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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.

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.

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

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

BACKGROUND Whether patients with inflammatory bowel disease (IBD) exhibit a higher risk of developing acute coronary syndrome (ACS) remains debatable. METHODS From the inpatient claims of Taiwan's National Health Insurance Research Database, we identified 11,822 patients with IBD symptoms in the 1998-2010 period and 47,288 control patients without the disorder, frequency matched by age, sex, and admission year. Both cohorts were followed-up until the end of 2010 to estimate the risk of ACS. RESULTS The incidence of ACS was 87% higher in the patients with IBD than in the control patients (5.76 versus 3.08 per 1000 person-years). The multivariable Cox proportional hazards regression model measured adjusted hazard ratios of ACS at 1.72 (95% confidence interval, 1.53-1.94) for the patients with IBD. The age-specific data showed that the adjusted hazard ratio for patients with IBD, compared with control patients, was the highest for the 20- to 39-year age group, at 3.28 (95% confidence interval, 1.73-6.22), which decreased to 1.70 (95% confidence interval, 1.45-1.99). Patients with IBD who, on average, required 2 or more hospitalization per year were nearly 20-fold more likely to have ACS than those who required 1 hospitalization per year (80.7 versus 4.10 per 1000 person-years). CONCLUSIONS The absolute risk of ACS increases sharply with age for patients with IBD, but young patients are at greater relative risk for the consequence. The risk of ACS was proportional to the severity of IBD. Careful follow-up observation and effective therapy should be sought for patients with IBD to reduce the risk of ACS.

Background: The role of autoimmune pathology in development and progression of chronic obstructive pulmonary disease (COPD) is becoming increasingly popular. Our aim was to assess the association between patients with rheumatoid arthritis (RA) and subsequent COPD risk in a nationwide population. Method: We conducted a retrospective cohort study using data from the National Health Insurance system of Taiwan. The RA cohort included patients who were newly diagnosed and recruited between 1998 and 2008. Each patient was randomly frequency-matched for age, sex and the year of index date with people without RA from the general population. The newly diagnosed COPD was followed up until the end of 2010. The relative risks of COPD were estimated using Cox proportional hazard models after adjusting for age, sex, index year and comorbidities. Result: The overall incidence rate of COPD was 1.74-fold higher in the RA cohort than in the non-RA cohort (5.25 vs. 3.01 per 1000 person-years, 95% confidence interval (CI) = 1.68–1.81). Age-related risk analysis showed an increased incidence of COPD with age in both RA and non-RA cohorts. However, adjusted hazard ratio (HR) maximum was witnessed in the age range of 20–34 years (adjusted HR: 7.67, 95% CI=1.94–30.3), whereas adjusted HR minimum was observed in the oldest age group (>65 years). Conclusion: Patients with RA have a significantly higher risk of developing COPD than that of the control population. Further, age-related risk analysis indicated much higher adjusted HR in younger patients although COPD incidence increased with age. It can be hypothesized that in addition to cigarette smoke, RA may be a determining factor for COPD incidence and/or facilitates shortening of the time course for developing COPD. However, further investigation is needed to corroborate this hypothesis.

Background: Several studies have indicated an association between venous thromboembolism (VTE) and a subsequent diagnosis of cancer in Western countries. However, information is scant on subsequent cancer incidence after idiopathic VTE events in Asian people. Through a nationwide cohort study, we evaluated the cancer prevalence of VTE and new cancer incidence in patients after the first episode of idiopathic VTE. Methods: To conduct a nationwide population cohort study on VTE, we retrieved data from the Taiwan National Health Insurance Database from 1998 to 2008, including a 2-year follow-up period extending to the end of 2010. The occurrence of cancer in the cohort was also determined by accessing the Registry for Catastrophic Illness Patient Database. Results: A total of 45 242 patients had the newly diagnosed VTE from 1998 to 2008. The incidence of VTE increased with age. Among 28 243 idiopathic VTE patients, 1944 patients (6.89%) had a subsequent cancer diagnosis within 2 years of the first idiopathic VTE episode. The three most common newly diagnosed cancers after idiopathic VTE were lung cancer, liver cancer and colorectal cancer (18.3%, 12.3% and 10.9%, respectively). Male sex and advanced age are independent risk factors of having an underlying malignant disorder among patients diagnosed with idiopathic VTE. Conclusion: Patients with symptomatic VTE without an identifiable risk factor have a 6.89% incidence of subsequent cancer diagnosis in Taiwan. An extensive screening for an occult cancer in an idiopathic VTE patient may be warranted.

Objectives We address the potential problem of stroke induced by morphine exposure by comparing the incidence of stroke in cancer patients treated with and without morphine. Methods We performed a population-based nested case–control retrospective analysis on the Longitudinal Health Insurance Database 2000 and Registry for Catastrophic Illness Patients of Taiwan. This study is based on a malignancy cohort of 31 611 patients without a history of stroke, and 1208 patients who subsequently developed stroke served as the stroke group. Four controls of matched age, sex, entry year and entry month for each case were selected from the malignancy cohort from the non-stroke group. We used logistic regression to estimate the odds ratios and 95% confidence intervals, and applied the multivariable model to control for age, sex, hypertension, diabetes, hyperlipidemia and cardiovascular disease. Results Cancer patients who received morphine had a 12% higher risk of developing stroke than non-morphine users. However, the difference was nonsignificant. A significant difference only appears in prostate cancer patients, where morphine users have a 3.02-fold (4.24- and 2.90-fold for hemorrhagic and ischemic strokes, respectively) higher risk of suffering from stroke. The risk increased significantly as the morphine dosage increased to 170 mg/year of treatment. Conclusions Intense morphine treatment may be associated with an increased stroke incidence in patients with malignancy, and the association is particularly significant for prostate cancer patients.

Learning Objectives After completing this course, the reader will be able to:Describe the effect of finasteride use on the incidence of prostate cancer and overall cancer.Describe the effect of dutasteride use on the incidence of renal cancer.Explain the relationship between finasteride dosage and risk of prostate cancer and overall cancer risk. CME This article is available for continuing medical education credit at CME.TheOncologist.com Background. 5α-Reductase inhibitors (5ARIs) are commonly used to treat benign prostate hyperplasia (BPH) by blocking the conversion of testosterone into the more potent dihydrotestosterone. This study explored a possible association between the use of the 5ARIs finasteride and dutasteride and the subsequent risk of prostate cancer or other cancers. Methods. We analyzed data from the Taiwanese National Health Insurance system. In a BPH cohort, we identified 1,489 patients with cancer and included them in our study group. For the control group, 3 patients without cancer were frequency matched with each BPH case for age, BPH diagnosis year, index year, and month. Information regarding past 5ARI use was obtained from the Taiwanese National Health Insurance Research Database (NHIRD). Multivariate logistic regression analysis was conducted, and odds ratio (OR) and 95% confidence interval (CI) were estimated. Results. Finasteride use marginally increased the incidence of prostate and overall cancer at a level of statistical significance (prostate cancer: OR = 1.90; 95% CI: 1.00–3.59; overall cancer: OR = 1.51; 95% CI: 1.00–2.28). Dutasteride use significantly increased kidney cancer risk (OR = 9.68, 95% CI: 1.17–80.0). Dosage analysis showed that lower doses of finasteride were associated with higher overall and prostate cancer risks. The major limitation is the lack of important data in the NHIRD, such as prostate cancer histologic grades, smoking habits, alcohol consumption, body mass index, socioeconomic status, and family history of cancer. Conclusions. This population-based nested case-control study suggested that finasteride use may increase prostate and overall cancer risks for patients with BPH. The effects were more prominent for patients using lower doses of finasteride.

Background and objectives Dislocations, sprains and strains are common childhood musculoskeletal injuries, requiring medical attentions. We investigated characteristics associated with using Traditional Chinese medicine (TCM) for children suffering from these injuries. Methods From a nationwide representative insurance database of Taiwan, this cross-sectional study identified 50,769 children with dislocations, sprains and strains under 18 …

Background. Renal vascular resistance [resistive index (RI)] has been associated with albuminuria in patients with type 2 diabetes. We studied the correlations between renal artery RI and urinary albumin excretion in adolescents and young adults. Methods. From May 2006 through September 2008, we established a cohort of adolescents and young adults based on previous history of elevated blood pressure (EBP) or normal blood pressure in childhood. This cohort was selected from the 1992–2000 nationwide mass urine screening of school children aged 6–18 years in Taiwan. From October through December 2008, we called back these adolescents and young adults living in Taipei to participate in a renal vascular stiffness study. Linear mixed regression models were applied to study the correlation between renal artery RI and urinary albumin excretion after controlling for cardiovascular (CV) risk factors. Results. Of the 147 subjects enrolled in this study, 67 had macroalbuminuria, 36 had microalbuminuria and 44 had normoalbuminuria. Except for high-density lipoprotein cholesterol, most CV risk factors did not differ significantly among these three groups. Mean RI were similar for the three groups. Neither log (urinary albumin concentration) nor log (urinary albumin:creatinine ratio) correlated with RI. Step-wise linear mixed regression models showed that RI was significantly associated only with male gender and diastolic blood pressure, but not with urinary albumin excretion or EBP in childhood. Conclusion. Renal artery RI is not associated with urinary albumin excretion in nondiabetic adolescents and young adults.

Mothers bearing small offspring are at increased risk of cardiovascular disease (CVD) mortality. The cardiovascular risk for fathers of small offspring is, however, inconclusive. Very few studies with sufficiently large sample sizes have been conducted to specifically differentiate the maternal/paternal CVD risk in association with offspring birth weight in the same population.This study followed 1,400,383 primigravida and their spouses with singleton births registered in Taiwan between 1978 and 1987 to the end of 2006. By linking to the mortality registry, the hazards ratio (HR) of parental cardiovascular mortality was measured in relation to lower offspring birth weights.The covariate-adjusted HR and 95% confidence interval (CI) of CVD mortality for 1 standard deviation higher offspring birth weight was reduced (HR = 0.89; 95% CI: 0.85-0.94) for mothers, but less obvious for fathers (HR = 0.97; 95% CI: 0.95-1.00). Analyses of the categorical offspring birth weights revealed that the association between bearing low-birth-weight offspring (2500 g) and CVD mortality was also stronger in mothers (adjusted HR = 1.85; 95% CI: 1.67-2.18) than in fathers (adjusted HR = 1.13; 95% CI: 1.03-1.24). On standardizing the birth weight for gestational age, the observed associations persisted, although these associations were relatively weak.This large cohort analysis confirmed that the bearing of smaller size infants is associated with a stronger elevated risk for CVD mortality in mothers than in fathers. Women who have had a lower birth-weight offspring can be targeted for CVD-prevention measures.

The authors investigated whether red blood cell distribution width (RDW) was associated with the development of cardiovascular disease (CVD) events and mortality in a community cohort in Taiwan. The influence of anemia on the association was also assessed. RDW levels were measured in 3,226 participants aged 35 years or older who reported no CVD or cancer at baseline in 1990. During a median follow-up period of 15.9 years (1990-2007), 358 participants experienced stroke and/or coronary heart disease, and 810 participants died. The multivariate-adjusted hazard ratio for subjects in the highest RDW quartile as compared with the lowest quartile was 1.46 for both all-cause mortality (95% confidence interval: 1.17, 1.81) and non-CVD mortality (95% confidence interval: 1.13, 1.88) (P for trend < 0.01 for both) but was not significant for CVD morbidity and mortality. Further analyses showed that in comparison with participants with low RDW and no anemia, persons with high RDW but no anemia had elevated risks of all-cause mortality and non-CVD mortality. The authors conclude that elevated RDW values are associated with increased risk of mortality but not the development of CVD in the general population. RDW may precede anemia in predicting the risk of non-CVD death.

Background: Little is known about lipoprotein(a) [Lp(a)] as a predictor of vascular events among ethnic Chinese. We prospectively investigated the association of Lp(a) with cardiovascular disease and all-cause death in a community-based cohort.Methods: We conducted a community-based prospective cohort study of 3484 participants (53% women; age range, 35–97 years) who had complete lipid measurements and were free of a cardiovascular disease history at the time of recruitment. Over a median follow-up of 13.8-years, we documented 210 cases of stroke, 122 cases of coronary heart disease (CHD), and 781 deaths.Results: The incidences for each event increased appreciably with Lp(a) quartile for stroke and all-cause death, but not for CHD. Baseline Lp(a) concentration by quartile was not significantly associated with stroke, all-cause death, and CHD in multivariate analyses. The multivariate relative risk was significant for stroke at the 90th and 95th percentiles and for total death at the 95th and 99th percentiles.Conclusions: Our findings suggest a threshold relationship with little gradient of risk across lower Lp(a) values for stroke and all-cause death in Chinese adults.

The relative importance of atherosclerotic risk factors, such as hypertension, dyslipidemia, diabetes and smoking, was associated with cardiovascular events and varied among different ethnic groups. For a population with relatively low coronary heart disease (CHD) such as Asian-Pacific countries, it is crucial to differentiate the roles of these risk factors.We examined the relative importance of various risk factors for CHD in a community-based cohort in Taiwan, consisting of 3602 adults aged 35 and older with a median follow-up time of 9.0 years since 1990. Regular death certificate verification and medical record reviews were performed in the follow-up activities.There were 85 cases defined as CHD. In the Cox proportional hazard analysis, men were at higher risk than women [hazard risk (HR)=2.22, 95% confidence interval (CI)=1.39-3.56]. Hypertension was the most common risk factor for CHD. Dyslipidemia, especially lowered high-density lipoprotein cholesterol, also played an important role (HR=2.09, 95% CI=1.33-3.29) in CHD events. Hypertension had a greater influence in males (HR=6.08, P0.001) than in females (HR=2.80, P0.001). No independent association was found for smoking or body mass index in cardiovascular events.This study found that in a community-based cohort, hypertension, and dyslipidemia attribute an important role to cardiovascular events.

Background: A population-based study was conducted in Taiwan to investigate the prevalence of insulin resistance and high serum insulin concentrations and their relationships with potential atherosclerotic risk factors.Methods: We studied 2165 subjects, ages >35, from a community cohort.Results: The distributions of fasting insulin were skewed to the right, with higher concentrations in women than in men. As age increased, insulin increased in women, but decreased in men. As fasting insulin concentrations increased, postloading insulin, glucose, blood pressure, body mass index, waist-to-hip ratio, total cholesterol, triglycerides, LDL-cholesterol, apoprotein B, plasminogen activator inhibitor 1, tissue plasminogen activator, and fibrinogen increased, but lipoprotein(a), HDL-cholesterol, and apoprotein A1 decreased. Multiple logistic regression showed that obesity, high LDL-cholesterol, and low HDL-cholesterol were significant predictors of hyperinsulinemic status.Conclusion: The study subjects with insulin resistance syndrome and related risk factors may be at risk for atherosclerosis, thrombosis, and other coronary heart diseases.

Using compensation records of Taiwan, we conducted a case-control study nested within a cohort of 77,846 active workers who experienced at least one incidence of non-fatal work-related injury between 1994 and 1996 in order to explore factors associated with risk of sustaining multiple non-fatal injuries in the workplace. Cases (n = 2,616) were workers with more than three incidences of non-fatal injury during the study period and controls (n = 3,974) were randomly sampled from workers who experienced only one incidence of non-fatal injury during the same period. Compared with construction workers, workers employed in mining and quarrying (OR = 2.7), manufacturing (OR = 1.2), commerce (OR = 1.6), transport, storage and communication (OR = 1.3) and social, personal and community service (OR = 1.4) were all at significantly elevated risk of multiple non-fatal injuries. Both age and wage showed a significant dose-response effect on the risk of developing multiple non-fatal injuries. The preliminary analysis suggests that workers in certain industries are at significantly elevated risks of multiple work-related non-fatal injuries, in particular those in the mining and quarry industries. Additionally, further preventive measures should be aimed at protecting older workers from such injuries and further studies would help provide more specific interpretations on the positive association between higher wage earning and risk of multiple non-fatal injuries.

Background Studies on the effectiveness of seasonal influenza vaccination in peritoneal dialysis (PD) patients are limited. The aim of the present study is to evaluate the effectiveness of seasonal influenza vaccination in reducing morbidity and mortality in incident end-stage renal disease patients on PD. Methods From Taiwan's National Health Insurance Research Database, we identified 2089 incident PD patients with seasonal influenza vaccination and 2089 propensity score matched incident PD patients without the vaccination during 1998-2010. Each study subject was followed up to measure the 12-month incident cardiovascular and infectious diseases, and deaths. The effects of multi-year vaccinations were also estimated. Results Compared with the non-vaccinated cohort, the vaccinated cohort had a lower hospitalization rate (68.5 versus 80.2 per 100 person-years) with an adjusted hazard ratio (aHR) of 0.85 [95% confidence interval (CI) = 0.78-0.92]. Hazards of hospitalization were significantly reduced for sepsis (aHR = 0.79, 95% CI = 0.65-0.96), heart disease (aHR = 0.74, 95% CI = 0.63-0.89) and intensive care (aHR = 0.85, 95% CI = 0.73-0.99). In addition, hazards of peritonitis (aHR = 0.84, 95% CI = 0.73-0.97) and overall mortality (aHR = 0.66, 95% CI = 0.55-0.78) were also reduced. The aHR of mortality was reduced much further to 0.28 (95% CI = 0.22-0.35) for those with multiple-year vaccinations. Conclusions Seasonal influenza vaccination for PD patients is associated with significant reduction in morbidities and a 34% reduction in mortality. Multi-year vaccinations could reduce the death hazard further to 72%.