Work readiness of pharmacy graduates: An exploratory study.

Introduction: The recent global pandemic of Covid-19 caused various disruptions. Among them were face-to-face teaching and learning activities being switched to virtual sessions in accordance with health authorities recommendations. The impact of these changes on work readiness of pharmacy graduates is unknown. Aim: This study aims to determine the impact of pharmacy graduate's work readiness, particularly those that had their studies disrupted from the pandemic. Methods: Practicing pharmacists with supervisory experience were interviewed on their opinions on work readiness of early career and intern pharmacists. Specifically, they were asked to comment on work readiness of pharmacy graduates who had their later stage of pharmacy education impacted by the pandemic. Data was transcribed verbatim and thematically analysed. This was also supplemented with quantitative data from graduating students in 2020 and 2021 using the Work Readiness Scale. Results: Qualitative feedback showed four themes related to workforce readiness: work competence, social intelligence, personal characteristics, and organizational acumen. Preceptors interviewed noted differences in communication abilities when interacting with patients. However, this improved with time. Quantitative data collected from graduates via the validated Work-Readiness Scale also showed a more positive agreement towards perceived work readiness. These graduates were comfortable with using technology as they had used these extensively in their learning during the pandemic and thus was comfortable in adopting digital health tools in their practice. Conclusion: Although graduates reported to be work ready, there were gaps in communication skills and confidence levels when interacting with patients, as reported by supervising preceptors. Graduates also described this sense of 'missing out' from not having the opportunity to attend face-to-face activities like their originally planned hospital placements and how it impacted their choice of career. As pharmacists continue to play vital roles as members of the broader healthcare workforce, both in clinical and nonclinical settings, learnings from this study should be considered in designing educational activities to train and develop the workforce of the future.

Remote extemporaneous compounding lab practical for pharmacy students during the COVID-19 pandemic.

BACKGROUND AND PURPOSE: Due to COVID-19 movement restrictions, institutes of higher learning had to deliver pharmacy curricula remotely. One major challenge was teaching practical lab skills, such as extemporaneous compounding, remotely due to the need for hands-on learning and its associated logistical requirements. EDUCATIONAL ACTIVITY AND SETTING: We present the approach to remote extemporaneous compounding teaching taken by three pharmacy schools: Monash University Malaysia, University of Michigan, and University of Maryland. Prior to delivery, students were either supplied with or asked to procure a set of easily accessible ingredients and equipment to conduct the extemporaneous practicals from home. We conducted lessons remotely using both synchronous and asynchronous delivery, and demonstrated, taught, and assessed practical lab skills using video conferencing modalities. FINDINGS: We successfully conducted remote teaching of extemporaneous compounding, where similar learning outcomes to the face-to-face implementation were achieved. At Monash University Malaysia, > 90% of students responding to the post-activity surveys found the remote extemporaneous sessions useful for their learning, and qualitative comments supported these views. Mean scores from the remote extemporaneous labs in 2021 were similar to those when conducted physically in 2019, supporting the effectiveness of the approach. The different approaches attempted by the three institutions highlighted the flexibility in implementation that can be considered to achieve similar outcomes. SUMMARY: Combining technology-based approaches with synchronous and asynchronous teaching and learning methods can successfully deliver extemporaneous compounding skills remotely.

Perspectives on opportunities and challenges in a predominantly flipped classroom-based pharmacy curriculum: A qualitative study.

INTRODUCTION: To adapt to flipped classroom pedagogy in universities, factors such as the amount of the program that is flipped, students' pre-existing educational experiences, and cultural background may influence adjusting to the approach. We investigated students' perspectives across four years of a predominantly flipped classroom-based pharmacy curriculum in a low to middle income country. METHODS: We conducted five semi-structured focus groups with 18 pharmacy students from years one to four of the bachelor of pharmacy program at Monash University Malaysia where students came from different pre-university backgrounds. Focus group recordings were transcribed verbatim and thematically analysed. Interrater reliability was performed to ascertain reliability of themes. RESULTS: Three major themes were identified. Firstly, students cited issues moving past the initial barrier when starting flipped classrooms in terms of education background impacting adaptability and how/why they eventually adapted. Another theme was how flipped classrooms helped development of life skills such as adaptability, communication, teamwork, self-reflection, and time management. The final theme was on requiring a sufficient safety net and support system in flipped classrooms that included well designed pre-classroom materials and well-implemented feedback mechanisms. CONCLUSIONS: We have identified students' perspectives on the benefits and challenges associated with a predominantly flipped classroom pharmacy curriculum in a low to middle income country setting. We suggest using scaffolding and effective feedback approaches to guide the implementation of flipped classrooms successfully. This work can aid future educational designers in preparation and supporting a more equitable learning experience regardless of student background.

Reproduction and production in a social context: Group size, reproductive skew and increasing returns.

Evolutionary success requires both production (acquisition of food, protection and warmth) and reproduction. We suggest that both may increase disproportionately as group size grows, reflecting 'increasing returns' or 'group augmentation benefits', raising fitness in groups that cooperate in production and limit reproduction to one or a few high fertility females supported by non-reproductives, with high reproductive skew. In our optimisation theory both Allee effects (when individual fitness increases with group size or density) and reproductive skew arise when increasing returns determine optimal group size and proportion of reproductive females. Depending on which of food or maternal time is more important for reproduction, evolutionary trajectories of lineages may (1) reach a boundary constraint where only one female reproduces in a period (as with African wild dogs) or (2) reach a boundary where all females reproduce during their lifetimes but only during an early life stage (human menopause) or a late life stage (birds with non-dispersing helpers), where stage length optimises the proportion of females that is reproductive at any time or (3) reach the intersection of these boundary constraints where a single reproductive female is fully specialised in reproduction (as with eusocial insects). We end with some testable hypotheses.

A Community-Based Pancreatic Cancer Screening Study in High-Risk Individuals: Preliminary Efficacy and Safety Results.

INTRODUCTION: Pancreatic cancer (PC) screening recommendations have been based on studies performed solely at high-volume academic centers. To make PC screening more widely available, community-based efforts are essential. We implemented a prospective PC screening study in the community of Fairfield County, CT, and report our early safety and efficacy results. METHODS: Eligible individuals were enrolled into an investigator-initiated study and underwent a baseline and 3 annual magnetic resonance imagings/magnetic resonance cholangiopancreatographies (MRIs/MRCPs) with gadolinium, biannual blood donations for biobanking, and assessments for anxiety and depression. All MRIs were presented at a multidisciplinary board to determine whether further investigation was warranted. RESULTS: Seventy-five individuals have been enrolled and 201 MRIs performed over a 2.6-year average length of follow-up. Abnormal pancreatic findings (predominantly small cysts) were detected in 58.7% of the participants. Among these, 6.7% underwent endoscopic ultrasound, with 1 case complicated by postprocedural pancreatitis. One surgical resection was performed on a 4.7-cm intraductal papillary mucinous neoplasm with a focus on low-grade pancreatic intraepithelial neoplasia. One incidental finding of fibrosing mediastinitis was detected. Anxiety and depression scores decreased over the course of this study from 21.4% to 5.4% and 10.7% to 3.6%, respectively. DISCUSSION: This preliminary report supports the feasibility of performing MRI/magnetic resonance cholangiopancreatographies-based PC screening as part of a clinical trial in a community setting. A longer follow-up is needed to better assess safety and efficacy. To the best of our knowledge, this is the first report from a community-based PC screening effort ( clinicaltrials.gov ID: NCT03250078).

Data-driven contact network models of COVID-19 reveal trade-offs between costs and infections for optimal local containment policies.

While several non-pharmacological measures have been implemented for a few months in an effort to slow the coronavirus disease (COVID-19) pandemic in the United States, the disease remains a danger in a number of counties as restrictions are lifted to revive the economy. Making a trade-off between economic recovery and infection control is a major challenge confronting many hard-hit counties. Understanding the transmission process and quantifying the costs of local policies are essential to the task of tackling this challenge. Here, we investigate the dynamic contact patterns of the populations from anonymized, geo-localized mobility data and census and demographic data to create data-driven, agent-based contact networks. We then simulate the epidemic spread with a time-varying contagion model in ten large metropolitan counties in the United States and evaluate a combination of mobility reduction, mask use, and reopening policies. We find that our model captures the spatial-temporal and heterogeneous case trajectory within various counties based on dynamic population behaviors. Our results show that a decision-making tool that considers both economic cost and infection outcomes of policies can be informative in making decisions of local containment strategies for optimal balancing of economic slowdown and virus spread.

Cultural adaptation and validation of instruments for measuring the flipped classroom experience.

INTRODUCTION: In 2017, a revamped bachelor of pharmacy program was introduced at Monash University and incorporated a predominantly flipped classroom-based pedagogy. The attitudes and preferences of students towards this program had yet to be assessed using a reliable instrument. Since no instrument was readily available, the objective of this study was to identify, contextualize, and validate a suitable instrument. METHODS: We conducted a literature search to identify and adapt a validated instrument. Cognitive interviews were conducted to examine students' understanding of scales and definitions of items. The instrument was then evaluated by education experts for further refinement. The reliability of the final instrument was assessed in a cohort of students, and unsuitable items were removed. RESULTS: Students had issues understanding the scales and specific terms used in the original instrument, potentially due to differences in terminologies used in the university's context and variance in English proficiency levels and exposure. In the preference domain, wording of the instrument to present exclusively traditional classroom or exclusively flipped classroom statements greatly influenced its reliability. This could be due to exposure of students to a predominantly flipped classroom environment since inception. The final instrument optimized in this study had α = 0.85, 0.86, and 0.9 for the pre-activities, in-class lectures, and in-class workshops attitude domains, respectively, and α = 0.73 for the preference domain. CONCLUSIONS: Our study highlights the necessity of contextualizing instruments to fit the local context in which they are administered and provides key recommendations when conducting such adaptations.

Fine-grained data reveal segregated mobility networks and opportunities for local containment of COVID-19.

Deriving effective mobility control measures is critical for the control of COVID-19 spreading. In response to the COVID-19 pandemic, many countries and regions implemented travel restrictions and quarantines to reduce human mobility and thus reduce virus transmission. But since human mobility decreased heterogeneously, we lack empirical evidence of the extent to which the reductions in mobility alter the way people from different regions of cities are connected, and what containment policies could complement mobility reductions to conquer the pandemic. Here, we examined individual movements in 21 of the most affected counties in the United States, showing that mobility reduction leads to a segregated place network and alters its relationship with pandemic spread. Our findings suggest localized area-specific policies, such as geo-fencing, as viable alternatives to city-wide lockdown for conquering the pandemic after mobility was reduced.

Characteristics and outcomes of young patients with ST segment elevation myocardial infarction undergoing primary percutaneous coronary intervention: retrospective analysis in a multiethnic Asian population.

OBJECTIVE: ST segment elevation myocardial infarction (STEMI) is associated with significant mortality leading to loss of productive life years, especially in younger patients. This study aims to compare the characteristics and outcomes of young versus older patients with STEMI undergoing primary percutaneous coronary intervention (PPCI) to help focus public health efforts in STEMI prevention. METHODS: Data from the Coronary Care Unit database of the National University Hospital, Singapore from July 2015 to June 2019 were reviewed. Patients were divided into young (<50 years old) or older (≥50 years old) groups. RESULTS: Of the 1818 consecutive patients with STEMI who underwent PPCI, 465 (25.6%) were <50 years old. Young compared with older patients were more likely to be male, current smokers, of Indian ethnicity, have family history of ischaemic heart disease (IHD) and had lower 1 year mortality (3.4% vs 10.4%, p<0.0001). Although diabetes, hypertension or dyslipidaemia was less common among young patients, the prevalence of having any one of these risk factors was high in the range of 28% to 38%. Age was an independent predictor of mortality in the older but not younger patients with STEMI, and diabetes showed a trend towards mortality in both groups. CONCLUSION: Young patients with STEMI are more often smokers, of Indian ethnicity and had family history of IHD, although cardiometabolic risk factors are also prevalent. Mortality is lower, but not negligible, among the young patients with STEMI. Public health efforts are needed to reduce the prevalence of these risk factors among the constitutionally susceptible population.

Intergenerational resource sharing and mortality in a global perspective.

Resource sharing has always been a central component of human sociality. Children require heavy investments in human capital; during working years, help is needed due to illness, disability, or bad luck. While hunter-gatherer elders assisted their descendants, more recently, elderly withdraw from work and require assistance as well. Willingness to share has been critically important for our past evolutionary success and our present daily lives. Here, we document a strong linear relationship between the public and private sharing generosity of a society and the average length of life of its members. Our findings from 34 countries on six continents suggest that survival is higher in societies that provide more support and care for one another. We suggest that this support reduces mortality by meeting urgent material needs, but also that sharing generosity may reflect the strength of social connectedness, which itself benefits human health and wellbeing and indirectly raises survival.

Demographic perspectives on the mortality of COVID-19 and other epidemics.

To put estimates of COVID-19 mortality into perspective, we estimate age-specific mortality for an epidemic claiming for illustrative purposes 1 million US lives, with results approximately scalable over a broad range of deaths. We calculate the impact on period life expectancy (down 2.94 y) and remaining life years (11.7 y per death). Avoiding 1.75 million deaths or 20.5 trillion person years of life lost would be valued at $10.2 to $17.5 trillion. The age patterns of COVID-19 mortality in other countries are quite similar and increase at rates close to each country's rate for all-cause mortality. The scenario of 1 million COVID-19 deaths is similar in scale to that of the decades-long HIV/AIDS and opioid-overdose epidemics but considerably smaller than that of the Spanish flu of 1918. Unlike HIV/AIDS and opioid epidemics, the COVID-19 deaths are concentrated in a period of months rather than spread out over decades.

Redistributive effects of different pension systems when longevity varies by socioeconomic status.

We propose a general analytical framework to model the redistributive features of alternative pension systems when individuals face ex ante differences in mortality. Differences in life expectancy between high and low socioeconomic groups are often large and have widened recently in many countries. Such longevity gaps affect the actuarial fairness and progressivity of public pension systems. However, behavioral responses to longevity and policy complicate analysis of possible reforms. Here we consider how various pension systems would perform in an OLG setting with heterogeneous longevity and ability. We evaluate redistributive effects of three Notional Defined Contribution plans and three Defined Benefit plans, calibrated on the US case. Compared to a benchmark non-redistributive plan that accounts for differences in mortality, US Social Security reduces regressivity from longevity differences, but would require group-specific life tables to achieve progressivity. Moreover, without separate life tables, despite apparent accounting gains, lower income groups would suffer welfare losses and higher income groups would enjoy welfare gains through indirect effects of pension systems on labor supply.

Single Coronary Artery in a Young Male with Chest Pain.

A young male presented to the hospital with chest pain. A coronary angiogram and a subsequent computed tomography coronary angiogram revealed a single coronary artery arising from the right coronary sinus which bifurcated into the right coronary artery and a large branch which supplies the left coronary artery territory. (Level of Difficulty: Beginner.).

ATM-Mutated Pancreatic Cancer: Clinical and Molecular Response to Gemcitabine/Nab-Paclitaxel After Genome-Based Therapy Resistance.

Metastatic pancreatic cancer (PC) is an aggressive malignancy, with most patients deriving benefit only from first-line chemotherapy. Increasingly, the recommended treatment for those with a germline mutation in a gene involved in homologous recombination repair is with a platinum drug followed by a poly (ADP-ribose) polymerase (poly adenosine phosphate-ribose polymerase [PARP]) inhibitor. Yet, this is based largely on studies of BRCA1/2 or PALB2 mutated PC. We present the case of a 44-year-old woman with ATM-mutated PC who achieved stable disease as the best response to first-line fluorouracil, leucovorin, irinotecan, and oxaliplatin, followed by progression on a PARP inhibitor. In the setting of jaundice, painful hepatomegaly, and a declining performance status, she experienced rapid disease regression with the nonplatinum regimen, gemcitabine plus nab-paclitaxel. Both physical stigmata and abnormal laboratory values resolved, imaging studies showed a reduction in metastases and her performance status returned to normal. Measurement of circulating tumor DNA for KRAS G12R by digital droplet polymerase chain reaction confirmed a deep molecular response. This case highlights that first-line treatment with a platinum-containing regimen followed by PARP inhibition may not be the best choice for individuals with ATM-mutated pancreatic cancer. Additional predictors of treatment response are needed in this setting.

Disposition and metabolism of the G protein-coupled receptor 40 agonist TAK-875 (fasiglifam) in rats, dogs, and humans.

The absorption, distribution, metabolism, and excretion of fasiglifam were investigated in rats, dogs, and humans. The absolute oral bioavailability of fasiglifam was high in all species (>76.0%). After oral administration of [14C]fasiglifam, the administered radioactivity was quantitatively recovered and the major route of excretion of radioactivity was via feces in all species. Fasiglifam was a major component in the plasma and feces in all species. Its oxidative metabolite (M-I) was observed as a minor metabolite in rat and human plasma (<10% of plasma radioactivity). In human plasma, hydroxylated fasiglifam (T-1676427), the glucuronide of fasiglifam (fasiglifam-G), and the glucuronide of M-I were detected as additional minor metabolites (<2% of plasma radioactivity). None of these metabolites were specific to humans. Fasiglifam-G was the major component in the rat and dog bile. In vitro cytochrome P450 (CYP) and uridine diphosphate glucuronosyltransferase (UGT) reaction phenotyping indicated that oxidation (to form M-I and T-1676427) and glucuronidation of fasiglifam are mainly mediated by CYP3A4/5 and UGT1A3, respectively. Fasiglifam and fasiglifam-G are substrates of BCRP and Mrp2/MRP2, respectively. Glucuronidation of fasiglifam-G was found to be the predominant elimination pathway of fasiglifam in all species tested, including humans.

Versatile Tool for the Analysis of Metal-Protein Interactions Reveals the Promiscuity of Metallodrug-Protein Interactions.

Metallodrug-protein interactions contribute to their therapeutic effect (even when DNA is the dominant target), side-effects and are implicit in drug resistance. Here, we provide mass spectrometric-based evidence to show that metallodrug interactions with proteins are considerably more complex than current literature would suggest. Using native-like incubation and electrospray conditions together with an automated tool we designed for exhaustive mass spectra matching, the promiscuity of binding of cisplatin to ubiquitin is revealed, with 14 different binding sites observed. There is a binding preference to negatively charged sites on the protein, consistent with the cationic nature of the cisplatin adduct following aquation. These results have implications in metallodrug development and beyond to the toxicological effects of metal ions more generally.

Differences in cisplatin distribution in sensitive and resistant ovarian cancer cells: a TEM/NanoSIMS study.

Cisplatin is a widely used anti-cancer drug, but its effect is often limited by acquired resistance to the compound during treatment. Here, we use a combination of transmission electron microscopy (TEM) and nanoscale-secondary ion mass spectrometry (NanoSIMS) to reveal differences between cisplatin uptake in human ovarian cancers cells, which are known to be susceptible to acquired resistance to cisplatin. Both cisplatin sensitive and resistant cell lines were studied, revealing markedly less cisplatin in the resistant cell line. In cisplatin sensitive cells, Pt was seen to distribute diffusely in the cells with hotspots in the nucleolus, mitochondria, and autophagosomes. Inductively coupled plasma mass spectrometry (ICP-MS) was used to validate the NanoSIMS results.

The Differential Distribution of RAPTA-T in Non-Invasive and Invasive Breast Cancer Cells Correlates with Its Anti-Invasive and Anti-Metastatic Effects.

Nanoscale secondary ion mass spectrometry (NanoSIMS) combined with transmission electron microscopy (TEM) can be a powerful approach to visualize the exact distribution of drugs at the sub-cellular level. In this work, we exploit this approach to identify the distribution and localisation of the organometallic ruthenium(II)-arene drug Ru(η6-C6H5Me)(pta)Cl2, termed RAPTA-T, in MDA-MB-231 and MCF-7 human breast cancer cells. These cell lines have been chosen because the former cell lines are highly invasive and resistant to most chemotherapeutic agents and the latter ones are very sensitive to hormonal-based therapies. In the MDA-MB-231 cells, RAPTA-T was found to predominantly localise on the cell membrane and to a lesser extent in the nucleolus. These findings are consistent with the previously reported anti-metastatic properties of RAPTA-T and the observation that once internalized RAPTA-T is associated with chromatin. RAPTA-T shows a lack of membrane accumulation on the non-invasive MCF-7 cells, which correlates well with its selective anti-metastatic properties on invasive cell lines.

Biochemical and biophysical characterization of ruthenation of BRCA1 RING protein by RAPTA complexes and its E3 ubiquitin ligase activity.

RAPTA compounds, ([Ru(η6-arene)(PTA)Cl2], PTA = 1,3,5-triaza-7-phosphaadamantane), have been reported to overcome drug resistance in cisplatin resistant cells. However, the exact mechanism of these complexes is still largely unexplored. In this study, the interaction of some RAPTA compounds with the N-terminal fragment of the BRCA1 RING domain protein was investigated. The binding of the RAPTA compounds to the BRCA1 protein resulted in a release of Zn2+ ions in a dose and time dependent manner, as well as thermal alteration of ruthenated-BRCA1 proteins. Electron Transfer Dissociation (ETD) fragmentation mass spectrometry revealed the preferential binding sites of the RAPTA complexes on the BRCA1 zinc finger RING domain at a similar short peptide stretch, Cys24Lys25Phe26Cys27Met28Leu29 and Lys35 (residues 44-49 and 55 on full length BRCA1). Changes in the conformation and binding constants of ruthenium-BRCA1 adducts were established, resulting in inactivation of the RING heterodimer BRCA1/BARD1-mediated E3 ubiquitin ligase function. These findings could provide mechanistic insight into the mode of action of RAPTA complexes for on tested BRCA1 model protein.