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Introduction: Depression and aphasia impair the quality of life after a stroke. Studies linking depression risk to post-stroke aphasia (PSA) lacked confirmation using a large database. Methods: Using Taiwan's National Health Insurance claims data, we identified ≥18 years old patients hospitalized for stroke from 2005 to 2009, and those diagnosed with aphasia during hospitalization or within three months after discharge were selected to form the aphasic group. We estimated depression incidence by December 31, 2018, and used the Cox proportional hazards model to estimate aphasia group to non-aphasia group hazard ratios (HRs). Results: With a median follow-up period of 7.91 and 8.62 years for aphasia (n=26,754) and non-aphasia groups (n=139,102), respectively, the incidence of depression was higher in the aphasia group than in the non-aphasia group (9.02 vs.8.13 per 1000 person-years), with an adjusted HR (95% confidence intervals, CI) of 1.21 (1.15-1.29) for depression. The adjusted HRs [95% CI] of depression were homogenous for females, 1.26 [1.15-1.37] and for males, 1.18 [1.09-1.27] and for hemorrhagic stroke, 1.22 [1.09-1.37] and ischemic stroke, 1.21 [1.13-1.30]. Results in analyzing 25939 propensity score matched pairs demonstrated an equivalent effect. Conclusion: Patients with PSA are at an increased risk of developing depression regardless of sex or stroke type.

This study evaluated the risks of childhood acute bronchitis and bronchiolitis (CABs) for children with asthma or allergic rhinitis (AR). Using insurance claims data of Taiwan, we identified, from children of ≤12 years old in 2000–2016, cohorts with and without asthma (N = 192,126, each) and cohorts with and without AR (N = 1,062,903, each) matched by sex and age. By the end of 2016, the asthma cohort had the highest bronchitis incidence, AR and non-asthma cohorts followed, and the lowest in the non-AR cohort (525.1, 322.4, 236.0 and 169.9 per 1000 person-years, respectively). The Cox method estimated adjusted hazard ratios (aHRs) of bronchitis were 1.82 (95% confidence interval (CI), 1.80–1.83) for the asthma cohort and 1.68 (95% CI, 1.68–1.69) for the AR cohort, relative to the respective comparisons. The bronchiolitis incidence rates for these cohorts were 42.7, 29.5, 28.5 and 20.1 per 1000 person-years, respectively. The aHRs of bronchiolitis were 1.50 (95% CI, 1.48–1.52) for the asthma cohort and 1.46 (95% CI, 1.45–1.47) for the AR cohort relative to their comparisons. The CABs incidence rates decreased substantially with increasing age, but were relatively similar for boys and girls. In conclusion, children with asthma are more likely to develop CABs than are children with AR.

Background: Exposure to lead and cadmium has been linked to changes in lipid metabolism and the development of arteriosclerosis, but the role of lipoprotein profiles in this relationship is not well understood, including the potential role of novel lipid biomarkers. Methods: In this study, we enrolled 736 young Taiwanese subjects aged 12 to 30 years to assess the correlation between urine levels of lead and cadmium, lipoprotein profiles, and carotid intima-media thickness (CIMT). Results: Higher levels of lead and cadmium were significantly associated with higher levels of low-density lipoprotein cholesterol (LDL-C), small dense LDL-C (sdLDL-C), LDL-triglyceride (LDL-TG), and CIMT. Participants with higher levels of lead and cadmium had the highest mean values of CIMT, LDL-C, sdLDL-C, and LDL-TG. In a structural equation model, lead had a direct and indirect association with CIMT through LDL-C and sdLDL-C, whereas cadmium had a direct association with CIMT and an indirect association through LDL-C. Conclusion: Our results suggest higher levels of lead and cadmium are associated with abnormal lipid profiles and increased CIMT. These heavy metals could have additive effects on lipids and CIMT, and the relationship between them may be mediated by lipoprotein levels. Further research is needed to determine the causal relationship.

Ya-Wen Lin,1 San-Ni Chen,2 Chih-Hsin Muo,3 Fung-Chang Sung,3– 5,* Ming-Hung Lin6,7,* 1School of Nursing and Graduate Institute of Nursing, China Medical University, Taichung, Taiwan; 2Department of Ophthalmology, Eye Center, China Medical University Hospital, Taichung, Taiwan; 3Management Office for Health Data, China Medical University Hospital, Taichung, Taiwan; 4Department of Health Services Administration, China Medical University, Taichung, Taiwan; 5Department of Food Nutrition and Health Biotechnology, Asia University, Taichung, Taiwan; 6Department of Pharmacy, Chia Nan University of Pharmacy and Science, Tainan, Taiwan; 7Department of Nursing, National Taichung University of Science and Technology, Taichung, Taiwan*These authors contributed equally to this workCorrespondence: Ming-Hung Lin, Department of Pharmacy, Chia Nan University of Pharmacy and Science, No. 60, Sec. 1, Erren Road, Rende District, Tainan City, 71710, Taiwan, Email lmh.roger@msa.hinet.net Fung-Chang Sung, Department of Public Health, China Medical University, No. 100, Sec. 1, Jingmao Road, Beitun District, Taichung City, 406040, Taiwan, Email fcsung1008@yahoo.comBackground: Respiratory distress syndrome (RDS) is a risk factor that plays an important role in retinopathy in preterm infants. We used population data of infants to investigate this relationship. This study evaluated whether respiratory distress syndrome was associated with an increased incidence of ROP in preterm infants.Methods: From the National Health Insurance claims data of Taiwan in the 2000– 2009 period, preterm infants were identified to establish a RDS cohort (N = 7573) and a comparison cohort without RDS (N = 11428). We followed each infant for one year to identify incident retinopathy of prematurity (ROP) for comparison between the two cohorts. The RDS cohort for comparisons of hazard ratio (HR) with 95% confidence interval (CI) were calculated.Results: Low birth weight, an extended stay in the neonatal intensive care unit (NICU), female gender, and RDS were factors associated with an increased incidence of ROP. The ROP incidence was 2.5-fold higher in RDS children than in control (30.3 versus 11.9 per 100 person-years), with an adjusted HR (aHR) of 1.28 (95% CI = 1.18– 1.39). The incidence increased as the birth weight decreased in both cohorts, but the RDS cohort to the comparison cohort aHR decreased as the birth weight decreased, not significant for groups with birth weights less than 1500g. The aHR for RDS children was the highest for infants with a normal birth weight: 3.33 (95% CI = 2.09– 5.31). Among infants with RDS, the ROP incidence increased to 51.0 per 100 person-years in those who underwent invasive ventilation, or to 76.3 per 100 person-years for NICU stay for ≥ 30 days.Conclusion: Preterm infants with RDS are at an elevated risk of developing ROP, not limited to those with low birth weights.Keywords: retinopathy of prematurity, low birth weight, gestational age, preterm birth, respiratory distress syndrome

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.

The awareness on ischemic heart disease (IHD) in women with dysmenorrhea is insufficient. We utilized the National Health Insurance Research Database (NHIRD) of Taiwan to evaluate this relationship. From the claims data, we established a cohort of women aged 15–50 years with primary dysmenorrhea diagnosed from 2000 to 2008 (n = 18,455) and a comparison cohort (n = 36,910) without dysmenorrhea, frequency matched by age and diagnosis date. Both cohorts were followed until the end of 2013 to assess IHD events. With 75% of study population aged 15–29 years, the incidence of IHD was greater in the dysmenorrheal cohort than in the comparison cohort (1.93 versus 1.18 per 10,000 person-years), with an adjusted hazard ratio of 1.60 (95% confidence interval [CI] = 1.38–1.85). The incidence increased with age and the rate of increase was greater in the dysmenorrheal cohort than the comparison cohort. Nested case-control analysis in the dysmenorrhea cohort showed that IHD risk was also associated with hypertension and arrhythmia, with adjusted odds ratios of 2.50 (95% CI = 1.64–3.81) and 3.30 (95% CI = 2.25–4.86), respectively. Women with dysmenorrhea are at a higher risk of developing IHD, particularly for older patients and patients with comorbidity.

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.

Studies have associated the human respiratory syncytial virus which causes seasonal childhood acute bronchitis and bronchiolitis (CABs) with climate change and air pollution. We investigated this association using the insurance claims data of 3,965,560 children aged ≤ 12 years from Taiwan from 2006-2016. The monthly average incident CABs increased with increasing PM

BackgroundStudies comparing mental disorder risks between women with breast cancer and cervical cancer are lacking. This study compared risks of developing anxiety and depression between women with breast cancer (BC cohort) and women with cervical cancer (CC cohort) using insurance claims data of Taiwan.MethodsFrom the 2000 to 2016 data, we identified a BC cohort and BC controls (N = 96,862) and a CC cohort and CC controls (N = 26,703), matched by propensity scores. Incident mental disorders and the Cox method estimated the related cancer cohort to control cohort hazard ratios (HRs), and 95% confidence intervals (CIs) were estimated by the end of 2016.ResultsCompared to the CC cohort, the BC cohort had slightly higher incident anxiety (15.9 versus 15.5 per 1,000 person-years) and depression (6.92 vs. 6.28 per 1,000 person-years). These mental disorders were higher in respective cancer cohorts than controls. The BC cohort to BC control adjusted HRs of anxiety and depression were 1.29 (95% CI = 1.25–1.33) and 1.78 (95% CI = 1.69–1.87), respectively. The corresponding adjusted HRs for the CC cohort were 1.12 (95% CI = 1.06–1.18) and 1.29 (95% CI = 1.18–1.41). The combined incidence rates of both disorders were 1.4-fold greater in the BC cohort than in BC controls (22.8 vs. 15.8 per 1,000 person-years), and 1.2-fold greater in the CC cohort than in the CC controls (21.7 vs. 18.3 per 1,000 person-years).ConclusionWomen with breast cancer or cervical cancer are at an elevated likelihood of developing anxiety and depression disorders. These incident disorders are slightly higher in those with breast cancer.

Background: Studies on strokes associated with dysmenorrhea are limited. We conducted a propensity-score-matched retrospective cohort study to assess the risk of stroke in women with primary dysmenorrhea (PD). Methods: From the claims data of one million people in Taiwan’s insurance program, we identified 18,783 women aged 15–40 years, newly diagnosed with PD in 2000–2010, without a history of stroke. We randomly selected a comparison cohort without stroke history and dysmenorrhea, with the same sample size matched by age, index date, and propensity score. We began a follow-up with individuals one year after cohort entry to the end of 2013 to capture stroke events. Results: The two study cohorts were well-matched for age and comorbidities, with 54% of women aged 15–24. Stroke incidence was 1.5-fold higher in the PD cohort than in the comparison cohort (6.05 vs. 4.01 per 10,000 person-years, or 99 vs. 65 cases), with an adjusted hazard ratio (aHR) of 1.51 (95%CI 1.11–2.06) after adjustment for matched pairs. Nearly 70% of strokes were ischemic strokes, which occurred 1.6 times more frequently in the PD cohort than in the comparison cohort (4.40 vs. 2.71 per 10,000 person-years, or 72 vs. 44 cases), aHR = 1.61 (95% CI 1.11–2.33), after adjustment for matched pairs. The incidence of hemorrhagic stroke was also higher in the PD cohort than in the comparison cohort (1.65 vs. 1.29 per 10,000 person-years, or 27 versus 21 cases), but the difference was not significant. Conclusion: Women of reproductive age with PD are at increased risk for ischemic stroke.

Background: For non-dialysis patients with hyperlipidemia, statins may provide clinical benefits in reducing mortality risk; however, the optimal treatment for dialysis patients with hyperlipidemia remains debatable. We evaluated the mortality risks for hyperlipidemic patients with renal disorders associated with statin therapy (ST), using the insurance claims data of Taiwan.Methods: From hyperlipidemic patients diagnosed in 2000–2011, we identified 555,153 patients receiving statin treatment for at least 90 days continuously and 1,141,901 non-statin users, and then randomly selected, from both groups, the propensity score-matched subcohorts of statin users and nonusers in a 1:1 pair by renal function: 415,453 pairs with normal renal function , 43,632 pairs with chronic kidney disease (CKD), and 3,624 pairs with end-stage renal disease (ESRD). We compared the mortalities, by the end of 2016, from all causes, cancer, heart disease, and septicemia between statin users and non-users and between hydrophilic-statin users and lipophilic-statin users. The Cox method estimated ST users to non-user hazard ratios. The time-dependent model was also conducted as sensitivity analysis.Results: The mean ages were 58.7 ± 10.7, 64.2 ± 10.7, and 62.2 ± 10.8 years in normal renal function, CKD, and ESRD groups, respectively. Compared with non-users, statin users had reduced mortality risks from all causes for 32%–38%, from cancer for 37%–46%, from heart disease for 6%–24%, and from septicemia for 17%–21% in all three renal groups. The hydrophilic statin therapy was superior than the lipophilic statin therapy, particularly for reducing deaths from all-causes and cancer. The results under the time-dependent model were similar.Conclusion: Statin therapy is associated with reduced all-causes and non-cardiovascular mortality in ESRD patients.

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

Hepatocellular carcinoma (HCC) is the most common cancer in end-stage renal disease (ESRD) patients in Taiwan. Whether statin therapy associated with the HCC risk in hyperlipidemic patients with chronic kidney disease (CKD) and ESRD is unclear. Using population-based insurance claim data from Taiwan, we identified from hyperlipidemic patients taking statins or not (677,364 versus 867,707) in 1999–2015. Among them, three pairs of propensity score matched statin and non-statin cohorts were established by renal function: 413,867 pairs with normal renal function (NRF), 46,851 pairs with CKD and 6372 pairs with ESRD. Incidence rates of HCC were compared, by the end of 2016, between statin and non-statin cohorts, between hydrophilic statins (HS) and lipophilic statins (LS) users, and between statin-ezetimibe combination therapy (SECT) and statin monotherapy (SM) users. The HCC incidence increased progressively from NRF to CKD and ESRD groups, was lower in the statin cohort than in the non-statin cohort, with the differences of incidence per 10,000 person-years increased from (7.77 vs. 21.4) in NRF group to (15.8 vs. 37.1) in CKD group to (19.1 vs. 47.8) in ESRD group. The incidence increased with age, but the Cox method estimated hazard ratios showed a greater statin effectiveness in older patients. Among statin users, the HCC incidence was lower in HS users than in LS users, and lower in SECT users than in SM users, but the difference was significant only in the NRF group. Hyperlipidemic patients with CKD and ESRD receiving statins are at reduced HCC risks; the treatment effectiveness is superior for HS users than for LS users, and for SECT users than for SM users, but not significant.

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.

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

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

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.

Di-(2-ethylhexyl) phthalate (DEHP) has been used as a plasticizer for decades. Recent research evidence has revealed that environmental factors can alter vascular endothelial cell function through DNA methylation. However, no previous in vitro/vivo study has explored the role of DNA methylation in DEHP exposure and vascular endothelial cell function. In the present study, we enrolled 793 subjects aged 12 to 30 years from a young Taiwanese cohort to investigate the association between mono-2-ethylhexyl phthalate (MEHP) (urine DEHP metabolite), 5mdC/dG (global DNA methylation marker), CD31+/CD42a−, CD31+/CD42a+, and CD14 (apoptotic microparticles of vascular cells). In multiple regression analyses, the levels of mono-2-ethylhexyl phthalate (MEHP) were positively associated with 5mdC/dG and all three apoptotic microparticles. In addition, the regression coefficients between MEHP and the three types of apoptotic microparticles were higher when the 5mdC/dG levels were higher than the 50th percentile. In the structural equation model (SEM), we found that MEHP had a direct correlation with CD31+/CD42a− and an indirect association with CD31+/CD42a− through the effect of 5mdC/dG. Moreover, MEHP only had a direct association with CD31+/CD42a+ and an indirect association with CD14. In conclusion, the results show that global DNA methylation mediates the relationship between MEHP and apoptotic microparticles. These findings indicate that DNA methylation may play a role in the pathogenesis of DEHP-induced endothelial cell apoptosis in humans. Further studies are needed to clarify the causal inference.

(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.

This population-based retrospective cohort study investigated the effectiveness of erythropoietin (EPO) treatment in reducing the risk of age-related macular degeneration (AMD) in hemodialysis patients, using the National Health Insurance Research Data of Taiwan. From the database, we identified 147,318 end-stage renal disease (ESRD) patients on hemodialysis who had been diagnosed in 2000–2014 to establish the propensity-score-matched EPO user cohort and non-EPO user cohort with equal sample size of 15,992. By the end of 2016, the cumulative incidence of AMD in EPO users was about 3.29% lower than that in non-EPO users (Kaplan–Meier survival p < 0.0001). The risk of AMD was 43% lower in EPO users than in non-EPO users, with an adjusted hazard ratio (aHR) of 0.57 (95% confidence interval (CI) = 0.51–0.64) estimated in the multivariate Cox model. A significant negative dose–response relationship was identified between the EPO dosage and the risk of AMD (p < 0.0001). Another beneficial effect of EPO treatment was a reduced risk of both exudative AMD (aHR = 0.48, 95% CI = 0.40–0.61) and non-exudative AMD (aHR = 0.61, 95% CI = 0.53–0.69), also in similar dose–response relationships (p < 0.0001). Our findings suggest that EPO treatment for hemodialysis patients could reduce AMD risk in a dose–response relationship.

Perfluoroalkyl and polyfluoroalkyl substances (PFAS) are a group of synthetic chemicals used in the manufacture of many everyday products. Previous reports have shown PFAS exposure may contribute to cardiovascular diseases (CVD). Recent studies have also identified a critical role for DNA methylation, a model of epigenetic regulation, in the pathogenesis of CVD. Additionally, PFAS has been shown to affect DNA methylation. Our previous study reported the positive association between serum perfluorooctane sulfonate (PFOS) levels and mean carotid intima-media thickness (CIMT), a biomarker of arteriosclerosis, in a cohort composed of adolescent and young adult Taiwanese. However, the contribution of DNA methylation in the mechanism of PFOS-induced arteriosclerosis has never been explored in previous literature.In this cross-sectional study, we included 1425 young and middle-aged Taiwanese individuals (12-63 years) to investigate the correlation between serum PFOS levels, 5mdC/dG (a global DNA methylation marker) and the mean CIMT. We showed that the positive association between serum PFOS levels, 5mdC/dG, and mean CIMT. The regression coefficients of mean CIMT with a one-unit increase in ln-PFOS concentration were higher when the levels of 5mdC/dG were above the 50th percentile in the multiple regression analysis. In the structural equation model (SEM), the results showed that serum PFOS levels were directly correlated with mean CIMT and indirectly correlated with CIMT through 5mdC/dG.Our results showed that PFOS exposure has direct associations on arteriosclerosis and indirect direct associations on arteriosclerosis through DNA methylation. The results suggest that DNA methylation might regulate the relationship between PFOS and arteriosclerosis in the study subjects. Additional works are required to understand the causal inference between PFOS, DNA methylation, and arteriosclerosis.

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.

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.

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.

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.