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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/Purpose Type 2 diabetes has become an important cause of diabetes in children. Since most children with type 2 diabetes are asymptomatic, a screening method is needed. However, physicians are required in the screening methods recommended by professional associations. We aimed to develop a simple and efficient screening method for children with diabetes. Methods A nationwide survey was conducted, which included 2,270,496 seventh-grade students. Students with two abnormal results in sequential urinalyses were given a fasting blood test. Three screening methods were developed. Results Among the screening methods, method C is simple, and can be performed by parents, teachers, or school nurses. It suggests children with two abnormal results in sequential urinalyses and who are overweight or have a family history of diabetes receive blood tests. As a result, 0.10% of boys and 0.16% of girls were recommended to receive blood tests, and 7.0% of boys and 6.7% of girls receiving blood tests were diagnosed diabetes. On average, 15,002 boys and 9056 girls had to be screened to find one child with diabetes. The cost per 1000 children by method C was 2466.84 US dollars. Conclusion Urinalysis screening followed by evaluation of risk factors is a simple and efficient way to identify children with diabetes in schools.

We aim to evaluate breast cancer risk relating to PPIs usage in women with peptic ulcer. From 2000 to 2013, incidence rates of breast cancer were compared between the two cohorts (with or without PPIs). Each study cohort consisted of 4838 women. The incidence density rate of breast cancer in the PPI cohort was 0.29 that in the comparison cohort (10.0 vs 31.6 per 10 000 person-years), with an adjusted HR (hazard ratio) of 0.32 (95% CI = 0.20-0.49) for the PPI cohort. In conclusion, the medication of PPIs is associated with reduced breast cancer risk for women with gastric ulcer.

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.

Background Environmental lead exposure is a known risk factor of cardiovascular disease (CVD) in animal and human epidemiological studies of adults, but limited research has been conducted in young populations. Moreover, the association between lead level and common carotid artery intima-media thickness (CIMT) has never been documented. Design and Participants: In this study, 738 subjects were recruited from a cohort of Taiwanese adolescents and young adults to study the relationship between lead levels in urine and CVD risk factors, metabolic syndrome (MS) and CIMT. Results The geometric mean of the urine lead level was 1.50 μg/g creatinine. We found a significant positive association between urine lead levels and CVD risk factors, including diastolic blood pressure (DBP), mean arterial pressure (MAP), as well as markers of glucose homeostasis, such as serum glucose, serum insulin, homeostasis model assessment of insulin resistance (HOMA-IR), homeostasis model assessment of β-cell function (HOMA-β), body mass index (BMI) z score, and CIMT. Overall, increased urine lead concentrations were positively correlated with the prevalence of MS, specifically the criteria of waist/BMI and serum HDL-C. The relationship between urine lead levels and CIMT remained unchanged in all subgroups. Conclusion In this study, we found that increased urinary levels of lead were positively associated with CVD risk factors, CIMT, and MS in this cohort. Future research to explore the pathogenic basis of exposure to lead and risk of CVDs and their risk factors are warranted.

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.

Increased prevalence of sleep disorders has been found in patients with functional dyspepsia; however, direction of causality remains unclear. Our aim was to compare the risk of incident functional dyspepsia between patients with and without sleep disturbance from a large population-based sample. Utilizing a nation-wide health insurance administrative dataset, we assembled an 11-year historic cohort study to compare subsequent incidence of diagnosed functional dyspepsia between adult patients with any diagnosis of sleep disturbance and age- and gender-matched controls. Hazard ratios adjusted for other relevant comorbidities and medications were calculated using Cox regression models. 45,310 patients with sleep disorder and 90,620 controls were compared. Patients with sleep apnea had a 3.3-fold (95% confidence interval: 2.82 ~ 3.89) increased hazard of functional dyspepsia compared with controls. This increased risk persisted regardless of previously diagnosed depression coexisted. Sleep disturbance was associated with an increased risk of subsequent functional dyspepsia. Potential mechanisms are discussed.

Objective: This study investigated the medical care costs of stroke type between age-matched cohorts with and without dysmenorrhea using the National Health Insurance Research Database (NHIRD).Methods: We collected all 66,048 women with dysmenorrhea and 66,048 women without dysmenorrhea whose age (15-44-year-old) and index year (from 1997 to 2013) were matched for comparison. We assessed the incidence and compared the risk of stroke and stroke subtype in two cohorts. The proportional distributions of stroke subtypes by age between the two cohorts were compared among the women with stroke, and their hospitalization rate was also estimated. In addition, medical cost, length of stay, and the medical cost within 30 days after stroke were compared between the two cohorts.Results: The stroke risk in dysmenorrhea was greater than comparisons (HR = 1.26, 95% CI = 1.11–1.42). Proportionally, hemorrhagic stroke (HS) significantly decreased with age in both cohorts, whereas ischemic stroke (IS) significantly increased with age when both cohorts were combined. The dysmenorrhea cohort had a higher portion of transient cerebral ischemia (TIA) stroke than comparisons (31.3 vs. 24.2%, p = 0.01) and a lower risk of hospitalization for IS (OR = 0.48, 95% CI = 0.21–0.69). Among the four-stroke subtypes, the cost of care for TIA was the least (US$157 ± 254). The average cost for stroke care was not significantly different between women with and without dysmenorrhea.Conclusion: The hospitalization rate and medical costs of TIA are lower than other types. All women should prevent and treat TIA as soon as possible to avoid recurrence or progression to major stroke events and reduce medical costs, regardless of whether they have dysmenorrhea.

(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.

AIM This study assessed the incidence of epilepsy in preterm infants and those small for gestational age (SGA) at term and identified risk factors associated with higher epilepsy incidence in these children. METHODS We enrolled children (from 2000 to 2010) who were premature (n = 21 474) or SGA (n = 2206); we then included a matched control cohort (n = 94 720). Cox regression was used to assess the epilepsy risk in preterm and SGA children. To determine the associated factors for epilepsy, the preterm and SGA infants were divided into six groups according to the common complications related to brain development and were separated into three subgroups based on birthweight (BW). RESULTS The cumulative incidence of epilepsy was significantly higher in preterm or SGA children than in the control group. The overall incidence densities (per 1000 person-years) of epilepsy were: 0.37 in the control, 2.96 in the preterm, 2.90 in the SGA, 15.9 in the preterm with cerebral haemorrhage, 14.6 in the SGA with cerebral haemorrhage, 6.92 in the preterm with asphyxia, 3.82 in the SGA with asphyxia, 14.3 in the preterm with congenital brain anomalies, and 25.4 in the SGA with congenital brain anomalies cohorts. Infants with BW

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.

Per- and polyfluoroalkyl substances (PFAS) are a class of man-made chemicals used in many products. Recent in vitro and epidemiological reports have found that PFAS exposure can modify the function of platelets. Platelet size has been shown to affect platelet activity, and thrombograms are a simple method of indirect assessment of platelet function. However, there has been no large-scale research investigating the association between PFAS levels and complete thrombograms in humans.In the current cross-sectional study, we enrolled 1779 Taiwanese subjects (aged between 12 and 63 years) to study the associations between serum PFAS concentrations and thrombograms. There were 1175 men and 604 women with a mean age of 34.5 years. When all four PFAS were fitted by the multiple linear models at the same time, platelet counts decreased significantly with increasing quartiles of perfluorooctanoate acid (PFOA) and perfluorooctane sulfonate (PFOS), while platelet distribution width (PDW), mean platelet volume (MPV), and platelet-large cell ratio (PLCR) also increased significantly with increasing quartiles of PFOS. The mean platelet count was the lowest (264.02 k/µL [95% CI 256.00-272.04]; P 0.001) when both PFOA and PFOS concentrations were above the 50th percentile.We report that serum PFAS levels were correlated with thrombograms. If the association is etiologic, PFOA/PFOS may decrease the number of platelets, while PFOS may also increase the variation and the average size of platelets in the subjects of the study. Interestingly, PFOA and PFOS may have synergistic effects on the decrease in platelet counts. Further research is needed to study the effect of PFAS on platelets in humans.

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.

Background: This retrospective cohort study compared patient survival and technique survival between patients on continuous ambulatory peritoneal dialysis (CAPD) and automated peritoneal dialysis (APD) using recent data at a single tertiary medical center in Taiwan. Methods: From medical records, we identified incident 459 CAPD patients and 266 APD patients on dialysis for at least 90 days and aged more than 18 years to estimate mortality and technique failure rates, and related hazard ratio (HR) and 95% confidence interval (CI) from 2007 to 2018. Results: There were more women (52.3%) in the CAPD group, whereas patients in the APD group were younger. Compared to CAPD patients, APD patients had a lower mortality rate (2.83 vs. 5.79 per 100 person-years) with an adjusted HR of 0.69 (95% CI = 0.47–1.02), and a lower technique failure rate (9.70 vs. 17.52 per 100 person-years) with an adjusted HR of 0.65 (95% CI = 0.51–0.83). Further subgroup analyses revealed that, compared to CAPD, APD was associated with a significant lower risk of technique failure in male patients, patients aged 50–65 years, diabetic patients, patients without cardiovascular disease (CVD), patients with higher peritoneal permeability, or patients initiating PD in an earlier era. Conclusions: The mortality risk was not significant between CAPD and APD patients. APD is associated with a lower risk of technique failure than CAPD, particularly for male patients, and patients aged 50–65 years, with diabetes, without CVD, with high or high average peritoneal permeability, or initiating PD in an earlier era.

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.

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.

Acrylonitrile is a colorless volatile liquid mostly present in tobacco smoke. Acrylonitrile exposure has shown to increase oxidative stress in animal studies; however, there was no previous research in human epidemiology. In this study, 853 subjects were recruited from a cohort of Taiwanese adolescents and young adults to investigate the association between urinary concentrations of the acrylonitrile metabolite N-acetyl-S-(2-cyanoethyl)-L-cysteine (CEMA), the oxidative stress product 8-hydroxydeoxyguanosine (8-OHdG) and cardiovascular disease (CVD) risk factors. The geometric mean (SD) of CEMA and 8-OHdG concentrations were 4.67 (8.61) μg/L and 2.97 (2.14) μg/L, respectively. 10% elevated in CEMA (μg/L) was positively correlated with the change of 8-OHdG levels (μg/L) (β = 0.325, SE = 0.105, P = 0.002) in multiple linear regression analyses. The urinary CEMA was not related to other CVD risk factors. In subpopulation analyses, the association between CEMA and 8-OHdG was evident in all genders, adolescents, homeostasis model assessment of insulin resistance score ≥0.89, and environmental tobacco smokers. In this study, we observed that higher levels of CEMA levels were correlated with increased levels of 8-OHdG in this cohort. Future research on exposure to acrylonitrile and oxidative stress was warranted.

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.

Purpose Per- and polyfluoroalkyl substances (PFAS) are human-made chemicals used in daily use products. Recent studies have shown that different perfluorooctanoic acid (PFOA) and/or perfluorooctane sulfonate (PFOS) isomers may have different biological effects. In vitro studies have also reported that PFAS exposure can alter the structure of hemoglobin (Hb). In epidemiology, however, few studies have investigated the relationship between PFAS exposure and erythrocytes. Additionally, the correlation between PFOA/PFOS isomers and full erythrograms has never been explored. Approach and results In cohorts comprising young and middle-aged Taiwanese populations, we enrolled 1483 participants (aged between 12 and 63 years) to analyze the correlations between the plasma levels of PFOA/PFOS isomers and whole-blood erythrograms. The study comprised 868 men and 615 women with a mean age of 31.2 years. When all PFOA/PFOS isomers were entered into the multiple linear regression model, the linear PFOA ( L -PFOA) levels were positively correlated with the Hb, hematocrit (HCT), mean corpuscular volume (MCV), and mean corpuscular hemoglobin (MCH) levels while the branched PFOS (B-PFOS) levels were positively associated with the Hb, HCT, and mean corpuscular hemoglobin concentration (MCHC). The mean value of Hb was the highest (14.66 mg/dL (95% CI =14.52–14.80); P for trend L -PFOA and B-PFOS levels were above the 50th percentile. Conclusions The results imply that PFOA/PFOS isomers may increase the weight and volume of Hb/RBC and that L -PFOA/B-PFOS may have an additive effect on the Hb levels. However, it is also possible PFAS detected at a higher concentration may due to its binding to higher levels of Hb. Further studies are needed to investigate the effects of PFOA/PFOS isomers on RBCs in humans.

No study has ever investigated how ambient temperature and PM2.5 mediate rotavirus infection (RvI) in children. We used insurance claims data from Taiwan in 2006–2012 to evaluate the RvI characteristics in children aged ≤ 9. The RvI incidence rates were higher in colder months, reaching the highest in March (117.0/100 days), and then declining to the lowest in July (29.2/100 days). The age–sex-specific average incident cases were all higher in boys than in girls. Stratified analysis by temperature (2.5 (3) showed that the highest incidence was 16.4/100 days at average temperatures of 2.5 of 31.5–41.9 μg/m3, with Poisson regression analysis estimating an adjusted relative risk (aRR) of 1.26 (95% confidence interval (CI) = 1.11–1.43), compared to the incidence at the reference condition (2.5 < 17.5 μg/m3). As the temperature increased, the incident RvI cases reduced to 4.84 cases/100 days (aRR = 0.40, 95% CI = 0.35–0.45) when it was >25 °C with PM2.5 < 17.5 μg/m3, or to 9.84/100 days (aRR = 0.81, 95% CI = 0.77–0.93) when it was >25 °C with PM2.5 > 42 μg/m3. The seasonal RvI is associated with frequent indoor personal contact among children in the cold months. The association with PM2.5 could be an alternative assessment due to temperature inversion.

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.

BackgroundDysmenorrhea and stroke are health problems affecting women worldwide in their day-to-day lives; however, there is limited knowledge of the stroke risk in women with dysmenorrhea, and there have been no studies assessing the specific distribution of stroke subtypes. This case-control study assessed stroke subtypes by age and the role of comorbidities in women with dysmenorrhea.Methods and findingsData obtained between 1997 and 2013 from Taiwan's health insurance database identified 514 stroke cases and 31,201 non-stroke controls in women with dysmenorrhea aged 15-49 years. Proportional distributions of subtypes and odds ratios (ORs) of stroke associated with comorbidities by age and subtype were measured. We found that the stroke risk in dysmenorrheal patients increased with age, and that hypertension was nine-fold more prevalent in the stroke cases than in the controls and was associated with an adjusted OR of 4.53 (95% confidence interval (CI) = 3.46-5.92) for all stroke cases. Moreover, the proportion of hemorrhagic stroke was greater than that of ischemic stroke in younger dysmenorrheal patients between 15-24 years old (50.5% vs. 11.4%), whereas this was reversed in those aged 30-49 years old (16.1% vs. 21.0%). Overall, 25.3% of the stroke cases consisted of transient cerebral ischemia and 31.3% were other acute but ill-defined cerebrovascular diseases, in which the prevalence increased with age for both types of strokes. Hypertension was the comorbidity with the highest OR associated with each subtype stroke; diabetes, hyperlipidemia, arrhythmia, and thyroid disease were also comorbidities that were significantly associated with ill-defined cerebrovascular diseases.ConclusionsThe stroke type varies by age in dysmenorrheal patients, and hypertension is the most important comorbidity associated with all types of stroke; therefore, more attention for stroke prevention must be paid to women with dysmenorrhea, particularly when combined with comorbidities.

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.

This study used insurance claims data to evaluate obstetric outcomes in pregnant women with and without depression because population study for Asian women on the issue is limited. We identified 5,064 women with depression at pregnancy in 2005-2013, and 20,024 pregnant women without depression, frequency matched by age, pregnant year and parity. Obstetric events during pregnancy and deliveries were evaluated. The depression group had more events than comparisons for hyperemesis (39.3 vs. 35.5%), abortion (3.3 vs. 2.6%), malpresentation (12.3 vs. 10.3%), C-section (40.2 vs. 34.6%) and intrauterine fetal demise (0.7 vs. 0.4%); risks of these events were significant for childbearing depressed women, not for the 35+ years subgroup. These incidences were higher in depressed women taking antidepressant than those without the medication, but were significant in childbearing depressed subgroup for hyperemesis and C-section with odds ratios of 1.18 (95% confidence intervals (CI), 1.02-1.36) and 1.29 (95% CI, 1.11-1.49), respectively. Incident preterm and low birth weight births were also higher in the depression group than in comparisons, but weren't significant. In conclusion, women with depression during pregnancy may develop more adverse events than comparisons and are more likely to have a C-section delivery.

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.

Perfluorinated chemicals (PFCs) have been widely used in a variety of products worldwide. Our previous study has documented a close association of higher serum level of perfluorooctane sulfonate (PFOS) with an increased carotid intima-media thickness (CIMT) in a cohort of adolescents and young adults. Herein, we further investigated the association of oxidative stress, circulating endothelial microparticles (EMPs) and platelet microparticles (PMPs) with PFCs and CIMT in humans. We recruited 848 subjects (12–30 years old) from a population-based sample to determine the relationship between serum levels of PFCs, EMPs (CD62E and CD31+/CD42a−), PMPs (CD62P and CD31+/CD42a+), and the urine levels of 8-hydroxydeoxyguanosine (8-OHdG) and CIMT. The results showed that CD31+/CD42a− (endothelial apoptosis marker) and CD31+/CD42a+ (platelet apoptosis marker) increased significantly across quartiles of PFOS in multiple linear regression analysis. Furthermore, the elevation of CD31+/CD42a− and CD31+/CD42a+ corresponded to the increase of the odds ratios of thicker CIMT (greater than 50th percentile) with higher serum PFOS concentration (greater than 50%) (OR = 2.86, 95% C.I. = 1.69–4.84, P

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