Long-Term Use of Statins Lowering the Risk of Rehospitalization Caused by Ischemic Stroke Among Middle-Aged Hyperlipidemic Patients: A Population-Based Study

Background: The long-term effects of statin use on rehospitalization due to ischemic stroke (reHospIS) in hyperlipidemic patients are still unknown. Therefore, we aimed to assess the long-term risks of reHospIS for hyperlipidemic patients who were taking statins and nonstatin lipid-lowering medicines on a regular basis.Methods and Materials: The National Health Insurance Research Database in Taiwan was used to conduct a 6-year cohort study of patients >45 years old (n = 9,098) who were newly diagnosed with hyperlipidemia and hospitalized for the first or second time due to ischemic stroke (IS). The risk of reHospIS was assessed using Cox proportional hazards regression model.Results: Nonstatin lipid-lowering medicines regular users were associated with a higher risk of reHospIS compared to stains users (hazard ratio, HR = 1.29–1.39, p < 0.05). Rosuvastatin was the most preferred lipid-lowering medicine with lower HRs of reHospIS in hyperlipidemic patients whether they developed diabetes or not. Bezafibrate regular users of hyperlipidemic patients developing diabetes (HR = 2.15, p < 0.01) had nearly 50% lower reHospIS risks than those without diabetes (HR = 4.27, p < 0.05). Age, gender, drug dosage, comorbidities of diabetes and heart failure (HF), and characteristics of the first hospitalization due to IS were all adjusted in models. Moreover, increasing trends of HRs of reHospIS were observed from Rosuvastatin, nonstatin lipid-lowering medicines, Lovastatin, and Gemfibrozil to Bezafibrate users.Conclusion: Statins were associated with long-term secondary prevention of reHospIS for hyperlipidemic patients. Rosuvastatin seemed to have the best protective effects. On the other hand, Bezafibrate appears to be beneficial for hyperlipidemic patients developing diabetes. Further research into the combination treatment of statin and nonstatin lipid-lowering medicines in hyperlipidemic patients developing diabetes is warranted.

Download Full-text

Longitudinal association between ambient nitrogen dioxide exposure and all-cause mortality in Chinese adults

10.21203/rs.3.rs-634789/v2 ◽

2021 ◽

Author(s):

Yunquan Zhang ◽

Jing Wei ◽

Yu Zhan ◽

Zhiming Yang ◽

Riyang Liu ◽

...

Keyword(s):

Nitrogen Dioxide ◽

Proportional Hazards ◽

Ambient Air ◽

Population Based ◽

Cox Proportional Hazards ◽

Long Term Effects ◽

Chinese Adults ◽

All Cause Mortality ◽

Longitudinal Association

Abstract A number of population-based studies have investigated long-term effects of nitrogen dioxide (NO2) on mortality, while great heterogeneities exist between studies. In highly populated countries in Asia, cohort evidence for NO2-mortality association was extensively sparse. This study aimed to quantify longitudinal association of ambient NO2 exposure with all-cause mortality in Chinese adults. A national cohort of 30,843 adult men and women were drawn from 25 provincial regions across mainland China, and followed up from 2010 through 2018. Participants’ exposures to ambient air pollutants were assigned according to their residential counties at baseline, through deriving monthly estimates from high-quality gridded datasets developed by machine learning methods. Cox proportional hazards models with time-varying exposures were utilized to assess the association of all-cause mortality with long-term exposure to ambient NO2. An approximately linear NO2-mortality relation (p=0.273 for nonlinearity) was identified across a broad exposure range of 6.9–57.4 μg/m3. Per 10-µg/m3 increase in annual NO2 exposure was associated with an hazard ratio of 1.127 (95% confidence interval: 1.042–1.219, p<0.003) for all-cause mortality. Risk estimates remained robust after additionally adjusting for the confounding effects of co-pollutants (i.e., PM2.5 or O3). In 2018, 1.65 million deaths could be attributed to ambient NO2 exposure (national average 17.3 µg/m3) in China, representing a decrease of 4.3% compared with the estimate of 1.72 million in 2010 (20.5 µg/m3). This cohort study provided national evidence for elevated risk of all-cause mortality associated with long-term exposure to ambient NO2 in Chinese adults.

Download Full-text

Effects of long-term anti-seizure medication monotherapy on all-cause death in patients with post-stroke epilepsy: a nationwide population-based study in Taiwan

BMC Neurology ◽

10.1186/s12883-021-02241-5 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Chia-Yu Hsu ◽

Chun-Yu Cheng ◽

Jiann-Der Lee ◽

Meng Lee ◽

Bruce Ovbiagele

Keyword(s):

Valproic Acid ◽

Ischemic Stroke ◽

Cox Regression ◽

Population Based ◽

Primary Diagnosis ◽

Research Database ◽

Post Stroke ◽

Risk Of Death ◽

Index Stroke

Abstract Objective We aim to compare the effect of long-term anti-seizure medication (ASM) monotherapy on the risk of death and new ischemic stroke in patients with post-stroke epilepsy (PSE). Patients and methods We identified all hospitalized patients (≥ 20 years) with a primary diagnosis of ischemic or hemorrhagic stroke from 2001 to 2012 using the National Health Insurance Research Database in Taiwan. The PSE cohort were defined as the stroke patients (1) who had no epilepsy and no ASMs use before the index stroke, and (2) who had epilepsy and ASMs use after 14 days from the stroke onset. The patients with PSE receiving ASM monotherapy were enrolled and were categorized into phenytoin, valproic acid, carbamazepine, and new ASM groups. We employed the Cox regression model to estimate the unadjusted and adjusted hazard ratios (HRs) with 95 % confidence intervals (CIs) of death and new ischemic stroke within 5 years across all groups, using the new ASM group as the reference. Results Of 6962 patients with PSE using ASM monotherapy, 3917 (56 %) were on phenytoin, 1623 (23 %) on valproic acid, 457 (7 %) on carbamazepine, and 965 (14 %) on new ASMs. After adjusting for confounders, compared with new ASM users, phenytoin users had a higher risk of death in 5 years (HR: 1.64; 95 % CI: 1.06–2.55). On the other hand, all ASM groups showed a similar risk of new ischemic stroke in 5 years. Conclusions Among patients with PSE on first-line monotherapy, compared to new ASMs, use of phenytoin was associated with a higher risk of death in 5 years.

Download Full-text

Inter-pregnancy interval and later pediatric cardiovascular health of the offspring – a population-based cohort study

Journal of Developmental Origins of Health and Disease ◽

10.1017/s2040174420001130 ◽

2020 ◽

pp. 1-5

Author(s):

Majdi Imterat ◽

Tamar Wainstock ◽

Eyal Sheiner ◽

Gali Pariente

Keyword(s):

Proportional Hazards ◽

Proportional Hazards Model ◽

Population Based ◽

Cox Proportional Hazards ◽

Cardiovascular Morbidity ◽

Cox Proportional Hazards Model ◽

Hazards Model ◽

Kaplan Meier ◽

Inter Pregnancy Interval

Abstract Recent evidence suggests that a long inter-pregnancy interval (IPI: time interval between live birth and estimated time of conception of subsequent pregnancy) poses a risk for adverse short-term perinatal outcome. We aimed to study the effect of short (<6 months) and long (>60 months) IPI on long-term cardiovascular morbidity of the offspring. A population-based cohort study was performed in which all singleton live births in parturients with at least one previous birth were included. Hospitalizations of the offspring up to the age of 18 years involving cardiovascular diseases and according to IPI length were evaluated. Intermediate interval, between 6 and 60 months, was considered the reference. Kaplan–Meier survival curves were used to compare the cumulative morbidity incidence between the groups. Cox proportional hazards model was used to control for confounders. During the study period, 161,793 deliveries met the inclusion criteria. Of them, 14.1% (n = 22,851) occurred in parturient following a short IPI, 78.6% (n = 127,146) following an intermediate IPI, and 7.3% (n = 11,796) following a long IPI. Total hospitalizations of the offspring, involving cardiovascular morbidity, were comparable between the groups. The Kaplan–Meier survival curves demonstrated similar cumulative incidences of cardiovascular morbidity in all groups. In a Cox proportional hazards model, short and long IPI did not appear as independent risk factors for later pediatric cardiovascular morbidity of the offspring (adjusted HR 0.97, 95% CI 0.80–1.18; adjusted HR 1.01, 95% CI 0.83–1.37, for short and long IPI, respectively). In our population, extreme IPIs do not appear to impact long-term cardiovascular hospitalizations of offspring.

Download Full-text

Alpha-1 blocker use increased risk of subsequent renal cell carcinoma: A nationwide population-based study in Taiwan

PLoS ONE ◽

10.1371/journal.pone.0242429 ◽

2020 ◽

Vol 15 (11) ◽

pp. e0242429

Author(s):

Shian-Ying Sung ◽

Trang Thi Huynh Le ◽

Jin- Hua Chen ◽

Teng-Fu Hsieh ◽

Chia-Ling Hsieh

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Proportional Hazards ◽

Population Based ◽

Cox Proportional Hazards ◽

Research Database ◽

Antihypertensive Medications ◽

Increased Risk ◽

Underlying Mechanisms

Elevated Renal cell carcinoma (RCC) risk has been associated with the use of several antihypertensive medications but has not yet been elucidated in the populations prescribed alpha-1 blockers that are commonly used in the treatment of hypertension and lower urinary tract symptoms associated with benign prostatic hyperplasia (LUTS-BPH). The aim of the present study was to investigate the association between alpha-1 blocker use and the risk of developing RCC using a nationwide population-based database in Taiwan. Patients who were treated with alpha-1 blockers for at least 28 days were identified through the Taiwan National Health Insurance Research Database from 2000 to 2010. The unexposed participants were matched with the exposed cases according to age, sex, and index year at a ratio of 3:1. Cox proportional hazards regression, stratified by sex and comorbidities and adjusted for age, was performed to estimate hazard ratios (HRs) for the risk of subsequent RCC. Among 2,232,092 subjects, patients who received alpha-1 blocker treatment had a higher risk of RCC than the unexposed group. Taking into account hypertension and BPH, the adjusted HR was significantly higher in male alpha-1 blocker users who had no BPH and either the presence (HR: 1.63, 95% confidence interval [CI] = 1.22–2.18) or absence (HR: 2.31, 95% CI = 1.40–3.81) of hypertension than in men not receiving these drugs. Taken together, male alpha-1 blocker users who had no comorbidity of BPH exhibited an increased risk for developing RCC independent of hypertension. Further study is warranted to elucidate the underlying mechanisms of this association.

Download Full-text

Abstract P005: Comparative Effectiveness of Rivaroxaban versus Warfarin for the Treatment of Patients with Non-valvular Atrial Fibrillation

Circulation ◽

10.1161/circ.133.suppl_1.p005 ◽

2016 ◽

Vol 133 (suppl_1) ◽

Author(s):

Faye L Norby ◽

Lindsay G Bengtson ◽

Lin Y Chen ◽

Richard F MacLehose ◽

Pamela L Lutsey ◽

...

Keyword(s):

Atrial Fibrillation ◽

Ischemic Stroke ◽

Real World ◽

Proportional Hazards ◽

Large Population ◽

Population Based ◽

Cox Proportional Hazards ◽

Gi Bleeding ◽

Cox Proportional Hazards Models ◽

The Us

Background: Rivaroxaban is a novel oral anticoagulant approved in the US in 2011 for prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation (NVAF). Information on risks and benefits among rivaroxaban users in real-world populations is limited. Methods: We used data from the US MarketScan Commercial and Medicare Supplemental databases between 2010 and 2013. We selected patients with a history of NVAF and initiating rivaroxaban or warfarin. Rivaroxaban users were matched with up to 5 warfarin users by age, sex, database enrollment date and drug initiation date. Ischemic stroke, intracranial bleeding (ICB), myocardial infarction (MI), and gastrointestinal (GI) bleeding outcomes were defined by ICD-9-CM codes in an inpatient claim after drug initiation date. Cox proportional hazards models were used to assess the association between rivaroxaban vs. warfarin use and outcomes adjusting for age, sex, and CHA2DS2-VASc score. Separate models were used to compare a) new rivaroxaban users with new warfarin users, and b) switchers from warfarin to rivaroxaban to continuous warfarin users. Results: Our analysis included 34,998 rivaroxaban users matched to 102,480 warfarin users with NVAF (39% female, mean age 71), in which 487 ischemic strokes, 179 ICB, 647 MI, and 1353 GI bleeds were identified during a mean follow-up of 9 months. Associations of rivaroxaban vs warfarin were similar in new users and switchers; therefore we pooled both analyses. Rivaroxaban users had lower rates of ICB (hazard ratio (HR) (95% confidence interval (CI)) = 0.72 (0.46, 1.12))) and ischemic stroke (HR (95% CI) = 0.88 (0.68, 1.13)), but higher rates of GI bleeding (HR (95% CI) = 1.15 (1.01, 1.33)) when compared to warfarin users (table). Conclusion: In this large population-based study of NVAF patients, rivaroxaban users had a non-significant lower risk of ICB and ischemic stroke than warfarin users, but a higher risk of GI bleeding. These real-world findings are comparable to results reported in published clinical trials.

Download Full-text

Hyperlipidemia and Statins Use for the Risk of New Diagnosed Sarcopenia in Patients with Chronic Kidney: A Population-Based Study

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph17051494 ◽

2020 ◽

Vol 17 (5) ◽

pp. 1494 ◽

Cited By ~ 2

Author(s):

Min-Hua Lin ◽

She-Yu Chiu ◽

Pei-Hsuan Chang ◽

Yu-Liang Lai ◽

Pau-Chung Chen ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Kidney Disease ◽

Proportional Hazards ◽

Proportional Hazards Model ◽

Population Based ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Research Database ◽

Newly Diagnosed ◽

Hazards Model

Background: Previous research found that statins, in addition to its efficiency in treating hyperlipidemia, may also incur adverse drug reactions, which mainly include myopathies and abnormalities in liver function. Aim: This study aims to assess the risk for newly onset sarcopenia among patients with chronic kidney disease using statins. Material and Method: In a nationwide retrospective population-based cohort study, 75,637 clinically confirmed cases of chronic kidney disease between 1997 and 2011were selected from the National Health Insurance Research Database of Taiwan. The selection of the chronic kidney disease cohort included a discharge diagnosis with chronic kidney disease or more than 3 outpatient visits with the diagnosis of chronic kidney disease found within 1 year. After consideration of patient exclusions, we finally got a total number of 67,001 cases of chronic kidney disease in the study. The Cox proportional hazards model was used to perform preliminary analysis on the effect of statins usage on the occurrence of newly diagnosed sarcopenia; the Cox proportional hazards model with time-dependent covariates was conducted to take into consideration the individual temporal differences in medication usage, and calculated the hazard ratio (HR) and 95% confidence interval after controlling for gender, age, income, and urbanization. Results: Our main findings indicated that patients with chronic kidney disease who use statins seem to effectively prevent patients from occurrences of sarcopenia, high dosage of statins seem to show more significant protective effects, and the results are similar over long-term follow-up. In addition, the risk for newly diagnosed sarcopenia among patients with lipophilic statins treatment was lower than that among patients with hydrophilic statins treatment. Conclusion: It seems that patients with chronic kidney disease could receive statin treatment to reduce the occurrence of newly diagnosed sarcopenia. Additionally, a higher dosage of statins could reduce the incidence of newly diagnosed sarcopenia in patients with chronic kidney disease.

Download Full-text

Risk of Erectile Dysfunction After Traumatic Brain Injury: A Nationwide Population-Based Cohort study in Taiwan

American Journal of Men s Health ◽

10.1177/1557988317750970 ◽

2018 ◽

Vol 12 (4) ◽

pp. 913-925 ◽

Cited By ~ 10

Author(s):

Yun-Ju Yang ◽

Wu-Chien Chien ◽

Chi-Hsiang Chung ◽

Kun-Ting Hong ◽

Yi-Lin Yu ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Erectile Dysfunction ◽

Health Insurance ◽

Brain Injury ◽

Proportional Hazards ◽

Population Based ◽

Cox Proportional Hazards ◽

Control Group ◽

Research Database ◽

Confounding Factors

Introduction: In our study, we aimed to investigate the association between a traumatic brain injury (TBI) and subsequent erectile dysfunction (ED). This is a population-based study using the claims dataset from The National Health Insurance Research Database. Methods: We included 72,642 patients with TBI aged over 20 years, retrospectively, selected from the longitudinal health insurance database during 2000–2010, according to the ICD-9-CM. The control group consisted of 217,872 patients without TBI that were randomly chosen from the database at a ratio of 1:3, with age- and index year matched. Cox proportional hazards analysis was used to estimate the association between the TBI and subsequent ED. Results: After a 10-year follow-up, the incidence rate of ED was higher in the TBI patients when compared with the non-TBI control group (24.66 and 19.07 per 100,000, respectively). Patients with TBI had a higher risk of developing ED than the non-TBI cohort after the adjustment of the confounding factors, such as age, comorbidity, residence of urbanization and locations, seasons, level of care, and insured premiums (adjusted hazard ratio (HR) = 2.569, 95% CI [1.890, 3.492], p < .001). Conclusion: This is the first study using a comprehensive nationwide database to analyze the association of ED and TBI in the Asian population. After adjusted the confounding factors, patients with TBI have a significantly higher risk of developing ED, especially organic ED, than the general population. This finding might remind clinicians that it’s crucial in early identification and treatment of ED in post-TBI patients.

Download Full-text

Risk of Appendicitis among Children with Different Piped Water Supply: A Nationwide Population-Based Study

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph15081601 ◽

2018 ◽

Vol 15 (8) ◽

pp. 1601

Author(s):

Hao-Ming Li ◽

Shi-Zuo Liu ◽

Ying-Kai Huang ◽

Yuan-Chih Su ◽

Chia-Hung Kao

Keyword(s):

Water Supply ◽

Proportional Hazards ◽

Population Based ◽

Incidence Rates ◽

Cox Proportional Hazards ◽

Sensitivity Analyses ◽

Study Cohort ◽

Research Database ◽

Piped Water ◽

Increased Risk

Appendicitis is a common surgical condition for children. However, environmental effects, such as piped water supply, on pediatric appendicitis risk remain unclear. This longitudinal, nationwide, cohort study aimed to compare the risk of appendicitis among children with different levels of piped water supply. Using data from Taiwan Water Resource Agency and National Health Insurance Research Database, we identified 119,128 children born in 1996–2010 from areas of the lowest piped water supply (prevalence 51.21% to 63.06%) as the study cohort; additional 119,128 children of the same period in areas of the highest piped water supply (prevalence 98.97% to 99.63%) were selected as the controls. Both cohorts were propensity-score matched by baseline variables. We calculated the hazard ratios (HRs) and 95% confidence intervals (CIs) of appendicitis in the study cohort compared to the controls by Cox proportional hazards regression. The study cohort had a raised overall incidence rates of appendicitis compared to the control cohort (12.8 vs. 8.7 per 10,000 person-years). After covariate adjustment, the risk of appendicitis was significantly increased in the study cohort (adjusted HR = 1.46, 95% CI: 1.35, 1.58, p < 0.001). Subgroup and sensitivity analyses showed consistent results that children with low piped water supply had a higher risk of appendicitis than those with high piped water supply. This study demonstrated that children with low piped water supply were at an increased risk of appendicitis. Enhancement of piped water availability in areas lacking adequate, secure, and sanitized water supply may protect children against appendicitis.

Download Full-text

Chemotherapy and Cardiotoxicity in Older Breast Cancer Patients: A Population-Based Study

Journal of Clinical Oncology ◽

10.1200/jco.2005.02.5841 ◽

2005 ◽

Vol 23 (34) ◽

pp. 8597-8605 ◽

Cited By ~ 226

Author(s):

John J. Doyle ◽

Alfred I. Neugut ◽

Judith S. Jacobson ◽

Victor R. Grann ◽

Dawn L. Hershman

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Proportional Hazards ◽

Population Based ◽

Cox Proportional Hazards ◽

Stage I ◽

Breast Cancer Patients ◽

Primary Tumors ◽

Increased Risk

Purpose Adjuvant chemotherapy, especially with anthracyclines, is known to cause acute and chronic cardiotoxicity in breast cancer patients. We studied the cardiac effects of chemotherapy in a population-based sample of breast cancer patients aged ≥ 65 years with long-term follow-up. Patients and Methods In the Surveillance, Epidemiology, and End Results (SEER)-Medicare database, we analyzed treatments and outcomes among women ≥ 65 years of age who were diagnosed with stage I to III breast cancer from January 1, 1992 to December 31, 1999. Propensity scores were used to control for baseline heart disease (HD) and other known predictors of chemotherapy, and Cox proportional hazards models were used to estimate the risk of cardiomyopathy (CM), congestive heart failure (CHF), and HD after chemotherapy. Results Of 31,748 women with stage I to III breast cancer, 5,575 (18%) received chemotherapy. Chemotherapy was associated with younger age, fewer comorbidities, hormone receptor negativity, multiple primary tumors, and advanced disease. Patients who received chemotherapy were less likely than other patients to have pre-existing HD (45% v 55%, respectively; P < .001). The hazard ratios for CM, CHF, and HD for patients treated with doxorubicin (DOX) compared with patients who received no chemotherapy were 2.48 (95% CI, 2.10 to 2.93), 1.38 (95% CI, 1.25 to 1.52), and 1.35 (95% CI, 1.26 to 1.44), respectively. The relative risk of cardiotoxicity among patients who received DOX compared with untreated patients remained elevated 5 years after diagnosis. Conclusion When baseline HD was taken into account, chemotherapy, especially with anthracyclines, was associated with a substantially increased risk of CM. As the number of long-term survivors grows, identifying and minimizing the late effects of treatment will become increasingly important.

Download Full-text

Increased Risk of Ulcerative Colitis in Patients with Periodontal Disease: A Nationwide Population-Based Cohort Study

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph15112602 ◽

2018 ◽

Vol 15 (11) ◽

pp. 2602 ◽

Cited By ~ 6

Author(s):

Chien-Yu Lin ◽

Kuo-Sen Tseng ◽

Jui-Ming Liu ◽

Heng-Chang Chuang ◽

Chi-Hone Lien ◽

...

Keyword(s):

Ulcerative Colitis ◽

Periodontal Disease ◽

Proportional Hazards ◽

Population Based ◽

Cox Proportional Hazards ◽

Control Group ◽

Research Database ◽

Immune Mediated ◽

Increased Risk ◽

Inflammatory Processes

Both periodontal disease (PD) and inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), are important diseases of the alimentary tract. Microbiome and immune-mediated inflammatory processes play important roles in these diseases. An association between PD and IBD may exist. This study investigated the risk of IBD in patients with PD. This study used data from the National Health Insurance Research Database of Taiwan from 1996 to 2013. A total of 27,041 patients with PD were enrolled as a study group, and 108,149 patients without PD were selected as the control group after matching by gender, age, insured region, urbanization, and income with a 1:4 ratio. Cox proportional hazards regression was used to calculate the risk of IBD. Of the 135,190 participants enrolled in this study, 5392 (4%) with newly diagnosed IBD were identified. The overall incidence of subsequent IBD was similar in both groups (3.8% vs. 4%, adjusted hazard ratio (aHR) = 1.01, 95% confidence interval (CI): 0.94–1.08). However, an increased risk of UC in the PD group was found after adjusting confounding factors (aHR: 1.56, 95% CI: 1.13–2.15; p < 0.05). This study demonstrated that patients with PD had approximately one-half higher risk of subsequent UC. Further studies are warranted to elucidate the relationship between PD and UC.

Download Full-text