Evaluation of jigsaw collaborative learning strategy on students' learning of clinical pharmacokinetics of special populations.

OBJECTIVES: To evaluate the learning gain and students' perceptions towards Jigsaw collaborative learning in comparison with lectures in learning about pharmacokinetic changes in special populations. METHODS: Undergraduates learn about A-D-M-E of specific populations via Jigsaw collaborative learning and didactic lectures. Pre- and post-lesson quizzes were conducted to evaluate the effectiveness of the teaching method in terms of knowledge gain. Surveys comprising Likert scale statements and open-ended questions were conducted to elucidate students' perception towards the teaching methods. RESULTS: From a class of 192 students, 118 (62%) and 110 (57%) students completed the pre- and post-lecture quizzes, respectively, while 176 (92%) and 168 (88%) students completed the pre- and post-Home Group discussion of Jigsaw quizzes, respectively. There was an improvement of 22.2% and 14.3% in median percentage quiz scores for the lecture and Jigsaw method respectively. Most students agreed that they have learned (54-60%) and collaborated (78-89%) through the Jigsaw method and rated Jigsaw as useful for their learning (54%). Open-ended survey responses offered a mixed conclusion where the didactic lecture was perceived to be as, or more effective than the Jigsaw method. CONCLUSION: Learning gains were observed through the Jigsaw collaborative learning method which relied solely on peer-teaching, despite students perceiving it to be not as effective as lecture. The method provided opportunities for active and peer-learning. Further studies are needed to evaluate the long-term effects of this teaching method.

A Critical Review on the Dosing and Safety of Antifungals Used in Exotic Avian and Reptile Species.

Antifungals are used in exotic avian and reptile species for the treatment of fungal diseases. Dose extrapolations across species are common due to lack of species-specific pharmacological data. This may not be ideal because interspecies physiological differences may result in subtherapeutic dosing or toxicity. This critical review aims to collate existing pharmacological data to identify antifungals with the most evidence to support their safe and effective use. In the process, significant trends and gaps are also identified and discussed. An extensive search was conducted on PubMed and JSTOR, and relevant data were critically appraised. Itraconazole or voriconazole showed promising results in Japanese quails, racing pigeons and inland bearded dragons for the treatment of aspergillosis and CANV-related infections. Voriconazole neurotoxicity manifested as seizures in multiple penguins, but as lethargy or torticollis in cottonmouths. Itraconazole toxicity was predominantly hepatotoxicity, observed as liver abnormalities in inland bearded dragons and a Parson's chameleon. Differences in formulations of itraconazole affected various absorption parameters. Non-linearities in voriconazole due to saturable metabolism and autoinduction showed opposing effects on clearance, especially in multiple-dosing regimens. These differences in pharmacokinetic parameters across species resulted in varying elimination half-lives. Terbinafine has been used in dermatomycoses, especially in reptiles, due to its keratinophilic nature, and no significant adverse events were observed. The use of fluconazole has declined due to resistance or its narrow spectrum of activity.

Area-Under-Curve-Guided Versus Trough-Guided Monitoring of Vancomycin and Its Impact on Nephrotoxicity: A Systematic Review and Meta-Analysis.

BACKGROUND: Conventionally, vancomycin trough levels have been used for therapeutic drug monitoring (TDM). Owing to the increasing evidence of trough levels being poor surrogates of area under the curve (AUC) and the advent of advanced pharmacokinetics software, a paradigm shift has been made toward AUC-guided dosing. This study aims to evaluate the impact of AUC-guided versus trough-guided TDM on vancomycin-associated nephrotoxicity. METHODS: A systematic review was conducted using PubMed, Embase, Web of Science, Cumulative Index to Nursing and Allied Health Literature, Google scholar, and Cochrane library databases; articles published from January 01, 2009, to January 01, 2021, were retrieved and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist. Studies that evaluated trough-guided or AUC-guided vancomycin TDM and vancomycin-associated nephrotoxicity were included. Random-effects models were used to compare the differences in nephrotoxicity. RESULTS: Of the 1191 retrieved studies, 57 were included. Most studies included adults and older adults (n = 47, 82.45%). The pooled prevalence of nephrotoxicity was lower in AUC-guided TDM [6.2%; 95% confidence interval (CI): 2.9%-9.5%] than in trough-guided TDM (17.0%; 95% CI: 14.7%-19.2%). Compared with the trough-guided approach, the AUC-guided approach had a lower risk of nephrotoxicity (odds ratio: 0.53; 95% CI: 0.32-0.89). The risk of nephrotoxicity was unaffected by the AUC derivation method. AUC thresholds correlated with nephrotoxicity only within the first 96 hours of therapy. CONCLUSIONS: The AUC-guided approach had a lower risk of nephrotoxicity, supporting the updated American Society of Health-System Pharmacists guidelines. Further studies are needed to evaluate the optimal AUC-derivation methods and clinical utility of repeated measurements of the AUC and trough levels of vancomycin.

Drug information-seeking behaviours of physicians, nurses and pharmacists: A systematic literature review.

BACKGROUND: Medication use typically involves physicians prescribing, pharmacists reviewing, and nurses administering medications to patients. Drug information (DI) is often required during the process, with the various health care professionals (HCPs) seeking information differently according to their needs and familiarity with various resources. OBJECTIVE: This systematic literature review aims to evaluate studies on drug information-seeking behaviour (ISB) of physicians, nurses and pharmacists to ascertain their DI needs, DI sources used, facilitators and barriers to DI-seeking. METHODS: A systematic search was conducted on PubMed, Embase.com, Scopus, PsycINFO, CINAHL and Cochrane Library to identify eligible primary research articles published between January 2000 and May 2020. RESULTS: The reviewed studies (N = 48) revealed that HCPs have a wide range of DI needs, with the top needs being similar across the three HCPs. Information sources used most often by all three groups were tertiary, followed by human and primary sources. Factors relating to the source characteristics were the most reported facilitators and barriers to DI-seeking. Some differences in drug ISB were also identified. CONCLUSION: Our findings can also guide information providers and educators to optimize information provision. It may also facilitate effective communication amongst HCPs when obtaining DI from or providing DI to one another.

A Critical Review on the Pharmacodynamics and Pharmacokinetics of Non-steroidal Anti-inflammatory Drugs and Opioid Drugs Used in Reptiles.

Non-steroidal anti-inflammatory drugs (NSAIDs) and opioids are analgesics used for moderate to severe pain in many animals, including reptiles. However, reptilian dosing regimens are often extrapolated from other animal species. This is not ideal as inter- and intra-species variability in physiology may result in varied drug disposition. Therefore, this critical review aims to collate data from pharmacological studies of selected NSAIDs and opioids performed in reptile and provide an analysis and discussion on the existing pharmacodynamic knowledge and pharmacokinetic data of NSAIDs and opioids use in reptiles. Additionally, key pharmacokinetic trends that may aid dosing of NSAIDs and opioids in reptiles will also be highlighted. Most of the existing reports of NSAID used in reptiles did not observe any adverse effects directly associated to the respective NSAID used, with meloxicam being the most well-studied. Despite the current absence of analgesic efficacy studies for NSAIDs in reptiles, most reports observed behavioural improvements in reptiles after NSAID treatment. Fentanyl and morphine were studied in the greatest number of reptile species with analgesic effects observed with the doses used, while adverse effects such as sedation were observed most with butorphanol use. While pharmacokinetic trends were drug- and species-specific, it was observed that clearance (CL) of drugs tended to be higher in squamates compared to chelonians. The half-life (t1/2) of meloxicam also appeared to be longer when dosed orally compared to other routes of drug administration. This could have been due to absorption-rate limited disposition. Although current data provided beneficial information, there is an urgent need for future research on NSAID and opioid pharmacology to ensure the safe and effective use of opioids in reptiles.

A Critical Review of the Pharmacokinetics, Pharmacodynamics, and Safety Data of Antibiotics in Avian Species.

In avian medicine, the use of antibiotic dosing regimens based on species-specific pharmacological studies is ideal. However, due to a lack of such studies, dose extrapolation, which may cause inefficacy and toxicity, is common practice. Multiple searches were performed using the PubMed and Web of Science databases to extract relevant pharmacological studies performed in exotic avian species. The pharmacokinetics (PK), pharmacodynamics (PD), and safety data of the selected antibiotics (enrofloxacin, marbofloxacin, gentamicin, amikacin, ceftiofur, doxycycline, and amoxicillin/clavulanate) from these studies were reviewed. This review aimed to identify trends amenable for safe inter-species dose extrapolation and provide updated findings on dosing regimens that are safe and efficacious for various exotic avian species. We observed that the half-life of antibiotics appears to be shorter in the common ostrich and that amikacin may be amenable to inter-species dose extrapolation as it is safe and shows little inter-species PK and PD variation. Species-specific enrofloxacin dosing regimens that were not listed in the Exotic Animal Formulary (5th ed.) were found for Caribbean flamingos, African penguins, southern crested caracaras, common ostriches, and greater rheas. Specific dosing regimens recommended for psittacine birds (doxycycline 130 mg/kg medicated water) and ratites (PO doxycycline 2-3.5 mg/kg q12 h, PO enrofloxacin 1.5-2.5 mg/kg q12 h and IM enrofloxacin 5 mg/kg q12 h) in the formulary may not be effective in budgerigars and common ostriches, respectively. Apart from the lack of species-specific pharmacological studies, a lack of multiple dose studies was also noted.

Impact of an aging simulation workshop with different debrief methods on the development of empathy in pharmacy undergraduates.

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.

Stirring deep thinking and learning through student-designed assessment problems.

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.

Patients' attitudes towards mobile health in Singapore: a cross-sectional study.

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.

An evaluation of the completeness of drug-drug interaction-related information in package inserts.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

An investigation of the bioactivation potential and metabolism profile of Zebrafish versus human.

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.

Zebrafish for drug toxicity screening: bridging the in vitro cell-based models and in vivo mammalian models.

INTRODUCTION: 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. AREAS COVERED: 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. EXPERT OPINION: 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.

A sensitive LC/MS/MS bioanalysis assay of orally administered lipoic acid in rat blood and brain tissue.

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 0.1ng/mL (0.485nM) in both blood and brain while on-column lower limit of detection (LLOD) was 0.03pg. 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.