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Abstract Limited data exist on long-term renal outcomes in patients with hyperglycemic crisis (HC) as initial type 2 diabetes presentation. We evaluated the risk of chronic kidney disease (CKD) development in those with concurrent HC at diagnosis. Utilizing Taiwan’s insurance claims from adults newly diagnosed with type 2 diabetes during 2006–2015, we created HC and matched non-HC cohorts. We assessed incident CKD/diabetic kidney disease (DKD) by 2018’s end, calculating the hazard ratio (HR) with the Cox model. Each cohort comprised 13,242 patients. The combined CKD and DKD incidence was two-fold higher in the HC cohort than in the non-HC cohort (56.47 versus 28.49 per 1000 person-years) with an adjusted HR (aHR) of 2.00 (95% confidence interval [CI] 1.91–2.10]). Risk increased from diabetic ketoacidosis (DKA) (aHR:1.69 [95% CI 1.59–1.79]) to hyperglycemic hyperosmolar state (HHS) (aHR:2.47 [95% CI 2.33–2.63]) and further to combined DKA-HHS (aHR:2.60 [95% CI 2.29–2.95]). Subgroup analysis in individuals aged ≥ 40 years revealed a similar trend with slightly reduced incidences and HRs. Patients with HC as their initial type 2 diabetes presentation face a higher CKD risk than do those without HC. Enhanced medical attention and customized interventions are crucial to reduce this risk.

Abstract Background A population-based follow-up study assessing the risk of developing hypertension and diabetes associated with alcohol use disorder (AUD) is crucial. We investigated this relationship by using insurance claims data from Taiwan. Methods From the claims data, an AUD cohort (N = 60,590) diagnosed between 2000 and 2006 and a non-AUD comparison cohort (N = 60,590) without the diagnosis of hypertension or diabetes at baseline were established and matched by propensity scores estimated by baseline demographic status and the Charlson comorbidity index (CCI). We assessed the incidence rates of hypertension and/or diabetes at the end of 2016 and used Cox’s method to estimate the related hazard ratios (HRs) and 95% confidence intervals (CIs). Results Relative to the comparison cohort, the AUD cohort had an approximately 1.70-fold higher incidence of hypertension (35.1 vs. 20.7 per 1,000 person-years), with an adjusted HR (aHR) of 1.72 (95% CI: 1.68–1.76), 2.16-fold higher incidence of diabetes (20.2 vs. 9.36 per 1,000 person-years), with an aHR of 2.18 (95% CI: 2.11–2.24), and 1.91-fold higher incidence of both diabetes and hypertension (10.3 vs. 5.38 per 1,000 person-years) with an aHR of 2.02 (95% CI: 1.94–2.10). The incidence rates of all outcomes were greater in men than in women, whereas the HRs were greater for AUD in women than for AUD in men relative to the respective comparison patients. The risk increased further for subjects with CCI ≥ 1, which was higher in the AUD cohort. Conclusions The increased risk of developing diabetes and hypertension in patients with AUD, especially the differences noted according to gender, indicates that clinicians should address potential comorbidities in these patients.

ObjectiveThe aim of the study is to investigate the effects of icodextrin on the risks of death, technique failure and the first episode of peritonitis in peritoneal dialysis (PD) patients.MethodsFrom medical records of a medical center in Taiwan, a total of 725 newly diagnosed end-stage kidney disease patients receiving PD for at least 90 days from January 1, 2007 to December 31, 2018 were identified. These patients were grouped as 190 icodextrin users and 535 non-users. Users were defined as utilization of icodextrin for ≥ 50% of their PD duration. The use of icodextrin was considered a time-varying exposure in the Cox proportional hazard model. The risks of death, technique failure and the first episode of peritonitis were compared between two cohorts by the end of 2018.ResultsCompared to the non-users, the icodextrin users had significant lower risks of mortality (6.5 vs.7.2 per 100 person-years; adjusted HR = 0.62, 95% CI = 0.42-0.91) and technique failure (12.7 vs. 15.2 per 100 person-years; adjusted HR = 0.61, 95% CI = 0.47-0.81), and the first peritonitis episode (5.0 vs. 17.0 per 100 person-years; adjusted HR = 0.22, 95% CI = 0.14-0.35). The risk of peritonitis reduced further in icodextrin users with diabetes and with cardiovascular disease.ConclusionIcodextrin was associated with lower risks of mortality, technique failure, and the first episode of peritonitis.

Abstract Background Adiponectin is a key protein produced in adipose tissue, with crucial involvement in multiple metabolic processes. Di-(2-ethylhexyl) phthalate (DEHP), one of the phthalate compounds used as a plasticizer, has been shown to decrease adiponectin levels in vitro and in vivo studies. However, the role of angiotensin I-converting enzyme (ACE) gene polymorphism and epigenetic changes in the relationship between DEHP exposure and adiponectin levels is not well understood. Methods This study examined the correlation between urine levels of DEHP metabolite, epigenetic marker 5mdC/dG, ACE gene phenotypes, and adiponectin levels in a sample of 699 individuals aged 12–30 from Taiwan. Results Results showed a positive relationship between mono-2-ethylhexyl phthalate (MEHP) and 5mdC/dG, and a negative association between both MEHP and 5mdC/dG with adiponectin. The study found that the inverse relationship between MEHP and adiponectin was stronger when levels of 5mdC/dG were above the median. This was supported by differential unstandardized regression coefficients (− 0.095 vs. − 0.049, P value for interaction = 0.038)). Subgroup analysis also showed a negative correlation between MEHP and adiponectin in individuals with the I/I ACE genotype, but not in those with other genotypes, although the P value for interaction was borderline significant (0.06). The structural equation model analysis indicated that MEHP has a direct inverse effect on adiponectin and an indirect effect via 5mdC/dG. Conclusions In this young Taiwanese population, our findings suggest that urine MEHP levels are negatively correlated with serum adiponectin levels, and epigenetic modifications may play a role in this association. Further study is needed to validate these results and determine causality.

Purpose: Patients with osteoporosis are at an increased risk of cardiovascular disease (CVD). Several antiosteoporosis medications have been demonstrated with the benefit of preventing osteoporosis. Our aim is to assess the CVD risks associated with antiosteoporosis medications using the National Health Insurance Research Database in Taiwan between 2000 and 2016.Methods: Among 41,102 patients of 40+ years old with newly diagnosed osteoporosis, 69.1% (N = 28,387) of patients were included in the user cohort of antiosteoporosis medicines, of whom 13, 472 developed CVD by the end of 2016, while 14,915 did not. Using the nested case–control analysis in the user cohort (88.0% women and 77.4% elderly), we applied conditional logistic regression to estimate odds ratios (ORs) of eight types of CVD for the users of denosumab, bisphosphonate, teriparatide, and hormone replacement therapy (HRT).Results: The adjusted ORs of overall CVDs were 0.13 (95% CI: 0.12–0.15) for denosumab users, 0.52 (95% CI: 0.45–0.61) for teriparatide users, and 0.80 (95% CI: 0.76–0.85) for bisphosphonate users. The HRT users were at higher odds of coronary artery and peripheral artery diseases, heart failure, pulmonary embolism, and deep vein thrombosis.Conclusion: Denosumab, teriparatide, and bisphosphonate may have more protective effects against CVD than hormone therapy. Physicians may take subsequent cardiovascular risks into account when choosing an adequate antiosteoporosis medication for patients with osteoporosis.

Previous studies reported that lead (Pb) and cadmium (Cd) exposure are linked to changes in serum adiponectin; an adipokine that promotes glycolysis and inhibits gluconeogenesis to regulate glucose metabolism. However, no study has ever explored the relationship between exposure to these two heavy metals and adiponectin in adolescents and young adults. Additionally, the role of adiponectin in the relationship between Pb and Cd exposure and vascular endothelial cell apoptosis has never been investigated. In this study, 724 Taiwanese participants, aged 12 to 30 years, were enrolled to investigate the association among urinary lead and cadmium, serum adiponectin, and apoptotic microparticles (CD31+/CD42a−, CD31+/CD42a+, and CD14). The results of the current study revealed a statistically significant inverse association between urine Pb and Cd levels and adiponectin levels, as well as a positive association with apoptotic microparticles (CD31+/CD42a−, CD31+/CD42a+, and CD14). Adiponectin was also inversely correlated with CD31+/CD42a− and CD31+/CD42a+. Moreover, when subjects with both Pb and Cd levels above the 50th percentile were compared to those below it, the former group exhibited the lowest average adiponectin value. Additionally, a more pronounced positive association between heavy metals and apoptotic microparticles (CD31+/CD42a− and CD31+/CD42a+) was observed when adiponectin levels were lower. Furthermore, an interaction between adiponectin and heavy metals was identified in the relationship between these metals and CD31+/CD42a−. In conclusion, these findings suggest that Pb and Cd exposure may have an adverse effect on adiponectin, and it may play a role in the link between heavy metal exposure and the dysfunction of vascular endothelial cells. Future studies are needed to establish whether a causal relationship exists.

Abstract Background 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. Methods Incident end-stage kidney disease patients who received peritoneal dialysis (PD) for more than 90 days were recruited in this study from 1 January 1, 2007 to December 31, 2018. 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. Results There were 126 patients under the usual care and 546 patients under the MDPC. 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). Conclusions 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.

Abstract 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.

ObjectiveThis study evaluated short-term (1-month) and long-term (1-year) mortality risks associated with the glomerular filtration rate (eGFR) on admission for patients with intracerebral hemorrhage.MethodsFrom the Taiwan Stroke Registry data from April 2006 to December 2016, we identified and stratified patients with intracerebral hemorrhage into five subgroups by the eGFR level on admission: ≥90, 60-89, 30-59, 15-29, and ResultsBoth the 1-month and 1-year mortality rates progressively increased with the decrease in eGFR levels. The 1-month mortality rate in patients with eGFR < 15 mL/min/1.73 m2 or on dialysis was approximately 5.5-fold greater than that in patients with eGFR ≥ 90 mL/min/1.73 m2 (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 in patients with eGFR < 15 mL/min/1.73 m2 or on dialysis was 7.5 times that in patients with eGFR ≥ 90 mL/min/1.73 m2 (2.34 versus 0.31 per 1000 person-days), with an adjusted HR of 4.54 (95% CI 2.95-6.98).ConclusionImpairment of renal function is an independent risk factor for mortality in patients with intracerebral hemorrhage in a gradual way. The eGFR level is a prognostic indicator for patients with intracerebral hemorrhage.

As one of the most common alkylphenols, 4-tertiary-octylphenol (4-tOP) is commonly used in many consumer products. Our previous epidemiological study revealed a negative correlation between serum 4-tOP levels and carotid intima-media thickness (CIMT), which serves as a biomarker of arteriosclerosis. We aimed to explore the role of apoptotic microparticles, markers of vascular endothelial cell function, in the 4-tOP and CIMT connection. To investigate this, we enrolled 886 Taiwanese adolescents and young adults (aged 12–30 years) and examined the relationships among serum 4-tOP levels, apoptotic microparticles (CD31+/CD42a−, CD31+/CD42a+), and CIMT. Our results showed negative associations among serum 4-tOP levels, both apoptotic microparticles, and CIMT in multiple linear regression analysis. The odds ratios for CIMT (≥75th percentile) and the natural logarithm of 4-tOP were highest when both CD31+/CD42a− and CD31+/CD42a+ were greater than the 50th percentile. Conversely, the odds ratios were lowest when both CD31+/CD42a− and CD31+/CD42a+ were less than the 50th percentile. In the structural equation model, we demonstrated that serum 4-tOP levels were negatively correlated with CIMT and indirectly and negatively correlated with CIMT through both apoptotic microparticles. In conclusion, our study reported the inverse association between 4-tOP apoptotic microparticles and CIMT in a young Taiwanese population. Further experimental studies are needed to clarify these associations.

Background: Osteoarthritis (OA) is more prevalent in women with age. Comorbidities are prevalent in OA patients. In this study, we conducted a follow-up study to evaluate whether women with OA are at an increased risk of ischemic stroke using insurance claims data of Taiwan. Methods: We identified 13,520 women with OA aged 20–99 newly diagnosed in 2000–2006 and 27,033 women without OA for comparison, frequency matched by age and diagnosis date. Women with baseline history of hypertension and other disorders associated with stroke were excluded for this study. Incident ischemic stroke was assessed by the end of 2013. A nested case-control analysis was used to identify factors associated with the stroke in the OA cohort. Results: The incidence rate of ischemic stroke in the OA cohort was 1.5-fold greater than that in comparisons (1.93 versus 1.26 per 1,000 person-years), with an adjusted hazard ratio of 1.34 (95% confidence interval [CI], 1.09–1.66). The nested case-control analysis showed that stroke cases were twice as likely to develop hypertension during the follow-up period than controls without stroke. The ischemic stroke risk was significantly associated with hypertension (odds ratio [OR] 1.84; 95% CI, 1.37–2.46) and atrial fibrillation (OR 2.25; 95% CI, 1.24–4.09). Ischemic stroke was not associated with the use of non-steroidal anti-inflammatory drugs or aspirin. Conclusion: Women with OA are at an elevated risk of ischemic stroke. A close monitoring of hypertension, atrial fibrillation, and other stroke related comorbidities is required for stroke prevention for OA patients.

Abstract 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.

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.

Purpose: 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. Approach and results: 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. Conclusions: 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.

Purpose: 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. Approach and results: 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

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.

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.

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

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.

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.

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.

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 PM2.5 levels and exhibited an inverse association with temperature. The incidence was 1.6-fold greater in January than in July (13.7/100 versus 8.81/100), declined during winter breaks (February) and summer breaks (June–August). The highest incidence was 698 cases/day at 2.5 > 37.0 μg/m3, with an adjusted relative risk (aRR) of 1.01 (95% confidence interval [CI] = 0.97–1.04) compared to 568 cases/day at 2.5 < 15.0 μg/m3 (reference). The incidence at ≥30 °C decreased to 536 cases/day (aRR = 0.95, 95% CI = 0.85–1.06) with PM2.5 > 37.0 μg/m3 and decreased further to 392 cases/day (aRR = 0.61, 95% CI = 0.58–0.65) when PM2.5 was 3. In conclusion, CABs infections in children were associated with lowered ambient temperatures and elevated PM2.5 concentrations, and the high PM2.5 levels coincided with low temperature levels. The role of temperature should be considered in the studies of association between PM2.5 and CABs.

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.

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.