ABSTRACT
Women comprise the majority of pediatricians in the United States and yet there has been slow progress in leadership diversity and equity in the field overall. While there have been many academic journal articles that examine women's roles, challenges and successes in the field, there is not one, overarching book that follows the path of women into the profession, the challenges they encountered in the early years - and still encounter - the successes they've had, and what the future might look like. This book fills that gap in medical literature. Because women are so well-represented in the field, one would think that pediatrics should be leading the way in gender equity achievements, but this is not the case. This text examines the disparities, the boundaries that are in place, the impact of intersectionality on equity, the toll gender discrimination has on the health and wellness of women in pediatrics, and best practices that can help achieve gender equity in the field. The COVID-19 pandemic has exacerbated the disparities that women, and in particular women with intersectionality, face. This book also examines the immediate impact of the pandemic on women in pediatrics, what future implications may be, and how we can potentially mitigate them. Equity strategies that can be implemented by healthcare institutions, professional societies and other medical organizations are also discussed. The book is divided into three main sections. The first section gives an overview of the history of women in pediatrics by describing stories of early leaders and the early days of women in pediatrics. The second section reviews the current state of affairs in women in pediatrics. Chapters in this section detail women entering and practicing in pediatrics;leadership;women of color;women conducting research;national campaigns and efforts focused on gender equity;and childbearing, adoption, motherhood and eldercare by women in pediatrics. The final section describes the future of women in pediatrics. The seven chapters in this section discuss leaders in pediatrics supporting women;policies and programs to advance equity;allies in gender equity efforts;research, funding and publication for women;networking, mentorship, sponsorship, coaching, and career development activities;advocacy efforts;and supporting the health and wellbeing of women in pediatrics. Written by experts in the field, Women in Pediatrics is a valuable resource for all pediatricians in academic or community-based medicine, as well as those involved in pediatric sub-specialties. On a broader level, this text is also of interest to all other women involved in medicine and science. © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG 2022.
ABSTRACT
Introduction: Remdesivir is indicated for the treatment of COVID-19 in patients requiring hospitalization. However, cases of QTc interval prolongation and torsade de pointes (TdP) have been reported to the FDA Adverse Event Reporting System. Drug-induced QTc prolongation and TdP is the single most common cause of withdrawal, relabeling and use restriction of marketed drugs. Most drugs that prolong the QTc inhibit a potassium current (IKr), which is encoded by the human ether-a-go-go-related gene (hERG) and is crucial for ventricular repolarization and action potential duration. Research Question or Hypothesis: To assess the potential for remdesivir and its metabolite, GS441524, to inhibit hERG-related currents. Study Design: Cell-based hERG Assay Methods: Whole-cell, voltage-clamp experiments were performed in HEK-293 cells stably expressing hERG. Borosilicate glass electrodes (resistance: 2-4 MW) filled with internal solution were used to record tail currents at depolarizing and repolarizing voltages tail current. To assess acute effects, drugs were added to the internal pipette solution, and for prolonged exposure;cells were incubated with remdesivir for 24 hours prior to recording. Results: Acute exposure to remdesivir and GS-441524 did not significantly inhibit peak activation or maximum tail current density. However, prolonged exposure to remdesivir 100 nM and 1 mM, but not 10 nM, inhibited peak activation currents by 32% (19±2 pA/pF, p = 0.03) and 36% (18±2 pA/pF, p = 0.02) respectively. Remdesivir 100 nM and 1 mM, also inhibited the maximum tail current density by 40% (18±2 pA/pF, p = 0.02) and 37% (19±2 pA/pF, p = 0.03), respectively. Conclusion: Prolonged exposure to physiological concentrations of remdesivir inhibits hERG-related currents. These results, coupled with clinical reports of QTc prolongation and TdP, highlight the need for a rigorous assessment of the effect of remdesivir on ventricular repolarization and risk of proarrhythmia.