Although agomelatine may be associated with an increased risk of hepatotoxicity, the incidence rate of acute hepatitis seemed divergent between clinical trials and daily practice. Whether aging or gender is a risk factor in developing hepatotoxicity due to agomelatine is not clear. We present 3 older female cases with acute hepatitis occurring due to highly probable idiosyncratic drug-induced liver injury caused by agomelatine. From these cases, regular surveillance on liver function in the older women taking antidepressants would be of benefits.

Alzheimer’s disease (AD) is a neurodegenerative disease with progressive memory loss and the cognitive decline. AD is mainly caused by abnormal accumulation of misfolded amyloid β (Aβ), which leads to neurodegeneration via a number of possible mechanisms such as down-regulation of brain-derived neurotrophic factor-tropomyosin-related kinase B (BDNF-TRKB) signaling pathway. 7 ,8-Dihydroxyflavone (7,8-DHF), a TRKB agonist, has demonstrated potential to enhance BDNF-TRKB pathway in various neurodegenerative diseases. T o expand the capacity of flavones as TRKB agonists, two natural flavones quercetin and apigenin, were evaluated. With tryptophan fluorescence quenching assay, we illustrated the direct interaction between quercetin/ apigenin and TRKB extracellular domain. Employing Aβ folding reporter SH-SY5Y cells, we showed that quercetin and apigenin reduced Aβ-aggregation, oxidative stress, caspase-1 and acetylcholinesterase activities, as well as improved the neurite outgrowth. Treatments with quercetin and apigenin increased TRKB Tyr516 and Tyr817 and downstream cAMP-response-element binding protein (CREB) Ser133 to activate transcription of BDNF and BCL2 apoptosis regulator (BCL2), as well as reduced the expression of pro-apoptotic BCL2 associated X protein (BAX). Knockdown of TRKB counteracted the improvement of neurite outgrowth by quercetin and apigenin. Our results demonstrate that quercetin and apigenin are to work likely as a direct agonist on TRKB for their neuroprotective action, strengthening the therapeutic potential of quercetin and apigenin in treating AD.

OBJECTIVE: The objective of this study was to explore the association of longitudinal CA-125 measurements with overall survival (OS) time by developing a flexible model for patient-specific CA-125 profiles, and to provide a simple and reliable prediction of OS. METHODS: A retrospective study was performed on 275 patients with ovarian cancer who underwent at least one cycle of primary chemotherapy in our institute. Serial measurements of patients' CA-125 levels were performed at different frequencies according to their clinical plans. A statistical model coupling the Cox proportional hazards and the mixed-effects models was applied to determine the association of OS with patient-specific longitudinal CA-125 values. Stage and residual tumor size were additional variables included in the analysis. RESULTS: A total of 1,601 values of CA-125 were included. Longitudinal CA-125 levels, stage, and the residual tumor size were all significantly associated with OS. A patient-specific survival probability could be calculated. Validation showed that, in average, 85.4% patients were correctly predicted to have a high or low risk of death at a given time point. Comparison with a traditional model using CA-125 half-life and time to reach CA-125 nadir showed that the longitudinal CA-125 model had an improved predicative value. CONCLUSION: Longitudinal CA-125 values, measured from the diagnosis of ovarian cancer to the completion of primary chemotherapy, could be used to reliably predict OS after adjusting for the stage and residual tumor disease. This model could be potentially useful in clinical counseling of patients with ovarian cancer.
Counseling ; Diagnosis ; Drug Therapy ; Half-Life ; Humans ; Models, Statistical ; Neoplasm, Residual ; Ovarian Neoplasms* ; Retrospective Studies

OBJECTIVE: The aim of this study was to determine changes in behaviour among patients with attention deficit/hyperactivity disorder (ADHD) by different informants during treatment in the clinical setting. METHODS: Seventy-nine patients with ADHD were recruited. They completed 12-months of treatment with oral short-acting methylphenidate, two-to-three times per day, at a dose of 0.3-1.0 mg/kg. Among the 79 patients (mean age, 9.1+/-1.9 years), 39 were classified as the ADHD-C/H type (hyperactive-impulsive type and combined type) and 40 as the ADHD-I type (inattentive type). At baseline, and after 12 months, their behaviour was assessed using the Child Behaviour Checklist (CBCL), Teacher's Report Form (TRF), ADHD Rating Scale (ADHD-RS), and Clinical Global Impression-Severity (CGI-S). RESULTS: Patients classified as the ADHD-C/H type had higher scores on three CBCL subscales, on the ADHD-RS and CGI-S compared to the ADHD-I type patients. After 12-months of treatment, for all patients, there were significant improvements in the four subscales of the TRF as well as the ADHD-RS and CGI-S scores, but not on the CBCL. In addition, the patients with the ADHD-C/H type had greater improvements on the four subscales of the TRF after treatment. However, there were no differences noted on the CBCL, ADHD-RS and CGI-S. CONCLUSION: The results of this study showed that during treatment, in the clinical setting, there are different assessments of behaviour symptoms, associated with ADHD, reported by different informants. Assessments of behaviour profiles from multiple informants are crucial for establishing a fuller picture of patients with ADHD.
Checklist ; Child ; Humans ; Methylphenidate ; Parents

INTRODUCTIONProblem-based learning (PBL), a pedagogic concept using a student-centred approach and problem-solving through small group discussions, has been adopted in varying degrees for years at all 11 medical institutes in Taiwan. Much evidence has shown that a number of factors can seriously affect student performance in PBL courses, such as the design of PBL scenarios, the tutors' character and students' attitudes and efforts.

MATERIALS AND METHODSThe aim of this study was to examine how the personal characters or knowledge base of Taiwanese medical students influence their performance in a hybrid-PBL curriculum. A total of 309 (234 male, 75 female) high-school entry undergraduate medical students participated in this survey. Self-assessed personal traits were presented in a 44-item questionnaire with a Big Five factor structure. Knowledge base was assessed by students' score point average (SPA) based on their previous 4-year education in medical school. Peer-assessed performance of students in the PBL curriculum was carried out using a well-developed, reliable and validated evaluation form.

RESULTSEach student's peer-evaluated PBL performance can be divided into 5 principal components, which included control-lead, assist-coordinate, written organisation and compromise- comply (Eigen value >1). The consistency and reliability of the Big Five questionnaire on personal traits was analysed and discordant items were deleted (Cronbach's alpha = 0.72 to 0.86 after deletion). The relationship between the personal traits, knowledge base and PBL performance, as analysed by simple regression, showed that "extraversion" and "openness to experience" were positively related to the "assist-coordinate" characteristic in PBL performance, and "conscientiousness" was positively related to the "control-lead" characteristic in PBL performance. The SPA was positively related to the "assist-coordinate" or "control-lead" characteristic in PBL performance. The "agreeableness" was negatively correlated with the "control-lead" characteristic in PBL performance. After stepwise regression between the Big Five and each component of PBL performance, only the correlation between conscientiousness and control/lead, and between extraversion and assist/coordinate remained significant.

CONCLUSIONKnowledge and personality characteristics appear to be associated with student performance in a hybrid-PBL curriculum. The implications of this study on the future development and application of this assessment tool in medical schools are presented.

Educational Measurement ; Female ; Humans ; Male ; Mental Competency ; psychology ; Problem-Based Learning ; methods ; Retrospective Studies ; Students, Medical ; psychology ; Surveys and Questionnaires ; Taiwan

Objective: Involuntary admission to psychiatric inpatient care can protect both patients with severe mental illnesses and individuals around them. This study analyzed annual healthcare costs per person for involuntary psychiatric admission and examined categories of mental disorders and other factors associated with mortality. Methods: This retrospective cohort study collected 1 million randomly sampled beneficiaries from the National Health Insurance Database for 2002–2013. It identified and matched 181 patients with involuntary psychiatric admissions (research group) with 724 patients with voluntary psychiatric admissions (control group) through 1:4 propensity-score matching for sex, age, comorbidities, mental disorder category, and index year of diagnosis. Results: Mean life expectancy of patients with involuntary psychiatric admissions was 33.13 years less than the general population. Average annual healthcare costs per person for involuntary psychiatric admissions were 3.94 times higher compared with voluntary admissions. The general linear model demonstrated that average annual medical costs per person per compulsory hospitalization were 5.8 times that of voluntary hospitalization. Survival analysis using the Cox proportional hazards model found no significant association between type of psychiatric admission (involuntary or voluntary) and death. Conclusion This study revealed no significant difference in mortality between involuntary and voluntary psychiatric admissions, indicating involuntary treatment’s effectiveness.

Objectives: . Laryngeal ultrasonography (LUS) has been suggested as an alternative diagnostic tool for unilateral vocal fold paralysis (UVFP). The present study applied LUS and quantitative laryngeal electromyography (LEMG) in female UVFP patients to investigate the pathophysiologic mechanisms of UVFP. Methods: . In this cross-sectional study, vocal fold (VF) length parameters included resting and phonating VF length measured using B-mode LUS, and color Doppler vibrating length (CDVL) measured using the color Doppler mode. Results: . Forty female patients with UVFP were enrolled, among whom 11 and 29 were assigned to the thyroarytenoid (TA) muscle+cricothyroid (CT) muscle group (with CT involvement) and the TA (without CT involvement) group, respectively. In the TA group, the turn frequency in thyroarytenoid-lateral cricoarytenoid (TA-LCA) on the paralyzed side, as observed through LEMG, correlated with the VF length during the resting phase (R=0.368, P=0.050) and CDVL values (R=0.627, P=0.000) on the paralyzed side. In the TA+CT group, the turn ratio in the CT muscle correlated with the normalized phonatory vocal length change (nPLC; R=0.621, P=0.041) on the paralyzed side. Conclusion . CDVL and nPLC are two parameters that can be utilized to predict the turn frequencies of TA-LCA in UVFP cases without CT involvement, and the turn ratio of CT in cases of UVFP with CT involvement, respectively. The findings suggest that LUS, as a noninvasive tool, can serve as an alternative method for assessing the severity of laryngeal nerve injury and offer valuable insights into the pathophysiology of UVFP.

OBJECTIVE: Choice of hysterectomy and adjuvant treatment for International Federation of Gynecology and Obstetrics (FIGO) 2009 stage II endometrioid endometrial cancer (EEC) is still controversial. Aims of this study were to evaluate survival benefits and adverse effects of different hysterectomies with or without adjuvant radiotherapy (RT), and to identify prognostic factors. METHODS: The patients at 14 member hospitals of the Taiwanese Gynecologic Oncology Group from 1992 to 2013 were retrospectively investigated. Patients were divided into simple hysterectomy (SH) alone, SH with RT, radical hysterectomy (RH) alone, and RH with RT groups. Endpoints were recurrence-free survival (RFS), overall survival (OS), disease-specific survival (DSS), adverse effects and prognostic factors for survival. RESULTS: Total of 246 patients were enrolled. The 5-year RFS, OS, DSS and recurrence rates for the entire cohort were 89.5%, 94.3%, 96.2% and 10.2%, respectively. Patients receiving RH had more adverse effects including blood loss (p < 0.001), recurrent urinary tract infections (p = 0.013), and leg lymphedema (p = 0.038). Age over 50-year (HR = 9.2; 95% confidence interval [CI], 1.2–70.9) and grade 3 histology (HR = 7.28; 95% CI, 1.45–36.6) were independent predictors of OS. Grade 3 histology was an independent predictor of RFS (HR = 5.13; 95% CI, 1.38–19.1) and DSS (HR = 5.97; 95% CI, 1.06–58.7). Patients receiving adjuvant RT had lower locoregional recurrence (p = 0.046), but no impact on survival. CONCLUSION: Different treatment modalities yield similar survival outcomes. Patients receiving SH with RT had lower locoregional recurrent with acceptable morbidity. Age and tumor grading remained significant predictors for survival among patients with FIGO 2009 stage II EEC.
Cohort Studies* ; Endometrial Neoplasms* ; European Union ; Female ; Gynecology ; Humans ; Hysterectomy ; Leg ; Lymphedema ; Neoplasm Grading ; Obstetrics ; Radiotherapy ; Radiotherapy, Adjuvant ; Recurrence ; Retrospective Studies* ; Urinary Tract Infections ; Uterine Neoplasms

BACKGROUNDBoth athletes with intensive exercise and aged people may have weakened immunity against virus infection. This study aimed to evaluate whether people undergoing aerobic exercises including competitive cyclists with moderate training (CMT) and middle-aged people practicing Tai Chi Chuan (TCC) exercise have higher immunity against hepatitis B virus than age-matched sedentary controls including college students (CSC) and middle-aged people (MSC).

METHODSHuman peripheral blood mononuclear cells from competitive cyclists and sedentary controls were stimulated by phytohemagglutinin (PHA) to prepare conditioned medium (MNC-CM) for the assessment of inhibitory effects on hepatitis B surface antigen (HBsAg) expression in human hepatoma Hep3B cells.

RESULTSThe inhibitory effects on the relative HBsAg expression of CMT's and TCC's MNC-CM were greater than those of the controls. The CMT's MNC-CM prepared from 5 microg/ml PHA decreased HBsAg expression to 61.5%, whereas that of CSC remained at 83.8%. Similarly, this expression by treatment of TCC group' MNC-CM was 68.4% whereas that of MSC group was 84.3%. The levels of cytokines such as interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), IFN-alpha and interleukin-1beta (IL-1beta) in the MNC-CM from the CMT and TCC groups were greater than those in the controls. Antibody neutralization of CMT's MNC-CM and addition of recombinant cytokines into CSC's MNC-CM indicated that IFN-gamma, TNF-alpha and IFN-alpha had synergistic effects against HBsAg expression. Similar blocking effect was noted in TCC versus MSC groups.

CONCLUSIONThese results suggest that the immunomodulatory response to suppress HBsAg expression in CMT and TCC with moderate aerobic exercise is greater than that in age-matched sedentary controls.

Adult ; Exercise ; Hepatitis B Surface Antigens ; analysis ; Humans ; Interferon-gamma ; physiology ; Male ; Oxygen Consumption ; Tai Ji ; Tumor Necrosis Factor-alpha ; physiology

BACKGROUND/AIMS: In Taiwan, due to budget limitations, the National Health Insurance only allows for a limited period of biologics use in treating moderate to severe Crohn's disease (CD). We aimed to access the outcomes of CD patients following a limited period use of biologics, specifically focusing on the relapse rate and remission duration; also the response rate to second use when applicable. METHODS: This was a multicenter, retrospective, observational study and we enrolled CD patients who had been treated with adalimumab (ADA) according to the insurance guidelines from 2009 to 2015. RESULTS: A total of 54 CD patients, with follow-up of more than 6 months after the withdrawal of ADA, were enrolled. The average period of treatment with ADA was 16.7±9.7 months. After discontinuing ADA, 59.3% patients suffered a clinical relapse. In the univariate analysis, the reason for withdrawal was a risk factor for relapse (P=0.042). In the multivariate analysis, current smoker became an important risk factor for relapse (OR, 3.9; 95% CI, 1.2−14.8; P=0.044) and male sex was another risk factor (OR, 2.9; 95% CI, 1.1−8.6; P=0.049). For those 48 patients who received a second round of biologics, the clinical response was seen in 60.4%, and 1 anaphylaxis occurred. CONCLUSIONS: Fifty-nine percent of patients experienced a relapse after discontinuing the limited period of ADA treatment, and most of them occurred within 1 year following cessation. Male sex and current smoker were risk factors for relapse. Though 60.4% of the relapse patients responded to ADA again.
Adalimumab* ; Anaphylaxis ; Biological Products ; Budgets ; Crohn Disease* ; Follow-Up Studies ; Humans ; Inflammatory Bowel Diseases* ; Insurance ; Male ; Multivariate Analysis ; National Health Programs ; Observational Study ; Recurrence ; Retrospective Studies ; Risk Factors ; Taiwan*