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Background Trough levels have been used for Vancomycin (VAN) therapeutic drug monitoring (TDM) historically due to its practicality. A paradigm shift towards the use of area under curve (AUC)-guided dosing TDM has been made due to availability of advanced pharmacokinetics software, variability between trough levels and AUC values and the potential for reducing toxicity. This review aims to evaluate the impact of AUC-guided vs trough-guided vancomycin TDM on nephrotoxicity-related outcomes. Methods A systematic review was conducted using PubMed®, Embase®, Web of Science®, CINAHL®, Google scholar and Cochrane library® up till 1st January 2021 and was reported according to the PRISMA checklist. Studies which evaluated AUC-guided or trough-guided VAN TDM and vancomycin-associated nephrotoxicity were included. Random effects models were used to compare differences in nephrotoxicity between trough level or AUC based vancomycin TDM due to expected heterogeneity in study designs. PRISMA Flowchart PRISMA flow chart depicting the selection process of studies included in the meta-analysis Results Of 1191 records retrieved, 57 studies were included. Majority of studies included adult and elderly patients (n=47, 82.5%). The pooled prevalence of nephrotoxicity was lower using the AUC-guided TDM [6.2%, 95% confidence interval (CI): 2.9 – 9.5%] compared to trough-guided TDM [17.0%; 95% CI: 14.7 – 19.2%]. The risk of nephrotoxicity was lower with the AUC-guided approach as compared with the trough-guided approach [OR: 0.53, 95% CI: 0.32–0.89]. AUC thresholds correlated with risk of nephrotoxicity only for the first 96 hours of therapy. A frequency analysis of significant multivariable factors showed that concomitant use of nephrotoxins, VAN trough levels and duration of VAN therapy were most commonly associated with nephrotoxicity. Forest plot comparing the risk of nephrotoxicity of AUC-guided vs trough-guided Forest plot comparing the risk of nephrotoxicity of AUC-guided vs trough-guided Pooled nephrotoxicity rates from AUC-guided monitoring Pooled nephrotoxicity rates from AUC-guided monitoring Pooled nephrotoxicity rates from trough-guided monitoring Pooled nephrotoxicity rates from trough-guided monitoring Conclusion The AUC-guided approach appeared to have lower risk of nephrotoxicity which supports the updated American Society of Health-System Pharmacists recommendations. More studies should be performed to evaluate the optimal derivation of AUC and clinical utility of repeated measurements of vancomycin AUC and trough levels. Disclosures All Authors: No reported disclosures

Background and purpose Deep thinking is a desirable trait for higher education especially at a time where knowledge application, rather than knowledge acquisition, is premium. As assessment plays a critical role in shaping learning behaviors, this study attempted to evaluate the benefits of administering a ‘student-designed assessment problems’ (SDAP) assignment as a tool to instill deeper learning among students. The supposition was that when tasked to design assessment problems, students are challenged to higher cognitive levels of thinking on the Bloom's revised taxonomy scale. Educational setting and activity This study was conducted on a group of third year pharmacy students taking an elective module on pharmacokinetics and toxicokinetics. Students were shown an example of a finished product and were given three weeks to complete the take-home assignment. The questions that students designed were characterized according to the revised Bloom's taxonomy category by two independent reviewers. Feedback on students' experience was also evaluated. Findings All 18 students reading the module submitted their SDAP with questions that demonstrated all levels of thinking, with application-based questions being most significant, followed by analytical questions. Feedback from the students was positive, with clear indications of self-directed and peer learning. Summary This exercise offered a surprising insight into students' way of thinking, by externalizing their inquiring minds and translating their thoughts into written questions. This positive outcome informed that it has stirred deep thinking and learning among the students who participated. Evidently, SDAP is impactful as an assessment for and of learning.

Introduction This study aimed to investigate a workshop's impact on empathy development, compare potential differences in effects among different workshop debrief methods, and identify if any demographic factors predict empathy development. Methods Participants were first randomly divided to receive either a didactic lecture, a jigsaw approach, or a fishbowl approach for the debrief method. In their respective arms, participants experienced simulation stations followed by their assigned debrief. Of 167 year-two National University of Singapore pharmacy undergraduates, 130 participated in the study and completed the Jefferson Scale of Empathy-Health Professions Student (JSE-HPS) version before and after the workshop. Results The JSE-HPS scores were significantly increased post-workshop; however, no significant differences in pre-post workshop score changes were observed among the three approaches. Overall, no demographic factor was identified to have significantly influenced empathy development. Conclusions The study demonstrated that the simulation workshop developed empathy among pharmacy students regardless of the debrief method employed within the workshop. Future work would be necessary to assess if there are long-term impacts of different debrief methods on empathy development.

The project aimed to evaluate the completeness of drug-drug interaction (DDI)-related information in package inserts (PIs) and develop a systematic approach to conduct the evaluation.DDI-related information in the branded PIs of statins, macrolides, protease inhibitors and selected drugs of narrow therapeutic index (DNTI) were evaluated against the criteria distilled from the Food and Drug Administration (FDA) labelling recommendation guidance document. Decision trees were crafted and employed in the evaluation process. Scores were computed to give each PI an overall completeness score and individual criterion completeness score. The Kruskal-Wallis test and Dunn's multiple comparison test were used to assess the differences in the completeness scores.The mean overall completeness score of the 21 PIs was 35.7 ± 13.4 % (range 12.2-62 %). Eight out of the 11 individual evaluation criterion had a mean completeness score below 50 %. A subclass analysis conducted revealed that PIs from the different drug classes differed in the type of DDI-related information, such that they are more complete or less complete.The completeness score of DDI-related information in the PIs varied extensively amongst and within drug classes. A consensus between the authorities and drug companies on the type and quality of DDI-related information to be included could improve their completeness in PIs and make PIs a valuable source of DDI reference. Decision trees, albeit not validated yet, lay the groundwork for a valuable tool to evaluate DDI-related or other drug information.

BACKGROUND: Smartphone-mediated mobile health (mHealth) has the potential to assist patients with medication adherence and disease monitoring. This study aimed to describe the awareness and usage of, and attitudes towards, mHealth among smartphone-owning patients in a tertiary hospital in Singapore. METHODS: A self-administered cross-sectional survey was systematically offered to patients at the Singapore General Hospital from August to September 2018. Participants were included if they were at least 18 years old, owned a smartphone, and could speak and read simple English. No identifiable data was collected. Responses were summarized using descriptive statistics. Multiple logistic regression analysis was used to identify factors associated with awareness and usage of, and attitudes towards, mHealth. RESULTS: Four-hundred and two eligible responses were received, with most participants reporting having completed tertiary education (63.7%) and having chronic medical conditions (71.1%), with a mean age of about 43 years. On average, participants were aware of 3.7 out of 7 mHealth functions and used 1.9 functions. Most patients were aware that smartphones could be used for general health/fitness tracking, obtaining health information, and appointment management. Most (76.3%) participants were keen to learn to use mHealth in future, and 63.2% agreed that mHealth could help them better manage their health. CONCLUSIONS: Although mHealth usage among patients was low, most patients held positive attitudes towards mHealth. For mHealth to fulfill its potential, strategies to improve the awareness and usage among patients need to be explored.

A sensitive liquid chromatography tandem mass spectrometry (LC/MS/MS) bioanalytical method was developed and validated to analyze lipoic acid (LA) in rat blood and brain samples. Ten mobile phase combinations were investigated during method development. Mobile phase combination of 0.1% acetic acid (pH 4 adjusted with ammonia solution)/acetonitrile was most optimum in terms of sensitivity and peak shape of LA and the internal standard, valproic acid. Sample extraction method was explored using liquid–liquid extraction and protein precipitation methods. Protein precipitation yielded the highest recovery of the analytes from blood and brain ranging from 92 to 115%. The lower limit of quantitation (LLOQ) of LA was 0.1 ng/mL (0.485 nM) in both blood and brain while on-column lower limit of detection (LLOD) was 0.03 pg. The precision (% R.S.D.) ranged from 1.49 to 26.39% and 1.49 to 10.89% for intra- and inter-day assays, respectively. The accuracy ranged from 91.2 to 116.17% for intra-day assay and 102.68 to 114.33% for inter-day assay.

The zebrafish model has been increasingly explored as an alternative model for toxicity screening of pharmaceutical drugs. However, little is understood about the bioactivation of drug to reactive metabolite and phase I and II metabolism of chemical in zebrafish as compared with human. The primary aim of our study was to establish the bioactivation potential of zebrafish using acetaminophen as a probe substrate. Our secondary aim was to perform metabolite profiling experiments on testosterone, a CYP3A probe substrate, in zebrafish and compare the metabolite profiles with that of human. The glutathione trapping assay of N-acetyl-p-benzoquinone imine demonstrated that zebrafish generates the same reactive metabolite as humans from the bioactivation of acetaminophen. Zebrafish possesses functional CYP3A4/5-like and UDP-glucuronosyltransferase metabolic activities on testosterone. Differential testosterone metabolism was observed among the two species. In silico docking studies suggested that the zebrafish CYP3A65 was responsible for the bioactivation of acetaminophen and phase I hydroxylation of testosterone. Our findings reinforce the need to further characterize the drug metabolism phenotype of zebrafish before the model can fully achieve its potential as an alternative toxicity screening model in drug research.

Over the past decade, zebrafish have been tasked to play important roles from modeling human diseases to finding cures for them. Inadvertently, these fish now find themselves swimming along the drug development pipeline. A number of studies have been conducted to see if these small fish are up to the task of drug toxicity testing, an important rite of passage along the pharmaceutical pipeline.This review covers the recent publications (2008 - 2010) on the state-of-the-art applications that couple advanced technologies with the unique advantages of zebrafish for drug toxicity screening. The paper looks at the several automated high-throughput platforms that have been developed for zebrafish teratogenicity, cardiotoxicity and neuro-sensory organ toxicity assays over the past 3 years as well as the important studies related to metabolism and biotransformation of selected drugs that have been initiated. This paper also reviews their mechanistic and predictive omics applications.While there have been a number of developments over the past 3 years and indeed over the last 10 years, challenges and limitations still exist, which, unless overcome, will prevent zebrafish from truly reaching their full potential as a drug toxicological model. That being said, recent developments have suggested that zebrafish could play a role in bridging the gap between in vitro cell-based models and in vivo mammalian models.

Lipoic acid (LA), an essential cofactor for mitochondrial enzymes and a natural antioxidant, has been explored for the treatment of Alzheimer's disease. However, lipoic acid distribution in brain has not been investigated via oral dosing in human subjects or animals. Therefore, we aim to investigate the distribution of orally administered LA from systemic circulation into rat brain tissues and understand the transport efficiency of lipoic acid across the blood-brain barrier. Brain and blood samples were obtained from male Lister Hooded rats at pre-defined time points after single and chronic oral dosing of LA at 50 mg/kg. Levels of LA were determined using liquid chromatography tandem mass spectrometry. An equilibrium dialysis method was employed to elucidate LA protein binding in brain and blood tissues. Basal endogenous levels of LA in control rats were found to fluctuate between 0.005 and 0.267 microM in blood and 0-0.024 microM in brain after correction for residual blood volume. Pharmacokinetic profiling demonstrated rapid biphasic elimination of LA in blood and poor distribution into various brain regions with levels ranging from 0.0009 to 0.0072 microM. The in vitro and in vivo LA brain:blood partition ratios were 0.1 and -0.01, respectively. Our results demonstrate for the first time that LA does not cross the blood-brain barrier readily and suggest that the antioxidant effect of LA in brain may not be due to its direct effect in the central nervous system.