. RA patients should be closely monitored to prevent the development of hypothyroidism.

ObjectivesOur objectives are to examine whether patients with fibromyalgia (FM) present an increased risk of hearing loss (HL) compared with those without FM and to explore the relationship between comorbidities/drugs and development of HL in patients with FM. Furthermore, we investigated the incidence rate of different types of HL and the joint effects for HL with FM and comorbidities.MethodsThis population-based retrospective cohort study included patients with new-onset FM from 2000 to 2002 (the FM group) and age- and sex-matched randomized patients without FM (the non-FM group) from Taiwan's National Health Insurance Research Database. Patients were followed up from baseline (3 months after FM diagnosis) until death, withdrawal, HL development, or December 31, 2013. The primary outcome was the risk of HL, which was assessed using Cox proportional-hazards analysis.ResultsThe overall HL risk in the FM group was 1.46-fold (95% confidence interval [CI]: 1.38-1.55) higher than that in the non-FM group after adjustment for sex, age, and comorbidities (p < 0.0001). Patients with FM had significantly greater sensorineural HL (adjusted hazard ratio = 1.46, 95% CI: 1.37-1.56) than those without FM. Patients with FM having comorbidities of diabetes, hyperlipidemia, depression, and Meniere's disease had a higher risk of HL than those without FM.ConclusionOur findings support the notion that FM influences HL and is in line with the hypothesis that the FM mechanism is related to a central nervous system abnormality in sensory processing. Health care professionals should provide appropriate screening for the risk of HL and prevention and counseling methods for patients with FM.

There is a dearth of research on the hourly risk of ambulance dispatches with respect to ambient conditions. We evaluated hourly relative risks (RR) and 95% confidence interval (CI) of ambulance dispatches in Taiwan to treat respiratory distress, coma and unconsciousness, and out-of-hospital cardiac arrest (OHCA), from 2006 to 2015. We considered island-wide ambient temperatures, fine particulate matter (PM2.5), and ozone (O3) at lag 0–180 h while using a distributed lag nonlinear model and meta-analysis. Results showed the pooled risks peaked at lag 16–18 h for all ambulance dispatches at 99th percentile of hourly temperature (32 °C, versus reference temperature of 25 °C), with significant excess risk of 0.11% (95% CI; 0.06, 0.17) for coma and unconsciousness, and 0.06% (95% CI; 0.01, 0.11) for OHCA. The risks of exposure to 90th percentile of hourly O3 of 52.3 ppb relative to the Q1 level of 17.3 ppb peaked at lag 14 h, with excess risk of 0.17% (95% CI; 0.11, 0.23) for respiratory distress, 0.11% (95% CI; 0.06, 0.16) for coma and unconsciousness, and 0.07% (95% CI; 0.01, 0.14) for OHCA. The population exposed to reference temperatures of 28 °C, 20 °C, and 26 °C were exposed to the lowest levels of ambulance dispatches risk for respiratory distress, coma and unconsciousness, and OHCA, respectively; the highest cumulative 0–96 h RRs of ambulance dispatches were 1.27 (95% CI; 1.19, 1.35) for OHCA at 5th percentile temperatures and 1.25 (95% CI; 1.11, 1.41) for OHCA at 99th percentile temperatures. Following an accumulating lag of 0–96 h, no significant risk was identified for hourly levels of PM2.5 and O3. In conclusion, the analytical results of hourly data speak to immediate and real-time responses to environmental changes, rather than to short-term relationships. In our analyses, we emphasized health events in extreme heat; thus, we recommend a comparative study of daily versus hourly associations.

This study evaluated the association between the risk of events requiring ambulance services and the ambient temperature and particulate matter of 2.5 μm (PM2.5) and 10 μm (PM10) for populations living in subtropical Taiwan. We used a distributed lag nonlinear model with a quasi-Poisson function to assess the roles of ambient temperature, PM10 and PM2.5 in the use of ambulance services for respiratory distress, coma and unconsciousness, chest pain, lying down in public, headaches/dizziness/vertigo/fainting/syncope and out-of-hospital cardiac arrest (OHCA). The relative risk (RR) and 95% confidence interval (CI) of each specific event were calculated in association with the ambient conditions. In general, the events that required ambulance services had a V-shaped or J-shaped association with the temperature, where the risks were higher at extreme temperatures. The RR of each event was significant when the patients were exposed to temperatures in the 5th percentile (th percentile temperatures of >30 °C. The risks for use of ambulance services increased with PM exposure and were significant for events of respiratory distress, chest pain and OHCA after exposure to the 99th percentile PM2.5 after controlling for temperatures. Events requiring ambulance services were more likely to occur when the ambient temperature was low than when it was high for the population on the subtropical island of Taiwan. The association of the risk of events requiring ambulance services with PM were not as strong as the association with low temperatures.

Background This study evaluated vulnerable subpopulation on mortality, emergency room visits (ERVs) and outpatient visits associated with ambient daily temperature from 2000 to 2014 using vital statistics and insurance claims of Taiwan. Methods We used the distributed lag non-linear model to assess circulatory disease-specific deaths, ERVs, and outpatient visits by mean temperature after controlling particulate matter (PM10) and other covariates. Lag effect of temperature changes on health risks accumulated for 0–10 days associated with low temperature and for 0–5 days for high temperature were evaluated. Cause-specific pooled relative risk (RR) and 95% confidence intervals (CI) were estimated for the whole population of Taiwan using random-effects meta-analysis. Results We used reference temperatures of 60th percentiles for mortality from circulatory diseases, 99th percentile for ERVs of circulatory diseases, 2nd percentile for ERVs of heart diseases and ischemic heart disease, 53th percentile for ERVs of cerebrovascular disease, and 12–16th percentiles for outpatient visits of circulatory diseases. The lag effects peaked at lag 4–5 day for low temperature exposure and at lag 0 for high temperature exposure. Pooled cold related health risk was the highest for mortality from and ERV of circulatory diseases with RR of 1.41 (95% CI: 1.34, 1.49) and 1.41 (95% CI: 1.35, 1.48), respectively, as daily mean temperatures was at 1st percentile (12.8 °C). Heat related health risk was significant for mortality from heart diseases [RR = 1.12 (95% CI: 1.07, 1.18)] and ischemic heart diseases [RR = 1.13 (95% CI: 1.06, 1.20)] as daily mean temperatures was at 99th percentile (29.9 °C). Conclusions Health authority should evaluate the effectiveness of adaptive policy, strategy, and actions responding to extreme temperatures to prevent mortality from circulatory diseases.

Chronic hepatitis B virus (HBV) infections and colorectal cancer (CRC) are prevalent in Taiwan. We carried out a population-based case-control study to assess the association between HBV infection and CRC risk. Using the National Health Insurance Research Database of Taiwan, we identified 69,478 newly diagnosed patients with CRC from 2005 to 2011. We further randomly selected 69,478 age- and gender-matched controls without CRC from the same database. Odds ratios (ORs) were calculated to evaluate the association between chronic HBV infection and CRC using a logistic regression analysis. HBV infection was found to be associated with the risk of CRC (OR = 1.27, 95% confidence interval (CI) = 1.20&ndash, 1.33). This relationship was similar in men and women. Age-specific analysis revealed that the CRC risk associated with HBV decreased with age. The adjusted ORs for patients aged &lt, 55, 55&ndash, 64, and 65&ndash, 74 years were 1.63 (95% CI = 1.48&ndash, 1.79), 1.24 (95% CI = 1.13&ndash, 1.37), and 1.02 (95% = 0.92&ndash, 1.13), respectively. In conclusion, this study suggests that chronic HBV infection is significantly associated with an increased risk of CRC. Monitoring the risk of CRC development in young patients with HBV infection is crucial.

Whether thyroidectomy contributes to osteoporosis (OP) and osteoporotic fracture (OF) is a subject of debate. This study aimed to determine the effect of thyroidectomy on the risk of OP and OF. This retrospective cohort study is based on patient data between January 2000 to December 2005 from the National Health Insurance Research Database. Patients who underwent thyroidectomy were enrolled in the thyroidectomy cohort, and the control cohort was selected by propensity score matching at a ratio of 1:4. Incident OP and OF cases were identified until the end of 2013. The thyroidectomy cohort to control cohort adjusted hazard ratio (aHR) for OP/OF was assessed through multivariable Cox proportional hazard regression analysis. Totals of 1426 and 5704 patients were included in the thyroidectomy and control cohorts, respectively. The incidence density of OP was higher in the thyroidectomy cohort (7.91/1000 person-years) than in the control cohort (5.98/1000 person-years), with an aHR of 1.43 (95% CI 1.16–1.77, p

Background and aims Renal dysfunction is a potent risk factor for cardiovascular diseases, including stroke. This study aimed to evaluate the impact of admission estimated glomerular filtration rate (eGFR) levels on short-term (1-month) and long-term (1-year) mortality in patients with acute ischemic stroke. Methods From the Taiwan Stroke Registry data, we classified ischemic stroke patients, identified from April 2006 to December 2015, into 5 groups by eGFR at admission: ≥ 90, 60–89, 30–59, 15–29, and Results Among 52,732 ischemic stroke patients, 1480 died within one month. The 1-month mortality rate was over 5-fold greater in patients with eGFR Conclusions After acute ischemic stroke, patients with reduced eGFR are at elevated risks of short-term and long-term deaths in a graded relationship.

Concerns about acute pelvic inflammatory disease (PID) after hysterosalpingography (HSG) have been raised since 1980. However, the effectiveness of prophylactic antibiotics remains unclear. This study investigated the effect of antibiotic prophylaxis in women undergoing HSG.Women undergoing HSG between 2000 and 2012 were screened from the Taiwan National Health Insurance Research Database for eligibility. The prophylactic cohort included patients using any antibiotics of 1st-generation cephalosporins, doxycycline, clindamycin, and metronidazole, within 7 days before HSG (n = 3257). Patients not using any antibiotics were registered as the non-prophylactic cohort (n = 4662). An unconditional logistic regression model was applied to calculate the odds ratio (OR) and 95% confidence interval (CI) of acute PID after HSG associated with prophylactic antibiotics.The cumulative incidences of acute PID after HSG were 0.46% and 1.42% in the prophylactic and non-prophylactic cohorts, respectively. Prophylactic patients had a significantly reduced estimated relative risk of acute PID compared with non-prophylactic patients (adjusted OR = 0.33, 95% CI = 0.19-0.58; p = .001). Doxycycline users had the lowest adjusted OR of 0.20 (95% CI = 0.04-0.81; p = .02), followed by users of 1st-generation cephalosporins (adjusted OR = 0.35, 95% CI = 0.18-0.68; p = .002). Multivariate sub-group analysis verified this protective effect for almost all sub-groups of prophylactic patients.Antibiotic prophylaxis is associated with a decreased estimated relative risk of acute PID in HSG patients. Doxycycline and 1st-generation cephalosporins may be effective prophylactic regimens for HSG.

Background This study compared the risk of developing new-onset diabetes between hemodialysis (HD) and peritoneal dialysis (PD) patients. We further investigated the effectiveness of icodextrin in reducing the risk of new-onset diabetes in PD patients. Methods From the Taiwan health insurance database, 36 879 incident HD patients and 6382 incident PD patients from 2000 to 2010 were identified as study cohorts. We further selected an additional HD cohort matched by propensity scores (PSs) of PD patients. Incidence rates and hazard ratios (HRs) of new-onset diabetes were assessed among cohorts and between icodextrin users and nonusers by the end of 2011. Results For the unmatched cohorts, the incidence of new-onset diabetes was higher in PD patients than in HD patients (9.16 versus 8.18 per 1000 person-years), with an adjusted HR of 1.51 (95% CI 1.30-1.75) for PD patients. For the PS-matched cohorts, the corresponding incidence rates were 9.43 and 5.90 per 1000 person-years, respectively, with an adjusted HR of 1.61 (95% CI 1.32-1.97). Among PD patients, the incidence was lower in icodextrin users than in nonusers (6.22 versus 12.1 per 1000 person-years), with an adjusted HR of 0.66 (95% CI 0.50-0.88) for users. Conclusions Our study suggests that PD patients are at a higher risk of developing new-onset diabetes than HD patients. Icodextrin is recommended for PD patients to reduce the risk of new-onset diabetes.

Pleural empyema is an important complication of pneumonia. Patients with stroke are at a higher risk developing pneumonia; however, the association between stroke and pleural empyema risk is largely unknown. We used the data from the National Health Insurance Research Database of Taiwan to establish a stroke group consisting of 466,170 patients diagnosed between 2000 and 2010, and a non-stroke group consisting of the same number of individuals matched by the propensity score. Incident pleural empyema was monitored toward the end of 2011. Adjusted hazard ratios (aHRs) of pleural empyema in the stroke group, compared to the non-stroke group, were estimated using the Cox proportional hazards model. We found that the incidence of pleural empyema is 2.69-fold higher in the stroke group than in the non-stroke group (15.2 vs. 5.59/10,000 person-years, p

We investigated the impact of serum cholesterol levels on 30-day mortality after ischemic stroke in dialysis patients.From the Taiwan Stroke Registry data, we identified 46,770 ischemic stroke cases, including 1101 dialysis patients and 45,669 nondialysis patients from 2006 to 2013.Overall, the 30-day mortality was 1.46-fold greater in the dialysis group than in the nondialysis group (1.75 versus 1.20 per 1000 person-days). The mortality rates were 1.64, .62, 2.82, and 2.23 per 1000 person-days in dialysis patients with serum total cholesterol levels of 120 mg/dL, 120-159 mg/dL, 160-199 mg/dL, and ≥200 mg/dL, respectively. Compared to dialysis patients with serum total cholesterol levels of 120-159 mg/dL, the corresponding adjusted hazard ratios of mortality were 4.20 (95% confidence interval [CI] = 1.01-17.4), 8.06 (95% CI = 2.02-32.2), and 6.89 (95% CI = 1.59-29.8) for those with cholesterol levels of 120 mg/dL, 160-199 mg/dL, and ≥200 mg/dL, respectively.Dialysis patients with serum total cholesterol levels of ≥160 mg/dL or 120 mg/dL on admission are at an elevated hazard of 30-day mortality after ischemic stroke.

Population-based cohort study investigating the depression risk for patients with uterine leiomyoma (UL) is unavailable. This study investigated the subsequent risk of depression among patients with UL in an Asian population.Using data from the National Health Insurance Research Database of Taiwan, we established a cohort with 21,168 patients diagnosed with UL between 2000 and 2010, and a non-UL cohort of 82,108 women without UL matched by age and year of diagnosis. The occurrence of depression and Cox method measured adjusted hazard ratios (aHRs) were monitored until the end of 2011. The depression risk altered by surgery was also evaluated.The overall incidence of depression was 54% higher in the UL cohort than in the non-UL cohort (7.48 vs. 4.88/1000 person-years, p0.001), with an aHR of 1.46 [95% confidence interval (CI)=1.36-1.57] for the UL cohort. The depression risk increased with age and with comorbidity in both cohorts. Surgical intervention reduced the depression incidence to 4.76/1000 person-years for women with UL, with an aHR of 0.64 (95% CI=0.51-0.81) compared with those without a surgical treatment.The risk of depression is significantly higher in patients with UL than in those without UL. Surgical intervention for UL could significantly reduce the risk of depression. Evaluation of psychiatric status in patients with UL is strongly recommended.

Background: Sleep disorders other than sleep apnea (non-apnea sleep disorder, NSD), esp. insomnia and excessive daytime sleepiness, has been reported to induce higher risk of cognitive decline and dementia in previous longitudinal follow-up studies. However, large-scale nationwide populationbased study may further confirm the association between NSD and dementia. Methods: It was a nationwide population-based retrospective study. We used data from Taiwan’s National Health Insurance Research Database (NHIRD) between January 2000 and December 2011. The NSD cohort comprised 92,079 patients aged over 20 years with no preexisting dementia. The comparison cohort was propensity-score matched 1:1 with 92079 controls. Incident dementia cases were identified to the end of 2011. The NSD cohort to non-NSD cohort adjusted hazard ratios (aHRs) of dementia were assessed using multivariable Cox proportional hazards regression analysis. Results: Incidence of dementia was 4.19 and 2.95 per 1,000 person-years in the NSD and non-NSD cohorts, respectively, with an aHR of 1.46 (95% CI=1.38–1.54; p Conclusion: NSD may be an early indicator of decline in cognitive functioning and onset of dementia in the short-term period. It also carries a higher risk for dementia in the long run. Patients with NSD should require close monitoring for cognitive decline.

Background: The association of renal cancer with viral hepatitis infection remains unclear. Using an insurance data set, this population-based case-control study evaluated the association of renal cancer with chronic hepatitis virus infection in an endemic area of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection. Methods: We enrolled 17,747 patients with renal cancer during the period from 2000 to 2011 from the National Health Insurance Research Database of Taiwan. The control group comprised 35,494 randomly selected people without renal cancer matched by age and gender to the patients in the study group. ORs were calculated to assess the association of chronic hepatitis virus infection with renal cancer by using logistic regression analysis. Results: Renal cancer was associated with HBV and HCV infection (OR 1.38, 95% CI 1.24-1.54; OR 1.24, 95% CI 1.07-1.44, respectively). An analysis stratified by gender and age revealed that young male HBV carriers had a higher risk of renal cancer compared with men without viral hepatitis (age Conclusions: Renal cancer is significantly associated with chronic hepatitis infection, particularly in younger HBV-infected men.

Background: Alzheimer’s disease, the most common cause of dementia among the elderly, is a progressive and irreversible neurodegenerative disease. Exposure to air pollutants is known to have adverse effects on human health, however, little is known about hydrocarbons in the air that can trigger a dementia event. Objective: We aimed to investigate whether long-term exposure to airborne hydrocarbons increases the risk of developing dementia. Method: The present cohort study included 178,085 people aged 50 years and older in Taiwan. Cox proportional hazards regression analysis was used to fit the multiple pollutant models for two targeted pollutants, including total hydrocarbons and non-methane hydrocarbons, and estimated the risk of dementia. Results: Before controlling for multiple pollutants, hazard ratios with 95% confidence intervals for the overall population were 7.63 (7.28-7.99, p Conclusion: Our findings suggest that total hydrocarbons and non-methane hydrocarbons may be contributing to dementia development.

BACKGROUND AND PURPOSE Studies on using antiplatelet agents for secondary prevention in ischaemic stroke patients with renal dysfunction are limited. The Taiwan Stroke Registry database was used to compare the efficacy of antiplatelet agents. METHODS From the Taiwan Stroke Registry data, 39 174 acute ischaemic stroke patients were identified and were classified into three groups by antiplatelet agent: aspirin, clopidogrel and dual antiplatelet therapy (DAPT) with a combination of aspirin and clopidogrel. The re-stroke incidence and 1-year mortality were stratified by estimated glomerular filtration rate (eGFR) levels at admission: ≥90, 60-89 and

Few studies have investigated the risk of physiological sequelae in living kidney donors (KDs). We conducted a population-based cohort study using the National Health Insurance Research Database of Taiwan, which covers more than 99% of citizens. We comprehensively investigated the risk of medical disorders after kidney donation in living KDs using a maximum follow-up of 13 years. From January 1997 to December 2010, 1081 living KDs and 1082 age- and sex-matched non-KDs were eligible. Primary outcomes comprised end-stage renal disease, chronic kidney disease, stroke, cancer, acute myocardial infarction, acute renal failure (ARF), and diabetes. The adjusted hazard ratios (HRs) for developing ARF, diabetes, hyperlipidemia, hypertension, cancer, end-stage renal disease, acute myocardial infarction, and stroke were similar between the KD and non-KD cohorts (P > .05). Although differences in the adjusted HRs of ARF were nonsignificant, the cumulative incidence rate of ARF 13 years after donation was 7.48 per 1000 person-years in the KD cohort compared with 3.46 in the matched non-KD cohort. The incidence rate ratio for ARF between donors and nondonors significantly increased to 2.16 (95% confidence interval, 1.61–2.71). Living KDs experienced no significant health disorders following kidney donation but should be alert to the higher incidence rate of ARF.

Aim To investigate the appropriate fasting plasma glucose threshold by which to define prediabetes in children and adolescents, based on its ability to predict incident paediatric diabetes. Methods In a nationwide survey of diabetes and renal disease conducted between 1992 and 2000 in all school-aged children in Taiwan, those with abnormal results in repeated urine tests received further physical examination and blood tests. Students who had blood tests for at least two time points were selected for the present study (N = 12 119). The incidence of paediatric diabetes, adjusted hazard ratio and predictive power of fasting plasma glucose were analysed. Results The incidence of paediatric diabetes increased with increasing fasting plasma glucose levels. Groups with fasting plasma glucose >5.6 mmol/l had a higher adjusted hazard ratio. The adjusted hazard ratio of incident diabetes for participants with higher fasting plasma glucose rose continuously when using a higher threshold for fasting plasma glucose. The area under the receiver-operating characteristic curve for fasting plasma glucose was 0.628 for predicting paediatric diabetes. The association between fasting plasma glucose and incident paediatric diabetes and the area under the receiver-operating characteristic curve were similar in boys and girls and were higher in the age group 12-18 years. According to receiver-operating characteristic curve analysis, the optimal thresholds, sensitivity and specificity were 4.75 mmol/l, 65% and 51%, respectively, for those aged 6-11 years and 5.19 mmol/l, 60% and 73%, respectively, for those aged 12-18 years. Conclusion Fasting plasma glucose is associated with the incidence of paediatric diabetes. The results of the present study can be used as reference data to suggest a cut-off value to define paediatric prediabetes.

It remains unclear how different uses of angiotensin-converting inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) influence the progression of chronic kidney disease (CKD). This study explored CKD progression in a multicentre, longitudinal cohort study that included 2639 patients with CKD stage 1–5 and hypertension. Patients treated with ACEI or ARB for ≥90 days during a 6-mo period comprised the study group, or no treatment, comprised the control group. The study group was subdivided on the basis of treatment: ACEI monotherapy or ARB monotherapy. Progression of renal deterioration was defined by an average eGFR decline of more than 5 mL/min/1.73 m2/yr or the commencement of dialysis. With at least 1-year follow up, a progression of renal deterioration was demonstrated in 29.70% of the control group and 25.09% of the study group. Patients in the study group had significantly reduced progression of CKD with adjusted odds ratio 0.79 (95% confidence interval: 0.63–0.99). However, when ACEI monotherapy and ARB monotherapy were analyzed separately, none of their associations with CKD progression was statistically significant. In conclusion, ACEI or ARB monotherapy may retard the deterioration of renal function among patients with CKD and hypertension.

The link between phthalate exposure and the risk of subclinical atherosclerosis in young population remains unclear. This study investigated the association between phthalate exposure and subclinical atherosclerosis, in terms of carotid intima-media thickness (CIMT), in young population. From a nationwide mass urine screening for renal health, conducted in 1992-2000 among school children 6-18 years of age in Taiwan, we recruited 789 subjects to participate in the cardiovascular health examination in 2006-2008. Among them, 787 received measurements of 7 urinary phthalate metabolites and CIMT. Results showed both mean and maximal values of CIMT at all segments of carotid arteries significantly increased with the urinary mono-2-ethylhexyl phthalate (MEHP), ∑ di-(2-ethylhexyl) phthalate (DEHP), and mono-n-butyl phthalate (MnBP) in a dose-response relationship after adjustment for multiple linear regression models. Multivariate logistic regression analysis showed that higher quartiles of urinary concentrations of MEHP, ∑DEHP, and MnBP were associated with a higher risk of thicker CIMT. Compared to subjects with the lowest quartile (Q1) of urinary MEHP, the adjusted odds ratios (95% confidence interval) for thicker CIMT among subjects with higher urinary MEHP were 2.13 (1.18-3.84) at Q2, 4.02 (2.26-7.15) at Q3 and 7.39 (4.16-13.12) at the highest Q4. In conclusion, urinary phthalate metabolites of MEHP, ∑DEHP, and MnBP are strongly associated with CIMT in adolescents and young adults in Taiwan.

Purpose Lead (Pb) or cadmium (Cd) exposure has been linked to atherosclerosis. Co-exposure of these two heavy metals often occurs in humans. Recent evidence has indicated a crucial role of DNA methylation in atherosclerosis, while Pb or Cd exposure has also been shown to alter DNA methylation. However, it is still unknown whether DNA methylation plays a role in the pathological mechanism of these two heavy metals in atherosclerosis. Approach and results We enrolled 738 participants (12–30 years) to investigate the association among concentrations of urine Pb or Cd, the 5mdC/dG value (a global DNA methylation marker) and the carotid intima-media thickness (CIMT). When each heavy metal was modeled separately, the results showed urine Pb and Cd concentrations were positively associated with the 5mdC/dG value and CIMT, respectively. When the two heavy metals were analyzed in the same model, urinary Pb concentrations were positively associated with the 5mdC/dG value and CIMT, while urinary Cd concentrations were only positively associated with the CIMT. When Pb and Cd are simultaneously considered in the same logistic regression model, the odds ratios (OR) of thicker CIMT (greater than 75th percentile) with one unit increase in ln-Pb level was 1.67 (95% C.I. = 1.17–2.46, P = 0.005) when levels of 5mdC/dG were above 50th percentile, which is higher than 5mdC/dG bellow the 50th percentile (OR = 1.50 (95% C.I. = 0.96–2.35), P = 0.076). In structural equation model (SEM), Pb or Cd levels are directly associated with CIMT. Moreover, Pb or Cd had an indirect association with CIMT through the 5mdC/dG. When we considered Pb and Cd together, Pb levels had a direct association with CIMT and an indirect association with CIMT through the 5mdC/dG value, while Cd only had a direct association with CIMT. Conclusions Our findings imply that Pb and Cd exposure might be associated with subclinical atherosclerosis, and global DNA methylation might mediate Pb-associated subclinical atherosclerosis in this young population. Future effort is necessary to elucidate the causal relationship.

BACKGROUND Studies investigating the risk of cardiac dysrhythmia warranting permanent pacemaker therapy for end-stage renal disease (ESRD) patients are limited. This study investigated the incidence rate of permanent cardiac pacing in dialysis patients. METHODS Using the Taiwan National Health Insurance Database, we identified 28 471 newly diagnosed ESRD patients in 2000-2010 [9700 on peritoneal dialysis (PD) and 18 771 on hemodialysis (HD)] and 113 769 randomly selected controls without kidney disease, frequency-matched by sex, age and diagnosis date. We also established propensity score-matched HD and PD cohorts with 9700 patients each. Incidence rates and hazard ratios (HRs) of implantation were evaluated by the end of 2011. Complications were also evaluated among patients with implantation. RESULTS The incidence rates of permanent pacemaker implantation were 5.93- and 3.50-fold greater in HD and PD patients than in controls (1.44 and 0.85 versus 0.24 per 1000 person-years, respectively). The adjusted HRs (aHRs) of implantation were 3.26 [95% confidence interval (CI) = 2.41-4.42] and 2.36 (95% CI = 1.56-3.58) for HD and PD patients, respectively, compared with controls. The pacemaker implantation rate was 0.33 per 1000 person-years greater in the propensity score-matched HD cohort than in the PD cohort, with an aHR of 1.30 (95% CI = 0.82-2.05) for the HD cohort compared with the PD cohort. CONCLUSIONS Dialysis patients are at an increased risk of dysrhythmia requiring pacemaker implantation compared with the general population. The risks are not significantly different between HD and PD patients.

Background Combination therapy with angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II receptor blockers (ARB) has been stressed for its comprehensive blocking of the renin-angiotensin-aldosterone system, but the evidence for their respective safety and efficacy, in particular with stroke prevention, is still insufficient in population-based follow-up studies in the real world. Methods Using Taiwan's National Health Insurance claims data, we identified 5445 subjects aged 18years and older who had newly diagnosed hypertension in 1997–2010, from them diagnosed type 2 diabetes later. Among them, 2161 patients took ACEI, 1703 patients took ARB, 165 patients took both ACEI and ARB, and 1416 patients had neither. Results During the follow-up period, the stroke incidence density was the lowest (23.02 per 1000person-years) in ARB group, followed by the group with neither medication, the ACEI group, and ARB/ACEI combination group (24.06, 30.23, and 37.86 per 1000person-years, respectively). Compared with patients taking neither medication, the adjusted hazard ratios (HRs) were 1.27 (95% CI 1.02–1.58) for ACEI group, 0.95 (95% CI 0.74–1.22) for ARB group, and 1.56 (95% CI 0.99–2.47) for ARB/ACEI combined group. Greater reduction in risk of stroke was observed in patients with high dose ARB (adjusted HR=0·42, 95% CI 0·24–0·75). Conclusion Our findings support the practice that ARBs could be used, from the perspective of stroke prevention, as a first-line antihypertensive drug for patients with both hypertension and diabetes. The group with ARB regimen reduces 26% of stroke in contrast to the group with ACEI regimen.

The long-term consequence of cardiovascular health has not been evaluated for patients with carbon monoxide (CO) poisoning. This study evaluated the risk of ischemic stroke using population-based data.We identified 8705 inpatients with CO intoxication diagnosed from 2000 to 2011 from the Taiwan National Health Insurance Research Database. The control cohort consisted of 34,820 persons randomly identified from patients without exposure frequency matched by age, sex, and the year of hospitalization. Incidence and hazard ratio (HR) of ischemic stroke were evaluated by sociodemographic factors and comorbidities by the end of 2011.The incidence of ischemic stroke revealed a significant increase in the CO-poisoning cohort over the follow-up period (p0.001). The overall incidence of ischemic stroke was near 2.5-fold greater in the CO-poisoned cohort than in controls (5.49 versus 2.02 per 1000 person-years), with an adjusted HR of 2.60 (95% confidence interval (CI)=2.15-3.15). The adjusted HR for those without comorbidities was slightly higher (2.76, 95% CI=2.13-3.58). The age-specific CO-poisoning to non-CO-poisoning relative risk was greatest in the youngest group (20-34years) (adjusted HR=6.45; 95% CI=3.30-12.6).CO poisoning is associated with a long-term risk of increased incident ischemic stroke. Further study on the mechanism of ischemic stroke for CO poisoning affects is needed.

OBJECTIVE: We investigated the relationship between antidepressant use and the risk of subsequent dementia development. METHOD: A population-based retrospective case-control analysis was conducted using the Taiwan National Health Insurance Research Database. From patients enrolled in the National Health Insurance program between 2005 and 2011, we identified 2 subsets: 5,394 cases, who had major depression in 1997-2004 and subsequently were diagnosed with dementia (ICD-9-CM code 290) in 2005-2011, and 5,232 controls, who had major depression in 2005-2011 but no dementia history. The proportional distributions of antidepressant use and comorbidities in the dementia case and nondementia control groups were compared. Univariable and multivariable logistic regression analyses were used to estimate the odds ratios (ORs) and 95% CIs for the association between dementia and antidepressant use. RESULTS: The dementia patients were more likely to have diabetes, hypertension, stroke, and head injury. The adjusted OR for dementia was 0.24 (95% CI, 0.22-0.27) in patients using tricyclics. By contrast, the use of selective serotonin reuptake inhibitors (SSRIs) (OR = 2.48; 95% CI, 2.27-2.71), monoamine oxidase inhibitors (MAOIs) (OR = 1.86; 95% CI, 1.47-2.36), heterocyclic antidepressants (OR = 1.44; 95% CI, 1.32-1.57), and other antidepressants (OR = 2.05; 95% CI, 1.85-2.27) was associated with an increased risk of dementia. Furthermore, as the cumulative dose was increased, tricyclic antidepressants reduced the risk of dementia, whereas SSRIs, MAOIs, heterocyclic antidepressants, and other antidepressants increased the risk of dementia. CONCLUSIONS: The incidence of dementia in patients is associated with antidepressant medication use. Treatment with tricyclic antidepressants was associated with a reduced risk of dementia, whereas treatment with SSRIs, MAOIs, heterocyclic antidepressants, and other antidepressants was associated with an increased risk of dementia. Language: en

Ethnopharmacological relevance The use of traditional Chinese medicine (TCM) was high in stroke patients but limited information was available on whether TCM is effective on post-stroke outcomes. The aim of this study is to compare the outcomes of stroke patients with and without receiving adjuvant TCM therapy. Materials and methods Using Taiwan's National Health Insurance Research Database, we conducted a nationwide cohort study and selected hospitalized stroke patients receiving routine care with (n=1734) and without (n=1734) in-hospital adjuvant TCM therapy by propensity score matching procedures. The adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of poststroke complications and mortality associated with in-hospital adjuvant TCM therapy were calculated. The use of medical resource was also compared between stroke patients with and without adjuvant TCM therapy. Results Compared with hospitalized stroke patients receiving routine care alone, hospitalized stroke patients receiving routine care and adjuvant TCM therapy exhibited decreased risks of urinary tract infection (HR 0.82, 95% CI 0.68-1.00), pneumonia (HR 0.60, 95% CI 0.47-0.76), epilepsy (HR 0.67, 95% CI 0.49-0.96), gastrointestinal hemorrhage (HR 0.68, 95% CI 0.47-0.98), and mortality (HR 0.37, 95% CI 0.19-0.70) within 3 months after stroke admission. The corresponding 6-month HRs for urinary tract infection, pneumonia, gastrointestinal hemorrhage, and mortality were 0.83, 0.63, 0.64, and 0.40, respectively. Less use and expenditure of hospitalization were found in those received adjuvant TCM therapy. Conclusions Hospitalized stroke patients who received routine care and adjuvant TCM therapy exhibited reduced adverse outcomes after admission within a 6-month follow-up period.

Of patients with end-stage renal disease (ESRD), 8–16 % had a history of stroke at dialysis initiation. We used the National Health Insurance Research Database of Taiwan to evaluate whether peritoneal dialysis (PD) or hemodialysis (HD) confers a survival advantage for patients with incident ESRD and prior stroke. We identified 975 patients undergoing PD and 975 propensity score-matched patients with newly diagnosed ESRD and prior stroke undergoing HD between 2000 and 2010. Both cohorts were followed up until the end of 2011. Comparisons of the risks of mortality between PD and HD were analyzed using the Cox proportional hazards regression model. In the propensity score-matched cohorts, there was a 2.4 per 100 person-years greater mortality in patients with PD (20.4 vs. 18.0 per 100 person-years) with an adjusted hazard ratio (HR) of 1.20 (95 % CI 1.06–1.36). For patients with diabetes, ESRD and prior stroke, patients undergoing PD had inferior survival compared with those undergoing HD (adjusted HR 1.22, 95 % CI 1.05–1.43), particularly among female patients (adjusted HR 1.55, 95 % CI 1.25–1.91). For patients with ESRD and prior stroke but without diabetes, there was no significant difference in mortality between PD and HD (adjusted HR 1.20, 95 % CI 0.96–1.50). PD was associated with overall poorer survival among patients with diabetes, ESRD and prior stroke and with similar overall survival among patients with ESRD and prior stroke, but without diabetes, compared with HD.

Background Previous studies have suggested that mycobacterial infections could trigger autoimmune diseases, including rheumatoid arthritis (RA). Objective To explore the association between previous tuberculosis (TB) and RA. Methods We conducted a case-control study using data obtained from the National Health Insurance (NHI) system of Taiwan. We identified 26 535 adults with RA from 2002 to 2011, with the date of diagnosis as the index date. This number was randomly selected and frequency-matched four times by age, sex and the year of index date from among non-RA individuals. Odds ratios (ORs) of RA were calculated for associations with TB. Results Compared with controls, RA patients had a crude OR of 1.77 for TB (95%CI 1.61-1.94). The strength of the association between RA and TB remained at the same level after controlling for other potential risk factors (adjusted OR 1.73, 95%CI 1.57-1.90), although RA patients tended to have a higher prevalence of hypertension, coronary artery disease and kidney disease. Conclusion TB was much more prevalent in RA patients than in control subjects. Prospective cohort studies are required to establish a causal relationship between previous TB and RA.

Purpose This study was carried out to assess the risk of gynecological malignancy in colorectal cancer survivors using a population-based retrospective cohort study. Method Using the National Health Insurance Research Database (NHIRD) of Taiwan, we identified 37,176 patients with colorectal cancer diagnosed in 1998–2009, aged 20 years and above, without other cancer history. We also randomly selected 148,700 women without any cancer in the comparison cohort, frequency matched by age and diagnosis date. Incidences and hazards of breast, cervix, endometrial and ovarian cancers were evaluated by 201l. Results The overall incidence of the 4 types of gynecological cancer was 39.0% higher in colorectal cancer patients than in comparisons (2.99 vs. 2.14 per 1000 person-years) with an adjusted hazard ratio (HR) of 1.46 (95% confidence interval (CI) = 1.31–1.62). Breast cancer accounted for most subsequent cancer. The multivariable Cox method measured HR was the highest for endometrial cancer (3.40, 95% CI = 2.59–4.47) for the colorectal cohort relative to comparisons, followed by ovarian cancer and breast cancer, except cervix cancer. The risk of gynecological malignancies was apparently elevated for colorectal cancer survivors Conclusions Follow-up measures are suggested for women with colorectal cancer for early detection and prevention of the subsequent gynecological malignancy.

We investigated the relationship between dermatomyositis/polymyositis (DM/PM) and the risk of subsequent osteoporosis development. A population-based retrospective cohort analysis was conducted using the National Health Insurance Research Database and the Catastrophic Illness Patients Database of Taiwan. We included 1179 patients and 4716 patients from 1999 to 2008 as the DM/PM cohort and the comparison cohort, respectively, and calculated the incidence rates of newly diagnosed osteoporosis. We used Cox proportional hazards models stratified on matched pair to assess the effect of DM/PM. The Kaplan-Meier method was applied to estimate the cumulative osteoporosis incidence curves. Patients with DM/PM were 2.99 times more likely to experience osteoporosis than those without DM/PM. The risk for osteoporosis in DM/PM patients was higher than comparisons in different propensity score quartiles. DM/PM cohort, no matter treated with or without corticosteroids and immunosuppressant, had a higher risk than the comparison cohort. The incidence of osteoporosis in Taiwan is associated with a priori DM/PM history. This risk was independent of the corticosteroids and immunosuppressant treatment.

Aspirin (ASA) exerts an anti-tumor effect via the COX pathway. Clinical studies on the chemopreventive effects of ASA on uterine cancer (UC) remain inconsistent. We used population-based retrospective cohort study to evaluate the UC in ASA users in Taiwanese women. From insurance claims data, we identified 23,342 women received ASA treatment between 2000 and 2010 and a comparison group of same sample size randomly selected from the same database matched by the propensity score. The incidence of UC in the ASA cohort was 10% of that in the comparison group (0.28 vs 2.73 per 10,000 person-years). The Poisson regression analysis estimated adjusted incidence rate ratio (IRR) was 0.10 (95% confidence interval (CI) = 0.09–0.11) for ASA users relatives to comparisons after controlling for covariates. The UC incidence in ASA users decreased with age, from 0.61 per 10,000 person-years in the 20 to 39 years old (adjusted IRR = 0.21, 95% CI = 0.15–0.29) to 0.21 per 10,000 person-years in the 65 to 80 years old (adjusted IRR = 0.15, 95% CI = 0.12–0.16). The incidence was higher in longer term users. Hormone therapy of estradiol was associated with the increase of UC risk in both cohorts, but less in ASA users than comparisons (1.34 vs 4.75 per 10,000 person-years). This study suggests that ASA use was associated with a decreased risk of UC. Further prospective randomized clinical trials are warranted to confirm the association.

Background Twin infants are likely at great risk for ROP, but studies reported conflicting findings and population studies examining the risk of retinopathy of prematurity (ROP) in twins is limited. We aimed to evaluate the ROP risk in the cohort of one of twins, comparing to singletons. Material and methods Using insurance claims data of a half of children in Taiwan ages 18 and less, we established a twin cohort (N = 27830) born in 1998–2009 and a randomly selected singleton cohort (N = 111080) frequency matched by sex, birth year, residential area and parental occupation and followed up to 2012 years. Results The overall incidence rate of ROP was 13.6-fold greater in the twin cohort than in the singleton cohort (35.1 vs. 2.58 per 10,000 person-years; adjusted HR = 13.4, 95% CI = 11.7–15.3; p

Exposure to air pollutants is known to have adverse effects on human health; however, little is known about the association between hydrocarbons in air and an ischemic stroke (IS) event. We investigated whether long-term exposure to airborne hydrocarbons, including volatile organic compounds, increased IS risk. This retrospective cohort study included 283,666 people aged 40 years or older in Taiwan. Cox proportional hazards regression analysis was used to fit single- and multiple-pollutant models for two targeted pollutants, total hydrocarbons (THC) and nonmethane hydrocarbons (NMHC), and estimated the risk of IS. Before controlling for multiple pollutants, hazard ratios (HRs) of IS with 95% confidence intervals for the overall population were 2.69 (2.64-2.74) at 0.16-ppm increase in THC and 1.62 (1.59-1.66) at 0.11-ppm increase in NMHC. For the multiple-pollutant models controlling for PM2.5, the adjusted HR was 3.64 (3.56-3.72) for THC and 2.21 (2.16-2.26) for NMHC. Our findings suggest that long-term exposure to THC and NMHC may be a risk factor for IS development.

ObjectiveThoracic infection and pneumonia are prevalent in patients with schizophrenia; however, it is unclear whether patients with schizophrenia are at an increased risk of developing pleural empyema.DesignA retrospective cohort study with propensity-matched cohorts with and without schizophrenia.SettingUsing the National Health Insurance Research Database of Taiwan.ParticipantsWe identified 55 888 patients with schizophrenia newly diagnosed in 2000–2011 and same number of individuals without schizophrenia as the comparison cohort, frequency matched by propensity scores estimated using age, sex, occupation, income, urbanisation, year of diagnosis and comorbidities.Primary outcome measuresWe assessed incident pleural empyema by the end of 2011 and used the Cox proportional hazards model to calculate the schizophrenia cohort to comparison cohort HR of pleural empyema.ResultsThe overall incidence of pleural empyema was 2.44-fold greater in the schizophrenia cohort than in the comparison cohort (4.39vs1.80 per 10 000 person-years), with an adjusted HR of 2.87(95% CI 2.14 to 3.84). Stratified analyses by age, sex, occupation, income, urbanisation and comorbidity revealed significant hazards for pleural empyema associated with schizophrenia in all subgroups.ConclusionsPatients with schizophrenia are at an increased risk of developing pleural empyema and require greater attention and appropriate support.