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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]

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]

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]

Purpose: To evaluate the effect of diagnostic coding system transition on the identification of common conditions recorded in Taiwan's national claims database. Methods: Using the National Health Insurance Research Database, we estimated the 3‐month prevalence of recorded diagnosis of 32 conditions based on the ICD‐9‐CM codes in 2014–2015 and the ICD‐10‐CM codes in 2016–2017. Two algorithms were assessed for ICD‐10‐CM: validated ICD‐10 codes in the literature and codes translated from ICD‐9‐CM using an established mapping algorithm. We used segmented regression analysis on time‐series data to examine changes in the 3‐month prevalence (both level and trend) before and after the ICD‐10‐CM implementation. Results: Significant changes in the level were found in 19 and 11 conditions when using the ICD‐10 codes from the literature and mapping algorithm, respectively. The conditions with inconsistent levels by both of the algorithms were valvular heart disease, peripheral vascular disease, mild liver disease, moderate to severe liver disease, metastatic cancer, rheumatoid arthritis and collagen vascular diseases, coagulopathy, blood loss anemia, deficiency anemia, alcohol abuse, and psychosis. Nine conditions had significant changes in the trend when using the ICD‐10 codes from the literature or mapping algorithm. Conclusions: Less than half of the 32 conditions studied had a smooth transition between the ICD‐9‐CM and ICD‐10‐CM coding systems. Researchers should pay attention to the conditions where the coding definitions result in inconsistent time series estimates. [ABSTRACT FROM AUTHOR]

Purpose Using real‐world data to support regulatory decision has become a global movement. However, a robust platform for active surveillance of medical product safety has not been established in Taiwan. Methods: Following the common data model structure of the U.S. Food and Drug Administration's Sentinel System, we built the Taiwan Sentinel Data Model (TSDM) using the National Health Insurance Research Database with longitudinal claims data from 23 million individuals, linked death and cause of death data from a national registry, and linked electronic health record data from a delivery system. We examined the conversion of the TSDM using the Sentinel Data Quality Review and Characterization Programs in a sample of sex‐ and age‐stratified cohort of 3 million individuals. Results: The TSDM fulfilled the requirements of data quality assurance. Only about 6% of sex and 0.0007% of birth year were missing, and <0.001% of date data had illogical values. Conclusions: The TSDM‐converted database could be a valuable data resource for domestic pharmacovigilance analysis in Taiwan and cross‐country evaluation. [ABSTRACT FROM AUTHOR]

Aims: The objective of this study was to estimate the nationwide annual incidence, healthcare utilization, and mortality among hospitalized heart failure (HF) patients in Taiwan. Methods and results: People aged 20 years or older and having been newly admitted for HF between 2010 and 2015 were identified from Taiwan's National Health Insurance Research Database. For 124 816 patients with incident HF hospitalizations between 2010 and 2012, we further analysed their treatment patterns, healthcare utilizations, and mortality during index hospitalization and within 3 years following discharge from the index hospitalization. The age‐stratified incidences were declined by 10–20% in people aged 55 years or older, but increased by ~4% among people younger than 44 years old between 2010 and 2015. For all incident hospitalized HF patients, the percentages of patients visiting the emergency room, were rehospitalized, and treated with guideline‐directed medical therapy were highest in the first year. Approximately two‐thirds of subsequent hospitalizations were due to non‐HF and non‐cardiovascular causes. The all‐cause mortality rate during index hospitalization was 8.5%, whereas the mortality rates at 30 days, 90 days, 180 days, 1 year, 2 years, and 3 years following discharge were 3.5%, 8.9%, 14.4%, 22.5%, 33.9%, and 42.8%, respectively, for those surviving index HF hospitalization. Non‐cardiovascular disease‐related deaths accounted for nearly 60% of all deaths. Conclusions: Our study reveals that, in contemporary Taiwan, the >10% annual mortality following the first year of hospitalization, 30% deaths occurring outside the hospital, and 60% non‐cardiovascular‐related deaths, along with the decreasing use of guideline‐directed medical therapy, highlight sectors requiring more attention. [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]

This nested case‐control study evaluated the potential interaction between repaglinide and clopidogrel. Cases were defined by inpatient admissions or emergency department visits due to hypoglycemia. Concomitant use of repaglinide and clopidogrel within 3 days before the hypoglycemic event was the exposure of interest. For each case, up to four controls were randomly selected and matched by age, sex, type of glinide used (repaglinide or nateglinide), and time since cohort entry to the index date. Hypoglycemic risk was estimated by conditional logistic regressions. Concomitant use of repaglinide and clopidogrel was associated with an increased risk of hypoglycemia compared with repaglinide alone (adjusted odds ratio: 2.42; 95% confidence interval: 1.75−3.35). No significant associations were found with the two negative control object drug concomitants: nateglinide and clopidogrel and repaglinide and aspirin (without clopidogrel use). Our study suggests drug interaction between clopidogrel and repaglinide is clinically relevant and could increase the risk for hypoglycemia. [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]

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]

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]

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]

Background To investigate the effectiveness and safety of withholding or restarting antithrombotic agents, and different antithrombotic therapies among patients with atrial fibrillation post-intracranial hemorrhage. Methods and Results This is a nationwide retrospective cohort study involving patients with atrial fibrillation receiving antithrombotic therapies who subsequently developed intracranial hemorrhage between January 1, 2011 and December 31, 2017. The risk of ischemic stroke (IS), recurrent intracerebral hemorrhage (ICH), and all-cause mortality were investigated between patients receiving no treatment versus patients reinitiating oral anticoagulants (OACs) or antiplatelet agents, and warfarin versus non-vitamin K antagonist OACs. We applied inverse probability of treatment weighting to balance the baseline characteristics and Cox proportional hazards model to estimate the hazard ratios (HRs) of different outcomes of interest. Compared with no treatment, OACs reduced the risk of IS (HR, 0.61; 0.42-0.89), without increase in the risk of ICH (1.15, 0.66-2.02); antiplatelet agent users showed a similar risk of IS (1.13, 0.81-1.56) and increased risk of ICH (1.81, 1.07-3.04). Use of OACs or antiplatelet agents did not reduce the risk of all-cause mortality (0.85, 0.72-1.01; and 0.88, 0.75-1.03, respectively). Compared with warfarin, non-vitamin K antagonist OAC users showed a similar risk of IS (0.92, 0.50-1.70), non-significantly reduced risk of ICH (0.53, 0.22-1.30), and significantly reduced all-cause mortality (0.60, 0.43-0.84). Conclusions OACs are recommended in patients with atrial fibrillation and intracranial hemorrhage because they reduced the risk of IS with no increase in the risk of subsequent ICH. Non-vitamin K antagonist OACs are recommended over warfarin owing to their survival benefits.