Taipei Medical University-Wan Fang Hospital Research Articles

Comparison of the predictive outcomes for anti-tuberculosis drug-induced hepatotoxicity by different machine learning techniques

BackgroundThe study compared the predictive outcomes of artificial neural network, support vector machine and random forest on the occurrence of anti-tuberculosis drug-induced hepatotoxicity. MethodsThe clinical and genomic data of patients treated with anti-tuberculosis drugs at Taipei Medical University-Wanfang Hospital were used as training sets, and those at Taipei Medical University-Shuang Ho Hospital served as test sets. Features were selected through a univariate risk factor analysis and literature evaluation. The accuracy, sensitivity, specificity, and the area under the receiver operating characteristic curve were calculated to compare the traditional, genomic, and combined models of the three techniques. ResultsNine models were created with 7 clinical factors and 4 genotypes. Artificial neural network with clinical and genomic factors exhibited the best performance, with an accuracy of 88.67%, a sensitivity of 80%, and a specificity of 90.4% for the test set. The area under the receiver operating characteristic curve of this best model reached 0.894 for training set and 0.898 for test set, which was significantly better than 0.801 for training set and 0.728 for test set by support vector machine and 0.724 for training set and 0.718 for test set by random forest. ConclusionsArtificial neural network with clinical and genomic data can become a clinical useful tool in predicting anti-tuberculosis drug-induced hepatotoxicity. The machine learning technique can be an innovation to predict and prevent adverse drug reaction.

Risk of Febuxostat-Associated Myopathy in Patients with CKD.

Febuxostat, a nonpurine xanthine oxidase inhibitor, is widely used to treat hyperuricemia. Although febuxostat-associated rhabdomyolysis was reported in some patients with CKD, the association between CKD and febuxostat-associated myopathy remains uncertain. Our retrospective cohort study included 1332 patients using febuxostat in Taipei Medical University-Wanfang Hospital from February of 2014 to January of 2016. The primary predictor was time-averaged eGFR as calculated by the equation proposed by the 2009 Chronic Kidney Disease Epidemiology Collaboration. The outcome was febuxostat-associated myopathy defined as elevated creatine kinase levels during febuxostat use that were not attributed to other muscular injuries. The median duration of febuxostat use was 224 days (25th, 75th percentiles: 86, 441.5 days). Of 1332 study participants, 1222 (91.7%) had CKD; the median eGFR was 20.8 ml/min per 1.73 m2 (25th, 75th percentiles: 9.0, 35.4 ml/min per 1.73 m2). Forty-one of the participants had febuxostat-associated myopathy (3.2%). All patients with myopathy had CKD, and the incident rate was 0.013 (95% confidence interval, 0.01 to 0.02) events per 100 patient-days in patients with CKD. Of 41 patients with myopathy, 37 had myositis, and four had rhabdomyolysis. Myopathy resolved in 17 patients who withdrew from treatment and eight patients who continued febuxostat treatment. Among the evaluated predictors, multivariate analysis showed that only the lowest eGFR tertile was significantly associated with myopathy in febuxostat users. The odds ratio of the lowest eGFR tertile to the highest tertile was 4.21 (95% confidence interval, 1.7 to 10.43). This finding remained consistent among subgroups stratified by age, sex, diabetes status, coronary artery disease, and statin or fibrate use. Patients with severely reduced eGFR had higher risk of myopathy with treatment of febuxostat. Regular monitoring of creatine kinase level is suggested for early detection of febuxostat-associated myopathy, particularly in patients with CKD.

Impact of food intake on the pharmacokinetics of first-line antituberculosis drugs in Taiwanese tuberculosis patients

Under the directly observed treatment, short course (DOTS) program, antituberculosis (anti-TB) medications were possibly taken at random time, regardless of whether it was prior to or after meals. This study was to evaluate the impact of food intake on pharmacokinetic profiles of first-line TB drugs in Taiwanese TB patients, as well as the relationship between drug levels and pharmacogenetics. This open-label, randomized, cross-over study included newly diagnosed Taiwanese TB patients treated between January 2010 and February 2011 at Taipei Medical University-Wan Fang Hospital. Rifater [a fixed-dose combination formulation of isoniazid (INH), rifampicin (RIF), and pyrazinamide (PZA)] and ethambutol (EMB) were given according to national TB guidelines. Blood samples were collected prior to and 1 hour, 2 hours, 4 hours, 6 hours, and 10 hours after dosing under fasting or postprandial conditions. Pharmacokinetic parameters of the maximum serum concentration (Cmax), time to Cmax, and area under the serum concentration-time curve from the beginning to the 10(th) hour (AUC0-10) were calculated. Sixteen TB patients were included and received anti-TB treatment under the DOTS program after discharge. The overall effects showed that food intake reduced the mean Cmax (INH: 40.6%, RIF: 40.2%, EMB 34.4%, PZA: 24.4%) and AUC0-10 (INH: 21.3%, RIF: 26.4%, EMB: 12.2%, PZA: 12.0%). Meanwhile, food increased the time to Cmax (INH: 78.1%, RIF: 151.3%, EMB: 41.4%, PZA: 148.9%). Significantly lower serum drug concentrations were observed under postprandial conditions than fasting conditions for INH, RIF, and PZA. The impact of taking random anti-TB drugs under the DOTS program instead of taking drugs regularly prior to meals requires further study.

Successful Implementation of a P&T-Approved Therapeutic Interchange Program of Angiotensin II Receptor Blockers in a Medical Center in Taiwan

Objective Therapeutic interchange is not a common practice in the medical society in Asia. We used clinic blood pressure readings, patients' tolerance, and cost saving as measures to evaluate the impact of a therapeutic interchange program implemented at a medical center in Taiwan. Methods Taipei Medical University-Wan Fang Hospital initiated a therapeutic interchange program involving angiotensin II receptor blockers (ARBs). Data were retrospectively collected for 444 outpatients who were converted from other ARBs to candesartan. Evaluation of therapeutic efficacy, adverse effects associated with therapy, and drug costs was conducted before and after the program implementation. Results Patients whose treatment was converted to candesartan experienced no statistically significant differences in blood pressure, and the average number of antihypertensive agents used per patient remained unchanged. A direct cost savings of US$62,237 was estimated for the 444 patients studied. Only 3.15% of the patients developed adverse drug reactions potentially related to candesartan, and none required hospitalization. Conclusions Based on the results of this retrospective chart review, the present ARB therapeutic interchange program was successfully developed and implemented. This is the first study to establish the positive impact of a well-run ARB therapeutic interchange program in Taiwan.

Ultrasonographic quantification of the endometrium during the menstrual cycle using computer-assisted analysis

Objective Sonographic gray-scale histogram is used to assess the endometrial changes in the different phases of the menstrual cycle. The objective was to examine the usefulness of a gray-scale histogram and computer-assisted image analysis software in assessing normal physiologic states of the endometrium with sonography. Materials and Methods Thirty-eight patients, who visited the Taipei Medical University-Wan Fang Hospital and matched the eligibility criteria, were categorized into one of three groups: (1) menstrual phase; (2) follicular phase; and (3) luteal phase of the menstrual cycle. Ultrasonography of the uterus was performed on each patient and the endometrium was analyzed with ImageJ image analysis software. Results A statistically significant difference in signal intensity scores of the gray-level histogram, represented as m j , was found among the three groups. Conclusion Sonographic images analyzed by using computer-assisted image analysis software and gray-level histogram are proven to be useful in assessing the physiological state of the endometrium.

Online detection of potential duplicate medications and changes of physician behavior for outpatients visiting multiple hospitals using national health insurance smart cards in Taiwan

Objectives Doctor shopping (or hospital shopping), which means changing doctors (or hospitals) without professional referral for the same or similar illness conditions, is common in Hong Kong, Taiwan and Japan. Due to the lack of infrastructure for sharing health information and medication history among hospitals, doctor-shopping patients are more likely to receive duplicate medications and suffer adverse drug reactions. The Bureau of National Health Insurance (BNHI) adopted smart cards (or NHI-IC cards) as health cards in Taiwan. With their NHI-IC cards, patients can freely access different medical institutions. Because an NHI-IC card carries information about a patient's prescribed medications received from different hospitals nationwide, we used this system to address the problem of duplicate medications for outpatients visiting multiple hospitals. Methods A computerized physician order entry (CPOE) system was enhanced with the capability of accessing NHI-IC cards and providing alerts to physicians when the system detects potential duplicate medications at the time of prescribing. Physician responses to the alerts were also collected to analyze changes in physicians’ behavior. Chi-square tests and two-sided z-tests with Bonferroni adjustments for multiple comparisons were used to assess statistical significance of differences in actions taken by physicians over the three months. Results The enhanced CPOE system for outpatient services was implemented and installed at the Pediatric and Urology Departments of Taipei Medical University Wan-Fang Hospital in March 2007. The “Change Log” that recorded physician behavior was activated during a 3-month study period from April to June 2007. In 67.93% of patient visits, the physicians read patient NHI-IC cards, and in 16.76% of the reads, the NHI-IC card contained at least one prescribed medication that was taken by the patient. Among the prescriptions issued by physicians, on average, there were 2.36% prescriptions containing at least one medication that might be duplicative to the prior prescriptions stored in NHI-IC cards. The rate of potential duplicate medication alerts for the Pediatric Department was higher than that for the Urology Department (2.78% versus 1.67%). However, the rate of revisions to prescriptions was higher in the Urology Department than the Pediatric Department. Overall, the rate of physicians reviewing and revising their prescriptions was 29.25%; the rate of physicians reviewing without revising their prescriptions was 43.62%; the rate of physicians turning off the alert screens right after the screens popped up (overridden) was 27.13%. Thus, physicians accepted alerts to review their prescriptions with patients in most situations (72.87%). Moreover, over the study period, the rate of total revisions made to prescriptions increased and the “overridden” rate decreased. Conclusions Our approach enhances the capability of CPOE systems using NHI-IC cards as a nationwide infrastructure to provide more complete patient health information and medication history sharing among hospitals in Taiwan. Thus, our system can provide a better prescribing tool to help physicians detect potential duplicate medications for frequent doctor-shopping patients and hence enhance patient safety across hospital boundaries. However, the effectiveness of detecting duplicate medications with our approach is very much dependent on the completeness of NHI-IC cards, which in turn primarily depends on physician use of the cards when prescribing.

Atherosclerosis modulates the electrophysiological effects of a peroxisome proliferator-activated receptor-gamma activator on pulmonary veins

a Division of Cardiology, Chi-Mei Medical Center, Tainan, Taiwan b Division of Cardiovascular Medicine, Taipei Medical University-Wan Fang Hospital, Taipei, Taiwan c Department of Biomedical Engineering, National Defense Medical Center, Taipei, Taiwan d Graduate Institute of Clinical Medicine, Taipei Medical University, Taipei, Taiwan e Department of Internal Medicine, Mackay Memorial Hospital, Mackay Medical College, Taipei, Taiwan f Institute of Physiology, National Defense Medical Center, Taipei, Taiwan g National Yang-Ming University, School of Medicine; Division of Cardiology and Cardiovascular Research Center, Veterans General Hospital-Taipei, Taipei, Taiwan

Hepatitis Associated With Prothionamide for Treatment of Multidrug-resistant Tuberculosis

Timely and intensive monitoring for, and management of, adverse effects caused by anti-tuberculosis drugs are essential components of control programs for multidrug-resistant tuberculosis (MDR-TB). This retrospective case series was conducted in northern Taiwan from January 2007 to December 2008 at Taipei Medical University-Wan Fang Hospital, a 750-bed tertiary-care center and MDR-TB referral center. Hepatitis associated with prothionamide was defined as the recurrence of hepatitis after a second prothionamide treatment re-challenge. In total, 47 patients with MDR-TB enrolled in the Directly Observed Therapy, Short Course-Plus Program were identified during the study period, and 44 (93.6%) were treated with prothionamide. Seven of these 44 patients (15.9%) developed hepatitis after being treated with prothionamide concurrent with other anti-tuberculosis agents. Hepatitis associated with prothionamide occurred in three of these seven patients (6.8%). In these three patients, hepatitis developed following treatment with prothionamide for 28 days, 39 days or 45 days. Hepatitis developed rapidly after re-challenge with prothionamide at 4 days, 4 days and 3 days, respectively. Liver function returned to the normal range after cessation of prothionamide treatment for 19 days, 27 days or 28 days. Close monitoring of liver function was necessary in MDR-TB patients who received prothionamide treatment.

Outcomes of Pharmacy Interventions on Pediatric Medication Prescribing Patterns in Taiwan

Background/Purpose The aim of this study was to assess the long-term effect of pharmacy interventions on patients and health care providers, and switching from prescribing extemporaneous powder dosage forms to liquid dosage forms. Methods An education program for parents was conducted. An attitude, knowledge and behavior questionnaire was employed to measure the efficacy of the education program. Medication management policies were then executed by providing an in-service to pediatricians, establishing dosage-switching guidelines and adding liquid dosage forms of necessary medications into the hospital formulary. Dosage-switching guidelines of pediatric medications were established by surveying the most prescribed extemporaneous powder dosage forms at the Taipei Medical University–Wan Fang Hospital. These guidelines were introduced to every pediatrician, nurse and pharmacist. The prescribing rate of extemporaneous powder prescriptions was monitored to measure the outcomes of the interventions. Results The mean scores of attitude, knowledge and practice significantly improved towards a positive use of commercially available liquid medications after the patient education program for the parents. Prescriptions for extemporaneous powder dosage forms significantly decreased from 1600 (2.54%) to 13 (0.022%) monthly in the 4 th year and were reduced to zero in the 6 th year. Conclusion This study demonstrated that the pharmacists' interventions were able to change the parents' knowledge, attitude and practice towards pediatric drug dosage forms and the prescribing pattern. Effective assurance in children's medication safety can be achieved through collaboration between medical professionals and parents.

Ultrasonographic evaluation of endometrial changes using computer assisted image analysis

To examine the usefulness of a gray scale histogram and computer assisted image analysis software in assessing physiologic states of the endometrium with ultrasonography. Seventy patients at the Taipei Medical University-Wan Fang Hospital who matched eligibility criteria were categorized into one of three groups: (i) normal menstrual cycle, (ii) postmenopausal, and (iii) post incomplete abortion. Ultrasonography of the uterus was performed on each patient and the endometrium was analyzed with ImageJ image analysis software. A statistically significant difference in signal intensity scores of the gray level histogram, represented as m(j), was found between the groups. Ultrasonographic images analyzed using computer assisted image analysis software and gray level histogram are useful in assessing the physiological state of the endometrium.

Comments on Article by Albers et al

*Department of Psychiatry, Songde Branch, Taipei City Hospital and †Department of Psychiatry, Taipei Medical University-Wan Fang Hospital, Taipei, Taiwan [email protected]

Recurrent coronary spasm with complete atrioventricular block in a patient with refractory acute myelocytic leukemia

Shian-Jiun Lin, Jyh-Ming Chow, Ming-Hsiung Hsieh*, Paul Chan Department of Internal Medicine and Division of Cardiovascular Medicine, Taipei Medical University, School of Medicine and Taipei Wan-Fang Hospital, Taiwan, ROC Division of Hematology, Department of Medicine, Taipei Medical University, School of Medicine and Taipei Wan-Fang Hospital, Taiwan, ROC Cardiovascular Medicine, Department of Medicine, Taipei Medical University Wan-Fang Hospital, Taiwan, ROC

Infrared Thermography to Mass-Screen Suspected Sars Patients with Fever

Fever greater than 38 degrees C is a cardinal sign of patients with the severe acute respiratory syndromes (SARS). To reduce the risk of nosocomial cross infections, screening all patients and visitors who visit hospitals and clinics for fever at the entrance of every hospital building has become a standard protocol in Taiwan during the SARS epidemic from mid-April to mid-June 2003. We used a digital infrared thermal imaging (DITI) system (Telesis Spectrum 9000 MB) to conduct mass screening of patients and visitors who entered the hospital to identify those with fever. The DITI system has two components: a sensor head and a PC imaging workstation. The sensor head is an optic-mechanical device which consists of imagining optics for focusing the infrared source information on the infrared detector. The infrared images are further converted into electrical signals, which are then processed for real-time display on the monitor. During the period from April 13 to May 12 2003, 72,327 outpatients and visitors entered Taipei Medical University-Wan Fang Hospital, Taipei, Taiwan. A total of 305 febrile patients (0.42%) was detected by infrared thermography. Among them, three probable SARS patients were identified after thorough studies including contact history, laboratory tests and radiology examinations. The findings suggests that infrared thermography was an effective and reliable tool ideal for mass-screening patients with fever in the initial phase of screening for SARS patients at a busy hospital which sees approximately 3,000 outpatients every weekday during the SARS epidemic.

Development and evaluation of an integrated pharmaceutical education system

There is increasing evidence that patient safety can be improved by the introduction of an integrated computer-based medical care system in hospital settings. In this paper, we describe an integrated pharmaceutical information system (IPIS) in which a patient’s profile including his/her medication records and prescriptions are collected from physician order entry systems and pharmaceutical systems along with the history of patient care in the hospital. Based on an individual patient’s profile the IPIS can provide pharmaceutical education information specifically to meet the patient’s needs. The IPIS has been developed and installed at Taipei Medical University Wanfang Hospital (TMUWFH) since July 2002. Evaluation of the system showed that it can help patients to effectively acquire drug information. This enables them to have a much better understanding of the pharmacological properties of the medicines they are taking, including adverse drug reactions and side-effects. In our opinion the system has the potential to improve both patient safety and treatment outcomes.

The flunitrazepam abuse prevention program at a general hospital in Taiwan: a descriptive study.

The Bureau of Controlled Drugs at Ministry of Health, Executive Yuan in Taiwan announced, on 1 April 2000, the schedules of controlled drugs with abuse potential and implemented a policy on 1 October 2000 to control them. Flunitrazepam (FM2), along with other two benzodiazepines (triazolam and brotizolam), is placed on Schedule III. The aim of the present study was to analyze the pattern of flunitrazepam prescriptions across all medical subspecialty departments at Taipei Medical University-Wan Fang Hospital (TMU-WFH), Taiwan. We analyzed 1170 prescriptions over 12 month period from 1 July 2000 to 31 May 2001. All prescription data were divided into three 4 month periods: period I was when the flunitrazepam prescription was not controlled, period II represented the time when flunitrazepam was placed on Schedule III and when physicians were required to use a special duplicated prescription form and period III was when the TMU-WFH started to set a stricter control for the prescription of flunitrazepam. The results indicated that the number of flunitrazepam prescriptions during period III had decreased significantly compared with period I (P < or = 0.05). Eventually, 45.7% of flunitrazepam-medicated patients were followed up monthly with a restriction of their flunitrazepam supply to no more than 14 days, 22.9% of patients were followed up fortnightly at clinics with a 14 day supply of flunitrazepam, 15.7% were followed up fortnightly with a 14 day restriction of flunitrazepam plus a non-flunitrazepan benzodiazepine supplement, 10.7% were referred to clinics within the Department of Psychiatry and 5% were switched from flunitrazepam to other drugs.