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Beta-blockers are widely used, but the benefit is now challenged in patients at risk of atherosclerotic cardiovascular disease (ASCVD) in the present coronary reperfusion era. We aimed to identify the risk factors of a major adverse cardiac event (MACE) and the long-term effect of beta-blockers in two large cohorts in Taiwan. Two prospective observational cohorts, including patients with known atherosclerosis cardiovascular disease (T-SPARCLE) and patients with at least one risk factor of ASCVD but without clinically evident ASCVD (T-PPARCLE), were conducted in Taiwan. The primary endpoint is the time of first occurrence of a MACE (cardiovascular death, nonfatal stroke, nonfatal myocardial infarction, and cardiac arrest with resuscitation). Between December 2009 and November 2014, with a median 2.4 years follow-up, 11,747 eligible patients (6921 and 4826 in T-SPARCLE and T-PPARCLE, respectively) were enrolled. Among them, 273 patients (2.3%) met the primary endpoint. With multivariate Cox PH model analysis, usage of beta-blocker was lower in patients with MACE (42.9% vs. 52.4%, p < 0.01). In patients with ASCVD, beta-blocker usage was associated with lower MACEs (hazard ratio 0.72; p < 0.001), but not in patients without ASCVD. The event-free survival of beta-blocker users remained higher during the follow-up period (p < 0.005) of ASCVD patients. In conclusion, in ASCVD patients, reduced MACE was associated with beta-blocker usage, and the effect was maintained during a six-year follow-up. Prescribing beta-blockers as secondary prevention is reasonable in the Taiwanese population. [ABSTRACT FROM AUTHOR]

Aims: Mineralocorticoid receptor antagonists (MRAs) have been shown to provide survival benefits in patients with heart failure; however, MRA use in patients with chronic kidney disease has been limited by safety concerns. The effects of MRAs on outcomes in patients with end‐stage renal disease (ESRD) and heart failure remain unknown. The aim of this study was to evaluate the effects of MRAs on cardiovascular outcomes in patients with heart failure under maintenance dialysis in a real‐world setting. Methods and results: A retrospective cohort study was conducted by collecting data from the Taiwan National Health Insurance Research Database (NHIRD). Patients diagnosed with heart failure and ESRD and who started maintenance dialysis between 1 January 2001 and 31 December 2013 were identified. Patients were grouped according to MRA prescription. The outcomes of interest included cardiovascular (CV) death, hospitalization for heart failure (HHF), all‐cause mortality, acute myocardial infarction (AMI), ischaemic stroke, any coronary revascularization procedures, and new‐onset hyperkalaemia. Propensity score matching was performed at a 1:3 ratio between MRA users and non‐users to minimize selection bias. A total of 50 872 patients who satisfied our inclusion and exclusion criteria were identified. After 1:3 matching, 2176 patients were included in the MRA group, and 6528 patients were included in the non‐MRA group. The risk of CV death was significantly lower among patients who received MRAs than those who did not (hazard ratio [HR] 0.88, 95% confidence interval [CI] 0.80–0.95), as was the risk of all‐cause mortality (HR 0.88, 95% CI 0.83–0.94). Reductions in the risks of CV death and all‐cause mortality were more prominent among patients undergoing haemodialysis and those with coronary artery disease. Conclusions: In patients undergoing regular dialysis who are diagnosed with heart failure, the use of MRAs is associated with lower risks of all‐cause mortality and CV death. The benefits of MRA treatment in heart failure may persist in patients with ESRD. Further investigations through randomized controlled trials are needed to assess the efficacy and safety of MRAs in this high‐risk population. [ABSTRACT FROM AUTHOR]

In addition to Pseudomonas aeruginosa, other organisms including Staphylococcus aureus have been reported to have associations with ecthyma gangrenosum (EG). There are very limited reports of Staphylococcus aureus EG causing systemic symptoms in an immunocompetent child. We present the case of an atopic child with transient neutropenia developing characteristic skin lesions of EG. Culture of the skin wounds yielded methicillin-susceptible Staphylococcus aureus (MSSA), and incisional biopsy of the skin lesions revealed aggregates of Gram-positive cocci at the subepidermal area and necrotic vasculitis but without perivascular bacterial invasion. In the literature review, seven cases of Staphylococcus aureus EG were reported, and only two were pediatric cases. From this case, we emphasize the importance of early culturing for microorganisms in cases presenting with EG. When toxin-mediated systemic symptoms accompany EG-like skin lesions, MSSA should be considered in an atopic child with transient neutropenia. [ABSTRACT FROM AUTHOR]

Obesity is an independent risk factor for atherosclerotic cardiovascular disease (ASCVD). However, 'obesity paradox' is observed in patients with coronary artery disease while defining obesity by body mass index (BMI). The purpose of this study is to identify a better anthropometric parameter to predict cardiovascular events in patients with ASCVD. The study was conducted using the Taiwanese Secondary Prevention for patients with AtheRosCLErotic disease (T-SPARCLE) Registry. A total of 6,920 adult patients with stable ASCVD, enrolled from January 2010 to November 2014, were included, with a mean age of 65.9 years, 73.9% males, and a mean BMI of 26.3 kg/m2 at baseline. These patients were followed up for a median of 2.5 years. The study endpoint was the composite major adverse cardiovascular event (MACE), defined as cardiovascular death, nonfatal myocardial infarction or stroke, or cardiac arrest with resuscitation. Multivariable Cox proportional hazards regression showed a significant positive association between waist-to-BMI ratio and MACE (adjusted hazard ratio 1.69 per cm‧m2/kg increase in waist-to-BMI ratio, 95% CI 1.12–2.49, p = 0.01) after adjusting for potential risk factors and confounders. Traditional anthropometric parameters, such as BMI, weight, waist and waist-hip ratio, or newer waist-based indices, such as body roundness index and a body shape index, did not show any significant linear associations (p = 0.09, 0.30, 0.89, 0.54, 0.79 and 0.06, respectively). In the restricted cubic spline regression analysis, the positive dose–response association between waist-to-BMI ratio and MACE persisted across all the range of waist-to-BMI ratio. The positive dose–response association was non-linear with a much steeper increase in the risk of MACE for waist-to-BMI ratio > 3.6 cm‧m2/kg. In conclusion, waist-to-BMI ratio may function as a positive predictor for the risk of MACE in established ASCVD patients. [ABSTRACT FROM AUTHOR]

Background: To assess the effect of sodium glucose cotransporter-2 inhibitors (SGLT-2is) for type 2 diabetes on kidney outcomes stratified by patient baseline estimated glomerular filtration rate (eGFR) levels (i.e., eGFR ≤ 60, 60 < eGFR ≤ 90, and eGFR > 90 mL/min/1.73 m2). Methods: Patients from three large healthcare delivery systems in Taiwan who had initiated SGLT-2is or other glucose-lowering drugs (oGLDs) between May 2016 and December 2017 were included. Main outcomes were the times to 30%, 40%, and 50% eGFR reduction after treatment initiation. One-to-one propensity score matching in the overall study cohort and in each eGFR subgroup between SGLT-2i and oGLD users was applied to ensure between-group comparability in baseline characteristics. Results: There were 13,666 matched pairs of SGLT-2is and oGLD users in the overall cohort. While a sustained eGFR decline was revealed in oGLD-treated patients (mean values [standard errors] from 85.61 [0.43] to 82.49 [0.44] mL/min/1.73 m2 during the 12 months after treatment initiation), the mean eGFR values of SGLT-2i users decreased in the first 3 months (85.68 [0.37] to 79.71 [0.41] mL/min/1.73 m2) but then improved and sustained until the end of follow-up. There were 2300, 5705, and 5509 matched SGLT-2i and oGLD users in the eGFR ≤ 60, 60 < eGFR ≤ 90, and eGFR > 90 subgroups, respectively. Using SGLT-2is versus oGLDs was significantly associated with slower eGFR declines; hazard ratios (HRs) were 0.51 (95% CI 0.37–0.69), 0.51 (0.37–0.70), and 0.47 (0.31–0.71) for 40% eGFR reduction in the eGFR ≤ 60, 60 < eGFR ≤ 90, and eGFR > 90 subgroups, respectively. The renoprotective effect of SGLT-2is versus oGLDs was confirmed in the outcomes of 30% and 50% eGFR reduction across the three eGFR subgroups. Conclusions: This study supports the renoprotective benefit of real-world SGLT-2i use irrespective of patient baseline kidney function. [ABSTRACT FROM AUTHOR]

Aligned crystallites of 1,6‐di‐(N‐carbazolyl)‐2,4‐hexadiyne (DCHD) were prepared on the phenyltrichlorosilane‐modified SiO2/Si surface using the brush‐coating method. The length and width as well as the orientation of the crystallites depend on the coating speed. At a lower coating speed of 0.2 ~ 0.3 mm/s, well‐separated fibers with a width of 1–2 μm and a length of hundreds of μm were grown along the coating direction. Higher speeds resulted in shorter fibers together with randomly oriented tiny crystallites appearing in between. The diacetylene crystallites upon UV irradiation gave polydiacetylene fibers with deformations along the fiber axis. The poly(ene‐yne) backbones were shown to align along the fiber axes. With these poly‐DCHD fibers as a conducting channel for transistor fabrication, a highest field‐effect mobility of 0.039 cm2/Vs was obtained. [ABSTRACT FROM AUTHOR]

Background: Statins possess neuroprotective effects. However, real-world evidence supporting their utility in post-stroke epilepsy (PSE) prevention is limited.Objective: The association between statin use, including timing of prescribing (pre-stroke vs post-stroke), type (lipophilicity, intensity of therapy) and dose intensity, and risk of developing PSE were investigated by studying Taiwanese health claims (2003-2013).Methods: Patients with new-onset ischaemic stroke were identified. The main outcome was a diagnosis of epilepsy after ischaemic stroke. According to pre-stroke statin use, groups of current users, former users, and non-users were compared using ANOVA. An extended Cox regression model was utilized to estimate the hazard ratio (HR) of PSE, with post-stroke statin use and certain comedications as time-dependent variables. Serial sensitivity analyses were performed to ensure study robustness.Results: Of the 20,858 ischaemic stroke patients, 954 (4.6%) developed PSE. Post-stroke statin use (adjusted HR (aHR) 0.55; 95% confidence interval 0.46-0.67, p < 0.001), but not pre-stroke statin use was associated with a significantly reduced risk of developing PSE. A dose-response correlation was also observed between PSE risk reduction and quartiles of the statin cumulative defined daily dose (cDDD) (aHR 0.84, 0.67, 0.53, and 0.50 for the lowest, second, third, and highest quartiles of cDDD, respectively). Risk predictors and protectors against PSE were also characterized.Conclusion: The post-stroke use of statins after ischaemic stroke was associated with PSE risk reduction in a cDDD-dependent manner. Further clinical studies on the potential applications of statins for PSE prophylaxis, particularly among at-risk patients, are warranted. [ABSTRACT FROM AUTHOR]

Objectives To evaluate the association between zolpidem use and the risk of Alzheimer's disease among older people. Design A retrospective cohort study using data from 2001 to 2011 from the National Health Insurance Research Database. Setting Taiwan. Participants A total of 6,922 patients aged 65 years or older enrolled from January 2002 to December 2004 (the enrollment period). Intervention (Exposure) Zolpidem users were identified as patients who used zolpidem during the enrollment period. The index date was the date of the first zolpidem prescription. Dosage of zolpidem use was defined using cumulative defined daily dose ( cDDD) based on the cumulative dosage that patients took within one year after the index date (grouped as: less than 28, 28-90, 91-180, and more than 180 cDDD). Measurements The occurrence of Alzheimer's disease was defined as the time period from the end of one year after the index date to the date of the Alzheimer's disease diagnosis. The propensity score was used to adjust the measured confounders of Alzheimer's disease. Cox proportional hazards models were used to evaluate the association between zolpidem use and the incidence of Alzheimer's disease. Results Zolpidem users with a high cumulative dose (>180 cDDD) in the first year after initiation had a significantly greater risk of Alzheimer's disease than non-zolpidem users ( HR = 2.97, 95% CI = 1.61-5.49) and low cumulative dose (<28 cDDD) users ( HR = 4.18, 95% CI = 1.77-9.86). Conclusion We found the use of a high cumulative dose of zolpidem was associated with an increased risk of Alzheimer's disease among older people living in Taiwan. It is advised to use caution when considering long-term use of zolpidem in older patients. [ABSTRACT FROM AUTHOR]

Background/Aims: Limited evidence exists on the choice of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) in diabetic patients with nephropathy. We aim to assess the renal effectiveness and safety of these drugs among diabetic nephropathy patients. Methods: This retrospective cohort study was conducted with diabetic nephropathy patients who initiated ACEI or ARB monotherapy. The primary outcome was a composite of end stage of renal disease and renal transplantation, and the secondary outcome was all-cause mortality. The safety endpoint was hyperkalemia. Results: Three thousand seven hundred and thirty-nine ACEI users and 3,316 ARB users were identified. ARBs seemed to be inferior to ACEIs given their poorer renal outcome (HR 1.31; 95% CI, 1.15-1.50) and higher risk of hyperkalemia (HR 1.17; 95% CI, 1.04-1.32). Among the four ACEIs compared, captopril was an inferior treatment choice given its poorer renal outcomes (HR 1.42; 95% CI, 1.05-1.93) and higher mortality rate (HR 1.25; 95% CI, 1.01-1.55). Irbesartan appeared to be a poorer treatment choice among the three ARBs compared, given its inferior renal protective effect (HR 1.35; 95% CI, 1.03-1.78). Conclusions: Our findings suggest ACEIs as a relatively more renoprotective and safer treatment as compared to ARBs. Captopril and irbesartan may be inferior to the other ACEIs and ARBs respectively. [ABSTRACT FROM AUTHOR]

Rationale, aims and objectives The Global Initiative for Chronic Obstructive Lung Disease ( GOLD) guidelines are well-known international clinical practice guidelines for chronic obstructive pulmonary disease ( COPD). The objective of this study was to examine how treatment recommendations and the quality of supporting evidence for pharmacologic management of stable COPD have evolved since the initial guidance issued in 2001. Methods Recommendations in the 2001 and 2011 GOLD guidelines, along with the evidence grades (i.e. A, B, C, D), were identified and abstracted. We determined the distribution and evolution of recommendations across levels of evidence and treatment categories over time. Results There were 35 and 54 recommendations identified in the 2001 and 2011 guidelines, respectively. Twenty-six recommendations were common to the 2001 and 2011 guidelines, with eight having the same evidence grade in both versions and three having a grade change (one upgraded and two downgraded). Twenty-eight new recommendations were added in 2011. Bronchodilators, glucocorticosteroids, and phosphodiesterase-4 inhibitors are the classes of pharmacologic treatment with the most prominent changes regarding emerging evidence and the number of recommendations. Approximately 45% of the graded recommendations were supported by well-designed randomized controlled trials, i.e. grade A. Conclusions The GOLD guideline recommendations have changed considerably over the past 11 years, which reflects a dynamic evidence base and perhaps a change in the way guideline developers view the evidence to inform recommendations. Given the large number of recommendations with lower grade levels, there continues to be substantial opportunity to inform gaps in the evidence base with high-quality studies. [ABSTRACT FROM AUTHOR]

Purpose: The goal of this study was to appraise the extent of unique content on disease-specific preference-based measures (DSPMs) when contrasted with the EQ-5D using published studies and to inform whether EQ-5D could be inadequate as a utility measure in its content coverage for a given disease-specific application. Methods: A structured search of published literature was performed using PubMed and EMBASE/Medline database from Jan 1, 1990 to Mar 31, 2011. Articles were eligible for inclusion if algorithms were developed to convert components from disease-specific measures into utility scores. Results: Of 1,029 articles identified, 50 studies satisfied the inclusion criteria. The most frequent conditions where DSPMs were developed included cancer (12 studies), coronary artery disease (4 studies), osteoarthritis, rheumatoid arthritis (3 studies of each), obesity, and stroke (2 studies of each). Most studies involved mapping items or scores from disease-specific non-preference-based measures onto a preference-based measure of health such as the EQ-5D. A substantial number of DSPMs appeared to include unique content not covered by EQ-5D dimensions. Conclusions: Several conditions were identified as potential areas where the richness of the EQ-5D descriptive system could be enhanced. It is yet unclear whether added dimension(s) would contribute unique explained variance to a utility score. Given the resources required to rigorously develop a utility measure, the need for such measures should be carefully vetted. [ABSTRACT FROM AUTHOR]

In recent years, as credit cards have emerged into competitive markets, many credit card companies have turned to customer relationship management. This study used the concept of customer relationship management to investigate cause and effect among relationship norms, relationship benefit, and relationship value. The sampling population was taken from customers living in Taipei who use credit cards to pay bills. In January 2010, 500 questionnaires were mailed to customers; 401 were returned. A total of 371 valid questionnaires were obtained for analysis. Thus, the effective rate of response was 74%. The empirical results suggest that the main route for building relationships will be by means of encouraging solidarity, which affects functional value via confidence benefits. The managerial implications of this study can point to appropriate strategies for credit card companies in developing and executing their customer service activities more efficiently. [ABSTRACT FROM AUTHOR]

This document is a correction notice for an article titled "Valuation of the EQ-5D-5L in Taiwan" published in the journal PLoS ONE. The correction addresses errors in the Funding statement and Competing Interests statement. The correct Funding statement acknowledges the sponsorship of various organizations, while clarifying that they had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The correct Competing Interests statement clarifies that two of the authors were executive directors of sponsoring agencies but declared no competing interests. The document also mentions that the Acknowledgement section was missing from the original article and provides the correct section, which includes gratitude to study participants, research assistants, interviewers, and others involved in the study. [Extracted from the article]

Background and purpose: Levodopa‐induced dyskinesia (LID) is a common motor complication in patients with Parkinson's disease (PD). Although amantadine is indicated for LID treatment, it is uncertain whether early treatment with amantadine reduces the risk of LID in patients with PD. We aimed to evaluate the association between amantadine treatment and LID onset in patients with early‐stage PD. Methods: This was a hospital‐based retrospective cohort study that used electronic medical records from January 1, 2009 to October 31, 2016. The effect of amantadine on LID onset was compared with those of anticholinergics and monoamine oxidase type B inhibitors in patients with PD. Propensity‐score weighting and landmark analysis were used to reduce potential confounding. The time to LID onset was analyzed using Cox models. Sensitivity analyses were performed to determine the robustness of the results. Results: The analyses included 807, 661, and 518 patients at 6‐, 12‐, and 18‐month landmark points, respectively. Amantadine use was associated with delayed LID onset in the 6‐ and 12‐month landmark analyses, with adjusted hazard ratios of 0.65 (95% confidence interval [CI] = 0.49–0.86) and 0.64 (95% CI = 0.47–0.88), respectively. Sensitivity analysis findings were comparable to those of the main analysis. Conclusions: Early treatment with amantadine may delay LID onset more than treatment with other symptomatic agents. Further studies are needed to elucidate the mechanism of amantadine in LID onset delay and to validate our findings. [ABSTRACT FROM AUTHOR]

We compared the effectiveness and safety outcomes of non-vitamin K antagonist oral anticoagulants (NOACs) and warfarin in patients with AF and VHD, as these patients have been partially excluded from clinical trials. This retrospective cohort study was conducted using the National Health Insurance Research Database in Taiwan. Patients with AF and VHD and above 20 years of age, who were prescribed oral anticoagulants such as warfarin, dabigatran, rivaroxaban, and apixaban, were included. Propensity score matching was performed to balance intergroup differences. The Cox proportional hazards model was used to compare the effectiveness and safety of warfarin and NOACs. We included 5833 NOAC-warfarin pairs, 3001 dabigatran-warfarin pairs and 2595 rivaroxaban-warfarin pairs. Warfarin and NOACs had similar risk of ischemic stroke (hazard ratio [HR], 0.92; 95% confidence interval [CI], 0.79–1.06; p =.25) and bleeding events (HR, 0.90; 95% CI, 0.78–1.02; p =.10). NOACs showed reduced risk of venous thromboembolism, intracranial hemorrhage, and mortality (HR and 95% CI, 0.39 [0.20–0.77], p =.01; 0.62 [0.45–0.84], p <.01; and 0.47 [0.41–0.53], p <.01, respectively). The benefit of NOACs in reducing the risk of venous thromboembolism was mainly driven by dabigatran, and the benefit of reducing the risk of intracranial hemorrhage and mortality was observed in both dabigatran and rivaroxaban users. NOACs had a comparable risk of ischemic stroke and bleeding in patients with AF and VHD, and reduced the risk of venous thromboembolism, intracranial hemorrhage, and mortality, compared to warfarin. Therefore, NOAC is an effective and safe alternative to warfarin in these patients. [ABSTRACT FROM AUTHOR]

Organic small molecular materials with coplanar π-conjugated system as HTMs in perovskite solar cells (PSCs) have attracted considerable attention due to their high charge transport capability and thermal stability. Herein, three novel pentafulvalene-fused derivatives with or without fluorine atoms incorporated (YSH-oF and YSH-mF and YSH-H, respectively) are designed, synthesized, and applied as hole-transporting materials (HTMs) in PSCs fabrication. The fluorinated HTMs, YSH-oF and YSH-mF, exhibited higher hole mobility and better charge extraction at the perovskite/HTM interface than non-fluorinated one do, presumably due to the closer intermolecular π-π packing interactions. As a result, small-area (0.09 cm2) PSCs made with YSH-oF and YSH-mF achieved an impressive power conversion efficiency (PCE) of 23.59% and 22.76% respectively, with negligible hysteresis, in contrast with the 20.57% for the YSH-H-based devices. Furthermore, for large-area (1.00 cm2) devices, the PSCs employing YSH-oF exhibited a PCE of 21.92%. Moreover, excellent long-term device stability is demonstrated for PSCs with F-substituted HTMs (YSH-oF and YSH-mF), presumably due to the higher hydrophobicity. This study shows the great potential of fluorinated pentafulvalene-fused materials as low-cost HTM for efficient and stable PSCs. [ABSTRACT FROM AUTHOR]

Background and Aims: This study aimed to update the epidemiology, clinical, and economic outcomes of patients diagnosed with chronic hepatitis B (CHB) infection in Taiwan. Methods: This is a retrospective observational study using claims data from the National Health Insurance Research Database. Cases were identified between 2010 and 2019 using CHB diagnosis codes and claims for alanine aminotransferase laboratory tests or CHB treatment within one year of the first CHB diagnosis. Patient characteristics, epidemiology, clinical, and economic outcomes were described. Results: A total of 730 154 CHB‐diagnosed cases were identified. The prevalence of diagnosed CHB increased from 1.13% in 2010 to 2.43% in 2019, with the highest occurring among those aged 55–64 years (4.76%) and 45–54 years (4.37%) and being higher in men (2.98%) than in women (2.21%). The majority of newly diagnosed CHB patients were 35 years of age or older (86.6%), with a median age of 49 years. After a median follow‐up period of 6.42 years, 12.5%, 7.9%, 2.8%, and 0.35% were diagnosed with cirrhosis, decompensated cirrhosis, hepatocellular carcinoma, and liver transplantation respectively. Among 456 706 incident CHB‐diagnosed patients, 17.4% had received at least one CHB medication, with the majority taking entecavir (67.9%). Patients with increasing disease severity had higher healthcare resource utilization, and inpatient costs accounted for 48.9%–65.5% of the overall medical cost in different health states. Conclusion: Despite the decreasing incidence of newly diagnosed CHB, the prevalence of diagnosed CHB remains high and poses a significant healthcare challenge owing to the high economic burden associated with the complications of CHB. [ABSTRACT FROM AUTHOR]

Objectives: To date, a value set for the EQ-5D-5L based on the health state preferences of the general Taiwanese population has not been available. This study aimed to develop a Taiwanese value set for EQ-5D-5L to facilitate health technology assessment for medical products and services. Methods: An international standardized protocol for EQ-5D-5L valuation studies developed by the EuroQol group was adopted. Adult members of the general public were recruited from six geographic regions in Taiwan. In computer-based face-to-face interviews, each participant completed 10 composite time trade-off (C-TTO) tasks and 7 discrete choice experiment (DCE) tasks. The C-TTO and DCE data were modeled alone or in combination (using hybrid models) with additive models containing 20 dummy variables as main effects. The model performance was assessed both quantitatively and qualitatively (mainly logical consistency and prediction patterns). Results: Of 1,073 recruited participants, 1,000 completed the study. Approximately 13% of observed utility values were -1 in the C-TTO tasks. The hybrid model, using all available data that assumed C-TTO response values left-censored at -1 and with main effects coefficients with logical consistency (monotonicity), was considered as the most appropriate model. The predicted utility ranged from -1.0259 to 1. Conclusions: An EQ-5D-5L value set was developed for Taiwan using an established study protocol and a representative sample of the general population. This may facilitate health economic evaluations and decision making on resource allocation under Taiwan’s national health insurance program in the future. [ABSTRACT FROM AUTHOR]

Aims: To examine the association between statin use before and after intracranial haemorrhage (ICH) and the risk of poststroke epilepsy (PSE). Methods: Patients with new‐onset ICH between 2004 and 2012 were identified from the Taiwan National Health Insurance Research Database. The main outcome was the occurrence of epilepsy after stroke. Multivariable Cox regression modelling was used to estimate the association between statin use and the risk of PSE, with poststroke medication exposures being treated as time‐dependent variables. Results: A total of 7435 patients with ICH were enrolled with a median follow‐up of 17.6 months. Within the study cohort, 709 patients developed PSE. Poststroke, but not prestroke, stain use was associated with a reduced risk of PSE (adjusted hazard ratio 0.62, 95% confidence interval 0.42–0.90, P = 0.01). In subanalyses, a trend of a dose–response relationship was observed. A significant PSE risk reduction was correlated with a higher cumulative statin dose. Moreover, the risk of PSE was lower in patients receiving moderate‐to‐high‐intensity statin therapy (adjusted hazard ratio 0.37, 95% confidence interval 0.18–0.75, P = 0.01). Lipophilic and hydrophilic statins were similar with regard to their associations with the reduced risk of PSE. Conclusions: Statin therapy may reduce the risk of PSE after ICH, especially with moderate‐to‐high therapy intensity. Further research is needed to understand the mechanisms underlying the potential protective effects of statins against PSE in this patient population. [ABSTRACT FROM AUTHOR]

Aims: It remains inconclusive whether the use of nonsteroidal anti‐inflammatory drugs (NSAIDs) increases the risk of atrial fibrillation (AF), especially in middle‐aged Asian populations. In this study, we evaluated the association between NSAID use and the risk of AF in a nationwide population‐based study of middle‐aged individuals in Taiwan. Methods: A nested case–control study was conducted using the National Health Insurance Research Database (NHIRD) in Taiwan. We identified the cases with a diagnosis of AF (ICD‐9‐CM codes: 427.31) and the matched controls from three independent Longitudinal Health Insurance Databases (LHIDs) derived from the NHIRD from data collected from 2001 to 2013. Conditional logistic regression models with covariate adjustment were performed to evaluate the association between NSAID use and the risk of AF. Results: A total of 57 058 participants (28 529 AF cases and 28 529 matched controls) were included. Participants with NSAID use had an elevated risk of AF compared to non‐users [adjusted odds ratio (AOR) = 1.18, 95% confidence interval (CI): 1.14–1.23]. When further assessing the effects of different classes of NSAIDs on the risk of AF, the results showed that participants who used non‐selective NSAIDs had a significantly elevated risk of AF (AOR = 1.18, 95% CI: 1.13–1.23), as did participants with a combined use of selective and non‐selective NSAIDs (AOR = 1.30, 95% CI: 1.21–1.39). Conclusions: NSAID use was associated with an increased risk of AF occurrence among the participants included in our study cohort. Closely monitoring the adverse effects of NSAID treatment on the risk of AF will be important, particularly among individuals at high risk. [ABSTRACT FROM AUTHOR]

Background: Researchers have yet to obtain conclusive evidence differentiating among fixed-dose combinations (FDCs) of long-acting muscarinic antagonists (LAMAs) and long-acting beta-agonists (LABAs) for chronic obstructive pulmonary disease (COPD) in terms of real-world clinical outcomes.Research Question: What are the differences between available LAMA/LABA FDCs on the risk of acute exacerbation and cardiovascular events?Study Design and Methods: This retrospective cohort study based on a national insurance claims database included COPD patients aged 40 and older who were newly prescribed glycopyrronium/indacaterol (GLY/IND), umeclidinium/vilanterol (UMEC/VI), or tiotropium/olodaterol (TIO/OLO) FDC between January 1, 2015, and June 30, 2019. Propensity score matching and Cox regression models were used to compare outcomes of acute exacerbation (AE) and cardiovascular events associated with LAMA/LABA FDC treatment.Results: Among the 44,498 patients identified and included, 15,586 received GLY/IND, 20,460 received UMEC/VI, and 8,452 received TIO/OLO. Baseline characteristics were well balanced after 1:1 matching of UMEC/VI and GLY/IND, 2:1 matching of UMEC/VI and TIO/OLO, and 2:1 matching of GLY/IND and TIO/OLO. Risk of severe AE was lower among patients treated with UMEC/VI or GLY/IND than among those who received TIO/OLO (UMEC/VI vs. TIO/OLO: 17.85 vs. 29.32 per 100 person-years; hazard ratio [HR] 0.76, 95% confidence interval [CI] 0.68-0.84; GLY/IND vs. TIO/OLO: 15.54 vs. 25.53 per 100 person-years; HR 0.77, 95% CI 0.67-0.88). In addition, GLY/IND users tended to have a lower risk of cardiovascular events than TIO/OLO users, but the difference dissipated when restricting follow-up to a shorter duration.Interpretation: Our results revealed that the risk of severe AE was lower among COPD patients receiving UMEC/VI or GLY/IND than among those receiving TIO/OLO, while the incidence of cardiovascular events was similar across groups but was slightly lower in GLY/IND users when compared with TIO/OLO users. Further research will be required to confirm these findings. [ABSTRACT FROM AUTHOR]

Objective: This study examined the associations between mortality (all-cause and breast cancer-specific) and different antidiabetic medication use before breast cancer diagnosis. Methods: This study used a longitudinal, retrospective cohort design. Linked Surveillance, Epidemiology and End Results (SEER)-Medicare databases from 2007 to 2013 were used to identify female beneficiaries who had continuous Medicare enrollment, a new breast cancer diagnosis between 2008 and 2013, and exposure to the antidiabetic medication. Different classes of antidiabetic medications from one year before their breast cancer diagnosis were considered as users while all other non-users were excluded. Both all-cause mortality and breast cancer-specific mortality were treated as outcomes. Cox proportional hazards models for all-cause mortality and sub-distribution hazards models for breast cancer-specific mortality were employed to estimate both unadjusted and adjusted hazard ratios and 95% confidence intervals (CI) for risks of survival outcomes, controlling for severity of diabetes and other covariates. Key findings: A total of 1715 women with breast cancer used antidiabetic medications one year before their breast cancer diagnosis. Compared to metformin, women using insulin, sulfonylurea and combination treatments before their breast cancer diagnosis had a higher risk for all-cause mortality (adjusted Hazard Ratio, aHR: 1.64, 95% CI 1.29, 2.07; aHR: 1.35, 95% CI 1.04, 1.75 and aHR: 1.44, 95% CI 1.14, 1.83, respectively). Women with advanced-stage breast cancer and higher levels of diabetes severity were more likely to get all-cause mortality (all P < 0.05). Women with combination treatments had a statistically higher risk of breast cancer-specific mortality (aHR: 1.52, 95% CI 1.05, 2.19) than metformin users. Conclusions: Among women with breast cancer, mortality risk is associated with pre-diagnosis exposure to different types of antidiabetic medications. [ABSTRACT FROM AUTHOR]

Population aging is a global trend, and the elderly have a higher risk of atherosclerotic cardiovascular disease (ASCVD) and related mortality. Statins have been observed to reduce cardiovascular events in patients with ASCVD. However, compared with secondary prevention, the benefits of statins for primary prevention are undetermined among the elderly. This study aimed to evaluate the effectiveness of statins in an elderly population without a history of cardiovascular disease (CVD). The study was carried out using the National Taiwan University Hospital Integrated Medical Database and the National Health Insurance Research Database in Taiwan. Patients aged 65 years and older without a history of CVD were identified between 1 February 2008 and 31 December 2015. New statin users were 1:4 matched to nonusers based on certain variables. The risks of major adverse cardiovascular events (MACEs) and all-cause mortality were estimated using Cox proportional hazards models. Further, we applied marginal structural models to account for time-varying low-density lipoprotein cholesterol (LDL-C) levels. A total of 2761 new statin users and 9503 nonusers were selected after matching; the mean age was 71.8 years, and 63% were women. At a median follow-up of 4.8 years, statin use was associated with reduced risk of MACEs (hazard ratio [HR]: 0.75; 95% confidence interval [CI], 0.52–0.98) and mortality (HR: 0.72, 95% CI: 0.55–0.93) when accounting for time-varying LDL-C. No significant differences in effect were detected between subgroups. Statin use could be beneficial for the primary prevention of CVD in elderly Asians. • Statin therapy could be beneficial for primary prevention of cardiovascular disease in elderly Asians. • Compared with statin non-users, statin users had significantly lower risks of MACE and all-cause mortality. • The assessment was confirmed by marginal structural models to adjust for confounding effect of time-varying LDL-C levels. [ABSTRACT FROM AUTHOR]

Background: The Patient Reported Outcomes Measurement Information System 43-item short form (PROMIS-43) and the five-level EQ-5D (EQ-5D-5L) are recently developed measures of health-related quality of life (HRQL) that have potentially broad application in evaluating treatments and capturing burden of respiratory-related diseases. The aims of this study were: (1) to examine their psychometric properties in patients with chronic obstructive pulmonary disease (COPD), and (2) to identify dimensions of HRQL that differ and do not differ by lung function.Methods: We conducted a multi-center, cross-sectional study ("COPD Outcomes-based Network for Clinical Effectiveness & Research Translation" [CONCERT]). We analyzed patients who met spirometric criteria for COPD, and completed EQ-5D-5L and PROMIS questionnaires. Disease severity was graded based on the Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification. Pulmonary function test, PROMIS-43, EQ-5D (index score and EQ-Visual Analog Scale [EQ-VAS]), six minute walk test (6MWT), and three dyspnea scales (mMRC, Borg, FACIT-Dyspnea) were administered. Validity and reliability of EQ-5D-5L and PROMIS-43 were examined, and differences in HRQL by GOLD grade were assessed.Results: Data from 670 patients with COPD were analyzed (mean age 68.5 years; 58% male). More severe COPD was associated with more problems with mobility, self-care and usual activities (all p-values <0.01) according to EQ-5D-5L. Related domains on EQ-5D-5L, PROMIS and clinical measures were moderately (r = 0.30-0.49) to strongly (r ≥ 0.50) correlated. A statistically significant trend of decreasing HRQL with more severe lung functions was observed for EQ-5D-5L index scores, EQ-VAS scores, and PROMIS physical function and social roles.Conclusions: Results supported the validity of EQ-5D-5L and PROMIS-43 in COPD patients, and indicate that physical function and social activities decrease with level of lung function by GOLD grade, but not pain, mental health, sleep or fatigue as reported by patients. [ABSTRACT FROM AUTHOR]

Abstract: Combination of atom transfer radical and conventional free radical polymerizations has been successfully used to prepare poly(hydroxyethyl methacrylate-b-vinyl pyrrolidone) (PHEMA-b-PVP) copolymers with controlled molecular weight and low polydispersity (<1.4). The thermal behavior and specific interaction of PHEMA-b-PVP diblock copolymers and their corresponding PHEMA/PVP blends were characterized. The result shows that glass transition temperatures of diblock copolymers analysed by differential scanning calorimetry (DSC) are higher than those of the blends. Infrared and solid-state NMR spectroscopic analyses show that hydrogen-bonding interaction of hydroxyl–carbonyl groups of diblock copolymers was also greater than that of the blends. Measurement of the proton spin–lattice relaxation time in the rotating frame, , reveals that all diblock copolymers and blends possess one composition-dependent , indicating that both diblock copolymers and blends are homogeneous, which is consistent with the DSC analysis. [Copyright &y& Elsevier]

Background: We aimed to provide real-world information on survival, health care resource utilization (HCRU), and expenditures related to various first lines of therapy (1LOTs) in newly diagnosed multiple myeloma (NDMM) patients who were transplant ineligible (TI). Patients and methods: From the Taiwan National Health Insurance Database (2008–2016), we identified 1,511 NDMM-TI patients who had received 1LOT since June 2012. We categorized 1LOT regimens into four groups: bortezomib (V)+thalidomide (T), V, T, and non-V/T. Patients' characteristics were collected. The overall survival (OS), event-free survival (EFS), frequencies of HCRU (hospitalization, visiting outpatient and emergency departments), and related expenditures within one year after commencement of the 1LOT were evaluated and compared. Results: The mean age of the included patients was 71.3 (SD 10.7) years, and 40.4% of patients had a CCI score ≥3. Most patients (747; 49.4%) were in the V+T group and, after adjusting for covariates, had a significantly longer OS (median, 22.2 months) and EFS (9.1 months) than those in the T group (12.6 and 4.5 months, respectively) and the non-V/T group (12.2 and 3.2 months, respectively), but they were mostly comparable with patients in the V group (23.8 and 6.6 months, respectively). Compared to those in the V+T group, patients in the T and non-V/T groups had 29% and 39% fewer outpatient visits and 15% and 24% lower total expenditure, respectively. Conclusion: Our real-world data consolidate evidence for the effectiveness of bortezomib-containing regimens as the 1LOT in NDMM-TI patients at the expense of more outpatient visits and higher total costs. [ABSTRACT FROM AUTHOR]

Background: The concurrent use of vancomycin and piperacillin/tazobactam increases the risk of acute kidney injury (AKI) compared with vancomycin use with other anti-pseudomonal β-lactams (OAPBs). Teicoplanin is a glycopeptide antibiotic with lower nephrotoxicity than that of vancomycin. Whether the concomitant use of teicoplanin and piperacillin/tazobactam also increases the risk of AKI remains unknown.Objectives: To evaluate the AKI risk between teicoplanin-piperacillin/tazobactam and teicoplanin-OAPBs.Methods: This was a retrospective, propensity score-matched cohort study. Adult patients receiving teicoplanin-based combination therapy were included. OAPBs included cefepime, cefoperazone/sulbactam, ceftazidime, doripenem, imipenem/cilastatin and meropenem. Propensity score matching was performed to balance demographic and confounding factors. The primary endpoint was AKI during combination therapy.Results: After propensity score matching, 954 patients (teicoplanin-piperacillin/tazobactam: teicoplanin-OAPBs, 1:3 matched, 243 pairs in total) were included for analysis. The mean age was 66.3 years in the matched cohort and 17.1% of patients had shock. Use of nephrotoxic medications (45.7% versus 48.7%) and baseline renal function (78.88 ± 31.26 versus 81.05 ± 31.53 mL/min/1.73 m2) were similar in the two groups. The median teicoplanin dose was 10.7 mg/kg in both groups. The groups did not differ significantly in terms of AKI risk (14.8% versus 14.2%, P = 0.815). However, the time to AKI appeared shorter in the teicoplanin-piperacillin/tazobactam group (4.64 ± 2.33 versus 6.29 ± 4.72 days, P = 0.039).Conclusions: The combination of teicoplanin and piperacillin/tazobactam was not associated with an increased risk of AKI compared with teicoplanin and OAPBs. [ABSTRACT FROM AUTHOR]

In patients with atherosclerotic cardiovascular disease (ASCVD) under statin treatment, the influence of on-treatment level of high-density lipoprotein cholesterol (HDL-C) on cardiovascular (CV) events is controversial. Statin-treated patients were selected from the Taiwanese Secondary Prevention for patients with AtheRosCLErotic disease (T-SPARCLE) Registry, a multicenter, observational study of adult patients with ASCVD in Taiwan. Low HDL-C was defined as < 40 mg/dL for men and < 50 mg/dL for women. The primary outcome was a composite CV events including CV death, myocardial infarction (MI), stroke or cardiac arrest with resuscitation. A total of 3731 patients (mean age 65.6 years, 75.6% men) were included. Patients with on-treatment low HDL-C (44%, mean HDL-C 34.9 ± 6.8 mg/dL) were younger and with more diabetes and higher body weight. The mean follow-up time was 2.7 years. We used restricted cubic spline curves to examine the potential non-linear association between HDL-C and adverse outcomes. Decreased HDL-C levels were associated with a significantly increased risk of CV events in women (< 49 mg/dL in women) but not in men (< 42 mg/dL in men). However, the protective effect of elevated HDL-C levels was more prominent in men than in women. In ASCVD patients with statin therapy, low on-treatment HDL-C was common in Taiwan and associated with an increased risk of CV events in women. Higher HDL-C levels provided more protective effect in men than in women. [ABSTRACT FROM AUTHOR]

Drug lag—delayed approval or reimbursement—is a major barrier to accessing cutting‐edge drugs. Unlike approval lag, reimbursement lag is under‐researched. We investigated the key determinants of reimbursement lag under Taiwan National Health Insurance (NHI), and compared this lag with those in the United Kingdom, Canada, Australia, Japan, and South Korea. Using retrospective data on 190 new NHI‐reimbursed drugs from 2007 to 2014, we studied reimbursement lag in Taiwan vs. other countries, and investigated associated factors using generalized linear models (GLMs). The median reimbursement lags during before ("first‐generation") and after ("second‐generation") NHI drug reimbursement scheme in Taiwan were 378 and 458 days, respectively. The "first‐generation" lag was shorter only than that in South Korea, whereas the "second‐generation" lag only exceeded those of the United Kingdom and Japan. In GLM models, higher drug expenditure and the introduction of the "second‐generation" NHI were two statistically significant parameters associated with reimbursement lag among antineoplastic and immunomodulating agents. For other drug classes, the reimbursement price proposed by pharmaceutical companies and use of price‐volume agreements were two statistically significant parameters associated with longer reimbursement lags. The current reimbursement lag in Taiwan is longer than 1 year, but only longer than those of the United Kingdom and Japan. The determinants differ between drug categories. A specific review process for antineoplastic and immunomodulating drugs may expedite reimbursement. There is a clear need for systematic data collection and analysis to ascertain factors associated with reimbursement lag and thereby inform future policy making. [ABSTRACT FROM AUTHOR]

Background: The differential risk of pneumonia among inhaled corticosteroid (ICS) use in patients with COPD requires more investigation, especially regarding beclomethasone-containing inhalers. The goal of this study was to compare the risk and benefit profile of different ICS/long-acting β2-agonist (LABA) combinations in patients with COPD.Methods: This retrospective cohort study was conducted by using national health insurance claims data from the years 2009 to 2015 in Taiwan and included patients with COPD with new ICS/LABA use. Propensity score matching and Cox regression models were used to estimate the hazard ratios of severe pneumonia and acute exacerbation for different ICS/LABA users.Results: Both budesonide/formoterol (BUD/FOR) dry-powder inhalers and beclomethasone/formoterol (BEC/FOR) metered-dose inhalers, compared with fluticasone propionate/salmeterol (FLU/SAL) delivered via the same device type, were associated with a lower risk of severe pneumonia (BUD/FOR hazard ratio [HR], 0.83 [95% CI, 0.70-0.98]; BEC/FOR HR, 0.69 [95% CI, 0.58-0.81]) and severe acute exacerbation (BUD/FOR HR, 0.88 [95% CI, 0.78-0.99]; BEC/FOR HR, 0.82 [95% CI, 0.72-0.93]). After additionally adjusting for the average daily ICS dose, BUD/FOR dry-powder inhaler users continued to have a significantly decreased risk of severe pneumonia (18%), although BEC/FOR metered-dose inhaler users did not. The results were consistent in most of the prespecified subgroups and across all the sensitivity analyses.Conclusions: This study augments the existing evidence concerning the different safety and effectiveness outcomes of ICS/LABA combinations in patients with COPD, which may be considered when making clinical treatment decisions. [ABSTRACT FROM AUTHOR]

While basal insulin remains the most effective antidiabetic agent and substantially reduces the risk of hypoglycemia, few studies have examined the comparative effect of basal insulin in the real-world setting. This study aimed to assess the outcomes of adding basal insulin compared with thiazolidinediones (TZDs) or dipeptidyl peptidase-4 inhibitors (DPP-4is) as a third antidiabetic agent in patients with type 2 diabetes mellitus (T2DM). A retrospective cohort study involving T2DM was conducted with health administrative data in Taiwan. Patients starting a third antidiabetic agent after receiving a metformin-containing dual combination were identified. The study endpoints included composite major adverse cardiovascular events (MACEs), all-cause mortality, and hypoglycemia. Propensity score matching and Cox modeling were used for analysis. After matching, the basal insulin and TZD groups contained 6,101 and 11,823 patients, respectively, and the basal insulin and DPP-4i groups contained 6,051 and 11,900 patients, respectively. TZDs and DPP-4is were both associated with similar risks of MACEs and hypoglycemia but a lower risk of all-cause mortality than basal insulin (TZDs: HR 0.55, 95% CI 0.38–0.81; DPP-4is: HR 0.56, 95% CI 0.39–0.82). Further studies are needed to elucidate the findings of increased all-cause mortality risk in patients receiving basal insulin, especially those with advanced diabetes. [ABSTRACT FROM AUTHOR]

Objective: Whether a low-density lipoprotein cholesterol (LDL-C) goal is essential in secondary prevention is still being debated. The aim of our study was to investigate whether achieving particular LDL-C level goals is associated with the reduction in the risk of major adverse cardiac events (MACEs) in patients with atherosclerotic cardiovascular diseases (ASCVD) on statin therapy. Methods and results: From January 2010 to August 2014, a total of 4099 patients with ASCVD in the Taiwan Secondary Prevention for patients with AtheRosCLErotic disease (T-SPARCLE) registry were analyzed. The risk of a MACE was lower in patients with LDL-C level under control at < 100 mg/dL by statins than in patients with LDL-C level ≥100 mg/dL whether on statin therapy (hazard ratio [HR] 1.66, 95% confidence interval [CI] 1.04‒2.63, p = 0.03) or not (HR 2.04, 95% CI 1.06‒3.94, p = 0.03). In multivariate Cox model analyses, statin intensity had no significant predictive value, and LDL-C ≥ 100 mg/dL was associated with a slight but not significant trend toward increased risk of MACEs (HR 1.41, 95% CI 0.96‒2.07, p = 0.08). Conclusions: For patients with ASCVD on statin therapy guided by a target-driven strategy, failure to control LDL-C levels to < 100 mg/dL was associated with higher risk of MACEs. Statin intensity alone had no significant impact on the risk of MACEs after multivariate adjustment. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: The incidence of acute deep venous thrombosis as a result of penetrating proximity extremity trauma (PPET) to the thigh has been demonstrated to be 16% in a single report. The purpose of the current study is to demonstrate the incidence and clinical significance of venous injury as a result of proximity trauma to the thigh in a large cohort screened with colour flow duplex (CFD) ultrasound and to identify factors predictive of defining a wound in proximity to a major vascular structure. Patients and methods: A prospective observational study was conducted from January 1st, 2010 to January 1st, 2012 on all patients presenting with penetrating extremity trauma. Data on injury location, mechanism, associated extremity and non-extremity injuries, use and results of CFD, as well as the admitting trauma surgeon were recorded and analysed. Results: 220 thigh wounds with a normal physical examination were identified, of which 167 (75.9%) underwent CFD due to proximity. The incidence of acute venous injury was 4.8% (8/167). 37.5% (3/8) of these injuries resulted in morbidity. Injury mechanism and which attending physician was on call were predictive of a wound being defined as in proximity, whereas an injury with an associated fracture was a negative predictor. Conclusions: Occult venous injuries as a result of PPET occur in 4.8% of patients with thigh wounds in proximity to a major vascular structure. The designation of a wound as being in “proximity” was influenced by injury mechanism, associated fractures, and the judgement of the on-call attending. Colour flow duplex is a valuable tool with the ability to identify not only occult arterial injuries, but also venous injuries with the potential to cause significant morbidity as well. [Copyright &y& Elsevier]

Background: Little is known about the differences in the immunopathogenesis between elderly-onset rheumatoid arthritis (EORA) and younger-onset RA (YORA) and the factors responsible for their clinical characteristics. Objective: It was the aim of this study to investigate proinflammatory cytokines of EORA patients and compare them with those of YORA patients. Methods: Serum levels of interleukin (IL)-1β, IL-6, IL-8, tumor necrosis factor (TNF)-α and interferon (IFN)-γ were determined by cytometric bead array in 86 patients with active EORA, in 76 patients with active YORA and in 30 healthy controls. Disease activity of RA was assessed using the 28-joint disease activity score. Erosion scores were recorded using a modified version of the Sharp method. Levels of anti-cyclic citrullinated peptide antibodies were determined by ELISA, and levels of rheumatoid factor-IgM and C-reactive protein were measured by nephelometry. Results: A higher proportion of men and a higher frequency of acute onset with constitutional symptoms and comorbidities were observed in EORA compared with YORA patients. Increased levels of serum IL-1β, IL-6, TNF-α, IFN-γ and IL-8 were positively correlated with the 28-joint disease activity score, and elevated levels of IL-1β and TNF-α were positively correlated with erosion scores for both groups of RA patients. Significantly higher IL-6 levels and lower TNF-α levels were found in EORA compared with YORA patients. Higher levels of serum IL-6 were found in EORA patients with polymyalgia rheumatica-like symptoms than in those without and were also noted in male patients with EORA compared with female patients. Multivariate analysis showed that high levels of TNF-α were associated with the occurrence of constitutional symptoms, and high levels of IL-1β were associated with the presence of anti-cyclic citrullinated peptide antibodies in EORA patients. [ABSTRACT FROM AUTHOR]

Background: Low HDL-C is a common lipid phenotype in Asia. Although low HDL-C is a risk factor of atherosclerotic cardiovascular disease (ASCVD) in general population, it is controversial whether the on-treatment HDL-C level is still a predicting factor of cardiovascular (CV) events in ASCVD patients (pts) under statin treatment. Methods and Results: A total of 3,731 pts (age 65.6 yrs, 75% men) receiving statins were selected from the Taiwanese Secondary Prevention for patients with AtheRosCLErotic disease (T-SPARCLE) Registry, a multicenter, observational study of adult pts with stable coronary artery disease (CAD), cerebrovascular disease, or peripheral arterial disease in Taiwan. Low HDL-C was defined as < 40 mg/dL for male and < 50 mg/dL for female. The pts with low HDL-C (44%, mean HDL-C 34.9 ± 6.8 mg/dL) during statin treatment were younger and with more female, diabetes, CAD and higher body weight than pts with normal HDL-C. The primary outcome was a composite CV events including CV death, myocardial infarction (MI), stroke or cardiac arrest with resuscitation. The mean follow-up time was 2.7 years. Multivariate Cox proportional hazard analysis showed on-treatment low HDL-C was not an independent risk factor of primary outcome (normal vs. low HDL-C, hazard ratio [HR] 0.82, 95% confidence interval [CI] 0.55-1.20) after adjusting multiple clinical factors. The risk of CV events was recalculated for each quintile of HDL-C. In the univariate model, the CV event rate decreased progressively by 23% from the lowest (< 35 mg/dL) to the highest (> 54 mg/dL) quintile of HDL-C. However, multivariate Cox proportional hazard analysis showed no significant relationships between quintiles of HDL-C levels and the risk of CV events (HDL-C < 35 [HR 1.50, 95% CI 0.82-2.76], 35 to 40.2 [HR 0.99, 95% CI 0.52-1.88], 40.2 to <46 [HR 1.07, 95% CI 0.58-1.99], 46 to < 54 [HR 1.09, 95% CI 0.59-2.01] vs. >54 mg/dL). Conclusions: In Taiwanese pts with ASCVD under statin therapy, low on-treatment HDL-C was not associated with increased risk of CV events. [ABSTRACT FROM AUTHOR]