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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.

Summary Objective This study used the Taiwan Stroke Registry data to evaluate the efficacy and safety of intravenous tissue plasminogen activator (tPA) in treating acute ischemic stroke in patients with renal dysfunction. Design We identified 3525 ischemic stroke patients and classified them into two groups according to the estimated glomerular filtration rate (eGFR) at the emergency department: ≥60, and Results Among patients with eGFR levels of Conclusions tPA for acute ischemic stroke could improve functional outcomes without increasing the risks of upper gastrointestinal bleeding for patients with or without renal dysfunction. The low eGFR was not a significant risk factor for intracerebral hemorrhage among patients receiving tPA treatment.

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.

Background We aimed to identify associations between the risk of acute respiratory failure (ARF) and types of antihypertensive agents in patients with viral pneumonia. Methods In this case-control study, data extracted from the Taiwan National Health Insurance Research Database were analysed. The base population comprised patients with viral pneumonia treated from 2000 to 2013. The case group comprised patients with ARF and the control group comprised participants without ARF. Adjusted odds ratios (ORs) were calculated using a multivariable logistic regression model. Results In total, 4427 viral pneumonia patients with ARF and 4427 matched control participants without ARF were recruited. Patients with diabetes, alcohol-related disease, asthma, chronic kidney disease or end-stage renal disease, chronic obstructive pulmonary disease, cancer, congestive heart failure, stroke, acute pulmonary oedema and shock had increased odds of developing ARF, especially shock (adjusted OR = 49.3; 95% CI = 27.4, 88.7), cancer (12.6; 8.67, 18.2) and stroke (7.51; 5.32, 10.6). Increasing odds of developing ARF were noted in patients using potassium-sparing diuretics (2.95; 1.54, 5.64), loop diuretics (68.2; 48.1, 96.6), calcium channel blockers (1.64; 1.26, 2.13) and angiotensin-converting enzyme inhibitors (1.70; 1.15, 2.53). Patients with prescriptions of α-blockers (0.44; 0.26, 0.74), β-blockers (0.37; 0.26, 0.52), thiazides (0.38; 0.25, 0.59) and angiotensin receptor blockers (0.65; 0.51, 0.83) had lower odds of having ARF. Conclusion Patients with viral pneumonia who received α-blockers, β-blockers, thiazides or angiotensin receptor blockers during hospitalisation had a lower risk of developing ARF.

Background: This study evaluated short-term (1-month) and long-term (1-year) mortality risks associated with kidney function measured by estimated glomerular filtration rate (eGFR) levels at admission for patients with intracerebral hemorrhage. Methods: From the Taiwan Stroke Registry data, we identified and stratified patients with intracerebral hemorrhage into 5 subgroups by the eGFR levels at admission: ≥ 90, 60-89, 30-59, 15-29, and < 15 mL/min/1.73m2 or on dialysis from April 2006 to December 2016. Risks of 1-month mortality and 1-year mortality rates after intracerebral hemorrhage were investigated by the eGFR levels. Results: Both the 1-month mortality and 1-year mortality rates increased as the eGFR level decreased. The 1-month mortality rate was over 5-fold greater in patients with eGFR < 15 mL/min/1.73m2 or on dialysis than in patients with eGFR levels ≥ 90 mL/min/1.73m2 (8.31 versus 1.50 per 1000 person-days), with an adjusted hazard ratio (HR) of 4.59 [95% confidence interval (CI) = 2.71-7.78]. Similarly, the 1-year mortality rate was 7.5-fold greater in patients with eGFR < 15 mL/min/1.73m2 or on dialysis than in patients with eGFR ≥ 90 mL/min/1.73m2, with an adjusted HR of 4.54 (95% CI 2.95-6.98). Conclusion: The eGFR level can be an indicator of prognosis for patients with intracerebral hemorrhage.

This study aims to evaluate the impact of multidisciplinary pre-dialysis care (MDPC) on the risks of peritonitis, technique failure and mortality in peritoneal dialysis (PD) patients. Incident end-stage renal disease patients were classified into two groups, the MDPC group and the control group, that received the usual care by nephrologists. Risks of the first episode of peritonitis, technique failure and mortality were compared between the two groups. Patients in the MDPC group initiated dialysis earlier than those in the non-MDPC group. There was no significant difference between these two groups in time to the first episode of peritonitis. Compared to the non-MDPC group, the MDPC group was at similar risks of technique failure (adjusted HR = 0.85, 95% CI = 0.64–1.15) and mortality (adjusted HR = 0.66, 95% CI = 0.42–1.02). Among patients with diabetes, the risk of mortality was significantly reduced in the MDPC group with an adjusted HR of 0.45 (95% CI = 0.25–0.80).There was no significant difference in time to develop the first episode of peritonitis, and risks of technique failure and mortality between these two groups. Diabetic PD patients under MDPC had a lower risk of mortality than those under the usual care.

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

Benign Prostate Hyperplasia (BPH) has been associated with prostate cancer prevalent among men after 50 years of age, however, it is unclear whether the antidiabetic drug, metformin, can reduce prostate cancer for men with BPH. The insurance claims data of men aged 50 years or older, with both type 2 diabetes mellitus (T2DM) and BPH diagnosed from 1997 to 2007 were analyzed. Individuals were followed up for at least 5 years. We identified 2906 and 2906 patients as the metformin cohort and nonmetformin cohort, respectively. The Cox method analysis showed that the metformin cohort had an adjusted hazard ratio (aHR) of 0.69 (95% confidence interval [CI] = 0.49‐0.96, P = 0.0298) for prostate cancer, compared to the nonmetformin cohort after controlling for age, traditional Chinese medicine (TCM) use, prostate specific antigen, and Charlson comorbidity index. Patients using TCM for BPH (per 6 months) also had an aHR of 0.41 (95% CI = 0.24‐0.69; P = 0.0009). In conclusion, both metformin medication and TCM use could be associated with reduced risk of prostate cancer for men with BPH and diabetes.

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.

Background No study has investigated costs of stroke care for women with dysmenorrhea and stroke. This study compared types of stroke and costs of stroke care between women with and without dysmenorrhea, using the National Health Insurance Research Database of Taiwan. Methods From the insurance claims data, we identified women aged 15–44 to establish study cohorts with and without dysmenorrhea, frequency matched by age, with same sample size of 66048. Incidence of stroke and costs by stroke subtype were compared between the two cohorts at the end of follow-up. Results The incidence of stroke was 1.3-fold greater in the dysmenorrhea cohort than in comparisons. Proportionally, hemorrhagic stroke (HS) decreased with age, whereas ischemic stroke (IS) increased with age in both cohorts. Compared to comparisons, dysmenorrhea women had lower proportions of both HS (16.6% vs. 21.3%) and IS (19.8 vs. 20.1%), whereas dysmenorrhea women had higher proportion of transient cerebral ischemia (TIA) (31.3 vs. 24.2%). The average HS care and IS care cost ratios were 4.1 (3254/789, USD) for dysmenorrhea women, and 3.3-fold (3870/1171, USD) for comparisons. Hospitalization rate was lower in the dysmenorrhea than in comparisons (18.0 vs. 23.4%). Dysmenorrhea was associated with an increased risk of HS hospitalized (adjusted odds ratio (aOR) = 1.26, 95% confidence interval (CI) 0.71–2.23), but a lowered risk for IS (aOR = 0.48, 95% CI 0.21–0.69). Average costs for inpatient care, intensive care units, emergency and outpatient visits for dysmenorrheal women were all less than that for comparisons, but not significant. Conclusion The overall incidence of stroke was higher in dysmenorrheal women than in comparisons due to a higher proportion of TIA, but not HS and IS. However, costs for stroke care were slightly lower for dysmenorrhea women than for comparisons.

AimStudies evaluating colorectal cancer (CRC) risk associated with chronic hepatitis C virus (HCV) infection are limited.MethodsIn this case-control study, we identify 67,670 CRC cases newly diagnosed from 2005 to 2011 and randomly selected 67,670 controls without HCV and CRC from the same database, frequency matched by age and sex of cases.ResultsResults of logistic regression analysis revealed that the adjusted odds ratio (aOR) of CRC was 1.16 (95% confidence interval [CI] = 1.08–1.24, p < 0.001) in association with chronic HCV. The CRC risk was slightly greater for women than for men. The risk decreased with age, with the aOR decreased from 2.26 (95% CI = 1.32–3.87, p = 0.003) in patients under 45 years old to 1.31 (95% CI = 1.10–1.55, p = 0.03) in patients aged 50–59, and 1.10 (95% CI = 1.00–1.22, p = 0.061) in patients aged over 70.ConclusionsOur findings suggested that patients with chronic HCV infection are at an elevated risk of developing CRC. Our data also imply that the CRC prevention programs are needed to target younger HCV patients.

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.

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.

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.

Objective Previous literature investigating effects of diabetes complications on subsequent depression have been inconsistent. We aim to investigate associations of diabetes, complication severity, and depression. Design This study used a nationwide database to establish an 11-year cohort comprised of people with new onset Type II diabetes mellitus (DM) aged 20 and above. Method Severity of DM was measured using the adapted Diabetes Complication Severity Index (aDCSI). Status of depression was determined by having one recorded depression diagnosis from the inpatient setting or three recorded depression diagnoses from the outpatient setting. The risk of depression was analyzed by multivariate Cox proportional models. Results In 50,590 cases with new onset DM from years 2000 to 2011, the incidence of depression increased with severity and rates of progressions in diabetes complications regardless of demographic status, comorbidities, or medication compliance. Adjusted hazard ratios (aHR) of depression were 1.21, 1.25, 1.48 (p 3, respectively. Risks of depression were the highest in subgroup with the most serious progression (change of aDCSI score >2 per year) (aHR ranged between 11.6~26.0). Elevated risks of depression (aHR: 1.59~4.36) were also observed in the slower progression subgroups throughout the disease course. Conclusions Risks of depression were associated with multiple DM-related complications and rates of progression in severity.

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.

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.

Thiodiglycolic acid (TDGA) is a major metabolite of vinyl chloride monomer (VCM), and it has been suggested as an exposure biomarker for VCM. The validity of this biomarker when the level of VCM is less than 5 ppm, however, is questionable. The objective of this article is to evaluate the feasibility of using urinary TDGA as a biomarker of VCM exposure in a community health risk assessment setting where the concentration of VCM in air is typically very low (likely below 1 ppm). To achieve this objective, we examine the fraction of urinary TDGA associated with different levels of VCM exposures of three studies from different countries, using estimations of the TDGA metabolite predicted by a PBPK model. It is demonstrated that differences in background TDGA have considerable effect on the adequacy of TDGA as a biomarker of VCM. We conclude that, in a community health assessment setting, TDGA should not be used as an exposure biomarker for VCM without having a proper control group, and a PBPK model can be used first to determine whether or not the amount of TDGA in urine is of concern.

Aim The study aimed to investigate the role of two polymorphisms of methylenetetrahydrofolate reductase (MTHFR), C677T and A1298C, in the risk of potentially malignant oral disorders (PMODs). Materials and methods Genotypes of the MTHFR C677T and A1298C polymorphisms were determined using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) for 224 PMOD cases and 485 age-matched controls. Results The C677T T allele-carrying genotypes were significantly associated with a decreased risk of PMODs [odds ratio (OR)=0.62, 95% confidence interval (CI)=0.44-0.86]. Haplotype analysis also indicated that the 677T/1298A haplotype was associated with a decreased risk of PMODs (OR=0.56, 95%CI=0.40-0.80). No significant interaction was observed between MTHFR polymorphisms and lifestyle factors. Conclusion Our findings suggest that the T-allele-carrying MTHFR C677T genotype or haplotype may reduce the risk of PMODs. However, these observations require further confirmation using larger samples.

Parents of children with attention deficit hyperactivity disorder (ADHD) have been found to prefer sensory integration (SI) training rather than guideline-recommended ADHD treatment. This study investigated whether SI intervention for children with ADHD was associated with a reduced risk of subsequent mental disorders. From children

This study investigated the characteristics of patients with different chronic kidney disease (CKD) stages according to various body mass index (BMI) categories and determined the influence of BMI in renal function deterioration. We conducted a multicenter, longitudinal cohort study based on the Epidemiology and Risk Factors Surveillance of CKD project (2008–2013) and National Health Insurance Research Database (2001–2013). A total of 7357 patients with CKD aged 20–85 years from 14 hospitals were included in the study. A higher male sex, diabetes mellitus (DM) and hypertension were noted among overweight and obese CKD patients, while more cancer prevalence was noted among underweight CKD patients. Charlson comorbidity index was significantly higher and correlated with BMI among late CKD patients. Patients with BMI 2 exhibited non-significantly higher events of eGFR decline events in both early and late CKD stages than other BMI groups. BMI alone is not a determinant of CKD progression among our Taiwanese CKD patients. Obesity should be re-defined and body weight manipulation should be individualized in CKD patients.

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.

// Dah-Ching Ding 1, 2 , I-Ju Tsai 3, 4 , Jen-Hung Wang 5 , Shinn-Zong Lin 6 and Fung-Chang Sung 3, 7 1 Department of Obstetrics and Gynecology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Tzu Chi University, Hualien, Taiwan 2 Institute of Medical Sciences, Tzu Chi University, Hualien, Taiwan 3 Management Office for Health Data, China Medical University Hospital, Taichung, Taiwan 4 College of Medicine, China Medical University, Taichung, Taiwan 5 Department of Research, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Tzu Chi University, Hualien, Taiwan 6 Department of Neurosurgery, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Tzu Chi University, Hualien, Taiwan 7 Department of Health Services Administration, China Medical University, Taichung, Taiwan Correspondence to: Dah-Ching Ding, email: dah1003@yahoo.com.tw Fung-Chang Sung, email: fcsung1008@yahoo.com Keywords: cardiovascular disease; coronary artery disease; diabetes mellitus; hypertension; polycystic ovary syndrome Received: August 02, 2017 Accepted: November 16, 2017 Published: January 04, 2018 ABSTRACT Women with polycystic ovary syndrome are characterized by obesity, menstruation irregularity, hirsutism and infertility, and prevalent with cardiometabolic comorbidities, but population-based studies on the risk of developing coronary artery disease are limited. From claims data of the Taiwan National Health Insurance, we identified 8048 women with polycystic ovary syndrome aged 15-49 years newly diagnosed in 1998-2013, and 32192 women without the syndrome and CAD as controls, frequency matched by age and diagnosis date. By the end of 2013, after a mean follow-up period of 5.9 years, the overall incidence of coronary artery disease was 63% higher in women with polycystic ovary syndrome than in controls (2.25 vs. 1.38 per 1000 person-years). The adjusted hazard ratio [aHR] of coronary artery disease was 1.44 (95% confidence interval (CI) = 1.14–1.81) for women with polycystic ovary syndrome, compared with controls. Hazards of coronary artery disease were significant during follow-up periods of 3-4 years (aHR = 1.52, 95% CI = 1.00–2.30) and of 5–9 years (aHR = 1.58, 95% CI = 1.07–2.32). The incidence of coronary artery disease increased further in those with cardiometabolic comorbidities. Among women with polycystic ovary syndrome, those with comorbid diabetes had an incidence of 35.2 per 1000 person-years, 20-fold greater than those without cardiometabolic comorbidities. In conclusion, women with polycystic ovary syndrome are at an elevated risk of coronary artery disease. Preventive interventions should be provided to them, particularly for those with the comorbidity of metabolism symptom.

Background This retrospective cohort study sought to follow up patients with aplastic anemia (AA) to evaluate their risk of developing atrial fibrillation (AF).Methods and Results:From the National Health Insurance Research Database of Taiwan, this study identified an AA cohort (n=3,921), a general population cohort (n=17,617,843) and a propensity score-matched none AA cohort (PSM non-AA cohort in brief, n=15,684) in 2000-2010. By the end of 2011, the incident AF was higher in the AA cohort than in the general population and PSM non-AA cohorts (8.94 vs. 1.14 and 6.47 per 1,000 person-years, respectively). The adjusted hazards ratio of AF for the AA cohort was 2.12 (95% confidence interval 1.46-3.08) compared with the PSM non-AA cohort, after controlling for covariates. However, after further controlling for the competing risk of death, adjusted subhazard ratio was 1.21 (95% CI 0.97-1.50). Among those who developed AF, the AA cohort had a higher mortality rate (83.7 vs. 51.1 per 100), but a lower rate of incident stroke (26.0 vs. 41.5 per 100), compared with the PSM non-AA cohort. Conclusions Patients with AA could have an elevated risk for AF. The mortality risk increased further for those who develop AF.

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.

Bisphenol A (BPA) exposure is associated with atherosclerotic cardiovascular diseases. The interactions between BPA, extracellular microparticles (MPs), and atherosclerosis are unknown. A total of 103,756 young students participated in the mass urine-screening program in Taiwan between 1992 and 2000 were analyzed. After exclusion, 886 subjects were recruited to test the relationships between serum level of BPA, endothelial and platelet MPs as well as subclinical atherosclerosis represented by carotid artery intima-media thickness (CIMT). We found that an increment of one unit of log-BPA could lead to significant association between thicker CIMT and concentrations of endothelial microparticles and platelet microparticles in the cohort (odds ratio (OR) 1.23, P 50%, OR 1.229, P = 0.001) and CD31 + /CD42a+ (≦ 50%, OR 1.262, P = 0.017 and > 50%, OR 1.212, P = 0.006) were significantly associated with thicker CIMT in the presence of elevated BPA. When considering the interactions between CD31 + /CD42a- and CD31 + /CD42a+ , we observed increased OR as CD31 + /CD42a- was greater than 50% (CD31 +/CD42a- > 50% and CD31 +/CD42a+ ≦ 50%, OR 1.356, P = 0.029; CD31 +/CD42a- > 50% and CD31 +/CD42a+ > 50%, OR 1.204, P = 0.014). Our study identified a higher risk of thicker CIMT associated with altered MPs in the presence of elevated BPA levels. BPA exposure is associated with endothelial dysfunction and subclinical atherosclerosis in a young population.

AIM We used insurance claims data of Taiwan to compare the risk of non-traumatic lower extremity amputation between haemodialysis (HD) and peritoneal dialysis (PD) patients. METHODS We identified 77 669 HD patients and 10 035 PD patients without prior amputation from 2000 to 2010. Incidence rates and hazard ratios (HRs) of lower extremity amputation, and subsequent 30-day mortality after amputation were evaluated up to 31 December 2011. RESULTS There were 2427 and 216 patients undergoing lower extremity amputation during follow-up in the HD and PD groups with incidence rates of 8.35 and 5.79 per 1000 person-years, respectively. Compared with the HD group, the overall adjusted HR of lower extremity amputation for the PD group was 1.27 (95% CI = 1.10-1.46). The impact of diabetes status on the risk of lower extremity amputation interacted with dialysis modality significantly (P

There is controversy regarding the extent of risk for dementia in patients with end stage renal disease (ESRD) who are undergoing hemodialysis (HD) or peritoneal dialysis (PD). We examined data from Taiwan's Longitudinal Health Insurance Database, and used Cox proportional hazard regression analysis to compare the development of dementia in 72,934 HD and PD patients with 72,934 matched controls from January 1, 1999 to December 31, 2010. The results indicate an increased risk for dementia overall in HD patients (adjusted hazard ratio [aHR] = 1.64, p < 0.0001) and PD patients (aHR = 2.21, p < 0.0001). HD and PD patients also had significantly greater aHRs for vascular dementia (VaD) and unspecified dementia (UnD), but only HD patients had a significantly greater aHR for Alzheimer's disease (AD). Further research is needed to confirm whether management of ESRD with PD can reduce the incidence of AD, and to identify the mechanisms by which ESRD increases the risk of dementia.

We conducted a retrospective cohort study to evaluate the subsequent colorectal cancer (CRC) risk for women with gynecologic malignancy using insurance claims data of Taiwan. We identified patients who survived cervical cancer (N = 25,370), endometrial cancer (N = 8149) and ovarian cancer (N = 7933) newly diagnosed from 1998 to 2010, and randomly selected comparisons (N = 165,808) without cancer, matched by age and diagnosis date. By the end of 2011, the incidence and hazard ratio (HR) of CRC were estimated. We found that CRC incidence rates were 1.26-, 2.20-, and 1.61-fold higher in women with cervical, endometrial and ovarian cancers, respectively, than in comparisons (1.09/1000 person–years). The CRC incidence increased with age. Higher adjusted HRs of CRC appeared within 3 years for women with endometrial and ovarian cancers, but not until the 4th to 7th years of follow up for cervical cancer survivals. Cancer treatments could reduce CRC risks, but not significantly. However, ovarian cancer patients receiving surgery alone had an incidence of 3.33/1000 person–years for CRC with an adjusted HR of 3.79 (95% CI 1.11–12.9) compared to patients without any treatment. In conclusion, gynecologic cancer patients are at an increased risk of developing CRC, sooner for those with endometrial or ovarian cancer than those with cervical cancer.

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.