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Objective This study assesses the mortality outcomes of non‐vitamin K antagonist oral anticoagulants (NOACs) in cancer patients with venous thromboembolism (VTE) and atrial fibrillation (AF). Methods Medical records of cancer patients receiving NOACs for VTE or AF between January 1, 2011, and December 31, 2016, were retrieved from Taiwan's National Health Institute Research Database. NOACs were compared using the inverse probability of treatment weighting (IPTW) method. The primary outcome was cancer‐related death. Secondary outcomes were all‐cause mortality, major bleeding, and gastrointestinal (GI) bleeding. Results Among 202,754 patients who received anticoagulants, 3591 patients (dabigatran: 907; rivaroxaban: 2684) with active cancers were studied. Patients who received dabigatran were associated with lower risks of cancer‐related death at one year (HR = 0.71, 95% CI = 0.54–0.93) and at the end of follow‐ups (HR = 0.79, 95% CI = 0.64–0.98) compared with rivaroxaban. Patients who received dabigatran were also associated with lower risks of all‐cause mortality (HR = 0.81, 95% CI = 0.67–0.97), major bleeding (HR = 0.64, 95% CI = 0.47–0.88), and GI bleeding (HR = 0.57, 95% CI = 0.39–0.84) at the end of follow‐ups compared with rivaroxaban. Conclusion Compared with rivaroxaban, the use of dabigatran may be associated with a lower risk of cancer‐related death and all‐cause mortality., The outcomes of non‐vitamin K antagonist oral anticoagulants (NOACs) in cancer patients with venous thromboembolism (VTE) or atrial fibrillation (AF) are not known. A total of 3591 patients with active cancers were studied (907 on dabigatran; 2684 on rivaroxaban). In comparison with rivaroxaban, the use of dabigatran may be associated with lower risk of cancer‐related death and all‐cause mortality.

The incidence of herpes zoster in psoriasis patients is higher than in the general population. However, the association between herpes zoster risk and different systemic therapies, especially biologic agents, remains controversial. This study investigated the association between herpes zoster risk and several systemic antipsoriasis therapies. This prospective open cohort study was conducted using retrospectively collected data from the Taiwan National Health Insurance Research Database. We included 92,374 patients with newly diagnosed psoriasis between January 1, 2001, and December 31, 2013. The exposure of interest was the “on-treatment” effect of systemic antipsoriasis therapies documented by each person-quarter. The outcome was the occurrence of newly diagnosed herpes zoster. During a mean follow-up of 6.8 years, 4834 (5.2%) patients were diagnosed with herpes zoster after the index date. Among the systemic antipsoriasis therapies, etanercept (hazard ratio [HR] 4.78, 95% confidence interval [CI] 1.51–15.17), adalimumab (HR 5.52, 95% CI 1.72–17.71), and methotrexate plus azathioprine (HR 4.17, 95% CI 1.78–9.82) were significantly associated with an increased risk of herpes zoster. By contrast, phototherapy (HR 0.76, 95% CI 0.60–0.96) and acitretin (HR 0.39, 95% CI 0.24–0.64) were associated with a reduced risk of herpes zoster. Overall, this study identified an association of both etanercept and adalimumab with an increased risk of herpes zoster among psoriasis patients. Acitretin and phototherapy were associated with a reduced risk.

Little is known about the association between deep vein thrombosis (DVT) and arterial complications in patients with type 2 diabetes (T2DM). The aim of this retrospective cohort study was to assess the influence of prior DVT on major adverse limb events (MALEs) and major adverse cardiovascular events (MACEs) in T2DM. A total of 1,628,675 patients with T2DM with or without a history of DVT from 2001 to 2013 were identified in the National Health Insurance Research Database of Taiwan. Before matching, the patients in the DVT group (n = 2020) were older than the control group (66.3 vs. 58.3 years). Patients in the DVT group were more likely to be female than the control group (54.3% vs. 47.5%). Before matching, the DVT group had higher prevalence of most comorbidities, more prescription of antiplatelet, antihypertensive agents and insulins, but less prescription of metformin and sulfonylurea. During a mean follow-up of 5.2 years (standard deviation: 3.9 years), the matched DVT group (n = 2017) have a significantly increased risk of MALE (8.4% vs. 5.2%; subdistribution hazard ratio [SHR] 1.60, 95% CI 1.34–1.90), foot ulcer (5.2% vs. 2.6%, SHR 1.96, 95% CI 1.57–2.45), gangrene (3.4% vs. 2.3%, SHR 1.44, 95% CI 1.10–1.90) and amputation (2.5% vs. 1.7%; SHR 1.42, 95% CI 1.03–1.95) than the 10,085 matched controls without DVT. They also tended to have a greater risk of all-cause mortality (38.1% vs. 33.1%; hazard ratio [HR] 1.18, 95% CI 1.09–1.27) and systemic thromboembolism (4.2% vs. 2.6%; SHR 1.56, 95% CI 1.22–1.99), respectively. We showed the presence of DVT may be associated with an increased risk of MALEs, major amputation, and thromboembolism, contributing to a higher mortality rate in T2DM.

Involvement of extracellular nicotinamide phosphoribosyltransferase (eNAMPT, i.e., visfatin or pre-B-cell colony-enhancing factor), a cancer metabokine, in chronically hepatitis C virus (HCV)-infected (CHC) patients with sustained virological responses (SVRs) remains elusive. This 8-year prospective cohort study evaluated eNAMPT profiles of 842 consecutive CHC patients, including 519 who had completed an anti-HCV therapy course and pre-therapy and 24-week post-therapy surveys. For 842 patients, pre-therapy associations were HCV RNA, homeostatic model assessment for insulin resistance (HOMA-IR) index, and body mass index with eNAMPT levels, and NAMPT-rs61330082 T allele with total cholesterol levels. NAMPT-rs10953502, NAMPT-rs2058539, and NAMPT-rs61330082 were in a linkage disequilibrium block, which was associated with total cholesterol levels. Compared to pre-therapy levels, at 24 weeks post-therapy, decreased eNAMPT and increased lipid levels were observed in SVR patients (n = 427). Among SVR patients, higher cumulative incidences of cardiovascular events occurred in those with a NAMPT-rs61330082 TT genotype than those with non-TT genotypes (28.2% vs. 8.4%, p < 0.001). NAMPT-rs61330082 TT genotype was independently associated with incident cardiovascular events (95% CI hazard ratio (HR): 1.88–10.37; HR: 4.415); no eNAMPT profiles were associated with incident malignancies. Of CHC patients, hepatic vascular endothelial cells and baseline peripheral leukocytes expressed higher eNAMPT levels than controls, and peripheral eNAMPT-positive leukocyte proportions decreased after SVR. During HCV infection, eNAMPT involvement in glucose metabolism was modulated by HCV RNA linked to lipid metabolism and NAMPT-associated SNPs. Hepatic endothelial cells and peripheral leukocytes potentially secrete eNAMPT. Caution is required for incident cardiovascular events in SVR patients with NAMPT-rs61330082 TT genotype.

Background Sodium-glucose co-transporter 2 inhibitors (SGLT2i) has shown evidence of cardiovascular benefit in patients with type 2 diabetes mellitus (T2DM). Currently metformin is the guideline-recommended first-line treatment. We aimed to investigate the benefit of SGLT2i vs metformin as first-line therapy. Methods Electronic medical records from Chang Gung Research Database during 2016–2019 were retrieved for patients with T2DM. Patients aged Results After exclusion criteria, a total of 41,020 patients with T2DM were eligible for analysis. There were 1100 patients with SGLT2i as first-line and 39,920 patients with metformin as first-line treatment. IPTW was used for propensity score matching. During one year follow-up, the hazard ratio (HR) of patients on SGLT2i as first-line treatment to patients on metformin as first-line treatment were HR 0.47 (95% CI 0.41–0.54, p Conclusions In patients with T2DM, SGLT2i as first-line treatment may be associated with decreased events of heart failure hospitalization, acute coronary syndrome, and all-cause mortality, compared with metformin as first-line treatment. However, there may be an increased events of ischemic stroke using SGLT2i compared to metformin.

Background Women have been underrepresented in the literature; the effects of female sex on outcomes in patients with acute myocardial infarction (AMI) remain unclear. Objectives This study compares the real-world outcomes of women and men with AMI who have undergone revascularization via percutaneous coronary intervention (PCI) or coronary artery bypass graft surgery (CABG). Methods This is a retrospective cohort study utilizing data from the Taiwan National Health Insurance database. We identified patients who were admitted for AMI and who underwent coronary revascularization during the index admission period between January 1, 2001, and December 31, 2013. Patients were then categorized based on the treatment received into PCI and CABG groups. In-hospital and long-term outcomes were compared between women and men in each group. Interaction tests were then performed to determine whether the differences between sexes were modified by the mode of revascularization. Analyses were repeated after propensity score matching between women and men in each group to minimize possible confounders. We also conducted subgroup analyses, stratifying by the presence of diabetes mellitus, congestive heart failure, and chronic kidney disease. Results We enrolled 67,534 patients who met the inclusion criteria in the analysis; 60,207 patients had undergone PCI (13,514 female and 46,693 male), while 7327 patients had received CABG (1762 female and 5565 male). Prior to matching, enrolled female patients were older on average, with more comorbidities. In-hospital and long-term outcomes were worse in women, particularly in the PCI group. After matching, the incidence of hospitalization for heart failure (HHF) was higher in women (10.4% vs 8.0%, OR 1.32, 95% CI 1.22–1.43), with fewer repeat revascularizations (28.1% vs 32.4%, OR 0.84, 95% CI 0.81–0.88). Both observations were more pronounced in the PCI group (HHF: P for interaction = 0.0496; repeat revascularization: P for interaction = 0.021). Conclusions Women presenting with AMI exhibited worse in-hospital and long-term outcomes than men, especially among women who received PCI as the initial mode of revascularization. Women who underwent PCI were more likely to be admitted for heart failure during follow-up. Possible socioeconomic inequalities or a distinct pathobiology of cardiac ischemia between sexes may underlie these results; thus, further investigation is needed.

BackgroundThe serum aminotransferase elevation in metabolic syndrome (MetS) reflected hepatosteatosis, but there is a conflict with the coexistence of viral hepatitis, especially for the hepatitis B virus (HBV). Thus, this study aimed to investigate the relationship between the alanine aminotransferase (ALT)/aspartate aminotransferase (AST) ratio, MetS, and HBV infection in a rural Taiwanese population.MethodsWe conducted a cross-sectional analysis in southern Taiwan between March and December 2019. Multivariable logistic regression analyses adjusted for demographics, education, dietary behaviors, irregular exercise, substance use, and viral markers were performed to investigate the association between the ALT/AST ratio and MetS.ResultsAltogether, 2,416 participants (891 men and 1,525 women; mean age, 64.1 ± 14.9 years) were enrolled. Of the participants, 22.7% (n = 519) were seropositive for viral hepatitis. In the multivariable analysis, age [odds ratio (OR) 1.02, 95% CI 1.01–1.03, p 1 (OR 2.63, 95% CI 2.15–3.21, p p p = 0.021) were associated with the risk of MetS. The area under the curve of the ALT/AST ratio was 0.62 (95% CI 0.60–0.64, p 0.852 for the Youden index.ConclusionAn ALT/AST ratio >1 could be a simple index for MetS prediction during community checkups. In contrast to age and betel nut chewing, HBV seropositivity and higher education might be inversely associated with MetS. Aggressive health promotion for MetS prevention has emerged as essential in participants without HBV and with lower education levels. Further large-scale, longitudinal studies are needed to unlink these correlations.

Objective This study aimed to compare the efficacy of anticoagulation therapy and thrombolytic therapy for pulmonary embolism (PE) in patients complicated with shock. Methods This retrospective cohort study used administrative data from Taiwan's National Health Insurance Research Database. Patients admitted due to PE who received inotropic support between January 1, 1997, and December 31, 2011, were included. To closely mimic a randomized experiment, anticoagulation and thrombolysis plus anticoagulation groups were subjected to propensity score matching (PSM) according to demographic characteristics, comorbidities, and inotropic agent dosage. The primary outcome was in-hospital mortality. The secondary outcome was 3-month mortality after discharge. Results After PSM, a total of 820 patients, including 164 thrombolysis and 656 anticoagulation patients, were enrolled. The in-hospital mortality was 48.2% in the thrombolysis group and 52.4% in the anticoagulation group (odds ratio [OR] 0.84, 95% confidence interval [CI] 0.59–1.18). Major bleeding occurred in 19 (11.6%) of the thrombolysis patients and 57 (8.7%) of the anticoagulation patients (OR 1.37, 95% CI, 0.79–2.38). The 90-day mortality rates in the thrombolysis and anticoagulation groups were 15.3% (13 patients) and 17.6% (55 patients), respectively; this difference was not significant (hazard ratio 0.88, 95% CI 0.48–1.61). Conclusion In PE patients complicated with shock, anticoagulation therapy provides similar treatment efficacy to thrombolytic therapy in terms of in-hospital and 90-day mortality. The bleeding risk was also similar in the two treatment groups.

The link between psoriasis and suicidality remains elusive and understudied. The aim was to assess the risk of suicidal behavior in psoriasis patients. We used Taiwan’s National Health Insurance Research Database to conduct a nationwide retrospective cohort study to examine the risk for suicidal behavior among psoriasis patients. We performed subgroup analyses based on the severity of psoriasis and psoriatic arthritis. We included 169,909 psoriasis patients (including 13,959 with concomitant psoriatic arthritis and 155,950 with psoriasis alone) and 169,909 matched nonpsoriasis controls. Suicidal behavior occurred in 104 and 89 subjects in the psoriasis group and nonpsoriasis controls, respectively; we found no significantly increased risk for suicidal behavior among psoriasis patients when compared to nonpsoriasis controls [adjusted hazard ratio (HR) 1.17, 95% confidence interval (CI) 0.88‒1.55]. The subgroup analysis showed no significantly increased risk for suicidal behavior in both the severe psoriasis group (adjusted HR 0.92, 95% CI 0.51–1.64) and the mild psoriasis group (adjusted HR 1.26, 95% CI 0.91‒1.75) when compared to nonpsoriasis controls. Also, we found no significant increased risk for suicidal behavior in the group of psoriasis patients who also had psoriatic arthritis (adjusted HR 2.00, 95% CI 0.68‒5.85) and in the group of patients with psoriasis alone (adjusted HR 1.12, 95% CI 0.83‒1.50) when compared to nonpsoriasis controls. In a Taiwanese setting, no link between psoriasis or psoriatic arthritis and suicidal behavior was detected.

Summary Background Cardiac implantable electronic device (CIED) infection, a major complication of a CIED implant procedure, can prolong hospitalization and cause mortality. Aim To evaluate the efficacy of a bundled skin antiseptic preparation for preventing infection after implantation of a complex CIED. Methods This study analysed 1163 consecutive patients who had received a bundled skin antiseptic preparation before CIED implantation from July 2012 to December 2017. According to the complexity of the CIED implant procedure, the patients were divided into a complex CIED group (N = 370) and a non-complex CIED group (N = 793). A complex procedure was defined as a pacemaker replacement, implantation of implantable cardioverter defibrillator and cardiac resynchronization therapy, device upgrade, or lead revision. Findings During a mean follow-up of 2.9 ± 1.7 years, CIED infection developed in 15 patients (1.3%), and the incidence of minor and major infection was 1.1% and 0.2%, respectively. The incidence of CIED infection did not significantly differ between the complex CIED group and the non-complex CIED group (1.1% vs 1.4%, respectively; non-significant). Multivariate analysis indicated that procedural complexity was not an independent predictor of CIED infection. After 2:1 propensity score matching, the matched non-complex CIED group and the matched complex CIED group still showed no significant difference in the incidence of CIED infection. Conclusion Bundled skin antiseptic preparation is an effective and widely applicable strategy for decreasing infection risk after a complex CIED implantation.

Globally, 32% to 70% patients with atrial fibrillation (AF) are prescribed oral anticoagulants (OACs) with warfarin for stroke prevention. However, patients with AF on OACs may experience intracranial hemorrhage (ICH), which presents a treatment dilemma. We therefore investigated whether resuming OACs in these patients is beneficial. Electronic medical records of patients with AF on OACs discharged with ICH between 2001 and 2013 were retrieved from the Taiwan National Health Insurance Research Database for analysis. We excluded patients who were 6 weeks after ICH diagnosis. The remaining patients were categorized into those who resumed OAC and those who discontinued OAC. Propensity score matching was performed between the 2 groups. Primary outcomes were mortality/ischemic stroke (IS)/systemic embolism (SE), IS/SE, and recurrent ICH at 6 months and 1 year. After the exclusion criteria were applied, 604 eligible patients (408 discontinued OAC and 196 resumed OAC within 6 weeks) were included in this study, and 186 patients in each group were 1:1 matched. Patients who resumed OAC had significantly lower mortality/IS/SE (hazard ratio [HR] = 0.39, 95% confidence interval [CI] = 0.20–0.76) and IS/SE (HR = 0.12, 95% CI = 0.03–0.53) at 6-month follow-up than patients who discontinued OAC. In addition, patients who resumed OAC had significantly lower mortality/IS/SE (HR = 0.56, 95% CI = 0.34–0.93) and IS/SE (HR = 0.26, 95% CI = 0.09–0.75) at 1-year follow-up. No difference in recurrent ICH was noted between the 2 groups. In conclusion, in patients with AF on OACs with ICH, resuming anticoagulant use was associated with significantly lower risks of composite outcomes of mortality/IS/SE and IS/SE than patients who discontinued OACs. No difference in recurrent ICH was observed between the 2 groups.

Background Benefits of patients with end‐stage renal disease and atrial fibrillation undergoing peritoneal dialysis (PD) or hemodialysis are unknown. Methods and Results Patients undergoing dialysis were retrieved from Taiwan National Health Insurance Research Database during 2001 to 2013 and separated into PD or hemodialysis. Primary outcomes were ischemic stroke/systemic embolism, major bleeding, and intracranial hemorrhage (ICH). An inverse probability of treatment weighting based on propensity score was used to reduce the confounding. The risk of outcomes between PD and hemodialysis was compared using Cox proportional hazard model for fatal outcomes or Fine and Gray subdistribution hazard model which considered death a competing risk, respectively. A total of 7916 patients with end‐stage renal disease with atrial fibrillation undergoing PD or hemodialysis during 2001 to 2013 were identified. After exclusion criteria, 363 patients receiving PD and 5302 patients receiving hemodialysis were analyzed. At 1‐year follow‐up, the risk of ICH was significantly lower in the PD group compared with the hemodialysis group (0.2% versus 0.9%; subdistribution hazard ratio [SHR], 0.31; 95% CI, 0.17–0.57). At 3‐year follow‐up, the risks of major bleeding and ICH were significantly lower in the PD group compared with the hemodialysis group (major bleeding: 1.8% versus 3.2%; SHR, 0.68; 95% CI, 0.53–0.87; ICH: 0.5% versus 2%; SHR, 0.32; 95% CI, 0.21–0.48). At 5‐year follow‐up, ischemic stroke/systemic embolism, major bleeding, and ICH were significantly lower in the PD group compared with the hemodialysis group (ischemic stroke/systemic embolism: 12.4% versus 17.7%, SHR, 0.87; 95% CI, 0.79–0.96; major bleeding: 2.6% versus 4.1%; SHR, 0.79; 95% CI, 0.64–0.97; ICH: 0.5% versus 2.6%; SHR, 0.25; 95% CI, 0.17–0.37). Conclusions In patients with end‐stage renal disease and atrial fibrillation, dialytic modalities by PD or hemodialysis impacted these patients differently. There were overall reduced ischemic stroke/systemic embolism, major bleeding, and ICH at 5‐year follow‐up in patients undergoing PD compared with hemodialysis.

AIMS Pulmonary vein isolation (PVI) is an effective procedure for atrial fibrillation (AF). The role of additional cavotricuspid isthmus (CTI) block ablation remains controversial in AF patients without atrial flutter (AFL). Therefore, this study aimed to explore the clinical outcome of additional CTI block ablation in patients without AFL. METHODS Between January 2013 and December 2017, a total of 139 patients who did not have documented AFL and who underwent catheter ablation for AF were recruited. Fifty-seven patients were classified in additional CTI block ablation group and 82 patients were classified in without CTI group. The incidence of early-onset and late-onset atrial arrhythmia recurrence was compared between the two groups. RESULTS The additional CTI group had a higher prevalence of persistent or long-standing AF and larger left atrial volume. The additional CTI group had a higher incidence of late-onset atrial arrhythmia recurrence (38.6% vs 12.2%; P

Background and aims Intracerebral hemorrhage (ICH) has a higher mortality than ischemic stroke. Statin is beneficial for stroke, but high potency statin treatment has been associated with the risk of hemorrhagic stroke. The aim of this study was to assess the impact of initiating statin therapy after ICH on cardiovascular outcomes. Methods Dyslipidemic patients were retrieved from the ICH population from the National Health Insurance Research Database in Taiwan. We retrospectively compared patients prescribed with and without statin treatment after ICH. Outcomes of interest were mortality, myocardial infarction, ischemic stroke, and hemorrhagic stroke during 5 years of follow-up. Results Of 17,980 adult patients with ICH and dyslipidemia, 8927 were eligible for analysis over the study period, including 1613 patients receiving statin therapy and 7314 patients not taking statins. After propensity score matching, the mean age was 61.2 ± 12.2 years in the statin group and 61.6 ± 13.0 years in the non-statin group. Hypertension was dominant, followed by diabetes mellitus, and the mean estimated NIHSS score was 12.9. The patients who received statin therapy were associated with lower risks of all-cause mortality (12.7% vs . 21.3%; hazard ratio [HR], 0.54; 95% confidence interval [CI], 0.45–0.65), cardiovascular death (4.0% vs . 7.1%; HR, 0.54; 95% CI, 0.39–0.75) and ICH (5.4% vs . 8.5%; HR, 0.62; 95% CI, 0.46–0.83) compared to those who did not receive statins. Conclusions Initiating statin therapy after ICH was associated with a decreased risk of recurrent ICH and mortality for dyslipidemia patients.

There is conflicting results on whether prior antiplatelet therapy (APT) is associated with poor outcome in spontaneous intracerebral haemorrhage (ICH) patients. To determine whether prior APT is associated with spontaneous ICH, and whether there is a difference between the different types of APT, including cyclooxygenase inhibitor (COX-I), adenosine diphosphate receptor inhibitor (ADP-I) and phosphodiesterase inhibitor (PDE-I). A retrospective study of patients with ICH diagnosed between 2001 and 2013 in the National Health Insurance Research Database. Baseline unbalance between APT and non-APT groups was solved by multivariable adjustment (primary analysis) and propensity score matching (sensitivity analysis). Patients with prior APT had a higher rate of in-hospital death (odds ratio [OR], 1.16; 95% confidence interval [CI], 1.09-1.23) compared to non-APT group. Compared to non-APT group, there was a greater rate of in-hospital death with spontaneous ICH with ADP-I (OR, 1.49; 95% CI, 1.24-1.79) and COX-I (OR, 1.17; 95% CI, 1.09-1.25). PDE-I exhibited no difference in in-hospital death with spontaneous ICH (OR, 1.03; 95% CI, 0.91-1.16) compared to non-APT group. Remarkably, the in-hospital mortality rate was significantly higher in the ADP-I group than in the PDE-I group (hazard ratio, 1.45; 95% CI, 1.17-1.80). In this study, ADP-I and COX-1, but not PDE-I, are the most likely contributors to the association of APT with poor outcome with spontaneous ICH patients. These findings suggest that the complexity of the different mechanism of actions of prior APT can alter the outcome in spontaneous ICH.

Objective The impact of antithrombotic agents on patients with primary intracerebral hemorrhage (ICH) remains controversial, especially patients who require emergent craniotomy. This study was undertaken to evaluate clinical outcomes in operated patients with ICH with and without previous antithrombotic agents. Methods This is a retrospective cohort study. Between January 2001 and December 2013, all patients with ICH who received emergent craniotomy and who were present in Taiwan's National Health Insurance Research Database were screened and divided into those with previous antiplatelet therapy, anticoagulant therapy, and nonantithrombotic therapy according to their health care claims data within 3 months of index admission. The primary end points included in-hospital mortality and complications and short-term outcome. Results Of 18,872 eligible patients, 16,251 (87.1%) did not receive any antithrombotic therapy, 2267 patients had antiplatelet therapy, and 354 patients had anticoagulation therapy. After propensity score matching, significantly more blood transfusions and craniectomies were identified in the patients with previous antithrombotic treatment compared with those undergoing nonantithrombotic therapy. Compared with the nonantithrombotic treatment cohort, patients under previous anticoagulant treatment had significantly higher in-hospital mortality (odds ratio, 2.12; 95% confidence interval, 1.45–3.10). Furthermore, during the 6-month follow-up period, previous anticoagulant therapy was independently associated with a greater risk of all-cause mortality (P = 0.001). The in-hospital and 6-month all-cause mortality of patients with previous antiplatelet treatment was not significantly different from patients with nonantithrombotic treatment. Conclusions These findings suggested an increased risk of in-hospital mortality and poor short-term outcome among operated patients with ICH with previous antithrombotic therapy, particularly anticoagulant therapy, but not with antiplatelet therapy.

Aims High demand right ventricular pacing may elicit left ventricular systolic dysfunction known as pacing‐induced cardiomyopathy, increasing the risks of heart failure (HF) hospitalization. Percentage of demand ventricular pacing is different between patients with sick sinus syndrome (SSS) and those with complete atrioventricular block (CAVB). This study aims to compare the incidence of HF admission and pacing‐induced cardiomyopathy between patients with SSS and CAVB. Methods and results A total of 824 patients who received single ventricular or dual‐chamber pacemaker implantation at our hospital between January 2003 and December 2012 were recruited for the study. Patients with HF, those without complete cardiac echocardiography, and those with significant coronary artery disease were excluded. Finally, 315 patients with SSS and 289 patients with CAVB were enrolled in this study. The CAVB group had a higher pacing percentage (39.37 ± 9.17% vs. 83.82 ± 33.06%; P

Background Endocardial late fractionated potentials during sinus rhythm mapping may reflect abnormal "subendocardial" substrates associated with right ventricular outflow tract (RVOT) ventricular arrhythmias (VAs). The aim of this study was to explore the clinical outcomes of catheter ablation guided by these late fractionated potentials for RVOT VAs in patients without structural heart disease. Methods From January 2016 to March 2018, 28 patients underwent catheter ablation for RVOT premature ventricular contractions (PVCs) or ventricular tachycardia (VT), guided by the EnSite NavX or Velocity V5.0 three-dimensional mapping system (Abbott, St. Paul, MN, USA). Among them, 10 patients (35.7%) were found to have endocardial late fractionated potentials during sinus rhythm mapping (Group 1). Group 2 was composed of 18 patients in whom no endocardial late fractionated potentials were seen. The burden of VAs, acute procedural success, and 3-month clinical outcomes were analyzed. Results The average duration of late fractionated potentials after the end of QRS during sinus rhythm mapping in group 1 was 45.00 ± 17.15 ms. Baseline demographics and morphology and burden of PVCs were similarly distributed between both groups. Group 1 had higher acute procedural success compared to group 2 (100% vs 66.7%; P = .039). Moreover, at 3-month follow-up, group 1 had lower total PVCs (49 (1-5986) versus 4316 (1-23231); P = .048), PVC burden (0% (0-5.9) vs 4.3% (0-18.9); P = .055), and higher clinical success (100% vs 55.6%; P = .025) compared to group 2. Conclusion The identification and elimination of endocardial late fractionated potentials during sinus rhythm mapping could improve the acute success and short-term outcomes of ablation for RVOT VAs.

Context The safety of metformin usage by diabetic psoriasis patients is unclear. Objective To investigate the real-world safety of metformin in psoriatic patients with type 2 diabetes mellitus (T2DM). Design We used the National Health Insurance Research Database to perform a cohort study. Based on metformin and other antidiabetic agent prescriptions, we divided all psoriasis patients with T2DM into the metformin group and the nonmetformin group. The outcomes included all-cause mortality, severe psoriasis, hospitalization due to psoriasis, and any cause for readmission. Results The metformin group (n = 5520) and the nonmetformin group (n = 3062) did not significantly differ in the risk of all-cause mortality [hazard ratio (HR) 1.08; 95% CI, 0.90 to 1.30], severe psoriasis (HR, 0.95; 95% CI, 0.80 to 1.09), psoriasis-related admission (HR, 1.32; 95% CI, 0.90 to 1.93), and any-cause readmission (HR, 0.99; 95% CI, 0.90 to 1.11). The dose-response analysis found no significant increase in the risk of severe psoriasis and psoriasis-related admission, even with more than 80 defined daily doses or 1000 mg daily dose of metformin prescribed (P for linear trend > 0.05). Conclusion Metformin can be prescribed for diabetic psoriasis patients without safety concerns.

There is an increased tendency for hip fractures in patients with chronic kidney disease (CKD). Although surgery is the mainstay of treatment for hip fractures, there is scant information on outcomes after hip fracture surgery in diabetic patients at different stages of CKD. In this population-based cohort study, we compared the surgical outcome, readmission, and mortality rates after osteosynthesis of hip fractures in diabetic patients with different stages of renal function. Diabetic patients who received primary osteosynthesis for hip fracture between January 1997 and December 2013 were enrolled. The primary outcomes were surgical outcomes, including infection and revision surgery. The secondary outcomes were all-cause readmission and mortality. This study included 44,065 patients; 11,954 had CKD (diabetic CKD group), 1662 patients were receiving dialysis (diabetic dialysis group), and 30,449 patients had no CKD (diabetic non-CKD group). We found that the diabetic dialysis group had a significantly higher risk of infection and revision surgery compared with diabetic non-CKD patients (HR = 1.52, 95% CI, 1.24 to 1.87; HR = 1.62, 95% CI, 1.33 to 1.97, respectively, both P < 0.001) and diabetic CKD patients (HR = 1.62, 95% CI, 1.32 to 1.99; HR = 1.48, 95% CI, 1.22 to 1.80, respectively, both P < 0.001). Diabetic CKD patients had a comparable risk of surgical complications including infection and revision as diabetic non-CKD patients. For readmission and mortality, the diabetic dialysis group had the highest risk among the three groups at all time-points (3 months after surgery, 1 year, and the last follow-up, all P < 0.001). Compared with the diabetic non-CKD group, the diabetic CKD group had an elevated risk of readmission and mortality at all time-points (all P < 0.001). In conclusion, CKD was associated with worse outcomes after hip fracture fixation surgery. Although at significantly higher risk of readmission and mortality, CKD patients still had a comparable risk of infection and revision to non-CKD patients. © 2019 American Society for Bone and Mineral Research.

Background High-dose steroids and intravenous immunoglobulin (IVIG) are controversial treatments for pediatric patients with acute myocarditis. This study aimed to investigate their efficacies in the Taiwanese pediatric population. Methods This study evaluated 5563 acute myocarditis patients from the Taiwan’s National Health Insurance Research Database and identified 1542 pediatric patients hospitalized for acute myocarditis between January 1, 2001 and December 31, 2011. The exclusion criteria were age of > 11 years, associated cardiovascular comorbidities, autoimmune disease, malignancy before the index hospitalization, extracorporeal membrane oxygenation, intra-aortic balloon pumping, and dual therapy using IVIG and high-dose steroids. Results After 2:1 propensity score matching, we identified 208 subjects without steroid therapy and 104 subjects who received high-dose steroids. The mean age in that cohort was 2.6 ± 2.9 years, and high-dose steroid therapy had no significant effects on major in-hospital complications and post-discharge outcomes. After 2:1 propensity score matching, we identified 178 subjects without IVIG therapy and 89 subjects who received IVIG. The mean age in that cohort was 2.0 ± 2.1 years, and IVIG had no significant effects on the major outcomes. Conclusions The present study revealed that high-dose steroid or IVIG therapy had no significant effects on major in-hospital complications, late heart failure hospitalization, and long-term mortality.

Nonalcoholic fatty liver disease (NAFLD) and childhood obesity are emerging global health issues. The aim of this study was to identify a simple predictor of NAFLD in children and adolescents. This community-based study was conducted from December 2012 to September 2013 in Taiwan and included 1,222 children between 10 and 19 years of age. After excluding alcohol consumption and hepatic-related lesions, NAFLD was diagnosed according to sonographic criteria. Potential confounding factors (including age, gender, and anthropometric and laboratory data) were tested by logistic regression analysis. The cutoff value was determined using receiver operating characteristic (ROC) curve analysis. In addition to older age, heavier weight, and wider waist, subjects with NAFLD had significantly higher blood pressure, lipid disturbances, and alanine aminotransferase/aspartate aminotransferase (ALT/AST) ratios. The correlation between NAFLD and ALT/AST ratio remained significant even after adjusting for confounders (adjusted odds ratio [OR], 2.19; 95% confidence interval [CI], 1.24-3.87; p = .007). The risk score of having a fatty liver, based on ALT/AST ratio, was greater than 0.981 according to ROC curve analysis (sensitivity, 60.5%; specificity, 80.3%; area under the curve, 0.756; CI, 0.71-0.80; p < .001). Therefore, ALT/AST ratio may represent a powerful index of hepatosteatosis in children and adolescents.

ObjectiveMetformin has been linked to anti-proliferative and anti-inflammatory mechanisms. In this study, we aimed to examine the long-term impact of metformin on mortality and organ damage in patients with autoimmune diseases and type 2 diabetes mellitus (T2DM).MethodsWe conducted a cohort study using the National Health Insurance Research Database in Taiwan between 1997 and 2013. Based on metformin and other anti-diabetic agent prescriptions, we categorized all patients with autoimmune diseases into either the metformin group (metformin administration for at least 28 days) or the non-metformin group. The primary outcomes were all-cause mortality and annual admission rate, while the secondary outcome was target organ damage. We followed patients from the index date to the date on which the event of interest occurred, death, or the end of this study.ResultsOur cohort study included 3,359 subjects for analysis. During a mean follow up of 5.2 ± 3.8 years, the event rate of all-cause mortality was 228 (33.6%) in the metformin group and 125 (36.9%) in the non-metformin group. The risk of both all-cause mortality and annual number of admissions for autoimmune diseases was significantly lower in the metformin group than in the non-metformin group [hazard ratio (HR) 0.77; 95% CI 0.62–0.96 and risk ratio (RR) 0.81; 95% CI 0.73–0.90, respectively].ConclusionMetformin may add benefits beyond T2DM control with regard to reducing all-cause mortality and admission rate, as well as minimizing end-organ injury in lungs and kidneys among patients with autoimmune diseases.

Background This study compared the efficacy and safety between catheter‐directed thrombolysis (CDT) and systemic thrombolysis for patients with acute pulmonary embolism (PE) with midterm follow‐up. Methods and Results We conducted a prospective open cohort study by using data from the Taiwan National Health Insurance Research Database for 2001 to 2013. Patients who were first admitted for PE and were treated by either systemic thrombolysis or CDT were included and compared. Inverse probability of treatment weighting, based on the propensity score, was used to mitigate possible selection bias. A total of 145 CDT‐treated and 1158 systemic thrombolysis–treated patients with PE were included. The in‐hospital mortality rate was significantly lower in the CDT group (12.7% versus 21.4%; odds ratio, 0.49; 95% CI, 0.36–0.67) after inverse probability of treatment weighting. No significant differences between the groups were observed for the safety (bleeding) outcomes. In patients who survived the index PE admission, the 1‐year all‐cause mortality rate was significantly lower in the CDT group after inverse probability of treatment weighting (12.2% versus 13.2%; hazard ratio [HR], 0.73; 95% CI, 0.56–0.94). Treatment with CDT was also associated with lower risks of recurrent PE (9.3% versus 17.5%; subdistribution HR, 0.52; 95% CI, 0.41–0.66). The difference remained through the last follow‐up. Conclusions Among patients with PE requiring reperfusion therapy, those accepting CDT had lower all‐cause mortality and recurrent PE over both short‐term and midterm follow‐up periods than those receiving systemic thrombolysis. The bleeding risk was similar for both groups. These findings should be cautiously validated in future randomized trials.

Atorvastatin 40 mg (ATOR 40) and ezetimibe 10 mg/simvastatin 20 mg (EZ-SIM 20) have similar reductions of low-density lipoprotein cholesterol (LDL-C) but cardiovascular (CV) outcomes between these two therapies are unclear. Our real-world cohort study is to test the hypothesis of pleiotropic effects of purely higher dose statin on CV outcomes beyond similar reductions of LDL-C, especially for extremely CV risk patients. Between January 1, 2007 and December 31, 2013, a total of 3,372 patients with type 2 diabetes mellitus (T2DM) admitted due to acute coronary syndrome (ACS) or acute ischemic stroke (AIS) were selected as the study cohort from the Taiwan National Health Insurance Research Database. Clinical outcomes were evaluated by ATOR 40 group (n = 1686) matched with EZ-SIM 20 group (n = 1686). Primary composite outcome includes CV death, non-fatal myocardial infarction, and non-fatal stroke. Secondary composite outcome includes hospitalization for unstable angina (HUA), percutaneous coronary intervention (PCI), and coronary artery bypass grafting (CABG). With a mean follow-up of 2.4 years, no significant difference of primary composite outcome was observed between ATOR 40 and EZ-SIM 20 groups (subdistribution hazard ratio [SHR], 1.09; 95% confidence interval [CI], 0.95–1.25). Nevertheless, ATOR 40 group had lower risks of HUA (SHR, 0.50; 95% CI, 0.35–0.72), PCI (SHR, 0.82; 95% CI, 0.69–0.97) and CABG (SHR, 0.62; 95% CI, 0.40–0.97) than EZ-SIM 20 group. For T2DM patients after ACS or AIS, ATOR 40 and EZ-SIM 20 had similar major CV outcomes, which still supported the main driver for CV risk reductions is LDL-C lowering.

The aim of this study was to evaluate the effect of beta-blockers, angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) after cardiac surgery in the liver cirrhosis (LC) patients. We conducted a population-based cohort study using data from the Taiwanese National Health Insurance Research Database (NHIRD) from 2001 to 2013. The outcomes of interest included all-cause mortality, major adverse cardiac and cerebrovascular events (MACCE) and liver and renal outcomes. Among 1470 LC patients, 35.6% (n = 524) received beta-blockers and 33.4% (n = 491) were prescribed ACEIs and/or ARBs after cardiac surgery. The risk of negative liver outcomes was significantly lower in the ARB group compared with the ACEI group (9.6% vs 22.7%, hazard ratio [HR] 0.50, 95% confidence interval [CI] 0.31-0.83). Furthermore, the risk of MACCE (44.2% vs 54.7%, HR 0.79, 95% CI 0.65-0.96), all-cause mortality (35.3% vs 46.4%, HR 0.74, 95% CI 0.60-0.92), composite liver outcomes (9.6% vs 16.5%, HR 0.56, 95% CI 0.38-0.85) and hepatic encephalopathy (2.7% vs 5.7%, HR 0.45, 95% CI 0.21-0.94) were lower in the ARB group than the control group. Our study demonstrated that ARBs provide a greater protective effect than ACEIs in regard to long-term outcomes following cardiac surgery in patients with LC.

Cryptochromes are photoreceptors that mediate the circadian entrainment by light in plants and animals. They are also involved in magnetic field sensing in some animals. Recent studies suggest that cryptochromes play an essential role in metabolism and cardiovascular disease. However, the tissue-specific function of cryptochromes in atherosclerosis is unknown. We transplanted bone marrow from wild-type (WT) and cryptochrome 1/2 knockout (Cry1/2 KO) mice into irradiated recipient low-density lipoprotein receptor knockout (LDLR-/- ) mice and induced atherosclerosis with a high cholesterol diet for 12 weeks. There was a reduction in atherosclerotic plaques and macrophage accumulation in the aorta of LDLR-/- mice that received Cry1/2 KO bone marrow compared to mice that received WT bone marrow. Bone marrow-derived macrophages (BMDMs) from Cry1/2 KO mice exhibited impaired uptake of low-density lipoprotein, and subsequently, impaired foam cell formation. Analysis of macrophage mRNA circadian oscillations revealed that the circadian rhythm of the LDLR mRNAs was lost in Cry1/2 KO BMDMs. Reinstalling the circadian oscillatory LDLR mRNAs using adenovirus into the BMDMs was able to rescue the lipid uptake and foam cell formation function. However, the noncircadian oscillatory LDLR mRNAs exhibited reduced ability to rescue the macrophage functions. These findings indicate that cryptochromes in bone marrow-derived cells are critical mediators of atherosclerosis through regulation of the LDLR mRNA circadian rhythm. Therapeutic measures targeting cryptochromes in the macrophage may have important implications for atherosclerosis.

Summary Background The existence of vascular disease in patients with atrial fibrillation (AF) is associated with an increased risk of thromboembolic events. It is unclear whether coronary artery disease (CAD) and/or peripheral artery disease (PAD) have similar presentations and complication rates. Aim To investigate thromboembolic events among patients with AF who have CAD, PAD or polyvascular disease. Methods Patients with a new diagnosis of AF without anticoagulation (n = 306,386) were identified from the National Health Insurance Research Database in Taiwan (2001–2013). Ischaemic stroke (IS), systemic thromboembolism (STE) and their combination (IS/STE) were compared in four groups (No-CAD/PAD, CAD-only, PAD-only, CAD + PAD), and secondarily in patients with only CAD versus only PAD. Last, we compared propensity score-matched patients with only CAD or PAD with those with CAD and PAD. Results There were 185,169 patients without CAD or PAD, 8113 patients with only PAD, 105,715 patients with only CAD, and 7389 patients with CAD and PAD eligible for analysis (mean ± SD follow-up 3.2 ± 3.2 years). The incidences of STE and IS/STE differed in the four groups, with the highest in the CAD + PAD group and the lowest in the No-CAD/PAD group. The proportions of IS and STE also varied, with higher proportions of STE in patients with PAD, but higher proportions of IS in patients with CAD. After propensity score matching, the PAD-only group had significantly higher incidences of STE and IS/STE than the CAD-only group, across all levels of CHA2DS2-VASc score. Patients with CAD and PAD had a significantly higher incidence of STE and IS/STE than propensity score-matched patients with CAD or PAD. Conclusions PAD or CAD in patients with AF did not contribute equally to the risk prediction and presentation of IS and STE. Patients with polyvascular disease should be considered at higher risk than those with either condition.

The objective was to examine key determinants in the body burden of lead in adolescents as lead poisoning remains a major public health challenge. Data from 2,925 teenagers aged 12-18 older in the National Health and Nutrition Examination Survey (NHANES), 1999-2012 were analyzed. Lead in both blood and urine was significantly correlated among individuals. Despite higher blood lead in males, urinary lead measures corrected for dilution were similar between male and female adolescents. Thus, the urine-to-blood ratio was approximately 30% lower in male than female adolescents, suggesting that differences in renal disposal contributed to the greater body burden for young males. Differences in urinary lead disposal appear to be a key determinant in lead accumulation and thus, the degree of lead poisoning. Direct renal studies should be conducted to determine mechanisms and potential solutions.

Cardiac remodeling is common in the athletes. Little data is available regarding the cardiac remodeling on the recently proposed 4 sport disciplines among the elite university athletes. A total of 7639 athletes participated in the 2017 Taipei Summer Universiade. Cardiac evaluation via history, ECG, and echocardiography were performed in 826 athletes who signed up for Check Up Your Heart. Athletes were grouped into one of 4 sport disciplines Skill, Power, Mixed, and Endurance. After excluding 66 participants with missing demographic data, 13 missing echocardiographic data, and 24 inadequate echocardiographic images, a total number of 723 university athletes (mean age 23 ± 3 years, 419 males) from 99 countries engaging in 25 different sporting events were analyzed. Electrocardiograms showed that Endurance group had a slower heart rate and higher percentage of left ventricular (LV) hypertrophy (39%). Echocardiograms showed there were significant differences in LV mass index (P

Supplemental Digital Content is available in the text, Endovascular aneurysm repair (EVAR) and thoracic endovascular aortic repair (TEVAR) are effective and minimally invasive treatment options for high-risk surgical candidates. Nevertheless, knowledge about the management of aortic stent graft therapy in chronic kidney disease (CKD) is scarce. This study aimed to examine outcomes after EVAR and TEVAR in patients with CKD. Utilizing data from the Taiwan National Health Insurance Research Database, we retrospectively assessed patients who underwent EVAR and TEVAR therapy between January 1, 2006, and December 31, 2013. Patients were divided into CKD and non-CKD groups. Outcomes were in-hospital mortality, all-cause mortality, readmission, heart failure, and major adverse cardiac and cerebrovascular events. There were 1019 patients in either group after matching. The CKD group had a higher in-hospital mortality rate than the non-CKD group (15.2% vs 8.3%, respectively; odds ratio, 1.92; 95% confidence interval [CI], 1.46–2.54). Patients with CKD had higher risks of all-cause mortality including in-hospital death (46.1% vs 33.1%; hazard ratio [HR], 1.61; 95% CI, 1.35–1.92), readmission rate (62.6% vs 55.0%; subdistribution HR [SHR], 1.61; 95% CI, 1.32–1.69), redo stent (7.8% vs 6.2%; SHR, 1.50; 95% CI, 1.09–2.07), and major adverse cardiac and cerebrovascular events (13.3% vs 8.8%; SHR, 1.50; 95% CI, 1.15–1.95). The subgroup analysis did not demonstrate a variation in mortality between the TEVAR and EVAR cohorts (P for interaction = .725). The dialysis group had higher risks of all-cause mortality and readmission than the CKD without dialysis and non-CKD groups. Among EVAR/TEVAR recipients, CKD was independently associated with higher in-hospital mortality, postoperative complication, and all-cause mortality rates. Patients with end-stage renal disease on dialysis had worse outcomes than those in the CKD non-dialysis and non-CKD groups.

Background Advances in voice technology have raised new possibilities for apps related to daily health maintenance. However, the usability of such technologies for older users remains unclear and requires further investigation. Objective We designed and evaluated two innovative mobile voice-added apps for food intake reporting, namely voice-only reporting (VOR) and voice-button reporting (VBR). Each app features a unique interactive procedure for reporting food intake. With VOR, users verbally report the main contents of each dish, while VBR provides both voice and existing touch screen inputs for food intake reporting. The relative usability of the two apps was assessed through the metrics of accuracy, efficiency, and user perception. Methods The two mobile apps were compared in a head-to-head parallel randomized trial evaluation. A group of 57 adults aged 60-90 years (12 male and 45 female participants) was recruited from a retirement community and randomized into two experimental groups, that is, VOR (n=30) and VBR (n=27) groups. Both groups were tested using the same set of 17 food items including dishes and beverages selected and allocated to present distinct breakfast, lunch, and dinner meals. All participants used a 7-inch tablet computer for the test. The resulting data were analyzed to evaluate reporting accuracy and time efficiency, and the system usability scale (SUS) was used to measure user perception. Results For eight error types identified in the experiment, the VBR group participants were significantly (P Conclusions Experimental results showed that VOR outperformed VBR, suggesting that voice-only food input reporting is preferable for elderly users. Voice-added apps offer a potential mechanism for the self-management of dietary intake by elderly users. Our study contributes an evidence-based evaluation of prototype design and selection under a user-centered design model. The results provide a useful reference for selecting optimal user interaction design. Trial Registration International Standard Randomized Controlled Trial Registry ISRCTN17335889; http://www.isrctn.com/ISRCTN17335889.

We investigated the association among metabolically healthy obesity (MHO), cardiovascular disease (CVD)risk, and all-cause mortality in the Asian population. We searched databases from inception to 16 November, 2019 and pooled data using a random-effects model. Subgroup analysis was conducted according to the following comparison groups: MHNW (without overweight or underweight participants) and MHNO (non-obese, including overweight and underweight participants). Nineteen studies were included. The mean Newcastle&ndash, Ottawa Scale score was 7.8. Participants with MHO had a significantly higher CVD risk (odds ratio (OR) = 1.36, 95% confidence interval (CI) = 1.13&ndash, 1.63) and significantly lower risk of all-cause mortality (OR = 0.88, 95% CI = 0.78&ndash, 1.00) than the comparison group. Subgroup analyses revealed participants with MHO had a significantly higher CVD risk than MHNW participants (OR = 1.61, 95% CI = 1.24&ndash, 2.08, I2 = 73%), but there was no significant difference compared with MHNO participants (OR, 1.04, 95% CI, 0.80&ndash, 1.36, I2 = 68%). Participants with MHO had a significantly lower risk of all-cause mortality (OR = 0.83, 95% CI = 0.78&ndash, 0.88, I2 = 9%) than MHNO participants, but a borderline significantly higher risk of all-cause mortality than MHNW participants (OR = 1.30, 95% CI = 0.99&ndash, 1.72, I2 = 0%). The CVD risk and all-cause mortality of the MHO group changed depending on the control group. Thus, future studies should select control groups carefully.

BackgroundUremic pruritus (UP) is a multifactorial problem that contributes to low quality of life in dialysis patients. The long-term influences of UP on dialysis patients are still poorly understood. This study aims to elucidate the contribution of UP to long-term outcomes.Materials and methodWe used the Taiwan National Health Insurance Research Database to conduct this study. Patients on chronic dialysis were included and divided into UP and non-UP groups according to the long-term prescription of antihistamine in the absence of other indications. The outcomes include infection-related hospitalization, catheter-related infection, major adverse cardiac and cerebrovascular events (MACCE) and parathyroidectomy.ResultsAfter propensity score matching, 14,760 patients with UP and 29,520 patients without UP were eligible for analysis. After a mean follow-up of 5 years, we found that infection-related hospitalization, MACCE, catheter-related infection, heart failure and parathyroidectomy were all slightly higher in the UP than non-UP group (hazard ratio: 1.18 [1.16-1.21], 1.05 [1.01-1.09], 1.16 [1.12-1.21], 1.08 [1.01-1.16] and 1.10 [1.01-1.20], respectively). Subgroup analysis revealed that the increased risk of adverse events by UP was generally more apparent in younger patients and patients who underwent peritoneal dialysis.ConclusionUP may be significantly associated with an increased risk of long-term morbidities.

Background and aim Peroxisome proliferator-activated receptor-γ (PPAR-γ) modulating treatment may have cardiovascular benefits in type 2 diabetes mellitus (T2DM) patients after ischemic stroke (IS). However, whether there are additional benefits from intensive PPAR-γ modulating treatments in Asian patients with T2DM and hypertension (HTN) after IS remains unknown. Methods Between 2001 and 2013, patients admitted due to IS were identified from the National Health Insurance Research Database of Taiwan. Patients with T2DM and HTN using angiotensin receptor blockers were further included. Eligible patients were divided into two groups: (1) pioglitazone and (2) non-pioglitazone oral anti-diabetic agent groups. Propensity score matching (1:2) was used to balance the distribution of baseline characteristics, stroke severity and medications. The primary outcome was recurrent IS. Subgroup analysis for recurrent IS in pioglitazone and/or telmisartan users, the trend of IS risks across different PPAR-γ intensity treatments, and dose-dependent outcomes across different pioglitazone possession ratios were further studied. Statistical significance was set at p p Results There were 3190 and 32,645 patients in the pioglitazone and non-pioglitazone groups. Patients of the pioglitazone group had a lower risk of recurrent IS (subdistribution hazard ratio, 0.91; 95% confidence interval 0.84–0.99). Pioglitazone was also associated with reduced recurrent IS in patients who also used telmisartan (p for interaction = 0.071). A graded correlation was found a borderline significant trend between the intensity of PPAR-γ therapy and following IS (p = 0.076). The dose-dependent outcome also showed that a borderline significant trend that higher pioglitazone possession ratio was associated with a lower risk of recurrent IS (p = 0.068). Conclusions The current study suggests that the use of pioglitazone in type 2 diabetic and hypertensive IS patients is associated with fewer recurrent IS events in an Asian population. Concurrent telmisartan use or a higher pioglitazone possession ratio may have a trend of increased pleiotropic effects, which could possibly be related to higher PPAR-γ effects. Future studies are warranted to confirm or refute the clinical effects and the possible mechanism of more intensive PPAR-γ-modulating treatments.

OBJECTIVE Tracheostomy in children is a surgical procedure with considerable morbidity and mortality. However, there is still a lack of population-based survey in pediatric tracheostomy. This study analyses population-based data in pediatric tracheostomy among different ages in Taiwan. METHODS This study used National Health Insurance Research Database in Taiwan. All children (aged

Aims Anticoagulation therapy is indicated to prevent stroke in atrial flutter (AFL) and atrial fibrillation (AF) patients. However, the outcomes of solitary AFL patients may differ from those with AFL who develop AF during follow-up. This study aimed to investigate the differences in clinical outcomes: (i) among patients with solitary AFL, AF, and AFL developing AF thereafter and (ii) between solitary AFL patients with vs. without anticoagulation therapy. Methods and results This nationwide cohort study enrolled patients with solitary AFL, solitary AF, and AFL developing AF from a 12 years National Health Insurance Research Database in Taiwan. There were 230 367 patients without anticoagulation therapy in the solitary AF cohort, 8064 in the solitary AFL cohort, and 4495 in the AFL with AF cohort. The AFL with AF and solitary AF cohorts had higher incidences of ischaemic stroke and major bleeding than the solitary AFL cohort. Solitary AFL patients with anticoagulation therapy had a lower ischaemic stroke rate than those without (P

Published studies seldom tested the weight of different waist circumference (WC) cut-off values for the diagnosis of metabolic syndrome (MetS) in predicting clinical outcomes, including cardiovascular disease and diabetes.This is a Chinese population-based cross-sectional study screening subjects from a Health Examination Program since 1999 to 2015. The MetS identification and scores were determined either according to the Adult Treatment Panel III/American Heart Association/National Heart, Lung, and Blood Institute (ATP III/AHA/NHLBI)- or Asian-WC cut-off points. The developments of a higher brachial-ankle pulse wave velocity (baPWV), defined as ≥1400 cm/s, and diabetic-level hyperglycemia, defined as a high fasting glucose level ≥6.99 mmol/L or postprandial glucose level ≧11.10 mmol/L, were surveyed by comparing the areas under receiver operating characteristic curves (AUC-ROC) for both MetS scores.According to the ATP III/AHA/NHLBI- vs Asian-MetS criteria, 6633 vs 9133 (24.8% vs 34.2%, p 0.001) subjects were diagnosed as the MetS among 26,735 study subjects with a mean age of 55 ± 12 years. The stepwise increases in baPWV and prevalence of diabetic-level hyperglycemia were associated with both MetS scores after adjusting for age and sex. Both MetS scores yielded similar results for correlation with a higher baPWV (AUC-ROC = 0.685 for ATP III/AHA/HLBI- vs 0.680 for Asian-MetS, p = 0.271) and diabetic-level hyperglycemia (AUC-ROC = 0.791 for ATP III/AHA/HLBI- vs 0.784 for Asian-MetS, p = 0.546).In a stepwise manner, both ATP III/AHA/NHLBI- or Asian-MetS scores were strong risk factors for arterial stiffness and diabetes. Through a novel and holistic approach, the performance of the ATP III/AHA/NHLBI-MetS score for the risks of arterial stiffness and diabetes was comparable to the Asian-MetS score among a Chinese population.

Background Primary Sjögren’s syndrome (pSS) is associated with dental caries. Pilocarpine, a salivary stimulant, can improve the amount and flow rate of saliva in patients with pSS. This study aimed to assess whether the risk of dental caries decreases with the use of pilocarpine in patients with pSS. Methods For this prospective cohort study, we identified pSS patients from the catastrophic illnesses registry of the National Health Insurance Research Database of Taiwan between 2009 and 2013. We divided participants into pilocarpine and non-user groups based on the pilocarpine prescriptions available during the first 3-month follow-up. The primary endpoint was dental caries. The secondary endpoints were periodontitis and oral candidiasis. We compared the risk of these oral manifestations using the Cox proportional hazard model. Results A total of 4973 patients with new-onset pSS were eligible for analysis. After propensity score matching, we included 1014 patients in the pilocarpine group and 2028 patients in the non-user group. During the mean follow-up of 2.6 years, the number of events was 487 in the pilocarpine group (48.0%) and 1047 in the non-user group (51.6%); however, the difference was not significant (hazard ratio [HR] 0.93, 95% confidence interval [CI] 0.82 to 1.06). Furthermore, there was no significant difference between groups regarding risk of periodontitis (HR 0.91, 95% CI 0.81 to 1.03) and oral candidiasis (HR 1.16, 95% CI 0.70 to 1.94). Conclusion Pilocarpine may have no protective effect on dental caries, periodontitis, or oral candidiasis in patients with pSS.

The purpose of this study was to retrospectively compare the imaging features of hepatic epithelioid angiomyolipoma (HEAML) to those of hepatocellular carcinoma negative for hepatitis B surface antigen and hepatitis C antibody (NBNC-HCC) on contrast-enhanced ultrasound (CEUS) with sulphur hexafluoride microbubbles.Twenty-two patients (4 men, 18 women) with a mean age of 42.6±10.2 (SD) years (range: 22-63 years) with histopathologically confirmed HEMAL were included in the study. Forty-four patients (30 men, 14 women) with a mean age of 57.3±15.9 years (range: 19-85 years) with histopathologically confirmed NBNC-HCC were randomly selected from our institution's database as a control group. The CEUS characteristics of the two groups were compared.On conventional ultrasound, significant differences in tumor diameter were found between HEAML (4.0±2.0 [SD] cm; range: 1.3-8.9cm) and NBNC-HCC (8.4±4.4 [SD] cm; range: 1.6-18cm) (P0.001) as well as in degrees of enhancement during the portal (P=0.001) and late phases (P=0.003), contrast distribution (P0.001) and absence of pseudocaspule (P0.001). On CEUS, hyperenhancement during the arterial phase was observed in 21/22 (95.5%) HEAMLs and in 43/44 (97.7%) NBNC-HCCs (P0.999). Homogeneous enhancement was more frequent in HEAMLs (20/22; 90.9%) than in NBNC-HCCs (13/44; 29.6%) (P0.001). Pseudocapsule was observed in 0/22 HEAMLs (0.0%) and in 36/44 NBNC-HCCs (81.8%) (P=0.017). A prolonged enhancement was observed in 5/22 HEAMLs (22.7%) and in 0/44 NBNC-HCCs (0.0%) (P0.001) during the late phase.CEUS with sulphur hexafluoride microbubbles is helpful in discriminating between HEAML and NBNC-HCC. Homogeneous enhancement and lack of pseudocapsule are suggestive features for the diagnosis of HEAML.

Objectives HCQ, which is known to decrease SLE activity, may have a protective effect on survival, but this has not been proven in Asia. This study aimed to determine whether HCQ treatment is associated with increased survival in patients with SLE. Methods We designed this prospective SLE cohort study using data from the Taiwan National Health Insurance Research Database. The participants were divided into HCQ and control groups according to whether HCQ was prescribed during the first year after an SLE diagnosis. The primary outcome was mortality 1 year after inclusion. In the subgroup analysis, these participants were divided based on medication possession ratio (MPR) in the first year into non-users, MPR

Background Congenital heart defects (CHD) are known to cluster within families, but existing evidence varies for the estimates of familial relative risk (RR). We aimed to examine familial aggregation and heritability of CHD in the general population of Taiwan.Methods and Results:We conducted a population-based family study using the Taiwan National Health Insurance (NHI) research database. Individuals with affected first-degree (n=295,636) or second-degree (n=73,985) relatives were identified from all NHI beneficiaries (n=23,422,955) registered in 2012. Diagnoses of CHD for all study subjects were ascertained between January 1, 1996 and December 31, 2012. Having a twin, a first-degree relative and an affected second-degree relative were associated with an adjusted RR of 12.03 (11.59-12.49), 4.91 (4.85-4.97) and 1.21 (1.14-1.28) for CHD, respectively. Individuals with 1 affected first-degree relative had a RR of 4.78 (4.72-4.84), and those with ≥2 had an RR of 7.10 (6.77-7.45) for CHD. The estimated accountability for phenotypic variance of CHD was 37.3% for familial transmission and 62.8% for non-shared environmental factors. Conclusions Our results indicated that CHD tend to cluster within families, and approximately one-third of phenotypic variance was explained by familial factors.

Postmenopausal status is correlated with increased metabolic syndrome (MetS) and cardiovascular risks. However, the vital roles of age and MetS-associated risk factors in sex-specific arterial stiffness remain unclear.In this population-based cross-sectional study of the general population, we enrolled in our Health Examination Program 9812 adult participants who were measured for brachial-ankle pulse wave velocity (baPWV) to assess arterial stiffness. Piecewise linear regression models were used to survey pre-defined ages associated with menopause and andropause in relation to arterial stiffness. Multivariate linear regression analyses were used to evaluate independent determinants.Across gender, stepwise increases in baPWV corresponded to increased MetS-associated risk scores (MetSRS) and aging (all p for trend 0.001), while a turning point was found at 50 years of age (50age). The incremental ratios of baPWV presented inverse U curves with aging, whereas the highest RArterial stiffness increased with aging across nearly lifelong ages more in women than in men. While menopause and andropause may both play a role, 50age was the most critical factor across gender. The sex-specific differences in determinants of arterial stiffness may remind us of sex-specific targets for further interventional studies associated with arterial stiffness.

Background MicroRNAs (miRs) regulate gene expression in heart failure. Circulating miRs as biomarkers for heart failure in mitral regurgitation patients (MR) remain unexplored. Methods This case–control study enrolled 32 MR patients with heart failure, 16 asymptomatic MR patients, and 12 control subjects without heart failure. We used next generation sequencing to study the gene expression profiles in the sera, and quantitative RT-PCR to study serum and tissue miRs in the left atria. Results Next generation sequencing analysis and enrichment analysis showed that 25 miRs were differentially expressed in the sera of MR patients with heart failure compared to control subjects. The circulating miR-148b-3p (p=0.002) and miR-409-3p (p=0.010) were significantly down-regulated in the MR patients with heart failure compared to control subjects. However, only circulation miR-148b-3p was significantly down-regulated in the MR patients without heart failure compared to control subjects (p=0.009). The tissue miR-409-3p was significantly down-regulated in the MR patients with heart failure compared to 3 purchased normal controls (p=0.041). Notably, the tissue RASGRP3 mRNA, target gene of miR-409-3p, was significantly up-regulated in the MR patients with heart failure compared to normal controls (p=0.010). The tissue FRY (p=0.010) and GADD45A (p=0.010) mRNAs, target genes of miR-148b-3p, were significantly up-regulated in the MR patients with heart failure compared to normal controls. Conclusions Circulating miR-148b-3p might serve as biomarker for future development of heart failure and miR-409-3p might serve as biomarker for incident heart failure in MR patients.

It remains unclear whether infection events before entering end stage renal disease (ESRD) have a long-term negative impact on patients with advanced chronic kidney disease (CKD) who survive to permanent dialysis. We enrolled 62,872 patients with advanced CKD who transitioned to maintenance dialysis between January 1, 2004 and December 31, 2013. We used multivariable Cox as well as Fine and Gray models to determine the association of pre-dialysis infection exposure with all-cause mortality after starting dialysis. Compared with no infection during advanced CKD, the presence of infection exposure during that period was independently associated with a higher risk of all-cause mortality in the first year of dialysis (hazard ratio [HR] 1.34, 95% confidence interval [CI] 1.27–1.42) and also during the entire follow-up period (HR 1.19, 95% CI 1.16–1.22). The increased risks of all-cause mortality increased incrementally with higher annual number of infections during advanced CKD. Similar results were found for all other adverse outcomes, e.g. post-ESRD infection-related hospitalization and major cardiac and cerebrovascular events. In conclusion, infection events during advanced CKD was associated with increased risks of adverse outcomes after dialysis has been started. Timely interventions in such a vulnerable group may help attenuate these risks.

Background Young adults are more likely to use self-managed dietary reporting apps. However, there is scant research examining the user experience of different measurement approaches for mobile dietary reporting apps when dealing with a wide variety of food shapes and container sizes. Objective Field user experience testing was conducted under actual meal conditions to assess the accuracy, efficiency, and subjective reaction of three food portion measurement methods embedded in a developed mobile app. Key-in–based aid (KBA), commonly used in many current apps, relies on the user’s ability to key in volumes or weights. Photo-based aid (PBA) extends traditional assessment methods, allowing users to scroll, observe, and select a reduced-size image from a set of options. Gesture-based aid (GBA) is a new experimental approach in which the user makes finger movements on the screen to roughly describe food portion boundaries accompanied by a background reference. Methods A group of 124 young adults aged 19 to 26 years was recruited for a head-to-head randomized comparison and divided into 3 groups: a KBA (n=42) control group and PBA (n=41) and GBA (n=41) experimental groups. In total, 3 meals (ie, breakfast, lunch, and dinner) were served in a university cafeteria. Participants were provided with 25 dishes and beverages for selection, with a variety of food shapes and containers that reflect everyday life conditions. The accuracy of and time spent on realistic interaction during food portion estimation and the subjective reaction of each aid were recorded and analyzed. Results Participants in the KBA group provided the highest accuracy in terms of hash brown weight (P=.004) and outperformed PBA or GBA for many soft drinks in cups. PBA had the best results for a cylindrical hot dog (P Conclusions Experimental results show that each aid had some distinguishing advantages. In terms of user acceptance, participants considered all 3 aids to be usable. Furthermore, users’ subjective opinions regarding measurement accuracy contradicted the empirical findings. Future work will consider the use of each aid based on food or container shape and integrate the various advantages of the 3 different aids for better results. Our findings on the use of portion size aids are based on realistic and diverse food items, providing a useful reference for future app improvement of an effective, evidence-based, and acceptable feature. Trial Registration International Standard Randomized Controlled Trial Registry ISRCTN36710750; http://www.controlled-trials.com/ISRCTN36710750.

ObjectivesThis study determined the recurrence and complication rates after radiofrequency catheter ablation (RFCA) for those with paroxysmal supraventricular tachycardia (PSVT), Wolff-Parkinson-White syndrome (WPW), atrial flutter (AFL), atrial fibrillation (AF) and ventricular tachycardia (VT).Study design and settingThis retrospective study included RFCAs for 2001–2010 in the Taiwan National Health Insurance Research Database. Primary outcomes included perioperative complications (pericardial effusion and new-onset stroke), RFCA recurrence and long-term outcomes (high-grade atrioventricular block (AVB) and pacemaker implantation).ResultsOf 19,475 patients who underwent RFCA, prevalence rates were 56.7% for PSVT, 13.5% for WPW, 9.5% for AFL, 5.1% for AF and 2.7% for VT. Prevalence rates increased in AF, AFL and VT over the study years. During an average follow-up period of 4.3 years (SD: 2.8 years), recurrence rates for PSVT, WPW, VT, AFL and AF were 2.0%, 4.9%, 5.7%, 5.8% and 16.1%, respectively. Compared with the PSVT group, the WPW and AF groups had significantly higher risk of pericardial effusion during admission (adjusted OR (aOR) 2.98, 95% CI (CI) 1.24 to 7.15; aOR 4.09, 95% CI 1.90 to 8.79, respectively); the AFL group had a higher risk of new-onset stroke during admission (aOR 4.07, 95% CI 1.39 to 11.91); the WPW group had a lower risk of high-grade AVB during follow-up (adjusted HR (aHR) 0.37, 95% CI 0.19 to 0.71) while the AFL group had a greater risk (aHR 1.74, 95% CI 1.17 to 2.60); and the AFL group had a higher risk of permanent pacemaker (aHR 2.14, 95% CI 1.27 to 3.62).ConclusionsThe RFCA rate increased rapidly during 2001–2010 for AF, AFL and VT. Recurrence was associated with congenital heart disease in PSVT and WPW, and with age in AF and AFL. AFL had a higher risk of permanent pacemaker implantation and new stroke. AF had a higher risk of life-threatening pericardial effusion.

AIMS Catheter ablation has become an effective treatment modality for atrial fibrillation (AF). However, the relationship between common pulmonary vein (PV) and recurrent atrial tachyarrhythmia (ATA) after PV isolation (PVI) remains controversial. This study aimed to explore the function of common PV on the risk of recurrent ATA after PVI. METHODS We identified a total of 191 patients who received radiofrequency catheter ablation for paroxysmal AF at our hospital between July 2010 and December 2017 for retrospective chart review. We collected the following data for analysis: results of preprocedural computed tomography, including the anatomy of PV and left atrial (LA) volume; the incidence of early- and late-onset recurrence of ATA. We compared these characteristics between the two groups defined by the presence or absence of the late-onset recurrence of ATA. RESULTS Compared to the no ATA recurrence group, the ATA recurrence group had larger LA size, larger LA end-diastolic and systolic volumes, larger maximal diameter of PV, higher prevalence of common PV, and higher incidence of early-onset recurrence of ATA. In multivariate logistic regression analyses, presence of common PV and early-onset recurrence were independently associated with late-onset recurrence of ATA. Compared to patients without common PV, patients with common PV had larger diameter of PV and higher incidence of late-onset recurrent ATA. CONCLUSION In patients with paroxysmal AF, early-onset recurrence of ATA and the presence of common PV were independently associated with late-onset recurrent ATA after radiofrequency catheter ablation.

Background Studies have reported conflicting findings on the infection risk posed by intravenous iron supplementation among hemodialysis (HD) patients. We used a novel study design to assess associations between intravenous iron and infectious diseases. Methods Patients initiating HD between 1998 and 2008 were extracted from Taiwan’s National Health Insurance Research Database. Their first infectious disease in the period between 1.5 years after dialysis initiation and 2010 was identified and defined as the index date. Through the case-crossover design, the odds of exposure to intravenous iron within the 1-month period immediately preceding the index date (i.e., the case period) were compared with iron exposure in three different matched control periods for the same enrollee, thus possibly reducing some unmeasured confounders. Results A total of 1410 patients who met our enrollment criteria were extracted from incident HD patients. The odds of intravenous iron exposure during the case period versus total control periods exhibited no significant difference (odds ratio: 1.000, 95% confidence interval: 0.75–1.33). In subgroup analyses, this association remained nonsignificant across patients with diabetes mellitus, heart failure, chronic lung disease, venous catheter for HD, and higher iron load. Conclusions We found that intravenous iron supplementation did not increase short-term infection risk among HD patients. Electronic supplementary material The online version of this article (10.1186/s12882-019-1495-7) contains supplementary material, which is available to authorized users.