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Integration of non-noble transition metal oxides with graphene is known to construct high-activity electrocatalysts for oxygen evolution reduction (OER). In order to avoid the complexity of traditional synthesis process, a facile electrochemical method is elaborately designed to engineer efficient WO3- x/graphene (photo-)electrocatalyst for OER by a two-electrode electrolysis system, where graphite cathode is exfoliated into graphene and tungsten wire anode evolves into VO-rich WO3- x profiting from formed reductive electrolyte solution. Among as-prepared samples, WO3- x/G-2 shows the best electrocatalytic performance for OER with an overpotential of 320 mV (without iR compensation) at 10 mA/cm2, superior to commercial RuO2 (341 mV). With introduction of light illumination, the activity of WO3- x/G-2 is greatly enhanced and its overpotential decreases to 290 mV, benefiting from additional reaction path produced by photocurrent effect and extra active sites generated by photogenerated carriers (h+). Characterization results indicate that both VO-rich WO3- x and graphene contribute to the efficient OER performance. The activity of WO3- x for OER is decided by the synergistic effect between VO concentration and particle size. The graphene could not only disperse WO3- x nanoparticles, but also improve the holistic conductivity and promote electron transmission. This work supports a novel method for engineering WO3- x/graphene composite for highly efficient (photo-)electrocatalytic performance for OER.

Background/purpose Taiwan Drug-Injury Relief System (TDRS) has been implemented since 1999. More than 60% of the approved applications were associated with severe cutaneous adverse reactions (SCARs). Studies assessing SCARs using real-world evidence are very limited. TDRS offers abundant case information as a source of real-world evidence to investigate the characteristics of SCARs in Taiwan. The purpose of this study is to understand the trends and characteristics of SCARs in Taiwan. Methods Applications from Drug-Injury Relief Database (TDRD) from 1999 to 2016 were retrospectively analyzed. Results A declining trend in SCARs application was noticed after 2012, and 952 applications of SCARs were identified. The most common subtypes of SCARs were SJS/TEN (n = 455/206), DRESS (n = 228), GBFDE (n = 34) and AGEP (n = 18). The most common culprit drugs were allopurinol, carbamazepine, phenytoin, diclofenac and lamotrigine for SJS/TEN; allopurinol, phenytoin, co-trimoxazole, carbamazepine and phenobarbital for DRESS; mefenamic acid for GBFDE; non-steroidal anti-inflammatory drugs (NSAIDs) and beta-lactam antibacterials for AGEP. The proportions of mortality cases were 28.9% for SJS/TEN; 36% for DRESS; 11.8% for GBFDE and 5.6% for AGEP. The mean latent period of SJS/TEN, DRESS, GBFDE and AGEP were 21.8 days, 29.2 days, 3.3 days and 6.7 days, respectively. Conclusions The approved drug-injury relief applications associated with SCARs were mainly SJS, TEN and DRESS. The most common culprit drugs were antiepileptics, antibacterials, antigout agents, and NSAIDs. The latent periods showed some distinct features for different types of SCARs. In light of the high mortality rate, public awareness and vigilance of SCARs are crucial for the patient safety.

Riparian vegetation is crucial for maintaining terrestrial and aquatic biodiversity, but it is threatened by land-use activities. To assess the ecological impacts of riparian vegetation conversion to an oil tea (Camellia oleifera) plantation, we quantified the responses of small mammals in two natural habitats (mature forest and flood-meadow) and in Camellia forests at the community, population, and individual level. We found that the community diversity was similar between Camellia forests and mature forests, but higher than the flood-meadow. Meanwhile, the community composition differed across three habitats, with Camellia forests favoring habitat generalist species. At the population level, Camellia forests and flood-meadow had a similar population density, which were higher than mature forests. At the individual level, Rattus nitidus was less sensitive to this conversion, but the body condition index of Niviventer confucianus was higher in Camellia forests than in mature forests, and Apodemus agrarius in Camellia forests had more ectoparasite load than in the flood-meadow, indicating a species-specific response to the impacts of oil tea plantation. Our study highlights that the occurrence of habitat generalist species and high ectoparasite loads may threaten regional biodiversity and increase the risk of parasite transmission with enlarging the oil tea plantation area within riparian zones.

Miyuki Hsing-Chun Hsieh,1,2,* Hsun-Yin Liang,2,* Chih-Ying Tsai,2 Yu-Ting Tseng,2 Pi-Hui Chao,2 Wei-I Huang,2 Wen-Wen Chen,2 Swu-Jane Lin,3 Edward Chia-Cheng Lai1 1Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 2Taiwan Drug Relief Foundation (TDRF), Taipei, Taiwan; 3Department of Pharmacy Systems, Outcomes & Policy, College of Pharmacy, University of Illinois at Chicago, Chicago, IL, USA*These authors contributed equally to this workCorrespondence: Edward Chia-Cheng Lai, Email edward_lai@mail.ncku.edu.twPurpose: Development and evaluation of a drug-safety signal detection system integrating data-mining tools in longitudinal data is essential. This study aimed to construct a new triage system using longitudinal data for drug-safety signal detection, integrating data-mining tools, and evaluate adaptability of such system.Patients and Methods: Based on relevant guidelines and structural frameworks in Taiwan’s pharmacovigilance system, we constructed a triage system integrating sequence symmetry analysis (SSA) and tree-based scan statistics (TreeScan) as data-mining tools for detecting safety signals. We conducted an exploratory analysis utilizing Taiwan’s National Health Insurance Database and selecting two drug classes (sodium-glucose co-transporter-2 inhibitors (SGLT2i) and non-fluorinated quinolones (NFQ)) as chronic and episodic treatment respectively, as examples to test feasibility of the system.Results: Under the proposed system, either cohort-based or self-controlled mining with SSA and TreeScan was selected, based on whether the screened drug had an appropriate comparator. All detected alerts were further classified as known adverse drug reactions (ADRs), events related to other causes or potential signals from the triage algorithm, building on existing drug labels and clinical judgement. Exploratory analysis revealed greater numbers of signals for NFQ with a relatively low proportion of known ADRs; most were related to indication, patient characteristics or bias. No safety signals were found. By contrast, most SGLT2i signals were known ADRs or events related to patient characteristics. Four were potential signals warranting further investigation.Conclusion: The proposed system facilitated active and systematic screening to detect and classify potential safety signals. Countries with real-world longitudinal data could adopt it to streamline drug-safety surveillance.Keywords: drug safety, signal detection, triage, sequence symmetry analysis, tree-based scan statistics

BACKGROUND Whether hepatitis B virus (HBV) infection can affect the outcomes of drug-induced liver injury (DILI) is controversial. This study aimed to evaluate the characteristics and outcomes of DILI in Taiwan, with an emphasis on the impact of HBV infection. METHODS We prospectively recruited patients with DILI from multiple centers in Taiwan from 2010 to 2018. RESULTS A total of 1,014 patients were enrolled. The leading culprit drug category was antimicrobials (481, 47.4%), followed by non-steroidal anti-inflammatory drugs, anticonvulsants, and statins. Among the antimicrobials, antituberculosis agents were most likely to induce liver injury (257, 25.3%), followed by antibacterial, antifungal and antiviral agents. The liver-related mortality rate was 8.2% (83/1,014). The patients who died had higher rates of hepatocellular-type liver injury, elevated liver biochemical tests, preexisting liver cirrhosis, jaundice, chronic HBV infection and antituberculosis drug-induced liver injury (ATDILI) than the survivors. A total of 131 patients (12.9%) with DILI were HBV carriers, of whom 23 (17.6%) died of hepatic failure. The rate of HBV-DNA > 2000 IU/mL was higher in the patients who died (47.8% vs. 26.9%, p = 0.047) than in the survivors. After adjusting for possible risk factors, active HBV infection with HBV-DNA > 2000 IU/mL was the most significant risk factor for liver-related mortality (adjusted HR: 4.40, 95% CI: 2.31-8.38, p < 0.001). The other independent risk factors for mortality were ATDILI and albumin-bilirubin (ALBI) score (adjusted HR: 1.25 and 4.09, respectively, p < 0.003). CONCLUSION Antituberculosis agents were the leading cause of DILI in Taiwanese, and they were associated with poorer outcomes than other drug categories. Active HBV infection, ATDILI and ALBI score were independent risk factors for fatal DILI. Close monitoring of liver tests and timely anti-viral therapy should be implemented in HBV carriers during the administration of high-risk drugs, such as antituberculosis agents.

This study takes the three dimensions of CSR, namely, economic (G), social (S), and environmental(E) dimensions, and the three indicators of corporate governance performance, stakeholders and environmental information disclosure, to explore the relationship between family business of CSR and brand value and determine whether the CSR performance of companies in electronic and non-electronic industries has significantly positive effect on brand value. According to the empirical results, regardless of industry, a better CSR performance by a family business has stronger effect on brand value than that of non-family business. Regardless of industry, a better CSR in both electronics and non-electronics companies exerts a significantly positive effect on brand value. A strong tie between family business in an non-electronic industry and the stakeholder contributes to a higher brand value of an enterprise; a higher degree of environmental information disclosure of an electronics family business exerts greater influence on brand value than does a non-electronics family business.

Cancers are generally recognized as the leading cause of death and a predominant barrier to prolonging life expectancy in both developed and developing countries. Emodin is a typical anthraquinone derivative from various plants that exhibits a wide spectrum of biological activities, such as anticancer, antibacterial, hepatoprotective and anti-inflammatory activities. Much previous preclinical evidence has demonstrated that emodin exhibits reliable effects on several cancer types, including lung cancer, liver cancer, colon cancer, breast cancer, pancreatic cancer, leukemia, cervical cancer, and ovarian cancer

PURPOSE The magnetic compression technique (MCT) is a new surgical method that has been used for gastrointestinal anastomosis, choledochojejunostomy, and intestinal anastomosis, but there are no reports on its use for esophagogastric anastomosis. This study aimed to investigate the feasibility of using MCT to fashion esophagogastric anastomoses in rabbits. METHODS Twenty rabbits were randomized into an MCT group (study group, n = 10) and a hand-sewn group (control group, n = 10). The magnetic compression anastomosis device used in this study was made of neodymium iron boron (NdFeB) and possessed parent (PMR) and daughter (DMR) magnetic rings. To fashion the anastomosis, the PMR and DMR were inserted into the lower esophagus and gastric fundus, respectively. The coupled magnets automatically compressed the sandwiched tissues and were expelled once the anastomosis was installed. The two groups were further compared in terms of the anastomosis construction time, survival rate, and postoperative complications. One month after the anastomosis was installed, the burst pressure and gross appearance of the anastomoses were evaluated. RESULTS The anastomosis construction time in the study group was significantly shorter than that in the control group (10.50 ± 1.58 min vs. 18.60 ± 2.22 min; P 0.05). Anastomotic leakage was not found in either of the groups, and the anastomoses burst pressures were similar in the two groups. However, the magnetically compressed anastomoses in the study group had a relatively smoother gross appearance than the hand-sewn anastomoses. CONCLUSION The magnetic compression anastomosis device is a safe and feasible tool for fashioning esophagogastric anastomoses in this animal model.

Direct asymmetric functionalization of the inert α C-H bonds of N-unprotected propargylic amines is a big challenge in organic chemistry, due to the low acidity (pK

Patients with autoimmune diseases (AD) are at increased risk of complications, which adversely affect the quality of life and prognosis. Recently, a large amount of literature suggested reduced oxidative stress by hydrogen supplements in reducing inflammation and improving prognosis. In this study, clinical trial NCT05196295, we randomly assigned different dosages (low, medium, and high) of hydrogen-rich coral calcium (HRCC) to patients with autoimmune diseases, including Rheumatoid Arthritis (RA) and Systemic Lupus Erythematosus (SLE) patients in Ming-Sheng Hospital in Taiwan (age 54 years, 80% females). Participants were measured with their baseline health biomarkers including inflammatory indicators, haematologic, urinary biomarkers, and health status prior to the trial. Clinical and follow-up assessments were collected after 1 month of the treatment. We performed analyses to compare the baseline with the changes after the HRCC treatment. Together with the groups treated with different dosages, the treatment demonstrated no adverse effects on participants’ responses to the HRCC. While the primary endpoint of the trial was met, the potential therapeutic effects of HRCC are addressed for future studies. This clinical trial of HRCC in safety response is the first-in-human study.

Phytochemical investigation on the rhizomes of Paris fargesii var. petiolata (Baker ex C. H. Wright) Wang et Tang led to the isolation of five previously undescribed steroidal saponins, parpetiosides A-E (1-5), and six known analogs (6-11). Their structures were established by extensive spectroscopic data analysis and chemical methods. Compound 5 was a rare steroidal saponin with disaccharide moiety linked at C-26 of dehydrokryptogenin that was hardly seen in the genus Paris. The cytotoxicities of the isolated compounds against three human cancer cell lines (U87, HepG2 and SGC-7901) were evaluated, and compound 1 displayed certain inhibitory effect with IC

Two anthracene-based complexes [Ir(pbt)2(aip)]Cl (1) and [Ir(pbt)2(aipm)]Cl (2) have been synthesized based on the ligands aip = 2-(9-anthryl)-1H-imidazo[4,5-f][1,10]phenanthroline, aipm = 2-(9-anthryl)-1-methyl-imidazo[4,5-f][1,10]phenanthroline, and pbtH = 2-phenylbenzothiazole in order to explore both the influence of the substituent group R1 (R1 = H in 1 and CH3 in 2) on photo-oxidation activity and photo-oxidation-induced luminescence. Both 1H NMR spectra and ES mass spectra indicate that the anthracene moiety in complex 1 can be oxidized at room temperature upon irradiation with 365 nm light. Thus, this complex shows photo-oxidation-induced turn-on yellow luminescence. Compared to 1, complex 2 incorporates an R1 = CH3 group, resulting in very weak photo-oxidation activity. On the basis of experimental results and quantum chemical calculation, we report the differences between 1 and 2 in both photo-oxidation behavior and the related luminescence modulation and discuss the relationship between photo-oxidation activity and substituent group R1 in these complexes.

Owing to the strong nucleophilicity of the NH

Jing Hong,1,&ast; Wen-Yue Liu,1,&ast; Xiang Hu,1 Wen-Wen Chen,2 Fei-Fei Jiang,1 Ze-Ru Xu,1 Fei-Xia Shen,1 Hong Zhu1 1Department of Endocrinology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, People’s Republic of China; 2Department of Geriatrics, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hong Zhu, Department of Endocrinology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China, Tel +86 577-55579622, Fax +86 577-55578522, Email zhuhong@wmu.edu.cnPurpose: Free triiodothyronine (FT3) and FT3/free thyroxine (FT4) ratio have been associated with mortality in various diseases. However, no study to date has identified a link between FT3, FT3/FT4 ratio and all-cause mortality in patients with diabetic foot ulcers (DFUs). This study aimed to investigate this relationship.Methods: This retrospective cohort study included 726 patients diagnosed with DFUs in a public hospital from January 2015 to October 2019. Patients were classified by the optimal cut-off values of the FT3 and FT3/FT4 ratio, respectively. The association of FT3 and FT3/FT4 ratio with all-cause mortality was evaluated in a multivariable cox regression model. Directed acyclic graphs were used to assess the minimally sufficient sets of confounding variables.Results: Log rank tests indicated that patients with low FT3 and FT3/FT4 ratio had lower overall survival rates (all p < 0.001). The adjusted HRs for all-cause mortality were 0.48 (95% CI: 0.32– 0.73, P = 0.001) when comparing high versus low FT3 and 0.47 (95% CI: 0.32– 0.70, P < 0.001) when comparing high versus low FT3/FT4 ratio. Subgroup analyses showed that these associations existed only in elderly patients (≥ 65 years) and women, after adjustment. In men, only high FT3/FT4 ratio was associated with low all-cause mortality, after adjustment.Conclusion: Routine assessment of FT3 and FT3/FT4 ratio may be a simple and effective way to identify high-risk patients with DFUs, especially in elderly patients and women.Keywords: FT3, FT3/FT4 ratio, mortality, diabetic foot ulcer

A new type of chiral super Brønsted C-H acids, BINOL-derived phosphoryl bis((trifluoromethyl)sulfonyl) methanes (BPTMs), were developed. As compared to widely utilized BINOL-derived chiral phosphoric acids (BPAs) and

Purpose Real-world evidence has become increasingly relevant in regulatory decision making. Compared to large regulatory bodies, the national pharmacovigilance system in Taiwan is still under development, and the aim of this study is to demonstrate how a resource-limited health authority utilizes real-world evidence in decision making. Methods We described different sources of real-world data available in Taiwan and illustrated the structural framework that integrates real-world evidence into Taiwan's national pharmacovigilance system. Additionally, we reviewed real-world studies conducted in the past 10 years and provided examples to show how these studies influenced drug safety-related decision making in Taiwan. Results During the past 10 years, real-world evidence used when making drug safety-related regulatory decisions in Taiwan was mainly generated from nationwide claims databases, but other sources of real-world data, such as national registries and large electronic hospital databases, also became available recently. Different types of real-world evidence, including drug utilization studies, risk evaluation studies, and risk minimization measure evaluation studies, have been used to support regulatory decisions in Taiwan. Conclusions Through collaborations between the government and academics, Taiwan has started to integrate real-world evidence into the national pharmacovigilance system. However, future efforts, including linkages between different sources of real-world data and improvements in procedural and methodological practices, are needed to generate more regulatory-quality real-world evidence.

2-Azaallyl anions are valuable intermediates which have versatile applications in functionalization with various electrophiles. Decarboxylation of the imines formed from aromatic aldehydes and α,α-diphenylglycine provides an interesting and efficient way to generate delocalized 2-azaallyl anions, which display high reactivity toward different electrophiles with excellent regioselectivity at the diphenylketimino aryl carbon of the 2-azaallyl anions. The transformation produces various amines in good yields under very mild conditions. This Synpacts article highlights the recent advances on the decarboxylative umpolung synthesis of amines from carbonyl compounds.1 Introduction2 Decarboxylative Umpolung Reactions of Carbonyl Compounds with Different Electrophiles2.1 Reaction with π-Allyl–Pd(II) Species2.2 Reaction with Morita–Baylis–Hillman Adducts2.3 Reaction with Imines2.3.1 Intermolecular Reaction with N-Ts Imines2.3.2 Intramolecular Reaction with Chiral N-tert-Butanesulfinyl Imines2.4 Reaction with Aldehydes and Ketones3 Decarboxylative Umpolung Reaction of α,β-Unsaturated Aldehydes with Aldehydes4 Conclusion

An enantioselective asymmetric annulation of 2-formylboronic acids with internal alkynes has been realized using a chiral phosphinooxazoline/palladium(II) catalyst. The reaction tolerates a variety of alkynes including the relatively inert diaryl substituted internal ones. A wide range of optically active 2,3-disubstituted indenols was afforded in high yields with good to excellent enantioselectivities (up to 99% yield and 99% ee).

To investigate associations between isoniazid for latent tuberculosis and risk of severe hepatitis, affecting patients with rheumatoid arthritis or ankylosing spondylitis whose treatment includes tumor necrosis factor inhibitors. Our self-controlled case series study analyzed Taiwan's National Health Insurance Database from 2003 to 2015 to identify RA or AS patients, aged ≥ 20 years, receiving TNF inhibitors and a 9-month single isoniazid treatment. The outcome of interest was hospitalization due to severe hepatitis. We defined risk periods by isoniazid exposure (days): 1-28, 29-56, 57-84, 85-168, 169-252, and 253-280. To compare risk of severe hepatitis in exposed and non-exposed periods, we performed conditional Poisson regressions to generate incidence rate ratios (IRR) and 95% confidence intervals, with adjustment of patients' baseline covariates including age, sex, HBV, HCV and related medication. Of 54,267 RA patients and 137,889 AS patients identified between 2000 and 2015, 11,221 (20.7%) RA and 4,208 (3.1%) AS patients underwent TNFi therapy, with 722 (5%) receiving isoniazid for latent tuberculosis. We identified 31 incident cases (4.3%) of hospitalization due to severe hepatitis. Of these hospitalization events, 5 occurred in the exposed periods, 25 occurred in the INH unexposed periods, and 1 occurred in the pre-exposure period. Compared with non-exposure, the risk of severe hepatitis was higher in exposed periods (incidence rate ratio [IRR]: 5.1, 95% CI: 1.57-16.55), especially 57-84 days (IRR: 17.29, 95% CI: 3.11-96.25) and 85-168 days (IRR:10.55, 95% CI: 1.90-58.51). The INH related fatal hepatotoxicity was not identified in our study. Our findings suggest an association between risk of severe hepatitis and exposure to isoniazid in patients with RA or AS under TNFi therapy, particularly within the exposed period 57-168 days. A close monitoring of liver function is mandatory to minimize the risk, especially within the first 6 months after initiation of 9 months isoniazid.

To investigate associations between isoniazid for latent tuberculosis and risk of severe hepatitis, affecting patients with rheumatoid arthritis or ankylosing spondylitis whose treatment includes tumor necrosis factor inhibitors. Our self-controlled case series study analyzed Taiwan’s National Health Insurance Database from 2003 to 2015 to identify RA or AS patients, aged ≥ 20 years, receiving TNF inhibitors and a 9-month single isoniazid treatment. The outcome of interest was hospitalization due to severe hepatitis. We defined risk periods by isoniazid exposure (days): 1–28, 29–56, 57–84, 85–168, 169–252, and 253–280. To compare risk of severe hepatitis in exposed and non-exposed periods, we performed conditional Poisson regressions to generate incidence rate ratios (IRR) and 95% confidence intervals, with adjustment of patients’ baseline covariates including age, sex, HBV, HCV and related medication. Of 54,267 RA patients and 137,889 AS patients identified between 2000 and 2015, 11,221 (20.7%) RA and 4,208 (3.1%) AS patients underwent TNFi therapy, with 722 (5%) receiving isoniazid for latent tuberculosis. We identified 31 incident cases (4.3%) of hospitalization due to severe hepatitis. Of these hospitalization events, 5 occurred in the exposed periods, 25 occurred in the INH unexposed periods, and 1 occurred in the pre-exposure period. Compared with non-exposure, the risk of severe hepatitis was higher in exposed periods (incidence rate ratio [IRR]: 5.1, 95% CI: 1.57–16.55), especially 57–84 days (IRR: 17.29, 95% CI: 3.11–96.25) and 85–168 days (IRR:10.55, 95% CI: 1.90–58.51). The INH related fatal hepatotoxicity was not identified in our study. Our findings suggest an association between risk of severe hepatitis and exposure to isoniazid in patients with RA or AS under TNFi therapy, particularly within the exposed period 57–168 days. A close monitoring of liver function is mandatory to minimize the risk, especially within the first 6 months after initiation of 9 months isoniazid.

The magnetic compression technique (MCT) is a new surgical method that has been used for gastrointestinal anastomosis, choledochojejunostomy, and intestinal anastomosis, but there are no reports on its use for esophagogastric anastomosis. This study aimed to investigate the feasibility of using MCT to fashion esophagogastric anastomoses in rabbits.Twenty rabbits were randomized into an MCT group (study group, n = 10) and a hand-sewn group (control group, n = 10). The magnetic compression anastomosis device used in this study was made of neodymium iron boron (NdFeB) and possessed parent (PMR) and daughter (DMR) magnetic rings. To fashion the anastomosis, the PMR and DMR were inserted into the lower esophagus and gastric fundus, respectively. The coupled magnets automatically compressed the sandwiched tissues and were expelled once the anastomosis was installed. The two groups were further compared in terms of the anastomosis construction time, survival rate, and postoperative complications. One month after the anastomosis was installed, the burst pressure and gross appearance of the anastomoses were evaluated.The anastomosis construction time in the study group was significantly shorter than that in the control group (10.50 ± 1.58 min vs. 18.60 ± 2.22 min; P 0.05), and the magnetic rings were defecated out in 10.70 ± 3.49 days. The incidence of anastomotic blockage in both the study and control groups did not differ significantly (0%, 0/10 vs. 20%, 2/10; P 0.05). Anastomotic leakage was not found in either of the groups, and the anastomoses burst pressures were similar in the two groups. However, the magnetically compressed anastomoses in the study group had a relatively smoother gross appearance than the hand-sewn anastomoses.The magnetic compression anastomosis device is a safe and feasible tool for fashioning esophagogastric anastomoses in this animal model.

ObjectivesTo establish a training programme to cultivate trainee mediation skills through time investment, skill incorporation and formation of in-house mediation services.DesignA four-round consensus conference was conducted by a number of seasoned experts selected in the manner of purposive sampling to determine core competences and relevant curricula through the modified Delphi process.SettingResponses collected from enrolled experts through four rounds of the Delphi process from 11 November 2018 to 17 May 2019.ParticipantsOnboard seasoned mediators with different specialties.Outcome measuresItems with a median rating of 4 or more on a Likert scale of 1–7 points and 70% or more in agreement were identified as core competence and curricula.ResultsEleven enrolled experts reached the consensus about the training syllabus based on the 4-round agreement with four pillars of core competence, including ‘knowledge base of law’, ‘internalisation of the denotative and connotative meanings of care’, ‘effective, smooth and timely communication’ and ‘conflict resolution’. To grasp the dynamics and diversity of medical disputes on target, it is necessary to have sufficient knowledge and skills. We arrange our course in the order of teaching materials with pure didactics in the former two and with mixed contents comprising lectures and field exercises in the rest two.ConclusionsThe sample developed a syllabus to train apprentices to take intermediate responses to medical disputes through the skills of conflict resolution and establishment of effective communication to improve the relationship between patients/relatives and medical staff, as a result of eventually reducing the conversion rate from dispute into litigation or alternative pathway. Policy-makers in healthcare and top management in healthcare institutions can use this syllabus to guide their future education and training programme.

The drug-injury relief system in Taiwan was implemented 20 years ago with the goal of providing timely relief for drug injuries incurred by the proper use of legal drugs. This system utilizes a nonlitigation expert review process to evaluate drug-injury relief applications, and 2,732 applications have been reviewed from 1999-2016. Of these, 1,572 applications received relief payments, an approval rate of 58%. Average review timeframes per application have decreased from 248 days (2003-2011) to 182 days (2012-2016). Most adverse drug reactions (ADRs) for approved cases involved skin and subcutaneous tissue disorders (67%), with allopurinol being the primary culprit drug. A recent decline observed for such ADRs may reflect the influences of promotional activities and policy initiatives carried out according to informed analysis from drug-injury relief applications, which suggests that the drug-injury relief system can also play an important public health role in enhancing drug safety.

A microwave-assisted base-free intramolecular cross dehydrogenative coupling (CDC) of 3-aniline substituted coumarins and quinolinones have been developed. A broad range of indolo[2,3-c]coumarins and indolo[2,3-c]quinolinones can be easily afforded in good to high yields (up to 93%) under palladium catalysis. The method is among the most straightforward and convenient ways to access these fused polyheterocycles.

Two iridium(III) complexes [Ir(dfppy)2(pybbiH2)]PF6 ( 1 • PF 6 ) and [Ir(dfppy)2(pybbiH)] ( 2 ) have been synthesized, in which each pybbiH2/pybbiH− ligand contains two benzoimidazole units. At room temperature, 1 • PF 6 in CH2Cl2 reveals an emission at 537 nm. Complex 2 is non-luminescent in CH2Cl2, but shows aggregation-induced emission enhancement (AIEE) at 524 nm in CH3CN-H2O mixture. In solid state, strong emissions were observed for 1 • PF 6 (520 and 541 nm), while weak emission at 534 nm for 2 . Additionally, complexes 1 • PF 6 and 2 in CH2Cl2 reveal NEt3/TFA-induced luminescence switching between on state and off state.

Background/purpose: Previous studies have reported that the indication and starting dose of allopurinol may be associated with the incidence of hypersensitive reactions. As allopurinol-related severe cutaneous adverse reactions (SCARs) constitute a significant proportion of drug injury relief applications in Taiwan, this study sought to examine allopurinol use and related adverse reactions through an analysis of recent drug injury relief applications. Methods: Allopurinol-related drug injury relief applications from 1999 to 2016 were collected, and descriptive statistical methods were used to analyze recent applications dating from 2011 to 2016. Results: A total of 174 allopurinol-related drug injury relief applications were submitted between 2011 and 2016, with the majority involving cases over the age of 65 (75.3%; mean age of all cases was 69.2). Most allopurinol-related drug injuries concerned the skin (173 out of 174 cases, 99.4%). The majority of cases had other co-morbidities such as cardiovascular disease/hypertension (86.2%), chronic kidney disease (58.6%), or diabetes (46.6%). Over 70% of cases initiated allopurinol at a dose of 100 mg/day or less. Analysis revealed that the greatest number of cases (44.6%) occurred in those with an estimated glomerular filtration rate (eGFR) between 15 and 60 mL/min/1.73 m2 and who initiated allopurinol at a dose of 100 mg/day. Conclusion: Old age and renal dysfunction are key risk factors for allopurinol hypersensitivity. When considering allopurinol for elderly patients with impaired kidney function, a full risk-benefit assessment, dosage adjustments, and careful monitoring may be warranted. Keywords: Allopurinol, Compensation and redress, Drug-induced Stevens-Johnson syndrome, Taiwan, Toxic epidermal necrolysis

Objective Liver is uniquely vulnerable during sepsis. MicroRNA-155 (miR-155) is confirmed to play crucial roles in septic liver injury. The present study aims to investigate the mechanisms of miR-155 in septic liver injury. Methods The sepsis model was established by intraperitoneal injection of lipopolysaccharide (LPS) in mice. Mice were divided into four groups: Vehicle, miR-155 antagomir, LPS, LPS+ miR-155 antagomir. The survival rate and body weight were monitored. Liver injury was assessed by H&E staining. The levels of serum ALT and inflammatory cytokines were determined by ELISA kits. Oxidative stress was detected by MDA and SOD detection kits. The miR-155, Nrf-2, and markers related to oxidative stress, endoplasmic reticulum (ER) stress, mitochondrial injury and apoptosis were detected by western blotting and qPCR. Apoptosis in liver tissues was detected by TUNELstaining. Results MiR-155 antagomir alleviated liver injury as evidenced by enhancing survival rate and body weight, inhibiting inflammatory cell infiltration, liver cells necrosis and decreasing ALT level. The productions of TNF-α, IL-6 were suppressed, while anti-inflammatory cytokine IL-10 was promoted by miR-155 antagomir. Oxidative stress was inhibited by miR-155 antagomir via enhancing nuclear factor, erythroid 2-like 2 (Nrf-2) expression. ER stress and Cytochrome C (Cyto-C) release were restrained by miR-155 antagomir. Sepsis-induced apoptosis was repressed by miR-155 antagomir as manifested by the decreased levels of Bax, cleaved caspase-12, 9 and 3, and increased levels of Bcl-2 and uncleaved PARP. Conclusion MiR-155 antagomir relieved septic liver injury through inhibiting oxidative stress-mediated ER stress, mitochondrial dysfunction and apoptosis via targeting Nrf-2, suggesting miR-155 as a therapeutic target for septic liver injury.

Objective After discovering the association between the HLA-B*15:02 allele and carbamazepine-related severe cutaneous adverse reactions (SCARs), particularly in Southeastern Asian populations, clinical strategies to prevent carbamazepine-related SCARs have changed. We aimed to investigate 10-year trends in carbamazepine use and carbamazepine-related SCARs and to examine the patterns and determinants of HLA-B*15:02 screening in Taiwan. Methods A nationwide study was performed using Taiwan's National Health Insurance Research Database. In the first part of the study, new users of carbamazepine were included, and those who experienced SCAR-related admissions were further identified. In the second part of the study, recipients of HLA-B*15:02 screening (reimbursed by Taiwan's National Health Insurance since June 2010) were included and multivariate logistic regression was used to explore factors associated with the use of screening. Results The numbers of new users of carbamazepine and SCAR cases decreased remarkably during the 10-year period (-82.6% and -87.1%, respectively), and the incidence rates of SCARs showed a downward trend after 2011. The screening rate of the HLA-B*15:02 allele increased to 24.9% in 2014. Neurologists (odds ratio 12.33, 95% confidence interval 9.30-16.35), psychiatrists (9.97, 7.31-13.61), and neurosurgeons (3.23, 2.42-4.32) were more likely to perform screening tests than other specialties were. Physicians practicing in medical centers (6.00, 5.51-6.54) were more likely to perform screening tests than those practicing in other hospitals, whereas the screening rates in clinics remained at 0.0% throughout the study period. Significance In recent years, the number of carbamazepine-related SCAR cases has decreased substantially in Taiwan. However, only one-fourth of new users of carbamazepine received HLA-B*15:02 screening, and there were considerable disparities in the screening rates across different physician groups. Policymakers should consider solutions to barriers to implementing screening tests in clinical practice and should not neglect the value of other safety communications and regulations to complement the limitations of pharmacogenomic testing.