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Aims Limited data compared antiarrhythmic drugs (AADs) with concomitant non-vitamin K antagonist oral anticoagulants in atrial fibrillation patients, hence the aim of the study. Methods and results National health insurance database were retrieved during 2012–17 for study. We excluded patients not taking AADs, bradycardia, heart block, heart failure admission, mitral stenosis, prosthetic valve, incomplete demographic data, and follow-up Conclusion The use of dronedarone with NOACs was associated with cardiovascular benefits in an Asian population, compared with non-dronedarone AADs and amiodarone.

This study evaluated the risk of major bleeding associated with concomitant use of direct oral anticoagulant (DOAC) and anticancer drugs (ACDs), which share metabolic pathways, in patients with atrial fibrillation (AF) and cancer. We performed a retrospective cohort study using Taiwan’s National Health Insurance database and included patients with AF and cancer who received DOAC prescriptions from 1 to 2012 to 31 December 2017. The incidence of major bleeding in person-quarters with concomitant use of DOAC and any of 15 ACDs with inhibitory or competitive effects of CYP3A4 or P-gp activity (docetaxel, vinorelbine, methotrexate, irinotecan, etoposide, doxorubicin, cyclophosphamide, imatinib, nilotinib, abiraterone, bicalutamide, tamoxifen, anastrozole, cyclosporine, tacrolimus) was compared with that in person-quarters with DOAC alone. Adjusted incidence-rate differences between DOAC use with and without concurrent ACDs were estimated using Poisson regression models weighted by the inverse probability of treatment. In 13,158 patients with AF and cancer (76.9 ± 8.9 years; male 60%), 1545 major bleeding events occurred during 90,540 DOAC-exposed person-quarters. Concurrent use of DOAC and any of 15 ACDs occurred in only 18% of patients. Compared with use of DOAC alone, concomitant use of DOAC and these ACDs was not associated with an increased risk of major bleeding. Co-medication with DOAC and ACDs with inhibitory or competitive effects on CYP3A4 or P-gp activity was not associated with a higher risk of major bleeding than DOAC alone. Our findings may provide clinicians with confidence regarding the safety of concurrent use of DOAC and ACDs in patients with AF and cancer.

The long-term outcomes of surgical ablation for atrial fibrillation (AF) during cardiac surgery remain unclear.This nationwide population-based retrospective cohort study used data from Taiwan's National Health Insurance Research Database. Overall, 11,459 patients undergoing coronary artery bypass graft, valve, or aortic surgery and diagnosed as having AF between January 1, 2001, and December 31, 2016, were included. To reduce possible selection bias, we created a propensity score-matched cohort and compared outcomes between groups. The outcomes of interest were long-term survival and late ischemic stroke.The surgical ablation group had a significantly lower risk of all-cause mortality (5.74 and 7.69 events per 100 patient-years, respectively; hazard ratio, 0.75; 95% CI, 0.69-0.81) and ischemic stroke after discharge (1.88 and 2.52 events per 100 patient-years, respectively; subdistribution hazard ratio, 0.78; 95% CI, 0.67-0.91). AF ablation performed concomitantly with coronary artery bypass graft surgery, tissue aortic valve replacement, tissue mitral valve replacement, or mitral valve repair led to significantly better long-term survival (P = .0176, P = .0001, P.0001, P.0001, respectively). The surgical ablation group also had better long-term survival than the matched general AF population (log-rank test, P.001).Concomitant AF ablation during cardiac surgery is safe, does not increase the rate of perioperative complications, and confers the benefit of long-term survival after cardiac surgery in adults. AF ablation also improved cardiac surgery patients' long-term survival compared with the matched general AF population.

Introduction: Non-vitamin K antagonist oral anticoagulant (NOAC) do not normally require INR-monitoring. We aimed to investigate drug-drug interactions of NOACs in patients with atrial fibrillation (AF) using antiarrhythmic drugs. Hypothesis: Dronedarone may have less drug-drug interaction compared to non-dronedarone antiarrhythmic drugs. Methods: National Health Insurance Research Database were retrieved between 2012 and 2017 for patients with AF. We excluded patients not taking antiarrhythmic drugs, bradycardia, heart block, history of heart failure, mitral stenosis, prosthetic valve, incomplete demographic data, and follow-up Results: In total, 84,933 patients used NOAC in patients with AF were enrolled. After exclusion criteria, there were 26,773 patients with 204,937 person-quarters remained for analysis after the exclusion criteria were applied In terms of major bleeding, there was no increased major bleeding due to DDI between NOAC and dronedarone (adjusted rate ratio [aRR]: 0.77, 99% confidence interval [CI]: 0.54-1.12, p = 0.074). In terms of intracranial hemorrhage, there was no increased major bleeding due to DDI between NOAC and dronedarone (aRR: 0.64, 99% CI: 0.34-1.20, p = 0.0668). In terms of gastrointestinal bleeding, there was no increased major bleeding due to DDI between NOAC and dronedarone (aRR: 0.86, 99% CI: 0.55-1.35, p = 0.3819). Conclusions: In this study, NOACs and dronedarone coprescription is not associated with an increased risk of major bleeding, intracranial hemorrhage, nor gastrointestinal bleeding. The results suggest that such NOAC with dronedarone coprescription should be practiced in place of NOAC with amiodarone when the clinical criteria are appropriate.

Introduction: Dronedarone was developed to improve outcomes in patients with atrial fibrillation (AF) compared with other antiarrhythmic drugs. Hypothesis: Dronedarone may offer better cardiovascular outcomes compared to non-dronedarone antiarrhythmic drugs. Methods: Taiwan National Health Insurance Research Database were retrieved between 2012-2017 for patients with AF. Patients not taking antiarrhythmic drugs, having history of bradycardia, heart block, heart failure admission, mitral stenosis, prosthetic valve, incomplete demographic data, and follow-up less than 3 months were excluded. Protocol 1, outcomes of patients with AF using dronedarone were compared to non-dronedarone antiarrhythmic drugs (amiodarone, propafenone, flecainide, sotalol). In Protocol 2, outcomes of patients with AF using dronedarone were compared to amiodarone, the most frequently used antiarrhythmic drug. Propensity score matching performed to reduce bias. Primary outcomes were acute myocardial infarction (AMI), ischemic stroke/systemic embolism (IS/SE), intracranial hemorrhage (ICH), major bleeding, cardiovascular death, and all-cause mortality. Secondary outcome was composite of AMI, ischemic stroke, and cardiovascular death (MACE). Results: In Protocol 1, after 1:3 matching, 2,032 dronedarone patients and 6,096 non-dronedarone patients were analyzed. Dronedarone was associated with significantly lower IS/SE (p=0.0033), ICH (p=0.0111), major bleeding (p=0.0230), cardiovascular death (p Conclusions: Dronedarone was associated with lower ischemic stroke/systemic embolism, cardiovascular death, all-cause mortality and MACE compared to non-dronedarone or directly to amiodarone.

Direct oral anticoagulants (DOACs) are commonly prescribed with antidepressants that may increase bleeding risk. Here we assessed the association between DOACs with and without concurrent antidepressants and major bleeding risk in patients with atrial fibrillation (AF) by a retrospective cohort study included patients with AF who received prescriptions of DOACs in Taiwan’s National Health Insurance database between 2012 and 2017. Adjusted rate ratio (ARR) of major bleeding was calculated by comparing incidence rate adjusted with Poisson regression and inverse probability of treatment weighting using the propensity score between patient-times with and without antidepressants. Among 98863 patients with AF, concurrent use of bupropion with DOACs increased the risks of all major bleeding (ARR: 1.49, 95% CI: 1.02–2.16) and gastrointestinal hemorrhage (ARR: 1.57, 95% CI: 1.04–2.33). An increased risk of intracerebral hemorrhage (ICH) was associated with the combinations of DOACs with selective serotonin reuptake inhibitors (SSRIs, ARR: 1.38, 95% CI: 1.08–1.76), particularly in paroxetine (ARR: 2.11, 95% CI: 1.17–3.81), and tetracyclic antidepressants (TeCAs, ARR: 1.34, 95% CI: 1.01–1.78). In subgroup analyses stratified by individual NOACs, SSRIs increased the risk of ICH in the dabigatran-treated patients (ARR: 1.55, 95% CI: 1.04–2.33). The combinations of apixaban and serotonin-norepinephrine reuptake inhibitors (SNRIs) were associated with a higher risk of all major bleeding (ARR: 1.63, 95% CI: 1.04–2.55). These results clearly indicate the drug–drug interactions between DOACs and antidepressants, which should be carefully considered when prescribing DOACs in adult patients. Careful monitoring for bleeding should be performed while concurrently prescribing DOACs with bupropion, SSRI, SNRI, and TeCA. Concomitant use of DOACs and TCAs may be a relatively safe strategy for patients with AF.

This study evaluated the risk of major bleeding associated with concomitant use of direct oral anticoagulant (DOAC) and anticancer drugs (ACDs), which share metabolic pathways, in patients with atrial fibrillation (AF) and cancer. We performed a retrospective cohort study using Taiwan's National Health Insurance database and included patients with AF and cancer who received DOAC prescriptions from 1 to 2012 to 31 December 2017. The incidence of major bleeding in person-quarters with concomitant use of DOAC and any of 15 ACDs with inhibitory or competitive effects of CYP3A4 or P-gp activity (docetaxel, vinorelbine, methotrexate, irinotecan, etoposide, doxorubicin, cyclophosphamide, imatinib, nilotinib, abiraterone, bicalutamide, tamoxifen, anastrozole, cyclosporine, tacrolimus) was compared with that in person-quarters with DOAC alone. Adjusted incidence-rate differences between DOAC use with and without concurrent ACDs were estimated using Poisson regression models weighted by the inverse probability of treatment. In 13,158 patients with AF and cancer (76.9 ± 8.9 years; male 60%), 1545 major bleeding events occurred during 90,540 DOAC-exposed person-quarters. Concurrent use of DOAC and any of 15 ACDs occurred in only 18% of patients. Compared with use of DOAC alone, concomitant use of DOAC and these ACDs was not associated with an increased risk of major bleeding. Co-medication with DOAC and ACDs with inhibitory or competitive effects on CYP3A4 or P-gp activity was not associated with a higher risk of major bleeding than DOAC alone. Our findings may provide clinicians with confidence regarding the safety of concurrent use of DOAC and ACDs in patients with AF and cancer.

Aftercare programs' effectiveness for suicide ideators has seldom been reported. This study assessed rates and factors related to the recurrence of suicide-related episodes after the index suicidal ideation episode, index cases, and family members receiving aftercare. This is a secondary data analysis of 1787 suicidal ideation episodes from 1557 individuals reported to the National Suicide Surveillance System in New Taipei City, Taiwan, from January 2012 to June 2013 and followed up until September 2013. Among 1787 index suicidal ideations, 19.1% had recurrences of suicide-related episodes, including suicidal ideation (11.9%), attempt (6.7%), and death (0.5%) within 2 years after index ideation. These recurrences were significantly reduced after the index cases received aftercare twice, three, and four or higher. Family members receiving aftercare twice or more were associated with reduced suicidality in the index cases. Receiving aftercare among index cases was associated with being a woman, suicide due to occupation/finance, and reporting from suicide hotlines. Receiving aftercare among family members was associated with the index cases aged ≤ 19 years old, suicide reasons related to school, occupation/finance, and reporting from schools and hospitals. Aftercare programs for suicide ideators and family members of adolescent suicide ideators (aged ≤ 19 years old) decreased subsequent episodes of suicidal behavior.

Background and aims The coprescription of an angiotensin-converting enzyme inhibitor (ACEi) with clopidogrel reportedly increases bleeding risk. However, studies have not described such an increase in cases of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI). Methods We analyzed electronic medical records of patients with discharge records of having undergone DAPT after PCI from a national health insurance claims database for January 1, 2006 to December 31, 2014. The date of PCI was the index date, and the primary outcome was major bleeding. The unit of analysis was one person-quarter. We compared patients who were prescribed with those not prescribed an ACEi in the cohort. A Poisson model with inverse probability of treatment weighting was fitted using generalized estimating equations to measure the risk of outcomes. Results In total, 193,258 patients underwent DAPT after PCI; 46% had a coprescription of an ACEi. After screening, 170,775 patients (479,263 person-quarters) remained for analysis. The mean patient age was 65 ± 13 years, and 73.43% were men. In total, 79,739 prescriptions of an ACEi were written: 57%, 14.21%, 8.88%, 7.17%, and 4.68% were for captopril, ramipril, enalapril, perindopril, and imidapril, respectively. A concomitant prescription of an ACEi with clopidogrel was not associated with increased bleeding risk (adjusted rate ratio: 1.08, 99% confidence interval: 0.99–1.17). Conclusions The coadministration of an ACEi with clopidogrel after PCI is common. In this real-world cohort study, such coadministration was not associated with an increased risk of major bleeding in patients undergoing DAPT after PCI.

Glucagon-like peptide-1 (GLP-1) receptor agonist use is associated with reduced mortality and improved cardiovascular outcomes in the general population with diabetes. Dipeptidyl peptidase-4 (DPP-4) inhibitors are commonly used antidiabetic agents for patients with advanced-stage chronic kidney disease (CKD). The association of these 2 drug classes with outcomes among patients with diabetes and advanced-stage CKD or end-stage kidney disease (ESKD) is not well understood.To assess whether use of GLP-1 receptor agonists in a population with diabetes and advanced-stage CKD or ESKD is associated with better outcomes compared with use of DPP-4 inhibitors.This retrospective cohort study used data on patients with type 2 diabetes and stage 5 CKD or ESKD obtained from the National Health Insurance Research Database of Taiwan. The study was conducted between January 1, 2012, and December 31, 2018. Data were analyzed from June 2020 to July 2021.Treatment with GLP-1 receptor agonists compared with treatment with DPP-4 inhibitors.All-cause mortality, sepsis- and infection-related mortality, and mortality related to major adverse cardiovascular and cerebrovascular events were compared between patients treated with GLP-1 receptor agonists and patients treated with DPP-4 inhibitors. Propensity score weighting was used to mitigate the imbalance among covariates between the groups.Of 27 279 patients included in the study, 26 578 were in the DPP-4 inhibitor group (14 443 [54.34%] male; mean [SD] age, 65 [13] years) and 701 in the GLP-1 receptor agonist group (346 [49.36%] male; mean [SD] age, 59 [13] years). After weighting, the use of GLP-1 receptor agonists was associated with lower all-cause mortality (hazard ratio [HR], 0.79; 95% CI, 0.63-0.98) and lower sepsis- and infection-related mortality (HR, 0.61; 95% CI, 0.40-0.91). Subgroup analysis demonstrated a lower risk of mortality associated with use of GLP-1 receptor agonists compared with DDP-4 inhibitors among patients with cerebrovascular disease (HR, 0.33; 95% CI, 0.12-0.86) than among those without cerebrovascular disease (HR, 0.89; 95% CI, 0.71-1.12) (P = .04 for interaction).Treatment with GLP-1 receptor agonists was associated with lower all-cause mortality among patients with type 2 diabetes, advanced-stage CKD, and ESKD than was treatment with DPP-4 inhibitors. Additional well-designed, prospective studies are needed to confirm the potential benefit of GLP-1 receptor agonist treatment for patients with advanced CKD or ESKD.

Background The association between the use of angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) and mortality in end-stage renal disease (ESRD) patients lacks sufficient evidence. Aim To investigate the efficacy of ACEI and ARB in ESRD patients. Methods This nationwide retrospective cohort study using data from the Taiwan National Health Insurance Research Database enrolled ESRD patients from January 1997 to December 2011. Propensity score matching provided two study groups (ACEI/ARB users vs non-users), balanced in sample size, with similar comorbidities and prescriptions. These patients were followed up from the first date of receiving dialysis until mortality, 5 years or 31 December 2013 (whichever came first). We analysed the association of the use of ACEI or ARB with cardiovascular (CV) death and all-cause mortality in patients with ESRD using the Kaplan-Meier method and time-dependent Cox models, with a robust sandwich variance method. Results After propensity score matching, all characteristics of the user of ACEI or ARB (n = 17 280) and non-user (n = 17 280) groups were appropriately balanced (P > 0.05). In the Cox proportional hazards model, the user group exhibited lower CV death and all-cause mortality with adjusted hazard ratios and 95% CI of 0.58 (0.55-0.62) and 0.47 (0.46-0.49) than the non-user group did. Furthermore, the association of ACEI/ARB use with low mortality risk was observed in all examined subgroups. Conclusion In this large-scale, population-based cohort study, ESRD patients using ACEI/ARB had a lower risk of CV death and all-cause mortality than non-users did.

Background Whether or not non-vitamin K antagonist oral anticoagulants (NOACs) are associated with a lower risk of acute kidney injury (AKI) in patients with non-valvular atrial fibrillation (NVAF) remains unknown in real world practice. Methods In this nationwide retrospective cohort study, 1507, 3200, 5765 and 4227 NVAF patients with chronic kidney disease (CKD) and 4368, 16,945, 22,301, and 16,908 NVAF patients without CKD taking apixaban, dabigatran, rivaroxaban, and warfarin, respectively, from June 1, 2012 to December 31, 2016 were enrolled from the Taiwan National Health Insurance Program. Propensity-score weighted method was used to balance covariates across study groups. Patients were followed until occurrence of AKI or end date of study. Results Three NOACs were all associated with a significantly lower risk of AKI compared with warfarin for both CKD-free (hazard ratio, [95% confidential interval]; 0.65, [0.60–0.72] for apixaban; 0.68, [0.64–0.74] for dabigatran; 0.73, [0.68–0.79] for rivaroxaban) and CKD cohorts (0.50, [0.45–0.56] for apixaban; 0.54, [0.49–0.59] for dabigatran; 0.53, [0.49–0.58] for rivaroxaban). The annual incidence of AKI for all NOACs and warfarin increased gradually as the increment of CHA2DS2-VASc for both CKD-free and CKD cohorts after propensity score weighting. The reduced risk of AKI for three NOACs persisted in most subgroups in either CKD-free or CKD cohort. Multivariate analysis indicated that all three NOACs were all associated with lower risk of AKI than warfarin in either CKD-free or CKD cohort. Conclusions All three NOACs are associated with a lower risk of AKI than warfarin among Asians with NVAF in real-world practice.

Background/purpose Endodontic treatment success depends on treatment of all root canals, but the implementation status is affected by various factors. We examined whether the fee payment change affected the extra root canal endodontic treatment (EXRCT) in adult teeth in the National Health Insurance (NHI) system of Taiwan since 2008. The effect of hospital level, sex, and age on EXRCT was also examined. Materials and methods Two longitudinal health insurance databases for 2005 and 2010 were used. Excluding third molars and endodontic retreatment, the EXRCT rate in permanent dentition were compared for different tooth positions, hospital levels, sex and age between 2005 and 2010. Results In total, 80,995 teeth in 2005 and 76,018 in 2010 underwent root canal filling. The rate of EXRCT increased markedly from 2005 to 2010, particularly for the upper first molar (1.84% to 3.18%), lower first premolar (3.45% to 4.58%), lower first molar (12.4% to 18%), and lower second molar (0.95% to 1.87%). The difference between 2005 and 2010 remained statistically significant after adjustment for hospital level, sex, and age. The lower second molar had the highest adjusted odds ratio for the difference between 2005 and 2010 (1.99; CI: 1.49–2.66), followed by the upper first molar (1.91; CI: 1.55–2.35), lower first molar (1.60; CI: 1.47–1.75), and lower first premolar (1.38; CI: 1.11–1.72). Conclusion The payment change of Taiwan NHI seems to encourage the use of EXRCT in molars. Hospital level, sex, and age also affected the rate of EXRCT.

Rivaroxaban (20 mg/15 mg once daily) is an effective and safe alternative to warfarin for stroke prevention in patients with non-valvular AF (NVAF). Low-dose rivaroxaban (15 mg/10 mg once daily) has been only approved for NVAF patients in Japan and Taiwan, although its effectiveness and safety at low doses remain unclear among Asians with NVAF. The objective of the study is to compare the effectiveness and safety of low-dose rivaroxaban to those of warfarin among Asians with NVAF.This dynamic cohort study used data from the Taiwan National Health Insurance Database (NHIRD) to enroll 14,971 patients taking 15 mg rivaroxaban, 11,029 patients taking 10 mg rivaroxaban, and 16,000 NVAF patients taking warfarin. Inverse probability of weighting using propensity scores was used to balance covariates across study groups.The adjusted hazard ratio [95% confidence interval] comparing rivaroxaban 15 and 10 mg with warfarin (reference) was as follows: ischemic stroke/systemic embolism, 0.84 [0.74-0.96; P = 0.0080], and 0.84 [0.73-0.96; P = 0.0097]; myocardial infarction, 0.53 [0.37-0.74; P = 0.0002], and 0.88 [0.65-1.19; P = 0.3910]; intracranial hemorrhage, 0.44 [0.34-0.55; P 0.0001], and 0.53 [0.42-0.66; P 0.0001]; major gastrointestinal bleeding, 0.82 [0.67-0.99; P = 0.0387], and 0.58 [0.47-0.72; P 0.0001]; all hospitalized major bleeding, 0.63 [0.55-0.73; P 0.0001], and 0.56 [0.48-0.65; P 0.0001]; and all-cause mortality, 0.55 [0.51-0.60; P 0.0001], and 0.58 [0.53-0.63; P 0.0001].Both low doses of rivaroxaban were associated with a lower risk of ischemic stroke/systemic embolism, intracranial hemorrhage, gastrointestinal bleeding, all major bleeding, and all-cause mortality compared with warfarin in Asian NVAF patients. The 15 mg rivaroxaban dose was associated with a lower risk of acute myocardial infarction compared to warfarin.

To report the clinical characteristics of abusive head trauma (AHT) in Taiwan and identify the risk factors associated with mortality of these patients. Children with clinically diagnosed AHT from January 1, 2000, to October 31, 2015 were reviewed. The demographic data, clinical features, and associated retinal and radiologic findings were analyzed. The multivariable logistic regression model analysis was performed to identify the risk factors associated with in-hospital mortality. A total of 75 children were included. The mean age was 7.31 ± 6.57 months (range, 1–36 months). Retinal hemorrhages were detected in 69 children with AHT (92%). The majority of retinal hemorrhages were characterized by hemorrhagic numbers higher than ten (74.7%), multi-layered (54.7%), and extension beyond the posterior pole to the peripheral retina (73.3%). Twenty children (26.7%) had macular retinoschisis. As a direct result of AHT, ten children died in the hospital (13.3%). Logistic regression showed that respiratory distress or apnea (adjusted odds ratio [OR] = 22.46; 95% confidence interval [CI], 2.24–225.33; P = .0082), vomiting (adjusted OR = 11.94; 95% CI, 1.31–108.403; P = .0276), retinal finding of macular retinoschisis (adjusted OR = 8.9; 95% CI, 1.01–78.65; P = .0493), and the presence of subarachnoid hemorrhage (SAH) (adjusted OR = 15.17; 95% CI, 1.40–64.84; P = .0255) were independently associated with mortality. Respiratory distress or apnea, vomiting, SAH, and macular retinoschisis are independently associated with mortality in abusive head trauma. A complete ophthalmologic examination with the immediate visualization of intraocular injury should be performed to clarify the likelihood of child abuse and predict a potential poor neurologic outcome.

// Yi-Hsin Chan 1, 2, 3, * , Yung-Hsin Yeh 1, 2, * , Hui-Tzu Tu 4 , Chi-Tai Kuo 1, 2 , Shang-Hung Chang 1, 2, 5 , Lung-Sheng Wu 1, 2 , Hsin-Fu Lee 1, 2 and Lai-Chu See 4, 6, 7 1 The Cardiovascular Department, Chang-Gung Memorial Hospital, Taoyuan, Taiwan 2 College of Medicine, Chang-Gung University, Taoyuan, Taiwan 3 Microscopy Core Laboratory, Chang-Gung Memorial Hospital, Taoyuan, Taiwan 4 Department of Public Health, College of Medicine, Chang-Gung University, Taoyuan, Taiwan 5 Center for Big Data Analytics and Statistics, Chang-Gung Memorial Hospital, Taoyuan, Taiwan 6 Biostatistics Core Laboratory, Molecular Medicine Research Center, Chang-Gung University, Taoyuan, Taiwan 7 Division of Rheumatology, Allergy and Immunology, Department of Internal Medicine, Chang-Gung Memorial Hospital, Taoyuan, Taiwan * These authors have contributed equally to this work Correspondence to: Lai-Chu See, email: lichu@mail.cgu.edu.tw Keywords: atrial fibrillation; direct thrombin inhibitor; factor xa inhibitor; hemorrhage; warfarin Received: August 08, 2017 Accepted: September 22, 2017 Published: October 24, 2017 ABSTRACT It is not understood if dabigatran or rivaroxaban are superior to antiplatelet agents (AA) for safety outcomes in Asians with non-valvular atrial fibrillation (NVAF). In this study we evaluated the bleeding risk of dabigatran, rivaroxaban, warfarin and AA in Asians with NVAF. This national retrospective cohort study analyzed 6,600, 3,167, 5,338 and 8,238 consecutive NVAF patients taking dabigatran, rivaroxaban, warfarin or AAs (including aspirin, clopidogrel or ticlopidine), respectively, from June 1, 2012 to December 31, 2013. Propensity-score weighting was used to balance covariates across study groups. Patients were followed until the first occurrence of any bleeding outcome or the end of the study. The CHA 2 DS 2 -VASc scores were 4.1±1.6, 4.1±1.6, 3.3±1.8 and 2.4±1.6 for the dabigatran, rivaroxaban, warfarin, and AA groups, respectively. There were 5,822 (88.2%) and 164 (5.2%) patients taking low dose dabigatran and rivaroxaban, respectively. Hazard ratios (95% confidence intervals) for dabigatran, rivaroxaban, or warfarin versus AA were: intracranial hemorrhage, 0.36 (0.23-0.57; P

Aims This study compared the risk of major bleeding between atrial fibrillation (AF) patients who took non-vitamin K antagonist oral anticoagulants (NOACs) and antiepileptic drugs (AEDs) concurrently and those who took only NOACs. Methods and results We performed a retrospective cohort study using Taiwan National Health Insurance database and included AF patients who received NOAC prescriptions from 1 June 2012 to 31 December 2017. The major bleeding risks of person-quarters exposed to NOAC and 11 concurrent AEDs (carbamazepine, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, phenobarbital, phenytoin, pregabalin, topiramate, valproic acid, and zonisamide) were compared with person-quarters exposed to NOAC alone. Adjusted incidence rate differences between NOAC with or without concurrent AEDs were estimated using Poisson regression models weighted by the inverse probability of treatment. Among 104 319 patients (age 75.0 ± 10.3 years; men, 56.2%), 8546 major bleeding events occurred during 731 723 person-quarters with NOAC prescriptions. Concurrent AED use was found in 15.3% of NOAC-treated patients. Concurrent use of NOAC with valproic acid, phenytoin, or levetiracetam increased adjusted incidence rates per 1000 person-years of major bleeding more significantly than NOAC alone: 153.49 for NOAC plus valproic acid vs. 55.06 for NOAC alone [difference 98.43, 95% confidence interval (CI) 82.37–114.49]; 135.83 for NOAC plus phenytoin vs. 54.43 for NOAC alone (difference 81.4, 95% CI 60.14–102.66); and 132.96 for NOAC plus levetiracetam vs. 53.08 for NOAC alone (difference 79.88, 95% CI 64.47–95.30). Conclusion For AF patients, the concurrent use of NOACs and valproic acid, phenytoin, or levetiracetam was associated with a higher risk of major bleeding.

Background: Patients with diabetic kidney disease (DKD) are at higher risk of hypoglycemia than diabetic patients without DKD. We aimed to investigate the temporal trends of severe hypoglycemia in advanced DKD patients transitioning to dialysis and examine risk factors associated with severe hypoglycemia. We also investigated the association of severe hypoglycemia episodes with one-year mortality after initiation of dialysis in patients with advanced DKD. Methods: Using the Taiwan National Health Insurance Research Database, 46,779 advanced DKD patients transitioning to dialysis (Peritoneal dialysis 4216, hemodialysis 42,563) between 1997 and 2011 were enrolled. We calculated the rates of severe hypoglycemia from 5 years before dialysis until 10 years after dialysis. Cox proportional hazard model was used to examine the risk factors of post end stage renal disease (ESRD) one-year hypoglycemia and post ESRD one-year mortality in advanced DKD patients transitioning to dialysis. Results: We found that 11.5% of advanced DKD patients had at least one episode of severe hypoglycemia the year leading up to dialysis initiation. Multivariate analysis revealed hemodialysis compared with peritoneal dialysis, stroke, use of sulfonylurea, glinide, and insulin were associated with higher risk of severe hypoglycemia one year after transitioning to dialysis. Increased frequency of severe hypoglycemia-related hospitalizations was associated with incrementally higher mortality risk one year after transitioning to dialysis (Pre-ESRD hypoglycemia: Hazard ratios: 1.28 (1.18&ndash, 1.38, p &lt, 0.001), 1.64 (1.49&ndash, 1.81, p &lt, 0.001) for one, two hypoglycemia-related hospitalizations, respectively, post-ESRD hypoglycemia: HRs of 1.56 (1.40&ndash, 1.73, p &lt, 0.001), 1.72 (1.39&ndash, 2.12, p &lt, 0.001) for one, two hypoglycemia-related hospitalizations, respectively (reference group: no hypoglycemia related hospitalization)). Conclusions: Among advanced DKD patients, we observed a progressive elevated risk of hypoglycemia during the critical dialysis transition period. Increased frequency of severe hypoglycemia-related hospitalizations was associated with higher mortality risk one year after transitioning to dialysis. Further study of glycemic management strategies which prevent hypoglycemia during the critical transition period are warranted.

Background Liver cirrhotic patients with nonvalvular atrial fibrillation have been excluded from randomized clinical studies regarding oral anticoagulants for stroke prevention. Whether non–vitamin K antagonist oral anticoagulants (NOACs) are superior to warfarin for these patients remains unclear. Methods and Results This nationwide retrospective cohort study, with data collected from the Taiwan National Health Insurance Research Database, enrolled 2428 liver cirrhotic patients with nonvalvular atrial fibrillation taking apixaban (n=171), dabigatran (n=535), rivaroxaban (n=732), or warfarin (n=990) from June 1, 2012, to December 31, 2016. We used propensity score–based stabilized weights to balance covariates across study groups. Patients were followed until the occurrence of an event or the end date of study. The NOAC group (n=1438) showed risk of ischemic stroke/systemic embolism and intracranial hemorrhage comparable to that of the warfarin group (n=990) after adjustment. The NOAC group showed significantly lower risk of gastrointestinal bleeding (hazard ratio: 0.51 [95% CI, 0.32–0.79]; P=0.0030) and all major bleeding (hazard ratio: 0.51 [95% CI, 0.32–0.74]; P=0.0003) compared with warfarin group. Overall, 90% (n=1290) of patients were taking a low‐dose NOAC (apixaban 2.5 mg twice daily, rivaroxaban 10–15 mg daily, or dabigatran 110 mg twice daily). The subgroup analysis indicated that both dabigatran and rivaroxaban showed lower risk of all major bleeding than warfarin. The advantage of lower gastrointestinal and all major bleeding with NOACs over warfarin is contributed by those subgroups with either nonalcoholic or nonadvanced liver cirrhosis. Conclusions NOACs have a risk of thromboembolism comparable to that of warfarin and a lower risk of major bleeding among liver cirrhotic Asian patients with nonvalvular atrial fibrillation. Consequently, thromboprophylaxis with low‐dose NOACs may be considered for such patients., See Editorial by Gallagher et al

BackgroundWhether dabigatran is associated with a lower risk of acute kidney injury (AKI) in patients with nonvalvular atrial fibrillation (NVAF) remains unknown.ObjectivesThe authors compared the risk of AKI in Asians with NVAF who were prescribed dabigatran versus warfarin.MethodsThe authors analyzed patients enrolled in the Taiwan nationwide retrospective cohort study from June 1, 2012, to December 31, 2013. Dabigatran and warfarin were taken by 7,702 and 7,885 NVAF patients without a history of chronic kidney disease (CKD) and 2,256 and 2,089 NVAF patients with a history of CKD, respectively. A propensity-score weighted method was used to balance covariates across study groups.ResultsA total of 6,762 (88%) and 940 (12%) CKD-free patients and 2,025 (90%) and 231 (10%) CKD patients took dabigatran 110 mg and 150 mg twice daily, respectively. Dabigatran was associated with a lower risk of AKI than warfarin for either the CKD-free (hazard ratio [HR]: 0.62; 95% confidence interval [CI]: 0.49 to 0.77; p < 0.001) or CKD (HR: 0.56; 95% CI: 0.46 to 0.69; p < 0.001) cohort. As the increment in CHA2DS2-VASc score (a risk score based on congestive heart failure, hypertension, age 75 years or older, diabetes mellitus, previous stroke/transient ischemic attack, vascular disease, aged 65 to 74 years, and female sex) increased from 0/1 to 6+ points, the incidence of AKI for the dabigatran group was relatively stable (1.87% to 2.91% per year for the CKD-free cohort; 7.31% to 13.15% per year for the CKD cohort) but increased obviously for patients taking warfarin for either CKD-free (2.00% to 6.16% per year) or CKD cohorts (6.82 to 26.03% per year). The warfarin group had a significantly higher annual risk of AKI than the dabigatran group for those with a high CHA2DS2-VASc score (≥4 for the CKD-free cohort and ≥3 for the CKD cohort). Subgroup analysis revealed that among dabigatran users, those taking either low-dose or standard-dose dabigatran, those with a warfarin-naïve or warfarin-experienced history, those with or without diabetes, and those with CHA2DS2-VASc ≥4 or HAS-BLED ≥3 (risk score based on hypertension, abnormal renal and liver function, stroke, prior major bleeding, labile international normalized ratios, age 65 years or older, drugs or alcohol usage history) all had a lower risk of AKI than those taking warfarin.ConclusionsAmong Asians with NVAF, dabigatran is associated with a lower risk of AKI than warfarin.

Few data exist on the clinical outcomes of selective aspiration thrombectomy during primary percutaneous coronary intervention (PPCI).This was a nationwide retrospective cohort study. Patients who were diagnosed with ST-elevation myocardial infarction (STEMI) and received primary percutaneous coronary intervention (PCI) from July 2009 to December 2011 were identified from the National Health Insurance Research Database of Taiwan. Propensity score weighting was used to balance the covariates between the 2 study groups. The primary endpoints were all-cause mortality and stroke during hospitalization and at 30 days and 1 year of follow-up. Subgroup analyses were performed based on the hospital and physician volume of primary PCI.A total of 9100 ST-elevation myocardial infarction patients (29.4% of patients receiving aspiration thrombectomy and conventional PPCI vs 70.6% receiving PPCI alone) were identified. The incidence rates of all-cause mortality were comparable between the 2 groups during hospitalization (21.0 vs 27.37/100 person-months; P = .29) and 1-year follow-up (0.81 vs 1.26/100 person-months; P = .85). There were no significant differences in the stroke rates between the 2 groups during hospitalization (1.1 vs 2.34/100 person-months; P = .3) and 1-year follow-up (0.09 vs 0.15/100 person-months; P = .85). For the patients who survived to discharge, the post-discharge 1-year mortality was lower in the aspiration thrombectomy group of patients in whom the procedures were performed by physicians with a high volume of PPCI (hazard ratio: 0.47; 95% confidence interval: 0.24-0.94; P = .03).In this nationwide cohort study, selective aspiration thrombectomy at the operation's discretion had a comparable mortality rate compared with PCI alone and did not increase the risk of stroke. In the patients treated by physicians with a high volume of PPCI, aspiration thrombectomy appeared to have a beneficial effect on post-discharge survival at 1 year.

Background: Patients with atrial fibrillation (AF) are at a substantial risk of ischemic stroke. The CHA2DS2-VASc score predicts the risk of thromboembolism, but its role in predicting major bleeding in patients taking oral anticoagulants is unclear. Methods: We used the National Health Insurance Research Database (NHIRD) of Taiwan to identify patients with AF from 2010 to 2016. They were divided into four groups according to the oral anticoagulants. The outcomes were ischemic stroke/systemic thromboembolism, and major bleeding. Results: A total of 279,776 patients were identified. Ischemic stroke or systemic embolism events were observed in 1.73%, 3.62%, 4.36%, and 5.02% of the patients in the apixaban, rivaroxaban, dabigatran, and warfarin groups, respectively. Major bleeding was recorded in 1.18%, 2.66%, 3.23%, and 4.70% of the patients in the apixaban, rivaroxaban, dabigatran, and warfarin groups, respectively. The highest rates for both ischemic stroke and bleeding events occurred in the patients with a CHA2DS2-VASc score of five or more. Conclusion: Non-valvular AF patients with high CHA2DS2-VASc scores are susceptible to both systemic thromboembolism and major bleeding. The trend was consistently observed in patients who took non-vitamin K oral anticoagulants (NOACs) or warfarin. NOACs might be potentially more effective in reducing overall events.

Background Whether non–vitamin K antagonist oral anticoagulants ( NOAC s) are superior to warfarin among Asians with nonvalvular atrial fibrillation remains unclear. Methods and Results In this nationwide retrospective cohort study collected from Taiwan National Health Insurance Research Database, there were 5843, 20 079, 27 777, and 19 375 nonvalvular atrial fibrillation patients taking apixaban, dabigatran, rivaroxaban and warfarin, respectively, from June 1, 2012 to December 31, 2016. Propensity‐score weighting was used to balance covariates across study groups. Patients were followed until the first occurrence of any efficacy or safety outcome or the end date of study. Hazard ratios (95% confidence intervals) comparing apixaban, dabigatran, and rivaroxaban with warfarin were: ischemic stroke/systemic embolism ( IS / SE ), 0.55 (0.43–0.69), 0.82 (0.68–0.98), and 0.81 (0.67–0.97); major bleeding, 0.41 (0.31–0.53), 0.65 (0.53–0.80), and 0.58 (0.46–0.72); and all‐cause mortality, 0.58 (0.51–0.66), 0.61 (0.54–0.68), and 0.57 (0.51–0.65). A total of 3623 (62%), 17 760 (88%), and 26 000 (94%) patients were taking low‐dose apixaban (2.5 mg twice daily), dabigatran (110 mg twice daily), and rivaroxaban (10–15 mg once daily), respectively. Similar to all‐dose NOAC s, all low‐dose NOAC s had lower risk of IS / SE , major bleeding, and mortality when compared with warfarin. In contrast to other standard‐dose NOAC s, apixaban was associated with lower risks of IS / SE (0.45 [0.31–0.65]), major bleeding (0.29 [0.18–0.46]), and mortality (0.23 [0.17–0.31]) than warfarin. Conclusions All NOAC s were associated with lower risk of IS / SE , major bleeding, and mortality compared with warfarin in the largest real‐world practice among Asians with nonvalvular atrial fibrillation. All low‐dose NOAC s had lower risk of IS / SE , major bleeding, and mortality when compared with warfarin. Standard‐dose apixaban caused a lower risk of IS / SE , major bleeding, and mortality compared with warfarin.

Background and Purpose— Whether dabigatran is associated with different risks of cardiovascular, bleeding events, and mortality from warfarin in Asian patients with nonvalvular atrial fibrillation remains unclear. Methods— We used the Taiwan National Health Insurance Research Database to obtain 9940 and 9913 nonvalvular atrial fibrillation patients taking dabigatran and warfarin, respectively, from June 1, 2012, to December 31, 2013, as the dynamic cohort. Inverse probability of treatment weighting using propensity scores was used to balance covariates across 2 study groups. Patients were followed up until the first occurrence of any study outcome or end date of study. Results— During a median follow-up period of 0.67 years, there were 526 outcomes for dabigatran group. The hazard ratios (95% confidence intervals) comparing dabigatran with warfarin (reference) were as follows: ischemic stroke, 0.62 (0.52–0.73; P P =0.0803); intracranial hemorrhage, 0.44 (0.32–0.60; P P =0.9658); all hospitalized major bleeding, 0.58 (0.46–0.74; P P Conclusions— In real-world practice, dabigatran was associated with a reduced risk of ischemic stroke, intracranial hemorrhage, all hospitalized major bleeding, and all-cause mortality compared with warfarin in Asian patients with nonvalvular atrial fibrillation. Dabigatran did not increase the risk of major gastrointestinal bleeding or myocardial infarction compared with warfarin.

Aspirin has been one of the most widely used medications since its first synthesis more than 100 years ago. In addition to short-term use for pain and fever relief, regular use of aspirin has been shown to reduce the risk of cardiovascular diseases and strokes. The issue of regular aspirin use in cancer prevention is definitely promising, which has been supported by growing evidence from a number of observational studies and post-trial follow-up data. Among all cancers, aspirin is showing to be the most effective in reducing the risk of colorectal cancer, and even at lower doses demonstrates a 30-40% effectiveness in preventing colorectal cancer. Esophagus and stomach cancers are two cancers getting increased attention from emerging evidence of meta-analyses. Given the common side effects of aspirin, such as gastrointestinal complications, whether it is ready to take aspirin regularly for general population remains controversial since more studies are needed to clarify the net balance between harm and benefit. The decision might become more complicated since recently one molecular epidemiology study showed that different genetic traits may impact the effect of aspirin on colorectal cancer. Here we summarize recent evidence from meta-analyses related to gastrointestinal cancers. We reviewed updated observational studies and post-trial follow up data from randomized controlled trials focusing on the role of aspirin in the incidence and mortality of gastrointestinal cancers.

The association between the use of angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) and mortality in end-stage renal disease (ESRD) patients lacks sufficient evidence.To investigate the efficacy of ACEI and ARB in ESRD patients.This nationwide retrospective cohort study using data from the Taiwan National Health Insurance Research Database enrolled ESRD patients from January 1997 to December 2011. Propensity score matching provided two study groups (ACEI/ARB users vs non-users), balanced in sample size, with similar comorbidities and prescriptions. These patients were followed up from the first date of receiving dialysis until mortality, 5 years or 31 December 2013 (whichever came first). We analysed the association of the use of ACEI or ARB with cardiovascular (CV) death and all-cause mortality in patients with ESRD using the Kaplan-Meier method and time-dependent Cox models, with a robust sandwich variance method.After propensity score matching, all characteristics of the user of ACEI or ARB (n = 17 280) and non-user (n = 17 280) groups were appropriately balanced (P0.05). In the Cox proportional hazards model, the user group exhibited lower CV death and all-cause mortality with adjusted hazard ratios and 95% CI of 0.58 (0.55-0.62) and 0.47 (0.46-0.49) than the non-user group did. Furthermore, the association of ACEI/ARB use with low mortality risk was observed in all examined subgroups.In this large-scale, population-based cohort study, ESRD patients using ACEI/ARB had a lower risk of CV death and all-cause mortality than non-users did.

Background Most out-of-hospital cardiac arrest (OHCA) studies have been conducted in developed countries or metropolitan areas, and few in developing countries or rural areas. Objectives The aims of this study were to determine the weak links in the chain of survival and to estimate the outcomes of OHCA patients in Taoyuan, a nonmetropolitan area in Taiwan. Methods A retrospective review and analysis of OHCA data was conducted. The three outcomes were whether a return of spontaneous circulation (ROSC) was achieved, whether the patient survived to admission, or whether the patient survived to hospital discharge. Results From April to December 2008, 1048 OHCA patients were resuscitated, and 712 (67.9%) adult cardiac patients were used in this study. Among these 712 patients, 17.8% achieved ROSC (95% confidence interval [CI] 15.2–20.8%), 16.3% survived to admission (95% CI 13.6–19.0%), and 1.4% survived to discharge (95% CI 0.5–2.3%). Factors significantly associated with the three outcomes were witness status, response time to emergency medical services, and whether the patient had a shockable rhythm. Bystander cardiopulmonary resuscitation (CPR) did not add a notable benefit to the outcomes of OHCA. Conclusions The survival rate of OHCA patients in nonmetropolitan Taiwan was very low (1.4%). Lower witnessed rate, lower bystander CPR rate, and longer response interval in remote areas are the main causes of inferior survival rate.

Most cases of oral squamous cell carcinoma (OSCC) develop from visible oral potentially malignant disorders (OPMDs). The latter exhibit heterogeneous subtypes with different transformation potentials, complicating the early detection of OSCC during routine visual oral cancer screenings. To develop clinically applicable biomarkers, we collected saliva samples from 96 healthy controls, 103 low-risk OPMDs, 130 high-risk OPMDs, and 131 OSCC subjects. These individuals were enrolled in Taiwan's Oral Cancer Screening Program. We identified 302 protein biomarkers reported in the literature and/or through in-house studies and prioritized 49 proteins for quantification in the saliva samples using multiple reaction monitoring-MS. Twenty-eight proteins were successfully quantified with high confidence. The quantification data from non-OSCC subjects (healthy controls + low-risk OPMDs) and OSCC subjects in the training set were subjected to classification and regression tree analyses, through which we generated a four-protein panel consisting of MMP1, KNG1, ANXA2, and HSPA5. A risk-score scheme was established, and the panel showed high sensitivity (87.5%) and specificity (80.5%) in the test set to distinguish OSCC samples from non-OSCC samples. The risk score >0.4 detected 84% (42/50) of the stage I OSCCs and a significant portion (42%) of the high-risk OPMDs. Moreover, among 88 high-risk OPMD patients with available follow-up results, 18 developed OSCC within 5 y; of them, 77.8% (14/18) had risk scores >0.4. Our four-protein panel may therefore offer a clinically effective tool for detecting OSCC and monitoring high-risk OPMDs through a readily available biofluid.

BackgroundIt is unclear whether the non–vitamin K antagonist oral anticoagulant agents rivaroxaban and dabigatran are superior to warfarin for efficacy and safety outcomes in Asians with nonvalvular atrial fibrillation (NVAF).ObjectivesThe aim of this study was to compare the risk for thromboembolic events, bleeding, and mortality associated with rivaroxaban and dabigatran versus warfarin in Asians with NVAF.MethodsA nationwide retrospective cohort study was conducted of consecutive patients with NVAF taking rivaroxaban (n = 3,916), dabigatran (n = 5,921), or warfarin (n = 5,251) using data collected from the Taiwan National Health Insurance Research Database between February 1, 2013 and December 31, 2013. The propensity score weighting method was used to balance covariates across study groups. Patients were followed until the first occurrence of any study outcome or the study end date (December 31, 2013).ResultsA total of 3,425 (87%) and 5,301 (90%) patients were taking low-dose rivaroxaban (10 to 15 mg once daily) and dabigatran (110 mg twice daily), respectively. Compared with warfarin, both rivaroxaban and dabigatran significantly decreased the risk for ischemic stroke or systemic embolism (p = 0.0004 and p = 0.0006, respectively), intracranial hemorrhage (p = 0.0007 and p = 0.0005, respectively), and all-cause mortality (p < 0.0001 and p

Objective To investigate the efficacy and long-term clinical benefits of DES for dialysis patients. Background It is unclear whether percutaneous coronary intervention (PCI) with drug-eluting stent (DES) implantation is associated with lower rates of major adverse cardiovascular events (MACE) or mortality compared to bare-metal stents (BMS). Methods From a nationwide cohort selected from Taiwan’s National Health Insurance Research Database, we enrolled 2,835 dialysis patients who were hospitalized for PCI treatment with stent implantation from Dec 1, 2006. Follow-up was from the date of index hospitalization for PCI until the first MACE, date of death, or December 31, 2011, whichever came first. Results A total of 738 patients (26.0%) had DES implanted, and 2,097 (74%) had BMS implanted. The medium time to the first MACE was 0.53 years (interquartile range: 0.89 years; range: 0–4.62 years). At 1-year follow-up, patients treated with BMS had significantly, non-fatal myocardial infarction (MI), all-cause mortality, and composite MACE compared to those treated with DES. The overall repeat revascularization with coronary artery bypass graft (CABG), non-fatal MI, all-cause mortality, and composite MACE were significantly lower in patients treated with DES than those treated with BMS. Multivariate cox regression analysis showed that older age, history of diabetes, history of heart failure, history of stroke, and DES vs. BMS were independent significant predictors of MACE. Conclusions DES implantation conferred survival benefits in dialysis patients compared with BMS implantation.