Pilot Scale Production of Highly Efficacious and Stable Enterovirus 71 Vaccine Candidates

BACKGROUND: Enterovirus 71 (EV71) has caused several epidemics of hand, foot and mouth diseases (HFMD) in Asia and now is being recognized as an important neurotropic virus. Effective medications and prophylactic vaccine against EV71 infection are urgently needed. Based on the success of inactivated poliovirus vaccine, a prototype chemically inactivated EV71 vaccine candidate has been developed and currently in human phase 1 clinical trial. PRINCIPAL FINDING: In this report, we present the development of a serum-free cell-based EV71 vaccine. The optimization at each step of the manufacturing process was investigated, characterized and quantified. In the up-stream process development, different commercially available cell culture media either containing serum or serum-free was screened for cell growth and virus yield using the roller-bottle technology. VP-SFM serum-free medium was selected based on the Vero cell growth profile and EV71 virus production. After the up-stream processes (virus harvest, diafiltration and concentration), a combination of gel-filtration liquid chromatography and/or sucrose-gradient ultracentrifugation down-stream purification processes were investigated at a pilot scale of 40 liters each. Although the combination of chromatography and sucrose-gradient ultracentrifugation produced extremely pure EV71 infectious virus particles, the overall yield of vaccine was 7-10% as determined by a VP2-based quantitative ELISA. Using chromatography as the downstream purification, the virus yield was 30-43%. To retain the integrity of virus neutralization epitopes and the stability of the vaccine product, the best virus inactivation was found to be 0.025% formalin-treatment at 37 °C for 3 to 6 days. Furthermore, the formalin-inactivated virion vaccine candidate was found to be stable for >18 months at 4 °C and a microgram of viral proteins formulated with alum adjuvant could induce strong virus-neutralizing antibody responses in mice, rats, rabbits, and non-human primates. CONCLUSION: These results provide valuable information supporting the current cell-based serum-free EV71 vaccine candidate going into human Phase I clinical trials

Evaluation of a health-promoting school program to enhance correct medication use in Taiwan

This study was an evaluation of the Health Promoting School (HPS) program in Taiwan and its effectiveness in enhancing students' knowledge and abilities with regard to correct medication usage. In 2011, baseline and follow-up self-administered online surveys were received from 3520 middle-school and primary students from intervention schools, and 3738 students from comparison primary and secondary schools completed the same survey. The results indicated that after implementing the correct medication use HPS program, students' knowledge and abilities concerning correct medication usage (i.e., the need to express clearly personal conditions to physicians, to check information on the medication packages, to take medication correctly and adhere to prescribed medication regimens, not to buy or acquire medication from unlicensed sources, and to consult pharmacists/physicians) were significantly increased among the students in the intervention schools (p < 0.001). In addition, students' knowledge and abilities concerning correct medication usage were significantly higher in the intervention schools compared with the comparison schools (p < 0.001). In conclusion, the correct medication use HPS program significantly enhanced students' knowledge and abilities concerning correct medication usage. Copyright (C) 2013, Food and Drug Administration, Taiwan. Published by Elsevier Taiwan LLC. All rights reserved

Predictors of Sentinel Lymph Node Metastasis in Postoperatively Upgraded Invasive Breast Carcinoma Patients

Sentinel lymph node (SLN) biopsy (SLNB) usually need not be simultaneously performed with breast-conserving surgery (BCS) for patients diagnosed with ductal carcinoma in situ (DCIS) by preoperative core needle biopsy (CNB), but must be performed once there is invasive carcinoma (IC) found postoperatively. This study aimed to investigate the factors contributing to SLN metastasis in underestimated IC patients with an initial diagnosis of DCIS by CNB. We retrospectively reviewed 1240 consecutive cases of DCIS by image-guided CNB from January 2010 to December 2017 and identified 316 underestimated IC cases with SLNB. Data on clinical characteristics, radiologic features, and final pathological findings were examined. Twenty-three patients (7.3%) had SLN metastasis. Multivariate analysis indicated that an IC tumor size > 0.5 cm (odds ratio: 3.11, p = 0.033) and the presence of lymphovascular invasion (odds ratio: 32.85, p < 0.0001) were independent risk predictors of SLN metastasis. In the absence of any predictors, the incidence of positive SLNs was very low (2.6%) in the total population and extremely low (1.3%) in the BCS subgroup. Therefore, omitting SLNB may be an acceptable option for patients who initially underwent BCS without risk predictors on final pathological assessment. Further prospective studies are necessary before clinical application

Using a radical-derived character e-learning platform to increase learner knowledge of Chinese characters

The present study is aimed at investigating the effect of a radical-derived Chinese character teaching strategy on enhancing Chinese as a Foreign Language (CFL) learners’ Chinese orthographic awareness. An e-learning teaching platform, based on statistical data from the Chinese Orthography Database Explorer (Chen, Chang, L.Y., Chou, Sung, & Chang, K.E., 2011), was established and used as an auxiliary teaching tool. A nonequivalent pretest-posttest quasi-experiment was conducted, with 129 Chinese-American CFL learners as participants (69 people in the experimental group and 60 people in the comparison group), to examine the effectiveness of the e-learning platform. After a three-week course—involving instruction on Chinese orthographic knowledge and at least seven phonetic/semantic radicals and their derivative characters per week—the experimental group performed significantly better than the comparison group on a phonetic radical awareness test, a semantic radical awareness test, as well as an orthography knowledge test

Evaluation of a health-promoting school program to enhance correct medication use in Taiwan

This study was an evaluation of the Health Promoting School (HPS) program in Taiwan and its effectiveness in enhancing students' knowledge and abilities with regard to correct medication usage. In 2011, baseline and follow-up self-administered online surveys were received from 3520 middle-school and primary students from intervention schools, and 3738 students from comparison primary and secondary schools completed the same survey. The results indicated that after implementing the correct medication use HPS program, students' knowledge and abilities concerning correct medication usage (i.e., the need to express clearly personal conditions to physicians, to check information on the medication packages, to take medication correctly and adhere to prescribed medication regimens, not to buy or acquire medication from unlicensed sources, and to consult pharmacists/physicians) were significantly increased among the students in the intervention schools (p < 0.001). In addition, students' knowledge and abilities concerning correct medication usage were significantly higher in the intervention schools compared with the comparison schools (p < 0.001). In conclusion, the correct medication use HPS program significantly enhanced students' knowledge and abilities concerning correct medication usage

The validity and reliability of the Mandarin Chinese version of the drug abuse screening test among adolescents in Taiwan

Abstract Background This study aimed to investigate the validity and reliability of the Mandarin Chinese version of the Drug Abuse Screening Test (DAST-20) among adolescents, as well as examining the test’s predictability with regard to the actual level of drug abuse. Method A total of 100 adolescent participants were recruited with their consent, in which 49 were current drug users and 51 were non-users. Based on the frequency of their drug use, participants who had used drugs at least once every week during the past year were classified as regular users (34 participants); participants who had not reached the regular use frequency of once every week during the past year were classified as occasional users (15 participants). All of the participants were required to answer a sociodemographic questionnaire, and undergo a DAST-20 (Mandarin Chinese version). Results The DAST-20, which has a high reliability with a Cronbach’s alpha of 0.88, and a construct validity accounting for 61.87% of the variance. The area under the receiver operating characteristics (ROC) curve was 0.96 between the users and nonusers, and 0.93 between the occasional users and non-occasional users. A cut-off of three points could identify 93.5% of the drug users and 88.9% of nonusers, whereas a cut-off of six points could identify 85.3% of the regular users and 92.4% of non-regular users. Conclusions The DAST-20 was the strongest predictor of adolescents who were regular users, occasional users, and non-users after controlling for other potential covariates. The Mandarin Chinese version of the DAST is simple to use and has a satisfactory validity and reliability. It is an effective screening tool for drug users among adolescents

Evaluation of the pain intensity differences among hospitalized cancer patients based on a nursing information system.

Evaluating the absolute difference in pain intensity and the percentage difference in pain intensity could facilitate an understanding of pain reduction among cancer patients during repeated hospitalizations. Examinations of the absolute differences in pain intensity and the percentage differences in pain intensity according to the worst pain intensity and last evaluated pain intensity before discharge are lacking. The aim of this study was to evaluate the absolute and percentage difference in pain intensities among cancer patients with moderate or severe pain from their 1st to 18th hospitalizations from 2011-2013. A population-based retrospective cohort study was conducted. Pain intensity was assessed using scales and was recorded in a nursing information system. The absolute and percentage difference in pain intensities were examined via the one-sample Kolmogorov-Smirnov test, and group differences in moderate or severe pain were evaluated with the Mann-Whitney U test. For moderate pain patients, the mean absolute difference in pain intensity was 1.52, and the percentage difference in pain intensity was 29.0%; both these values were significant. More significant changes in the absolute and percentage difference in pain intensities were associated with severe pain patients. Both the average absolute difference in pain intensity (3.09) and the percentage difference in pain intensity (38.5%) in patients with severe pain were significantly higher than the average absolute difference in pain intensity (1.52) and the percentage difference in pain intensity (29.0%) in patients with moderate pain. Cancer patients with moderate and severe pain experienced pain reductions of approximately 30% and 40%, respectively. Early pain management intervention in patients with severe pain is necessary to achieve an obvious analgesic effect, and the formula of the percentage difference in pain intensity should be incorporated into the nursing information system to alert clinicians for early detection of the effectiveness of cancer pain management