Search

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.

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.

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.

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.

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 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.

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.

Using a 10,709 firm-year sample covering the 1998–2007 period, we investigate the determinants of capital structure among 1,491 ASEAN-4 (Indonesia, Malaysia, the Philippines, and Thailand) emerging market firms. Building on the work of previous authors, we apply the two-step generalized method of moments (Arellano & Bond, 1991) to develop country-specific dynamic models of target leverage decisions. The right-hand variables incorporate a lagged leverage term that controls for the firms' target adjustment process and the following four explanatory variables: firm size, profitability, tangibility, and nondebt tax shields. The sign and significance of each coefficient provides evidence regarding whether the impact of the associated variable is consistent with the trade-off or pecking order theories. We find that size is negatively associated with leverage among Malaysian, Philippine, and Thai firms but positively associated among Indonesian firms. Profitability is negatively associated with leverage among Indonesian and Malaysian firms but positively associated among Philippine firms. Tangibility is negatively associated with leverage among Malaysian firms but positively associated among Philippine firms. While the impacts of size and profitability are consistent with pecking order theory, the impact of tangibility is not supportive of a specific theory. Of the four variables, size is consistently influential, while nondebt tax shields have no significant impact among firms in any country.

Relatively little attention has been paid to ADP-ribosylated modifications of histones, especially to mono-ADP-ribosylation. As an increasing number of mono-ADP-ribosyltransferases have been identified in recent studies, the functions of mono-ADP-ribosylated proteins have aroused research interest. In particular, histones are substrates of some mono-ADP-ribosyltransferases and mono-ADP-ribosylated histone have been detected in physiological or pathological processes. In this research, arginine-117 (Arg-117; R-117) of hsitone3(H3) is identified as the a site of mono-ADP-ribosylation in colon carcinoma(the first such site to be identified); this posttranslational modification may promote the proliferation of colon carcinoma cells in vitro and in vivo. Using a point-mutant lentivirus transfection and using an activator of P300 allowed us to observe the mono-ADP-ribosylation at H3R117 and enhancement of the activity of P300 to up-regulate the level of acetylated β-catenin, which could increase the expression of c-myc and cyclin D1.

This study aimed to observe differences in the efficacy of laser and surgical treatments of middle-ear conductive hearing loss (MECHL).A total of 276 ears of 267 patients with MECHL were divided into laser (n=172) and surgical (n=104) treatment groups according to the treatment method. Changes in the air-bone gap (ABG) after treatment and at the time of final follow-up were compared. An ABG value20 dB was defined as effective and an ABG value10 dB, significantly effective. The long-term treatment effects were also compared at the time of final follow-up. Additionally, postoperative adverse reactions were recorded for both the groups.The mean follow-up period was 76.77±43.62 months (range: 12-168 months). No significant difference in ABG was found between the two groups (21.31±11.64 dB vs. 19.14±9.79 dB, p0.05). However, the laser treatment group showed slightly better results than the surgical treatment group at the final follow-up, although the difference between the groups was not found to be significant (11.69±9.98 dB vs. 12.62±10.94 dB, p0.05). There was no difference in the long-term treatment effects between the two groups (effective: 87.21% vs. 88.46%, p0.05; significantly effective: 55.81% vs. 56.73%, p0.05). The incidence rates of postoperative adverse reactions were not significantly different.The treatment efficacy of laser and surgical treatments for MECHL are similar.

Safety concerns regarding potential life-threatening adverse events associated with codeine have resulted in policy decisions to restrict its use in pediatrics. However, whether these drug safety communications have had an immediate and strong impact on codeine use remains in question. We aimed to investigate the impact of the two implemented safety-related regulations (label changes and reimbursement regulations) on the use of codeine for upper respiratory infection (URI) or cough. A quasi-experimental study was performed using Taiwan’s National Health Insurance Research Database. Quarterly data of codeine prescription rates for URI/cough visits were reported, and an interrupted time series design was used to assess the impact of the safety regulations on the uses of codeine among children with URI/cough visits. Multivariable logistic regression models were used to explore patient and provider characteristics associated with the use of codeine. The safety-related regulations were associated with a significant reduction in codeine prescription rates of −4.24% (95% confidence interval [CI] −4.78 to −3.70), and the relative reduction compared with predicted rates based on preregulation projections was 60.4, 56.6, and 53.2% in the first, second, and third year after the regulations began, respectively. In the postregulation period, physicians specializing in otolaryngology (odds ratio [OR] 1.47, 95% CI 1.45–1.49), practicing in district hospitals (OR 6.84, 95% CI 5.82–8.04) or clinics (OR 6.50, 95% CI 5.54–7.62), and practicing in the least urbanized areas (OR 1.60, 95% CI 1.55–1.64) were more likely to prescribe codeine to children than their counterparts. Our study provides a successful example of how to effectively reduce the codeine prescriptions in children in the ‘real-world’ settings, and highlights areas where future effort could be made to improve the safety use of codeine. Future research is warranted to explore whether there was a simultaneous decrease in the incidence rates of codeine-related adverse events following the safety-related regulations.

The coronavirus disease 2019 (COVID-19) has already become a pandemic wherein the infection’s timely diagnosis has proven beneficial to patient treatment and disease control. Nucleic acid detection has been the primary laboratory diagnostic method for the detection of SARS-CoV-2. To ensure laboratory staff safety and quality nucleic acid testing, the Chinese Society of Laboratory Medicine formulated this consensus, based on the Chinese National Recommendations and previous literature for nucleic acid detection. A working group comprises 34 hospital professionals experience with real-time polymerase chain reactions (PCR) testing for SARS-CoV-2 drafted guidance statements during online discussions. A modified Delphi methodology was used in forming a consensus among a wider group of hospital professionals with SARS-CoV-2 detection experience. Guidance statements were developed for four categories: (I) specimen type, priority, collecting, transportation and receiving; (II) nucleic acid isolation and amplification; (III) quality control; (IV) biosafety management and decontamination. The modified Delphi voting process included a total of 29 guidance statements and final agreement. Consensus was reached after two rounds of voting. Recommendations were established for the detection of SARS-CoV-2 using real time PCR testing based on evidence and group consensus. The manuscript was evaluated against The Appraisal of Guidelines for Research & Evaluation Instrument (AGREE II) and was developed to aid medical laboratory staff in the detection of the ribonucleic acid (RNA) of SARS-CoV-2.

Aims Allopurinol carries a well-known risk of cutaneous adverse reactions (CARs). Although febuxostat, a xanthine-oxidase inhibitor with different chemical structure, has been considered an alternative to allopurinol, post-marketing case reports of life-threatening febuxostat-related CARs have been reported. We aimed to compare the risk of CARs between allopurinol and febuxostat in real-world settings and to assess the impact of the market entry of febuxostat on allopurinol use and associated CARs. Methods A nationwide study was conducted using Taiwan's National Health Insurance Research Database. In the new-user cohort study, patients who received their first prescriptions of allopurinol or febuxostat were included, and Poisson regression was used to estimate the incidence rate ratios (IRRs) of CARs. In the interrupted time series analysis, time series data on new users and incidence rate of CARs were divided into three periods based on the reimbursement scheme of febuxostat in Taiwan, and segmented regression models were used to estimate changes in both the level and trend in each period. Results We identified 526 cases of CARs with 487 among new users of allopurinol and 39 among new users of febuxostat (incidence rate: 15.37 vs 3.48 per 1000 person-years). Allopurinol was associated with higher risk of CARs (adjusted IRR 5.55, 95% CI [3.97-7.76]), mild CARs (1.86, [1.24-2.81]), severe CARs (16.75, [8.87-31.62]) and fatal CARs (16.18, [5.05-51.83]) than febuxostat. The overall incidence rates of xanthine-oxidase inhibitor-related CARs decreased from 15.28 to 14.28 per 1000 person-years after the initial reimbursement of febuxostat and further decreased to 9.46 after the reimbursement coverage of febuxostat expanded; however, the changes were not statistically significant. Conclusion Febuxostat can be considered an alternative for patients carrying risk factors for allopurinol-related CARs. However, since there were fatal cases of febuxostat-related CARs, the closely monitoring of symptoms of CARs during the initiation of febuxostat is still warranted.

Background A pharmacovigilance database of real-world adverse drug reaction (ADR) reports is helpful for characterising adverse events and identifying new signals after drug approval. Objective This study aimed to analyse trends of ADR reporting in relation to liver injury and to delineate critical factors for suspected drug-related hepatotoxicity with a focus on reports associated with amiodarone. Setting The 2000–2014 Taiwan pharmacovigilance database. Method Relevant Standardized Medical Dictionary for Regulatory Activities queries were used to identify reports associated with liver injury. Information on ADR, patient characteristics, and the verbatim pertaining to amiodarone prescriptions, liver injury, comedications, and comorbidities were extracted and evaluated. Group comparisons between Hy’s Law cases and Temple’s Corollary cases of suspected amiodarone-related hepatotoxicity were performed. Main outcome measure Number and nature of drug-related liver injuries, particularly those associated with amiodarone. Results Of the 98,777 ADR reports over a 15-year period, 4261 (4.3%) were related to liver injury. Sixty-eight reports contained amiodarone prescriptions, but only 49 (1.1%) were eligible for further analysis. Hepatotoxic cases associated with amiodarone mostly occurred within 1 week, exhibited a hepatocellular pattern, and were more common among elderly individuals. Among 23 discernible cases, four (17.4%) recovered fully from liver injury. The critical Hy’s Law cases were associated with shorter height, lower body surface area, and higher average daily doses. Conclusion This study substantiates the importance of ADR reporting. Data pertaining to drug-associated liver injury and factors associated with suspected amiodarone-related hepatotoxicity warrants continual attention in pharmacovigilance for those at risk, especially the elderly.

Robotic endoscope is one of the development directions of the noninvasive medical instrument. According to the feature and requirements of an expanding-extending robotic endoscope, a wireless control system was designed which included the following four parts: human-machine interaction PC, external communication box, robotic internal control system, and portable video receiver. Combining with the characteristics of the mechanism of the robot, a double feedbacks control was adopted to control the three coreless DC motors of the robot. A communication chain from upper-computer to robot was designed to control the robot remotely. At last, experimental tests in simulative pipeline and in vitro intestinal tract were carried out, and the results showed that the control system could control the robot effectively.

PID controllers are widely used in industrial process control. The determination of the conventional PID controller parameter tuning is based on obtaining the mathematical model of controlled objects and according to certain rules, which is difficult to adapt to complex control systems. In this paper ,against its adverse effect parameter tuning, long time debugging, defects and poor adaptability of the controlled object,the fuzzy control and PID control are combined and the fuzzy PID controller is proposed. Then, I combine the examples of thermal power units using MATLAB to simulate. The simulation results show that the fuzzy self-tuning PID controller not only has the advantages of fuzzy control such as fast, adaptability, etc, but also the characteristics of high accuracy PID control, which make the system has a good control effect.

Concern about an increasing risk of acute pancreatitis associated with incretin-based drugs, including dipeptidyl peptidase-4 (DPP-4) inhibitors and glucagon-like peptide-1 analogs, has emerged recently.This nested case-control study examined the association between the use of DPP-4 inhibitors and acute pancreatitis using Taiwan's National Health Insurance Research Database.From a study cohort of patients with type 2 diabetes mellitus, we identified 1,957 acute pancreatitis cases (patients who had been admitted with a diagnosis of acute pancreatitis) and 7,828 age-, sex-, and cohort entry year-matched controls between 2000 and 2011. Multivariate conditional regression models were used to estimate the association between the use of DPP-4 inhibitors and acute pancreatitis. Sensitivity analyses were conducted by varying the definitions of timing of exposure to DPP-4 inhibitors.The risks of acute pancreatitis among current and past users of DPP-4 inhibitors were comparable with those of non-users (current users: adjusted odds ratio (aOR) 1.04; 95% CI [0.89-1.21]; past users: aOR 1.61 [0.93-2.77]). Similar results were found in sensitivity analyses with various definitions of "current users" of DPP-4 inhibitors. Nevertheless, the adjusted risk of acute pancreatitis was found to be increased significantly in patients with gallstone disease (aOR 5.89 [4.71-7.35]), alcohol-related disease (aOR 5.36 [4.05-7.08]), hypertriglyceridemia (aOR 1.80 [1.26-2.56]), pancreatic disease (aOR 17.29 [10.60-28.19]), and a higher Diabetes Complications Severity Index (DCSI) score (DCSI 3-4: aOR 1.49 [1.21-1.84]; DCSI≥5: aOR 1.32 [1.01-1.73]).This population-based study extends previous evidence by exploring the potential association between DPP-4 inhibitor use and the risk of acute pancreatitis in an ethnic Chinese type 2 diabetic cohort. We found that underlying diseases and severity of diabetes but not DPP-4 inhibitor use were associated with acute pancreatitis.

Objectives The objective of this study was to evaluate the impact of a regulatory action on use of parenteral ketorolac issued by Taiwan's Food and Drug Administration due to concern of its adverse events in a nationally representative population. Methods The data source of this study was the 2006–2010 Taiwan's National Health Insurance Research Database. The study employed a before–after design with a preregulation period consisting of a 2-year control phase (1 July 2006 to 30 June 2008) and a postregulation period (1 July 2008 to 30 June 2010). Monthly claim data on prescriptions of parenteral ketorolac during both periods were analyzed. Demographics of patients who received ketorolac and their prescribing physicians were examined. Key findings The percentage of nonpostoperative use against the restriction among inpatient prescriptions for parenteral ketorolac decreased from 27.44% in the preregulation period to 24.63% in the postregulation period (P

Our experience has shown that with proper support and medical care under programmatic conditions, it is feasible to achieve a high completion rate of 3HP even among the elderlyhttp://ow.ly/o3ED30nQfRx

A new damage assessment method is proposed for aging offshore platforms based on dynamic tests. The stiff nesses of the measured model corresponding to the two measurement moments are estimated by a series of stiffness-correction factors, respectively. Based on these stiffness-correction factors a new damage indicator is defined aiming at reducing influences of existed damages accumulated before the first measurement on damage assessment occurred between the two adjacent measurements. One theoretical improvement is that the requirement using the stiffness matrix of FEM to replace the one of the measured model can be ignored in the calculation of MSE of the measured model. The other development is influences of damages accumulated before the first measurement on damage detection occurs between the two measurements could be reduced greatly, which is very important for aging platforms because these platforms have not been tested aiming at damage detection during their previous service life, especially for most platforms in China. A jacket platform is chosen for numerical studies, and numerical results show that the proposed method could identify damages occurred between the two measurements properly, even including damage severity estimation.

This paper describes the design of a new prototype of a micro-robot for gastrointestine, which will avoid disadvantages of traditional endoscopes. After analyzing motion pattern of the robot, we decide to use two clamping mechanisms and a linear locomotion mechanism by simulating the squirm pattern of inchworm. Moreover, we make sure the mechanisms are operating effective and stable by using two-screw for transmission. After assembly process, the size of the robot is φ15.24mm×82.87mm, it can extend 9.06mm radically, axial pace is 13.8mm and therefore the theoretical speed is 0.86mm/s. Experimental tests show that the robot are capable of making movement under different environments effectively.

On November 1, 2009, Taiwan began a nationwide pandemic A(H1N1) 2009 vaccine ("H1N1 vaccine") program to control the influenza pandemic. Timely assessment of immunization safety during this mass vaccination campaign was a public health priority. Therefore, the government developed a national postlicensure safety surveillance strategy to identify and evaluate new, unexpected, or prioritized adverse events in recipients of H1N1 vaccine in near real-time. We describe the design and methodology of this new safety assessment infrastructure, address challenges encountered, and its potential future use for routine vaccine pharmacovigilance in Taiwan.

RATIONALE Hand, foot and mouth disease (HFMD) is caused by enterovirus. The virus may exist in secretions. PATIENT CONCERNS Five neonates had symptoms of fever and maculopapular rashes involving face, trunk, breech, arms, and legs, especially scattering on palms and feet. Blood, oropharyngeal fluid, urine, and cerebrospinal fluid (CSF) samples were collected and detected for further diagnoses with the consent of the infants' parents. Some of them suffered aseptic meningitis. DIAGNOSES They were diagnosed as HFMD with CSF enterovirus positive. INTERVENTIONS All of them continued breastfeed. Water bag was used during the pyrogenic stage. Antibiotics were administrated at first and withdrawn as soon as possible. OUTCOMES None of them developed into brainstem encephalitis or pulmonary edema and they all recovered well. LESSONS HFMD is more common in neonates than it has been thought. Enterovirus may exist in neonatal CSF and cause CSF cell to increase similar to purulent meningitis. Medical history, physical examination, and CSF enterovirus detection are important in making correct diagnosis. Unlike bacterial infection, HFMD is a self-limited disease. Once HFMD is determined and bacterial infection is ruled out, antibiotics should be avoided.

To analyze the findings and impact on the management of video-assisted thoracoscopic surgery (VATS) before planned abdominal exploration in patients with suspected advanced ovarian cancer and moderate to large pleural effusions.We reviewed the charts of all patients with suspected advanced ovarian cancer and moderate to large pleural effusions who underwent VATS from 10/01 to 7/03. VATS was performed under double lumen endotracheal anesthesia. A 2-cm chest wall incision was made in the fifth intercostal space on the side of the effusion. The thoracoscope was introduced and biopsies of suspicious lesions were performed through the single incision. After VATS, all patients had a chest tube placed through the incision, and those with malignant effusions underwent talc pleurodesis either intraoperatively or postoperatively.Twelve patients underwent VATS during the study period. Median operative time for VATS was 31 min (range: 20-49 min) with no complications attributable to the procedure. The median amount of pleural fluid drained was 1000 ml (range: 500-2000 ml). Solid, pleural-based tumor was found in six cases (50%), with nodules1 cm noted in four patients (33%) and nodules1 cm noted in two patients (17%). Of the six cases with no grossly visible pleural tumor, the pleural fluid was positive for malignant cells in two patients (17%) and negative in four patients (33%). Further initial patient management included the following: laparotomy with optimal cytoreduction, 6 (50%); diagnostic laparoscopy, 3 (25%); and no abdominal exploration, 3 (25%). Final diagnosis of primary disease site was as follows: ovary, 9 (75%); fallopian tube, 1 (8%); endometrium, 1 (8%); and lymphoma, 1 (8%). Based on the findings during VATS, laparotomy and attempted cytoreduction were avoided in four patients (33%), and the cytoreductive procedure was modified in one patient (8%).Fifty percent of patients with suspected advanced ovarian cancer and moderate to large pleural effusions who underwent VATS had solid pleural-based tumor identified, and in 33% of cases the tumor nodules were1 cm in diameter. VATS should be considered in these cases to delineate the extent of disease, treat the effusion, and to potentially select patients for either intrathoracic cytoreduction or a neoadjuvant chemotherapy approach.

Background Aberrant methylation of the global genome has been investigated as a prognostic indicator in various cancers, but the results are controversial and ambiguous. Methods and Findings This meta-analysis presents pooled estimates of the evidence to elucidate this issue. We searched the electronic databases: PubMed, Embase, ISI Web of Science and the Cochrane library (up to August 2013) to identify all of the relevant studies. The association between the level of surrogates' indexes of genome-wide hypomethylation (LINE-1, Alu and Sat–α) and the overall survival (OS) of cancer patients was examined. In addition, the pooled hazard ratios (HRs) with their 95% confidence interval (95%CI) were calculated to estimate the influences through fixed-effects and random-effects model. Finally, twenty studies with total population of 5447 met the inclusion criteria. The results indicate that the summary HRs for the studies employing LINE-1, Alu, and Sat-α repetitive elements also show that the global DNA hypomethylation have significant desirable effects on the tumour prognostic value. The pooled HRs (and CIs) of LINE-1, Alu and Sat-α were 1.83 (1.38–2.44), 2.00 (1.16–3.45), and 2.92 (1.04–8.25), with a heterogeneity measure index of I2 (and p-value) shows of 66.6% (p = 0.001), 57.1% (p = 0.053) and 68.2% (p = 0.076) respectively. The meta-regression and subgroup analysis indicated that the percentage of hypomethylated sample of cancer patients is one source of heterogeneity. Conclusion Our meta-analysis findings support the hypothesis that the global DNA hypomethylation is associated with a detrimental prognosis in tumour patients.