Ultrafast liquid chromatographytandem mass spectrometry determination of donepezil in human plasma: application to a bioequivalence study

A liquid chromatography equipped with tandem mass spectrometric method using multistage flow rates was developed for the determination of donepezil in human plasma to support a randomized, crossover bioequivalence (BE) study in which healthy volunteers each received a single oral dose of the reference and test formulations of 10 mg donepezil hydrochloride. This integrated liquid chromatography with tandem mass spectrometry (LC-MS/MS) system with electrospray ionization and a deuterium-labeled internal standard (IS) were employed for the positive multiple-reaction-monitoring (MRM) analyses. The baseline separation using a high-resolution monolithic column under gradient and flexible flowrate conditions between donepezil and multiple interfering peaks from the extracted quality control, calibration standard and study plasma samples following simple protein precipitation extraction procedures was accomplished within 1.5 minutes. The ultrafast monolithic column performance in terms of chromatographic separation efficiency, peak asymmetry and resolution and retention time reproducibility was found to be sustainable.The linear dynamic range was detected over a concentration range of 0.2–50 ng/mL. The intra- and inter-day assay accuracy and precision were within 15% for the analyte in individual biological fluids. A positive correlation coefficient (r) greater than 0.995 for donepezil concentrations in study plasma samplers measured by the proposed and the other validated LC-MS/MS methods in support of a bioequivalence study was observed.

A rare cause of gastrointestinal hemorrhage

No abstract available.

Outcomes of limited period of adalimumab treatment in moderate to severe Crohn's disease patients: Taiwan Society of Inflammatory Bowel Disease Study

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.

Management of ulcerative colitis in Taiwan: consensus guideline of the Taiwan Society of Inflammatory Bowel Disease

Ulcerative colitis (UC) is an inflammatory bowel disease characterized by chronic mucosal inflammation of the colon, and the prevalence and incidence of UC have been steadily increasing in Taiwan. A steering committee was established by the Taiwan Society of Inflammatory Bowel Disease to formulate statements on the diagnosis and management of UC taking into account currently available evidence and the expert opinion of the committee. Accurate diagnosis of UC requires thorough clinical, endoscopic, and histological assessment and careful exclusion of differential diagnoses, particularly infectious colitis. The goals of UC therapy are to induce and maintain remission, reduce the risk of complications, and improve quality of life. As outlined in the recommended treatment algorithm, choice of treatment is dictated by severity, extent, and course of disease. Patients should be evaluated for hepatitis B virus and tuberculosis infection prior to immunosuppressive treatment, especially with steroids and biologic agents, and should be regularly monitored for reactivation of latent infection. These consensus statements are also based on current local evidence with consideration of factors, and could be serve as concise and practical guidelines for supporting clinicians in the management of UC in Taiwan.

Management of Crohn's disease in Taiwan: consensus guideline of the Taiwan Society of Inflammatory Bowel Disease

Crohn's disease (CD) is a chronic relapsing and remitting inflammatory disease of the gastrointestinal tract. CD is rare in Taiwan and other Asian countries, but its prevalence and incidence have been steadily increasing. A steering committee was established by the Taiwan Society of Inflammatory Bowel Disease to formulate statements on the diagnosis and management of CD taking into account currently available evidence and the expert opinion of the committee. Thorough clinical, endoscopic, and histological assessments are required for accurate diagnosis of CD. Computed tomography and magnetic resonance imaging are complementary to endoscopic evaluation for disease staging and detecting complications. The goals of CD management are to induce and maintain remission, reduce the risk of complications, and improve quality of life. Corticosteroids are the mainstay for inducing re-mission. Immunomodulating and biologic therapies should be used to maintain remission. Patients should be evaluated for hepatitis B virus and tuberculosis infection prior to treatment and receive regular surveillance for cancer. These consensus statements are based on current local evidence with consideration of factors, and could be serve as concise and practical guidelines for supporting clinicians in the management of patients with CD in Taiwan.

A retrospective analysis of 20-year data of the surgical management of ulcerative colitis patients in Taiwan: a study of Taiwan Society of Inflammatory Bowel Disease

BACKGROUND/AIMS: With the recent progress in medical treatment, surgery still plays a necessary and important role in treating ulcerative colitis (UC) patients. In this study, we analyzed the surgical results and outcomes of UC in Taiwan in the recent 20 years, via a multi-center study through the collaboration of Taiwan Society of IBD. METHODS: A retrospective analysis of surgery data of UC patients from January 1, 1995, through December 31, 2014, in 6 Taiwan major medical centers was conducted. The patients' demographic data, indications for surgery, and outcome details were recorded and analyzed. RESULTS: The data of 87 UC patients who received surgical treatment were recorded. The median post-operative follow-up duration was 51.1 months and ranged from 0.4 to 300 months. The mean age at UC diagnosis was 45.3±16.0 years and that at operation was 48.5±15.2 years. The 3 leading indications for surgical intervention were uncontrolled bleeding (16.1%), perforation (13.8%), and intractability (12.6%). In total, 27.6% of surgeries were performed in an emergency setting. Total or subtotal colectomy with rectal preservation (41.4%) was the most common operation. There were 6 mortalities, all due to sepsis. Emergency operation and low pre-operative albumin level were significantly associated with poor survival (P=0.013 and 0.034, respectively). CONCLUSIONS: In the past 20 years, there was no significant change in the indications for surgery in UC patients. Emergency surgeries and low pre-operative albumin level were associated with poor survival. Therefore, an optimal timing of elective surgery for people with poorly controlled UC is paramount.

A Fatal Case of Naegleria fowleri Meningoencephalitis in Taiwan

After bathing at a hot spring resort, a 75-year-old man presented to the emergency department because of seizure-like attack with loss of conscious. This is the first case of primary amebic meningoencephalitis (PAM) caused by Naegleria fowleri in Taiwan. PAM was diagnosed based on detection of actively motile trophozoites in cerebrospinal fluid using a wet-mount smear and the Liu's stain. The amoebae were further confirmed by PCR and gene sequencing. In spite of administering amphotericin B treatment, the patient died 25 days later.