Establishing inclusion safety in pharmacy education: Wielding psychological safety as a tool to address student burnout.

INTRODUCTION: Burnout is a common issue that impacts students across professional programs, where symptoms such as loneliness and isolation lead to a decrease in student and faculty success. The primary tactic utilized to combat burnout in pharmacists has been an emphasis on wellbeing strategies. COMMENTARY: Psychological safety is an important cultural dynamic that allows individuals to feel included, supported, and heard. This is particularly important as developing a professional setting of inclusivity and safety is associated with reducing the impact of psychosocial stressors on an individual outside of their professional setting. However, psychological safety has not yet been explored as a means to combat burnout in pharmacy education. IMPLICATIONS: Making space for inclusion, learning, contribution, and challenge in pharmacy education curriculums is necessary to create psychologically safe learning environments, which thereby increases feelings of belonging and community among students and faculty and subsequently reduces feelings of isolation and burnout. A commitment from administrators, faculty, and preceptors is necessary to encourage egalitarian dialogue and imagine a more dynamic, collegial relationship among students and faculty. Ultimately, this commitment communicates to students that they are valued as human beings, respected as individuals, and empowered as future healthcare providers well before they are asked to rise to the role of pharmacist.

Blood-stage malaria vaccine candidate RH5.1/Matrix-M in healthy Tanzanian adults and children; an open-label, non-randomised, first-in-human, single-centre, phase 1b trial.

BACKGROUND: A blood-stage Plasmodium falciparum malaria vaccine would provide a second line of defence to complement partially effective or waning immunity conferred by the approved pre-erythrocytic vaccines. RH5.1 is a soluble protein vaccine candidate for blood-stage P falciparum, formulated with Matrix-M adjuvant to assess safety and immunogenicity in a malaria-endemic adult and paediatric population for the first time. METHODS: We did a non-randomised, phase 1b, single-centre, dose-escalation, age de-escalation, first-in-human trial of RH5.1/Matrix-M in Bagamoyo, Tanzania. We recruited healthy adults (aged 18-45 years) and children (aged 5-17 months) to receive the RH5.1/Matrix-M vaccine candidate in the following three-dose regimens: 10 µg RH5.1 at 0, 1, and 2 months (Adults 10M), and the higher dose of 50 µg RH5.1 at 0 and 1 month and 10 µg RH5.1 at 6 months (delayed-fractional third dose regimen; Adults DFx). Children received either 10 µg RH5.1 at 0, 1, and 2 months (Children 10M) or 10 µg RH5.1 at 0, 1, and 6 months (delayed third dose regimen; Children 10D), and were recruited in parallel, followed by children who received the dose-escalation regimen (Children DFx) and children with higher malaria pre-exposure who also received the dose-escalation regimen (High Children DFx). All RH5.1 doses were formulated with 50 µg Matrix-M adjuvant. Primary outcomes for vaccine safety were solicited and unsolicited adverse events after each vaccination, along with any serious adverse events during the study period. The secondary outcome measures for immunogenicity were the concentration and avidity of anti-RH5.1 serum IgG antibodies and their percentage growth inhibition activity (GIA) in vitro, as well as cellular immunogenicity to RH5.1. All participants receiving at least one dose of vaccine were included in the primary analyses. This trial is registered at ClinicalTrials.gov, NCT04318002, and is now complete. FINDINGS: Between Jan 25, 2021, and April 15, 2021, we recruited 12 adults (six [50%] in the Adults 10M group and six [50%] in the Adults DFx group) and 48 children (12 each in the Children 10M, Children 10D, Children DFx, and High Children DFx groups). 57 (95%) of 60 participants completed the vaccination series and 55 (92%) completed 22 months of follow-up following the third vaccination. Vaccinations were well-tolerated across both age groups. There were five serious adverse events involving four child participants during the trial, none of which were deemed related to vaccination. RH5-specific T cell and serum IgG antibody responses were induced by vaccination and purified total IgG showed in vitro GIA against P falciparum. We found similar functional quality (ie, GIA per µg RH5-specific IgG) across all age groups and dosing regimens at 14 days after the final vaccination; the concentration of RH5.1-specific polyclonal IgG required to give 50% GIA was 14·3 µg/mL (95% CI 13·4-15·2). 11 children were vaccinated with the delayed third dose regimen and showed the highest median anti-RH5 serum IgG concentration 14 days following the third vaccination (723 µg/mL [IQR 511-1000]), resulting in all 11 who received the full series showing greater than 60% GIA following dilution of total IgG to 2·5 mg/mL (median 88% [IQR 81-94]). INTERPRETATION: The RH5.1/Matrix-M vaccine candidate shows an acceptable safety and reactogenicity profile in both adults and 5-17-month-old children residing in a malaria-endemic area, with all children in the delayed third dose regimen reaching a level of GIA previously associated with protective outcome against blood-stage P falciparum challenge in non-human primates. These data support onward efficacy assessment of this vaccine candidate against clinical malaria in young African children. FUNDING: The European and Developing Countries Clinical Trials Partnership; the UK Medical Research Council; the UK Department for International Development; the National Institute for Health and Care Research Oxford Biomedical Research Centre; the Division of Intramural Research, National Institute of Allergy and Infectious Diseases; the US Agency for International Development; and the Wellcome Trust.

Amiodarone-Induced Leukocytoclastic Vasculitis in a Decompensated Heart Failure Patient: A Case Report.

Leukocytoclastic vasculitis (LCV) is a small-vessel vasculitis characterized by inflammation and damage to the walls of small blood vessels. It typically presents with palpable purpura and can be associated with various systemic conditions. Although its etiology is diverse, LCV has been associated with systemic diseases, infections, medications, and autoimmune disorders. Here, we present a case of LCV in a patient with decompensated heart failure. A 58-year-old man presented with progressively deteriorating swelling in both his lower limbs and scrotum, a persistent dry cough associated with minor ulcerative lesions on his shins, and a patchy rash with pustules and flat reddish spots. He was hospitalized three days prior due to atrial fibrillation and rapid ventricular rate, for which he was commenced on amiodarone. This rash persisted for three days, yet he denied experiencing any discomfort or itchiness along with it. Based on his clinical picture, laboratory evaluations, and imaging findings, he was diagnosed with LCV induced by amiodarone.

Can evidence drive health equity in the COVID-19 pandemic and beyond?

Using scoping review methods, we systematically searched multiple online databases for publications in the first year of the pandemic that proposed pragmatic population or health system-level solutions to health inequities. We found 77 publications with proposed solutions to pandemic-related health inequities. Most were commentaries, letters, or editorials from the USA, offering untested solutions, and no robust evidence on effectiveness. Some of the proposed solutions could unintentionally exacerbate health inequities. We call on health policymakers to co-create, co-design, and co-produce equity-focussed, evidence-based interventions with communities, focussing on those most at risk to protect the population as a whole. Epidemiologists collaborating with people from other relevant disciplines may provide methodological expertise for these processes. As epidemiologists, we must interrogate our own methods to avoid propagating any unscientific biases we may hold. Epidemiology must be used to address, and never exacerbate, health inequities-in the pandemic and beyond.

Per-patient Negative Predictive Value of the CT and MRI Liver Imaging Reporting and Data System Version 2018 Treatment Response Algorithm for Hepatocellular Carcinoma.

Background The Liver Imaging Reporting and Data System version 2018 (LI-RADS) treatment response algorithm (TRA) is a high-specificity, lower-sensitivity grading system to diagnose hepatocellular carcinoma (HCC) and recurrence after local-regional therapy. However, the emphasis on specificity can result in disease understaging, potentially leading to poorer posttransplant outcomes. Purpose To determine the negative predictive value (NPV) of pretransplant CT and MRI assessment for viable HCC on a per-patient basis using the LI-RADS TRA, considering explant pathology as the reference standard. Materials and Methods Patient records from 218 consecutive adult patients from a single institution with HCC who underwent liver transplant from January 2011 to November 2017 were retrospectively reviewed. Two readers blinded to the original report reviewed immediate (within 90 days) pretransplant imaging and characterized observations according to the LI-RADS TRA. Based on this, patients with LR-4, LR-5, or LR-TR (treatment response) viable tumors were designated as viable tumor; patients with solely LR-3 or LR-TR equivocal tumors were designated as equivocal; and patients with only LR-TR nonviable lesions were designated as no viable disease. Patients were designated as within or outside the Milan criteria. These per-patient designations were compared with the presence of viable disease at explant pathology. Fisher exact test was used to compare the differences between CT and MRI. Weighted κ values were used to calculate interreader reliability. Results Final study sample consisted of 206 patients (median age, 61 years [IQR, 57-65 years]; 157 male patients and 49 female patients). Per-patient LI-RADS TRA assessment of pretransplant imaging had an NPV of 32% (95% CI: 27, 38) and 26% (95% CI: 20, 33) (readers 1 and 2, respectively) for predicting viable disease. Seventy-five percent (reader 1) and 77% (reader 2) of patients deemed equivocal had residual tumors at explant pathology. Weighted interreader reliability was substantial (κ = 0.62). Conclusion Patient-based stratification of viable, equivocal, and nonviable disease at pretransplant CT or MRI, based on LI-RADS TRA, demonstrated low negative predictive value in excluding HCC at explant pathology. © RSNA, 2023 See also the editorial by Tamir and Tau in this issue.

Vitamin D and Cardiovascular Diseases: An Update.

Vitamin D is a vital nutrient that plays a significant part in several physiological processes within the human body, including calcium metabolism, bone health, immune function, and cell growth and differentiation. It is obtained mainly through exposure to sunlight but can be acquired from certain foods and supplements as well. Vitamin D deficiency (VDD) could be the risk factor for cardiovascular diseases (CVDs), such as heart disease and stroke. In blood vitamin D low levels have been linked with an enhanced risk of developing CVDs. However, it is unclear whether vitamin D levels are the leading cause or consequence of these conditions. While some studies highlight that taking vitamin D supplements could decrease the risk of CVD; however, more research is required to better understand the association between vitamin D and cardiovascular health. In this review, we aimed to summarize the currently available evidence supporting the association between vitamin D and CVDs and anesthesia considerations.