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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.

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

Background Mediation is increasingly used for medical dispute resolution, and the particularity of such mediation necessitates specialized training. In response to the promotion of compulsory mediation ahead of a legislation in Taiwan, we invited experts with an interdisciplinary team to design a case-based mediator training workshop. Our study aimed to investigate the learning outcomes of trainees and analyze their perspectives. Methods We recruited 129 trainees of a non-probability convenience sample who served as mediators or have dealt with medical dispute-related cases to undergo 2.5 h of lectures (introduction; procedure; roles of two mediators; principles and techniques of mediation; dispute arrangement; and issue analysis) and 1.5 h of case-based exercises. An after-class survey was conducted using a 4-point Likert-type scale to evaluate trainees’ viewpoints and learning outcomes. A total of 104 questionnaires were collected (response rate: 80.6%). Results The professions of the participants were medical (56%), law (16%), and administration and others (28%). Males considered the course more helpful (3.79 vs. 3.63, p = 0.053) and more important (3.88 vs. 3.74, p = 0.042) than did females. Participants with a legal background scored the highest in helpfulness (3.84), followed by medical (3.74) and administrative (3.63) professionals. Medical and administrative professionals scored the highest (3.85) and lowest (3.76), respectively, on importance. Respondents with more than 10 years (3.81) and less than 1 year (3.79) of experience produced higher scores in helpfulness. Respondents with 1–5 years of experience (3.68) were found to be less likely to agree with the practical importance of course content compared with other groups of trainees. Administrative professionals obtained the highest scores (89.68) in written examinations. Conclusions There are variations in mediators’ perspectives based on gender, occupation, and work experience. Our nationwide mediation training workshop can be utilized to cultivate capabilities of mediators for handling medical disputes to achieve the goal of non-litigation in medical disputes.

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

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.

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.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.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.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.

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.

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.

Arginine-specific ADP-ribosytransferases 1 (ART1) is able to modify the arginine of specific proteins by mono-ADP-ribosylation. We previously reported that the expression of ART1 in human colon adenocarcinoma tissues was higher than in adjacent tissues. Herein, we primarily revealed that ART1 could regulate the epithelial-mesenchymal transition (EMT) and, therefore, the development of colon carcinoma. In CT26 cells, which overexpressed ART1 by lentiviral transfection, the following were promoted: alterations of spindle-like non-polarization, expression of EMT inducers and mesenchymal markers, migration, invasion and adhesion. However, epithelial marker expression was decreased. Correspondingly, knockdown of ART1 in CT26 cells had the opposite effects. The effect of ART1 on EMT and carcinoma metastasis was also verified in a liver metastasis model of BALB/c mice. To further explore the molecular mechanism of ART1 in EMT, CT26 cells were treated with several specific inhibitors and gene silencing. Our data suggest that ART1 could regulate EMT by regulating the RhoA/ROCK1/AKT/β-catenin pathway and its downstream factors (snail1, vimentin, N-cadherin and E-cadherin) and that it therefore plays an important role in the progression of colon carcinoma.

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.

Type 2 diabetes mellitus (T2DM) is associated with an increased risk of the development of colorectal cancer (CRC). A previous study revealed that the levels of arginine-specific mono-ADP-ribosyltransferase 1 (ART1) in CRC tissues from patients with T2DM were higher than in non-diabetic patients. Hyperglycemia, which is a risk factor of cancer, is a common feature of T2DM; however, the effects of ART1 on glycolysis and energy metabolism in CRC cells under high-glucose conditions remains to be elucidated. β-caryophyllene (BCP) has been reported to exert anticancer and hypoglycemic effects. In the present study, CT26 cells were cultured under a high-glucose conditions and the expression levels of relevant factors were detected by western blotting. Cell Counting Kit-8 assay, flow cytometry, Hoechst 33258 staining, ATP assay and lactic acid assay were used to detect the proliferation, apoptosis and energy metabolism of CT26 cells. To observe the effects of ART1 and BCP on tumor growth in vivo, CT26 cell tumors were successfully transplanted into BALB/c mice with T2DM. The results demonstrated that overexpression of ART1 may increase glycolysis and energy metabolism in CT26 CRC cells under high glucose conditions by regulating the protein kinase B/mammalian target of rapamycin/c‑Myc signaling pathway and the expression of glycolytic enzymes. BCP inhibited the effects induced by ART1, which may be due to a BCP-induced reduction in the expression levels of ART1 via nuclear factor-κB. Therefore, ART1 may be considered a therapeutic target for the treatment of diabetic patients with CRC.

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.

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.

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.

We conducted a study to assess the use of the chorda tympani nerve in reconstruction of the ossicular chain. We retrospectively examined the medical records of 141 patients (154 ears) who had undergone middle ear surgery with 12 months of follow-up. The study population was made up of 58 males and 83 females, aged 9 to 83 years (mean: 45). These patients were divided into three groups based on the specific type of surgery they had undergone: in 35 patients, the chorda tympani nerve was used to spring and press the auricular bone prosthesis (CTN group); in 67 patients, the tympanic membrane was used to spring and press the auricular bone prosthesis (TM group); and in 39 patients, a gelatin sponge was used to support the auricular bone prosthesis (GS group). We compared pre- and postoperative air-bone gaps (ABGs) in each group, as well as the differences between these gaps among the three groups. We found significant differences between the pre- and postoperative ABGs in all three groups (all p0.01). These differences were also compared between the CTN and TM groups (t = 0.41; p0.05), between the CTN and GS groups (t = 2.07; p0.05), and between the TM and GS groups (t = 2.51; p0.05). In the CTN group, 1 patient experienced temporary postoperative hypogeusia, and another developed a mild case of delayed facial paralysis; both patients recovered within 2 weeks. We conclude that the chorda tympani nerve can be used to repair the ossicular chain to improve hearing without causing taste and facial nerve dysfunction and without the need for a second operation.

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.

Totally 81 surface soil samples were collected from Jiufeng Mountain Range, and 8 compounds of organochlorine pesticides (OCPs) were determined by a Ni electron capture detector (GC-ECD) to investigate the distribution, composition, source and potential health risks of these compounds in the study region. The detection ratio of HCHs and DDTs' isomers ranged from 77.78% to 100.00%. Concentrations of HCHs and DDTs in surface soils ranged from 0.97 ng x g(-1) to 247.40 ng x g(-1) (mean 10.17 ng x g(-1)) and 0.01 ng x g(-1) to 384.75 ng x g(-1) (mean 18.91 ng x g(-1)), respectively. Compared with other regions, the pollution of OCPs in Jiufeng Mountain Range stayed at a low level. The residue level in different types of lands was in the order as: paddy fieldvegetable landtea landwoodland. Source analysis indicated that Lindane and dicofol might be used recently in this area. The incremental lifetime, cancer risks (ILCRs) of different age groups (children, youths, and adults) were all within the acceptable risk range of 10(-6) to 10(-4) recommended by USEPA for carcinogenic chemicals. The residue level of OCPs in soil may not cause cancer risk for local residents basically.

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.

To investigate the potential protective effect of C-phycocyanin (PC) on paraquat (PQ)-induced acute lung injury, rats were divided into control, PQ-treated and PQ + PC-treated groups. Rats in PQ-treated group were orally administered with 50 mg/kg PQ and rats in PQ + PC-treated group were intraperitoneally injected with 50 mg/kg PC after administration of PQ. At 8, 24, 48 and 72 h after treatments, GSH-Px and SOD activities, MDA levels in plasma and BALF, HYP, NF-kappa B, I kappa B-alpha and TNF-alpha contents in lung tissues were measured. The pathological changes in lung were observed. After treatment with PC, the levels of MDA and the relative contents of NF-kappa B and TNF-alpha were significantly decreased, the activities of GSH-Px and SOD and the relative contents of I kappa B-alpha were significantly increased. The degree of rat lung damage was obviously reduced in PQ + PC-treated group. The results suggested that PC treatment significantly attenuated PQ-induced acute lung injury. (C) 2011 Elsevier B.V. All rights reserved.

To investigate the relationship between genetic polymorphism of dopamine β-hydroxylase (DBH) and manganese-induced nerve injury.In a cross-sectional study, 402 electric welders who had worked over one year in relatively fixed sites were recruited, and the concentration of manganese in which they worked was stable. These samples was divided into high exposure group (CEI1) and low exposure group (CEI1) by CEI. Between the two groups, the groups were divided into abnormal group and normal group according to the result of neurologic check (there were 81 workers with abnormal neurological dysfunction in high exposure group and 28 workers in low exposure group, P0.05). Polymorphism of DBH gene was analyzed with polymerase chain reaction-restriction fragment length polymorphism.The distribution of A2A2 genotype and A2 allele of DBH was significantly different. In high exposure group, the distribution of A2A2 genotype and A2 allele of DBH in abnormal group was significantly wider than in normal group (A2A2 genotype, OR = 1.248, P0.05, A2 allele, OR = 1.103, P0.05). In low exposure group, the distribution of A2 allele of DBH in abnormal group was significantly wider than in normal group (OR = 1.176, P0.05).The individuals who carry A2A2 genotype and A2 allele of DBH have increased risk of neurological dysfunction after explosion to manganese for a certain time, which suggests that polymorphism of DBH (intron 5 Taq I) would play a great role in hereditary susceptibility of neurological dysfunction cause by manganese.

To analyze the short-term and long-term effect of Er-yttrium aluminum garnet (Er-YAG) laser in stapes surgery.There were 86 patients operated by the Er-YAG laser stapedotomy from 2001 to 2007 were analyzed retrospectively, with 23 male, 63 female and 13 double ears and with the average age of 48 years old, ranging from 12 to 78. All of 99 ears suffered deafness of conduction. The average air-bone-gap (ABG) of all patients before surgery was (37.4+/-9.0) dB HL (ranging from 13.7 to 58.7 dB). The patients followed-up over 6 weeks after the surgery was regarded as the short-term result, while over one year follow-up as the long-term effect (according to the standard of the Committee on Hearing and Equilibrium of the American Academy of Otolaryngology-Head and Neck Surgery). The followed-up average time was (26.3+/-15.8) months (range from 14 to 73 months). The pre-post-operation average bone conduction auditory threshold of 2 kHz and 4 kHz were observed. The data of the patient whether or not has the symptoms of tinnitus and dizzy and the lasted days were also recorded.After surgery, short-term ABG of 99 ears was (15.7+/-8.7) dB, matched-pairs t test with the numbers of before surgery, t=22.79, P0.01. The results of 45 ears (45.5%) with ABG10 dB or air conduction improved more than 30 dB were regarded as excellence. The air conduction of 88 ears (88.9%) improved more than 15 dB was regarded as utility. With 82 ears (82.8%) followed-up more than 1 year, the average ABG was (11.7+/-6.8) dB, matched-pairs t test with the numbers of before surgery, t=23.37, P0.01, compared with the short-term visit result [(15.3+/-9.2) dB, 82 ears], t=4.82, P0.01, both of which were considered statistically extremely significant. Among them, 50 ears (61.0%) have the excellent effect while 74 ears with (90.2%) ABG20 dB. The average bone conduction auditory threshold in 2 kHz was (34.5+/-15.0) dB before surgery, matched-pairs t test with short-term visit result (33.4+/-15.9) dB, t=1.96, P=0.026 14, with long-term visit result (32.7+/-15.2) dB, t=3.24, P=0.000 87, all of which had the significant difference, manifest that the Cohort's notch had been improved after the surgery. The data of bone conduction auditory threshold of 4 kHz with long-term following-up result matched-pairs t test with that of surgery before, t=0.76 (P0.05), which showed the change of the bone conduction had no statistics difference. There were 55 ears had the persistent tinnitus before surgery, in which 42 ears (76.4%) with no the tinnitus, 13 ears with same to that of preoperative, and 3 ears (3.0%) with remaining tinnitus after surgery but who had not it preoperation and all disappeared after 2 - 3 days. There were 12 ears (12.1%) with light dizzy after surgery, but their live could deal with himself and the average dizzy lasted 2.3 days.Er-YAG laser stapes surgery is safe to the inner ear, and it primal free from the imminent risk in stapes surgery, so the effect can be affirmed.

Isolation of human cytochrome oxidase by a one-step affinity chromatography procedure on a Sepharose 4B-ferrocytochrome c matrix following solubilization with the nonionic detergent laurylmaltoside yields an enzyme isolate of adequate purity for producing polyclonal antisera. Such an antiserum produced a distinctive immunoreactive profile in Western immunoblot studies to that reported using the enzyme isolated with ionic detergents. A sensitive and highly reproducible Western immunoblotting method is described for probing mitochondrial fractions prepared from small frozen skeletal muscle biopsies with an antiserum against the human placenta cytochrome oxidase. Application of this method to mitochondrial cytopathy patients with partial cytochrome oxidase deficiency shows that the detected subunits are synthesized in these patients.

To assess the results of multi-technique with intact canal and scute rebuild operation for middle ear cholesteatoma.Analysis of 113 cases (males 60, females 53, with mean 42.7 years old), of which with double ears of 11 cases, and totally 124 ears (11 ears for one review, an ear for third time review, and totally 137 operations) was retrospectively performed. Ten cases less than 19 years old were operated from September 2001 to January 2006 for middle ear cholesteatoma as well as ossiculoplasty with intact canal and scute rebuild etc multi-technique. All cases were followed up for a mean (36.58 +/- 20.47) months.There were 118 ears (95.2%) without cholesteatoma recurrence. Six ears were found cholesteatoma recurrence. Other 6 post-operation ears with drum re-perforation and hearing drop were re-operated. The pre-operation air-bone gap (ABG, average of 0.5, 1, 2 kHz) of 124 ears, with in initial 112 ears, was (33. 61 +/- 12.35) dB, while that of post-operation ABG was (13.58 +/- 9. 27) dB, by partnership t test, t = 18.35, P0.01. The pre-operation ABG in reviewed 12 ears at the first pre-operation was (38.83 +/- 12.43) dB, but post-operation ABG (10.38 +/- 8.99) dB, by partnership t test, t = 5.38, P = 0.00022. The ABG closure to within 20 dB was tested in 100 ears while ABG over 20 dB but air conduct (AC) in 40 dB was in 6 ears, and then as succeed was in 106 ears (85.5%). ABG closure within 10 dB was in 50 ears and though ABG over 10 dB but ABG reduced over 30 dB was in 9 ears (59/124, 47.6%) as which as best result. Bone conduct (BC) threshold was tested of 21 ears (16.93%) with raise 1-9 dB, of 42 ears (33.9%) with no change and of 61 ears (49.2%) with descend 1-28 dB. Of 10 cases less than 19 years old post-operation ABG was (8.80 +/- 5.27) dB, which indicated that all cases was as succeed.Using intact canal and scute rebuild etc multi-technique a normal canal, hearing improvement and very low recurrent could be gained for middle ear cholesteatoma, especially in juvenile and children. The multi-technique should be almost no damage for hearing bone conduct.

To assess the effect of stapes surgery on advanced otosclerosis (AO).In 300 cases randomly collected of otosclerosis in 1970 to 1999, 68 cases (77ears) were selected for retrospective analysis, which met the criteria of advanced otosclerosis (mixed deafness, with bone-conduction levels exceeding 40 dB and air-conduction levels exceeding 70 dB in 500 - 2000 Hz).The air-conduction of sixty-eight cases (77 ears) were from 77.32 dB to 53.7 dB (500-2000 Hz) after operation, mean decreased 23.62 dB. Of 71 ears (92.21%) obtained air-conduction improved over 10 dB, of 46 ears (59.74%) gained A-B Gap closure in 10 dB. Air-conduction were from 79.01 dB to 58.23 dB (500 - 4000 Hz) after operation and mean decreased 20.78 dB. Of 68 ears (88.31%) obtained air-conduction improved over 10 dB, of 32 ears (41.56%) gained A-B gap closure in 10 dB. After followed up 5-25 years, of 67 ears were retained stabilization, of 28 ears obtained more improve than postoperation. But 4 ears had drop (all was stapes-elevation and re-improvement after them was reviewed).Stapes surgery is effective operation to cured otosclerosis, advanced otosclerosis or far-advanced otosclerosis had greater help to improved hearing.

To evaluate the curative effects of Betamethasone for treatment of voice hoarseness of chronic hypertrophic laryngitis.From July, 2001 to December, 2002, 48 cases of the chronic hypertrophic laryngitis had been treated by injected of Betamethasone at vocal cords. Fundamental frequency (FO), jitter, shimmer, normalized noise energy (NNE) acoustics' parameters were tested and paired t test were calculated. The voice quality of 1 month and 6 months after treatment were synthetically graded, one-way ANOVA and the DANCAN test were conducted.Eight cases were injected under surface anesthesia with indirect laryngoscopy at the clinic service. Thirty-eight cases were injected under general anesthesias with micro-laryngoscopes. After six months following up, the voice hoarseness was obviously improved, the congestion or oedema of vocal cord was lessened, and the voice quality was improved as well. The results of F0, jitter, shimmer, NNE acoustics' parameters after treatment 6 months showed: 8 of 48 cases (17.39%) had treatment effect, 22 out of 48 cases (47.83%) had obviously effect, 10 out of 48 cases (21.74%) had cured. The total effectiveness had reached 86.96% (40 of 48 cases). Six of 48 cases (13.04%) was failure.Vocal cord injection of Betamethasone for the hoarseness of chronic hypertrophic laryngitis is an effective treatment method.

To assessment result with multi-measures operation for adhering otitis media.A retrospective review of 108 cases (male 45, female 63), double ears 12, all was 120 ears. Of 20 ears had been radical operated for cholesteatoma some years ago. Of 46 ears had incorporate cholesteatoma now. Of 54 ears had only adhering in middle ear but no had been radical or incorporate cholesteatoma who underwent operation from January 1999 to May 2003 for chronic ear disease as well as ossiculoplasty with multi-technique measures (for example auto-bone cup-pole or gung-pole as total and partial ossicular replacement prostheses; scute rebuild by auto-bone; absorbable Metrogel; tympanic chorda nerve as a spring press prostheses etc) were used in operation, and were followed up mean (26.11 +/- 11.31) months (range 12 approximately 53 months).One hundred and twenty ears mean AB gap was (38.60 +/- 12.70) dB pre-operation. It was (15.28 +/- 11.69) dB post-operation. Partnership t test, t = 21.24, t 0.01 = 2.6021.24, P0.01. The air-bone gap (AB gap) closure to within 20 dB as succeed achieved in 70% (84 ears). AB gap closure in 10 dB as best result in 40% (48 ears). Air conduction was under 40 dB in 70% (83 ears). AB gap closure not enough 10 dB and Air conduction over 40 dB as no effect was 6% (7 ears) .As long as technique measures is right, even though adhering middle ear had much difficult in operation, it still can gain succeed to 70%. But had still 30% no succeed, more study is necessary.