A Prospective Study of Publicly Funded Molecular Testing of Indeterminate Thyroid Nodules: Canada's Experience.

CONTEXT: Indeterminate thyroid nodules (ITNs) lead to diagnostic surgeries in many countries. Use of molecular testing (MT) is endorsed by several guidelines, but costs are limitative, especially in public healthcare systems like in Canada. OBJECTIVES: Primary objective: evaluate the clinical value of Thyroseq® v3 (TSv3) using benign call rate (BCR) in a real-world practice. Secondary objective: assess cost-effectiveness of MT. DESIGN: This is a multicentric prospective study. SETTING: This study was conducted in 5 academic centers in Quebec, Canada. PATIENTS OR OTHER PARTICIPANTS: 500 consecutive patients with Bethesda III (on 2 consecutive cytopathologies) or IV and TIRADS 3 or 4 nodules measuring 1 to 4 cm were included. INTERVENTION: MT was performed between November 2021 and November 2022. Patients with a positive TSv3 were referred to surgery. Patients with a negative TSv3 were planned for follow-up by ultrasonography for a minimum of 2 years. MAIN OUTCOME MEASURE: The BCR, corresponding to the proportion of ITNs with negative TSv3 results, was assessed. RESULTS: 500 patients underwent TSv3 testing, with a BCR of 72.6% (95% CI: 68.5-76.5; p<0.001). 99.7% of patients with a negative result avoided surgery. The positive predictive value of TSv3 was 68.2% (95% CI: 58.5-76.9). The cost-benefit analysis identified that the implementation of MT would yield cost savings of $6.1 million over the next 10 years. CONCLUSIONS: Use of MT (TSv3) in a well-selected population with ITNs led to a BCR of 72.6%. It is cost-effective and prevents unnecessary surgeries in a public healthcare setting.

Competence By Design: a transformational national model of time-variable competency-based postgraduate medical education.

Postgraduate medical education is an essential societal enterprise that prepares highly skilled physicians for the health workforce. In recent years, PGME systems have been criticized worldwide for problems with variable graduate abilities, concerns about patient safety, and issues with teaching and assessment methods. In response, competency based medical education approaches, with an emphasis on graduate outcomes, have been proposed as the direction for 21st century health profession education. However, there are few published models of large-scale implementation of these approaches. We describe the rationale and design for a national, time-variable competency-based multi-specialty system for postgraduate medical education called Competence by Design. Fourteen innovations were bundled to create this new system, using the Van Melle Core Components of competency based medical education as the basis for the transformation. The successful execution of this transformational training system shows competency based medical education can be implemented at scale. The lessons learned in the early implementation of Competence by Design can inform competency based medical education innovation efforts across professions worldwide.

Strategies to Enable Transformation in Medical Education: Faculty and Trainee Development in Competence By Design.

Transformative changes in health professions education need to incorporate effective faculty development, but few very large-scale faculty development designs have been described. The Royal College of Physicians and Surgeons of Canada's Competence by Design project was launched to transform the delivery of postgraduate medical education in Canada using a competency-based model. In this paper we outline the goals, principles, and rationale of the Royal College's national strategy for faculty and resident development initiatives to support the implementation of Competence by Design. We describe the activities and resources for both faculty and trainees that facilitated the redesign of training programs for each specialty and subspecialty at the national level, as well as supporting the implementation of the redesign at the local level. This undertaking was not without its challenges: we thus reflect on those challenges, enablers, and the lessons learned, and discuss a continuous quality improvement approach that was taken to iteratively inform the implementation process moving forward.

Lenvatinib Therapy for Advanced Thyroid Cancer: Real-Life Data on Safety, Efficacy, and Some Rare Side Effects.

Context: The SELECT trial led to the approval of lenvatinib for the treatment of advanced radioiodine-refractory differentiated thyroid carcinomas (DTCs) but also revealed an important adverse event (AE) profile which may limit its use in clinical practice. Objective: We aim to describe the efficacy and toxicity profiles of lenvatinib in real life. Methods: We included all patients who received lenvatinib for an advanced DTC at our institution, enrolling 27 patients. We reviewed retrospectively electronic medical records to assess efficacy and AEs. Results: Among the 24 patients with evaluation of tumor response during treatment, overall response rate (ORR) was 37.0% (95% CI, 19.4%-57.6%), and disease control rate was 85.2% (95% CI, 66.3%-95.8%). The median progression-free survival (PFS) was 12 months (95% CI, 7.5-16.5]. The most prevalent AEs were hypertension (77.8%), fatigue (55.6%), and weight loss (51.9%). At least one grade ≥ 3 AE was experienced by 25/27 patients (92.6%), mostly hypertension (59.3%). Lenvatinib was discontinued due to AEs in 13/27 patients (48.1%). Interestingly, 1 patient experienced a grade 4 posterior reversible encephalopathy syndrome, and another developed a Takotsubo cardiomyopathy. Conclusion: The safety profile of lenvatinib in our cohort was similar to that reported in the literature, with a predominance of hypertension. Rigorous blood pressure control is therefore essential to avoid discontinuing therapy. We also report 2 severe and rarely described AEs that physicians should watch for. As for efficacy, although less than in the SELECT trial, ORR and PFS were similar to other real-life studies.

Canadian consensus statement on the management of radioactive iodine-resistant differentiated thyroid cancer.

Radioactive iodine-resistant differentiated thyroid cancer (RAIRTC) is an aggressive form of thyroid cancer that is uncommon and heterogeneous in its clinical behavior. With the emergence of more effective systemic therapy, the need for guidance in decision-making was recognized and a consensus committee of national experts was assembled. The consensus committee consisted of 13 clinicians involved in treating RAIRTC from across Canada and included endocrinologists, nuclear medicine physicians, surgeons, and radiation and medical oncologists. Domains of interest were identified by consensus, and evidence gathered using systematic reviews. Consensus recommendations for the diagnosis and management of RAIRTC were developed. It was recognized that the rarity of RAIRTC in practice and heterogeneous patterns of thyroid cancer care could limit access to effective therapy for some RAIRTC patients. This document offers guidance to manage RAIRTC patients in a multidisciplinary manner.

Responsiveness of a simple tool for assessing change in behavioral intention after continuing professional development activities.

BACKGROUND: Continuing professional development (CPD) activities are one way that new knowledge can be translated into changes in practice. However, few tools are available for evaluating the extent to which these activities change health professionals' behavior. We developed a questionnaire called CPD-Reaction for assessing the impact of CPD activities on health professionals' clinical behavioral intentions. We evaluated its responsiveness to change in behavioral intention and verified its acceptability among stakeholders. METHODS AND FINDINGS: We enrolled 376 health professionals who completed CPD-Reaction before and immediately after attending a CPD activity. We contacted them three months later and asked them to self-report on any behavior change. We compared the mean rankings on each CPD-Reaction construct before and immediately after CPD activities. To estimate its predictive validity, we compared the median behavioral intention score (post-activity) of health professionals reporting a behavior change three months later with the median behavioral intention score of physicians who reported no change. We explored stakeholders' views on CPD-Reaction in semi-structured interviews. Participants were mostly family physicians (62.2%), with an average of 19 years of clinical practice. Post-activity, we observed an increase in intention-related scores for all constructs (P < 0.001) with the most appreciable for the construct beliefs about capabilities. A total of 313 participants agreed to be contacted at follow up, and of these only 69 (22%) reported back. Of these, 43 (62%) self-reported a behavior change. We observed no statistically significant difference in intention between health professionals who later reported a behavior change and those who reported no change (P = 0.30). Overall, CPD stakeholders found the CPD-Reaction questionnaire of interest and suggested potential solutions to perceived barriers to its implementation. CONCLUSION: The CPD-Reaction questionnaire seems responsive to change in behavioral intention. Although CPD stakeholders found it interesting, future implementation will require addressing barriers they identified.

The majority of accredited continuing professional development activities do not target clinical behavior change.

PURPOSE: Continually improving patient outcomes requires that physicians start new behaviors, stop old behaviors, or adjust how they practice medicine. Continuing professional development (CPD) is the method most commonly used by physicians to improve their knowledge and skills. However, despite regular physician attendance at these activities, change in clinical behavior is rarely observed. The authors sought to identify which of Bloom's domains (cognitive, affective, or psychomotor) are targeted by the learning objectives of CPD activities offered by medical associations, regulatory bodies, and academic institutions in the province of Quebec, Canada. METHOD: The authors evaluated the objectives of 110 accredited CPD activities offered to physicians and other health professionals from November 2012 to March 2013. The objectives of each activity were extracted and classified into learning domains using Bloom's taxonomy. RESULTS: Ninety-six percent of the learning objectives analyzed targeted the cognitive domain, which consists of six levels of increasing complexity: knowledge, comprehension, application, analysis, synthesis, and evaluation. Half (47%) targeted knowledge and comprehension, whereas only 26% aimed to improve skills in analysis, synthesis, and evaluation. CONCLUSIONS: Most accredited CPD activities within this sample were generally not designed to promote clinical behavior change because the focus of these activities was on remembering and understanding information instead of preparing physicians to put knowledge into practice by analyzing information, evaluating new evidence, and planning operations that lead to behavior change. Educators and CPD providers should take advantage of well-established theories of health professional behavior change, such as sociocognitive theories, to develop their activities.

Treatment of advanced thyroid cancer with axitinib: Phase 2 study with pharmacokinetic/pharmacodynamic and quality-of-life assessments.

BACKGROUND: In a previous phase 2 trial, axitinib was active and well tolerated in patients with advanced thyroid cancer. In this second phase 2 trial, the efficacy and safety of axitinib were evaluated further in this population, and pharmacokinetic/pharmacodynamic relationships and patient-reported outcomes were assessed. METHODS: Patients (N = 52) with metastatic or unresectable, locally advanced medullary or differentiated thyroid cancer that was refractory or not amenable to iodine-131 received a starting dose of axitinib 5 mg twice daily. The primary endpoint was the objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), safety, pharmacokinetic parameters, and patient-reported outcomes assessed with the MD Anderson Symptom Inventory questionnaire. RESULTS: The overall ORR was 35% (18 partial responses), and 18 patients had stable disease for ≥16 weeks. The median PFS was 16.1 months, and the median OS was 27.2 months. All-causality, grade ≥3 adverse events (>5%) were fatigue, dyspnea, diarrhea, decreased weight, pain in extremity, hypertension, decreased appetite, palmar-plantar erythrodysesthesia, hypocalcemia, and myalgia. Patients who had greater axitinib exposure had a longer median PFS. Quality of life was maintained during treatment with axitinib, and no significant deterioration in symptoms or interference in daily life caused by symptoms, assessed on MD Anderson Symptom Inventory subscales, were observed. CONCLUSIONS: Axitinib has activity and a manageable safety profile while maintaining quality of life, and it represents an additional treatment option for patients with advanced thyroid cancer.

Integration and timing of basic and clinical sciences education.

BACKGROUND: Medical education has traditionally been compartmentalized into basic and clinical sciences, with the latter being viewed as the skillful application of the former. Over time, the relevance of basic sciences has become defined by their role in supporting clinical problem solving rather than being, of themselves, a defining knowledge base of physicians. METHODS: As part of the national Future of Medical Education in Canada (FMEC MD) project, a comprehensive empirical environmental scan identified the timing and integration of basic sciences as a key pressing issue for medical education. Using the literature review, key informant interviews, stakeholder meetings, and subsequent consultation forums from the FMEC project, this paper details the empirical basis for focusing on the role of basic science, the evidentiary foundations for current practices, and the implications for medical education. FINDINGS: Despite a dearth of definitive relevant studies, opinions about how best to integrate the sciences remain strong. Resource allocation, political power, educational philosophy, and the shift from a knowledge-based to a problem-solving profession all influence the debate. There was little disagreement that both sciences are important, that many traditional models emphasized deep understanding of limited basic science disciplines at the expense of other relevant content such as social sciences, or that teaching the sciences contemporaneously rather than sequentially has theoretical and practical merit. Innovations in integrated curriculum design have occurred internationally. Less clear are the appropriate balance of the sciences, the best integration model, and solutions to the political and practical challenges of integrated curricula. DISCUSSION: New curricula tend to emphasize integration, development of more diverse physician competencies, and preparation of physicians to adapt to evolving technology and patients' expectations. Refocusing the basic/clinical dichotomy to a foundational/applied model may yield benefits in training widely competent future physicians.

Varying conceptions of competence: an analysis of how health sciences educators define competence.

CONTEXT: Current debate in medical education focuses on the nature of 'competency-based medical education' (CBME) and whether or not it should be adopted. Many medical schools claim to run 'competency-based' curricula, but the structure of their programmes can differ radically. A review of the existing CBME literature reveals that little attention has been paid to defining the concept of competence. A straightforward examination of what is meant by the term 'competence' is noticeably missing from the literature, despite its impact on medical training. OBJECTIVES: This paper aims to illustrate the varying conceptions of 'competence' by comparing and contrasting definitions provided in the health sciences education literature and discussing their respective impacts on medical education. METHODS: A systematic review of recent publications in medical education journals published in English and French was conducted to extract definitions of competence or, if definitions were not explicitly stated, to derive the authors' implicit conception of competence. A sample of 14 definitions from articles in the health sciences education field was studied using thematic analysis. RESULTS: There is agreement that competence is composed of knowledge, skills and other components. Although agreement about the nature of these other components is lacking, attitudes and values are suggested to be essential ingredients of competence. Furthermore, a clear divergence in conceptions of how a competent person utilises these components is apparent. One view specifies that competence involves selecting components according to specific situations, as required. A second view places greater emphasis on the synergy that results from the use of a combination of components in a given situation. CONCLUSIONS: These conceptual distinctions have many implications for the way CBME is implemented. A conception of competence as the selection of components may lead to a greater emphasis, in a training setting, on the mastery of each component separately. A conception of competence as the use of a combination of components leads to greater emphasis on the synergy that results as they are deployed in clinical situations.

Role of zoledronic acid in the prevention and treatment of osteoporosis.

Taken once a year, intravenous zoledronic acid (Zol) (Reclast® or Aclasta®) is a third-generation nitrogen-containing bisphosphonate that is effective compared with placebo in reducing the risk of fractures in patients with postmenopausal osteoporosis and recent low-trauma hip fracture. In glucocorticoid-induced osteoporosis, there is no significant difference between Zol and risedronate for new fractures. Improvements in bone mineral density and early reduction of bone remodeling markers are observed in postmenopausal osteoporosis, recent low-trauma hip fracture, and glucocorticoid-induced osteoporosis. Given that Zol is generally well tolerated and very convenient, it is an interesting therapeutic option for aging patients who take multiple oral drugs, who have adherence or gastrointestinal tolerance issues, and who have an indication for oral bisphosphonates. Zol is not recommended for patients with severe renal impairment. Vitamin D deficiency should be corrected before the administration of Zol.

Developing a theory-based instrument to assess the impact of continuing professional development activities on clinical practice: a study protocol.

BACKGROUND: Continuing professional development (CPD) is one of the principal means by which health professionals (i.e. primary care physicians and specialists) maintain, improve, and broaden the knowledge and skills required for optimal patient care and safety. However, the lack of a widely accepted instrument to assess the impact of CPD activities on clinical practice thwarts researchers' comparisons of the effectiveness of CPD activities. Using an integrated model for the study of healthcare professionals' behaviour, our objective is to develop a theory-based, valid, reliable global instrument to assess the impact of accredited CPD activities on clinical practice. METHODS: Phase 1: We will analyze the instruments identified in a systematic review of factors influencing health professionals' behaviours using criteria that reflect the literature on measurement development and CPD decision makers' priorities. The outcome of this phase will be an inventory of instruments based on social cognitive theories. Phase 2: Working from this inventory, the most relevant instruments and their related items for assessing the concepts listed in the integrated model will be selected. Through an e-Delphi process, we will verify whether these instruments are acceptable, what aspects need revision, and whether important items are missing and should be added. The outcome of this phase will be a new global instrument integrating the most relevant tools to fit our integrated model of healthcare professionals' behaviour. Phase 3: Two data collections are planned: (1) a test-retest of the new instrument, including item analysis, to assess its reliability and (2) a study using the instrument before and after CPD activities with a randomly selected control group to explore the instrument's mere-measurement effect. Phase 4: We will conduct individual interviews and focus groups with key stakeholders to identify anticipated barriers and enablers for implementing the new instrument in CPD practice. Phase 5: Drawing on the results from the previous phases, we will use consensus-building methods to develop with the decision makers a plan to implement the new instrument. DISCUSSION: This project proposes to give stakeholders a theory-based global instrument to validly and reliably measure the impacts of CPD activities on clinical practice, thus laying the groundwork for more targeted and effective knowledge-translation interventions in the future.