Identifying leadership in medical trainees: evaluation of a competency-based approach.

BACKGROUND: As medical professional roles diversify, it is essential to understand what makes effective medical leaders. This study develops and validates a medical leadership competency framework that can be used to develop and evaluate leaders across all levels of medical organisations. METHOD: In Phase One, the authors derived desired leadership traits and behaviours in the medical context from a panel of subject matter experts (SMEs). Traits and behaviours were then combined into multifaceted competencies which were ranked and further refined through evaluation with additional SMEs. In Phase Two, the final seven competencies were evaluated with 181 medical trainees and 167 supervisors between 2017 and 2018 to determine the validity of rapid-form and long-form leadership assessments of medical trainees. Self and supervisor reports of the seven competencies were compared with validated trait and leadership behaviour measures as well as clinical performance evaluations. RESULTS: The final seven leadership competencies were: Ethical and Social Responsibility, Civility, Self-Leadership, Team Management, Vision and Strategy, Creativity and Innovation, and Communication and Interpersonal Influence. Results demonstrate initial validity for rapid-form and long-form leadership evaluations; however, perceptions of good leadership may differ between trainees and supervisors. Further, negative leadership behaviours (eg, incivility) are generally not punished by supervisors and some positive leadership behaviours (eg, ethical leadership) were associated with poor leadership and clinical performance evaluations by supervisors. Supervisor perceptions of leadership were significantly driven by trainee scores on social boldness (a facet of extraversion). CONCLUSIONS: A multicompetency framework effectively evaluates leadership in medicine. To more effectively reinforcepositive leadership behaviours and discourage negative leadership behaviours in medical students and resident physicians, we recommend that medical educators:: (1) Use validated frameworks to build leadership curriculum and evaluations. (2) Use short-term and long-term assessment tools. (3) Teach assessors how to evaluate leaders and encourage positive leadership behaviours early in training.

The relative incidence of cardiogenic and septic shock in neonates.

OBJECTIVE: To evaluate the relative incidence of cardiogenic and septic shock in term neonates and identify findings that help differentiate the two entities. STUDY DESIGN: We conducted a retrospective chart review of term neonates presenting to British Columbia Children's Hospital (BCCH) with decompensated shock of an undiagnosed etiology between January 1, 2008 and January 1, 2013. Charts were reviewed to determine the underlying diagnoses of all neonates meeting our inclusion criteria. Patients were categorized as having septic, cardiogenic, or other etiologies of shock. We then evaluated potential demographic, clinical, and biochemical parameters that could help differentiate between septic and cardiogenic shock. RESULTS: Cardiogenic shock was more common than septic shock (relative risk=1.53). A history of cyanosis was suggestive of cardiogenic shock (positive likelihood ratio, LR+=3.2 and negative likelihood ratio, LR-=0.4). Presence of a murmur or gallop (LR+=5.4, LR-=0.3), or decreased femoral pulses (LR+=5.1, LR-=0.5) on physical exam were also suggestive of cardiogenic shock as was cardiomegaly on chest x-ray (LR+=4.9, LR-=0.5). Notably, temperature instability (LR+=0.7, LR-=1.8) and white blood cell count elevation or depression (LR+=0.8, LR-=1.1) were all poor predictors of septic shock. CONCLUSION: Cardiogenic shock is a more common cause of decompensated shock than septic shock. A history of cyanosis, murmur or gallop, or decreased femoral pulses on exam and cardiomegaly on chest x-ray are useful indicators of cardiogenic shock. In evaluating the neonate with decompensated shock, early consideration for Cardiology consultation and interventions to treat the underlying condition is warranted.

Targeting the binding function 3 (BF3) site of the human androgen receptor through virtual screening.

The androgen receptor (AR) is the best studied drug target for the treatment of prostate cancer. While there are a number of drugs that target the AR, they all work through the same mechanism of action and are prone to the development of drug resistance. There is a large unmet need for novel AR inhibitors which work through alternative mechanism(s). Recent studies have identified a novel site on the AR called binding function 3 (BF3) that is involved into AR transcriptional activity. In order to identify inhibitors that target the BF3 site, we have conducted a large-scale in silico screen followed by experimental evaluation. A number of compounds were identified that effectively inhibited the AR transcriptional activity with no obvious cytotoxicity. The mechanism of action of these compounds was validated by biochemical assays and X-ray crystallography. These findings lay a foundation for the development of alternative or supplementary therapies capable of combating prostate cancer even in its antiandrogen resistant forms.

Inhibitors of androgen receptor activation function-2 (AF2) site identified through virtual screening.

The androgen receptor (AR) is one of the most studied drug targets for the treatment of prostate cancer. However, all current anti-androgens directly interact with the AR at the androgen binding site, which is prone to resistant mutations, calling for new strategies of the AR inhibition. The current study represents the first attempt to use virtual screening to identify inhibitors of activation function-2 (AF2) of the human AR. By combining large-scale docking with experimental approaches, we were able to identify several small molecules that interact with the AF2 and effectively prevent the transcriptional activation of the AR. The crystallographic structure of one of these inhibitors in complex with the AR provides critical insight into the corresponding protein-ligand interactions and suitable for future hit optimization. Taken together, our results provide a promising ground for development of novel anti-androgens that can help to address the problem of drug resistance in prostate cancer.