Impacts, Learner Diversity, and Curricular Framework of a Virtual Global Health Elective Catalyzed by the COVID-19 Pandemic.

Background: Place-based international electives that build global health competencies have existed for decades. However, these electives require travel and are infeasible for many trainees around the world, particularly those with insufficient financial resources, logistical complexities, or visa limitations. The emergence of virtual approaches to global health electives, catalyzed by the travel pause related to the COVID-19 pandemic, necessitates the exploration of learner impacts, participant diversity, and curricular frameworks. Child Family Health International (CFHI), a non-profit global health education organization that partners with universities to expand immersive educational offerings, launched a virtual global health elective in 2021. The elective drew on faculty from Bolivia, Ecuador, Ghana, Mexico, the Philippines, Uganda, and the United States. Objective: This study aimed to describe a newly developed virtual global health elective curriculum and evaluate the demographics of and impacts on trainee participants. Methods: Eighty-two trainees who were enrolled in the virtual global health elective from January to May 2021 completed both 1) pre- and post-elective self-assessments of domains of competency mapped to the elective curriculum and 2) free text responses to standardized questions. Data were analyzed through descriptive statistical analysis, paired t-testing, and qualitative thematic analysis. Findings: The virtual global health elective had 40% of its participants hail from countries other than the United States. Self-reported competency in global health broadly, planetary health, low resource clinical reasoning, and overall composite competency significantly increased. Qualitative analysis revealed learner development in health systems, social determinants of health, critical thinking, planetary health, cultural humility, and professional practice. Conclusion: Virtual global health electives effectively develop key competencies in global health. This virtual elective had a 40-fold increase in the proportion of trainees from outside the United States, compared to pre-pandemic place-based electives. The virtual platform facilitates accessibility for learners from a variety of health professions and a wide range of geographic and socioeconomic environments. Further research is needed to confirm and expand on self-reported data, and to pursue approaches to greater diversity, equity, and inclusion in virtual frameworks.

Investigation Into the Role of ERK in Tyrosine Kinase Inhibitor-Induced Neuropathy.

Chemotherapy-induced peripheral neuropathy (CIPN) is a common and debilitating adverse event that can alter patient treatment options and halt candidate drug development. A case study is presented here describing the preclinical and clinical development of CC-90003, a small molecule extracellular signal-regulated kinase (ERK)1/2 inhibitor investigated as an oncology therapy. In a Phase Ia clinical trial, CC-90003 elicited adverse drug-related neuropathy and neurotoxicity that contributed to discontinued development of CC-90003 for oncology therapy. Preclinical evaluation of CC-90003 in dogs revealed clinical signs and electrophysiological changes consistent with peripheral neuropathy that was reversible. Mice did not exhibit signs of neuropathy upon daily dosing with CC-90003, supporting that rodents generally poorly predict CIPN. We sought to investigate the mechanism of CC-90003-induced peripheral neuropathy using a phenotypic in vitro assay. Translating preclinical neuropathy findings to humans proves challenging as no robust in vitro models of CIPN exist. An approach was taken to examine the influence of CIPN-associated drugs on human-induced pluripotent stem cell-derived peripheral neuron (hiPSC-PN) electrophysiology on multielectrode arrays (MEAs). The MEA assay with hiPSC-PNs was sensitive to CIPN-associated drugs cisplatin, sunitinib, colchicine, and importantly, to CC-90003 in concordance with clinical neuropathy incidence. Biochemical data together with in vitro MEA data for CC-90003 and 12 of its structural analogs, all having similar ERK inhibitory activity, revealed that CC-90003 disrupted in vitro neuronal electrophysiology likely via on-target ERK inhibition combined with off-target kinase inhibition and translocator protein inhibition. This approach could prove useful for assessing CIPN risk and interrogating mechanisms of drug-induced neuropathy.