Developing Academic Advisors and Competence Committees members: A community approach to developing CBME faculty leaders

Introduction: Implementing competency-based medical education (CBME) at the institutional level poses many challenges including having to rapidly enable faculty to be facilitators and champions of a new curriculum which utilizes feedback, coaching, and models of programmatic assessment. This study presents the necessary competencies required for Academic Advisors (AA) and Competence Committee (CC) members, as identified in the literature and as perceived by faculty members at Queen’s University. Methods: This study integrated a review of available literature (n=26) yielding competencies that were reviewed by the authors followed by an external review consisting of CBME experts (n=5). These approved competencies were used in a cross-sectional community consultation survey distributed one year before (n=83) and one year after transitioning to CBME (n=144). Findings: Our newly identified competencies are a useful template for other institutions. Academic Advisor competencies focused on mentoring and coaching, whereas Competence Committee member’s competencies focused on integrating assessments and institutional policies. Competency discrepancies between stakeholder groups existing before the transition had disappeared in the post-implementation sample. Conclusions: We found value in taking an active community-based approach to developing and validating faculty leader competencies sooner rather than later when transitioning to CBME. The evolution of Competence Committees members and Academic Advisors requires the investment of specialized professional development and the sustained engagement of a collaborative community with shared concerns

Delivering on the promise of competency based medical education – an institutional approach

The Royal College of Physicians and Surgeons of Canada (RCPSC) adopted a plan to transform, over a seven-year horizon (2014-2021), residency education across all specialties to competency-based medical education (CBME) curriculum models. The RCPSC plan recommended implementing a more responsive and accountable training model with four discrete stages of training, explicit, specialty specific entrustable professional activities, with associated milestones, and a programmatic approach to assessment across residency education. Embracing this vision, the leadership at Queen’s University (in Kingston, Ontario, Canada) applied for and was granted special permission by the RCPSC to embark on an accelerated institutional path. Over a three-year period, Queen’s took CBME from concept to reality through the development and implementation of acomprehensive strategic plan. This perspective paper describes Queen’s University’s approach of creating a shared institutional vision, outlines the process of developing a centralized CBME executive team and twenty-nine CBME program teams, and summarizes proactive measures to ensure program readiness for launch. In so doing, Queen’s created a community of support and CBME expertise that reinforces shared values including fostering co-production, cultivating responsive leadership, emphasizing diffusion of innovation, and adopting a systems-based approach to transformative change.

An age-structured model of hepatitis B viral infection highlights the potential of different therapeutic strategies

Hepatitis B virus (HBV) is a global health threat, and its elimination by 2030 has been prioritised by the World Health Organisation. Here we present an age-structured model for the immune response to an HBV infection, which takes into account contributions from both cell-mediated and humoral immunity. The model has been validated using published patient data recorded during acute infection. It has been adapted to the scenarios of chronic infection, clearance of infection, and flare-ups via variation of the immune response parameters. The impacts of immune response exhaustion and non-infectious subviral particles on the immune response dynamics are analysed. A comparison of different treatment options in the context of this model reveals that drugs targeting aspects of the viral life cycle are more effective than exhaustion therapy, a form of therapy mitigating immune response exhaustion. Our results suggest that antiviral treatment is best started when viral load is declining rather than in a flare-up. The model suggests that a fast antibody production rate always leads to viral clearance, highlighting the promise of antibody therapies currently in clinical trials

Assembly of infectious enteroviruses depends on multiple, conserved genomic RNA-coat protein contacts.

Picornaviruses are important viral pathogens, but despite extensive study, the assembly process of their infectious virions is still incompletely understood, preventing the development of anti-viral strategies targeting this essential part of the life cycle. We report the identification, via RNA SELEX and bioinformatics, of multiple RNA sites across the genome of a typical enterovirus, enterovirus-E (EV-E), that each have affinity for the cognate viral capsid protein (CP) capsomer. Many of these sites are evolutionarily conserved across known EV-E variants, suggesting they play essential functional roles. Cryo-electron microscopy was used to reconstruct the EV-E particle at ~2.2 Å resolution, revealing extensive density for the genomic RNA. Relaxing the imposed symmetry within the reconstructed particles reveals multiple RNA-CP contacts, a first for any picornavirus. Conservative mutagenesis of the individual RNA-contacting amino acid side chains in EV-E, many of which are conserved across the enterovirus family including poliovirus, is lethal but does not interfere with replication or translation. Anti-EV-E and anti-poliovirus aptamers share sequence similarities with sites distributed across the poliovirus genome. These data are consistent with the hypothesis that these RNA-CP contacts are RNA Packaging Signals (PSs) that play vital roles in assembly and suggest that the RNA PSs are evolutionarily conserved between pathogens within the family, augmenting the current protein-only assembly paradigm for this family of viruses

Regulation of the androgen receptor by SET9-mediated methylation

The androgen receptor (AR) is a member of the nuclear hormone receptor family of transcription factors that plays a critical role in regulating expression of genes involved in prostate development and transformation. Upon hormone binding, the AR associates with numerous co-regulator proteins that regulate the activation status of target genes via flux to the post-translational modification status of histones and the receptor. Here we show that the AR interacts with and is directly methylated by the histone methyltransferase enzyme SET9. Methylation of the AR on lysine 632 is necessary for enhancing transcriptional activity of the receptor by facilitating both inter-domain communication between the N- and C-termini and recruitment to androgen-target genes. We also show that SET9 is pro-proliferative and anti-apoptotic in prostate cancer cells and demonstrates up-regulated nuclear expression in prostate cancer tissue. In all, our date indicate a new mechanism of AR regulation that may be therapeutically exploitable for prostate cancer treatment

An Intracellular Model of Hepatitis B Viral Infection: An In Silico Platform for Comparing Therapeutic Strategies

Hepatitis B virus (HBV) is a major focus of antiviral research worldwide. The International Coalition to Eliminate HBV, together with the World Health Organisation (WHO), have prioritised the search for a cure, with the goal of eliminating deaths from viral hepatitis by 2030. We present here a comprehensive model of intracellular HBV infection dynamics that includes all molecular processes currently targeted by drugs and agrees well with the observed outcomes of several clinical studies. The model reveals previously unsuspected kinetic behaviour in the formation of sub-viral particles, which could lead to a better understanding of the immune responses to infection. It also enables rapid comparative assessment of the impact of different treatment options and their potential synergies as combination therapies. A comparison of available and currently developed treatment options reveals that combinations of multiple capsid assembly inhibitors perform best

Model-based evaluation of the long-term cost-effectiveness of systematic case-finding for COPD in primary care

Introduction'One-off' systematic case-finding for COPD using a respiratory screening questionnaire is more effective and cost-effective than routine care at identifying new cases. However, it is not known whether early diagnosis and treatment is beneficial in the longer term. We estimated the long-term cost-effectiveness of a regular case-finding programme in primary care.MethodsA Markov decision analytic model was developed to compare the cost-effectiveness of a 3-yearly systematic case-finding programme targeted to ever smokers aged ≥50 years with the current routine diagnostic process in UK primary care. Patient-level data on case-finding pathways was obtained from a large randomised controlled trial. Information on the natural history of COPD and treatment effects was obtained from a linked COPD cohort, UK primary care database and published literature. The discounted lifetime cost per quality-adjusted life-year (QALY) gained was calculated from a health service perspective.ResultsThe incremental cost-effectiveness ratio of systematic case-finding versus current care was £16 596 per additional QALY gained, with a 78% probability of cost-effectiveness at a £20 000 per QALY willingness-to-pay threshold. The base case result was robust to multiple one-way sensitivity analyses. The main drivers were response rate to the initial screening questionnaire and attendance rate for the confirmatory spirometry test.DiscussionRegular systematic case-finding for COPD using a screening questionnaire in primary care is likely to be cost-effective in the long-term despite uncertainties in treatment effectiveness. Further knowledge of the natural history of case-found patients and the effectiveness of their management will improve confidence to implement such an approach