Search

Abstract Background Effective mentorship is an important contributor to academic success. Given the critical role of leadership in fostering mentorship, this study sought to explore the perspectives of departmental leadership regarding 1) current departmental mentorship processes; and 2) crucial components of a mentorship program that would enhance the effectiveness of mentorship. Methods Department Division Directors (DDDs), Vice-Chairs, and Mentorship Facilitators from the Department of Medicine at the University of Toronto Temerty Faculty of Medicine were interviewed between April and December 2021 using a semi-structured guide. Interviews were audio-recorded and transcribed verbatim, then coded. Analysis occurred in 2 steps: 1) codes were organized to identify emergent themes; then 2) the Social Ecological Model (SEM) was applied to interpret the findings. Results Nineteen interviews (14 DDDs, 3 Vice-Chairs, and 2 Mentorship Facilitator) were completed. Analysis revealed three themes: (1) a culture of mentorship permeated the department as evidenced by rigorous mentorship processes, divisional mentorship innovations, and faculty that were keen to mentor; (2) barriers to the establishment of effective mentoring relationships existed at 3 levels: departmental, interpersonal (mentee-mentor relationships), and mentee; and (3) strengthening the culture of mentorship could entail scaling up pre-existing mentorship processes and promoting faculty engagement. Application of SEM highlighted critical program features and determined that two components of interventions (creating tools to measure mentorship outcomes and systems for mentor recognition) were potential enablers of success. Conclusions Establishing ‘mentorship outcome measures’ can incentivize and maintain relationships. By tangibly delineating departmental expectations for mentorship and creating systems that recognize mentors, these measures can contribute to a culture of mentorship.

BackgroundTransgender people encounter significant barriers when seeking timely, high-quality healthcare, resulting in unmet medical needs with increased rates of diabetes, asthma, chronic obstructive pulmonary disease, and HIV. The paucity of postgraduate medical education to invest in standardization of transgender health training sustains these barriers, leaving physicians feeling unprepared and averse to provide transgender health care. Closing this education gap and improving transgender healthcare necessitates the development of consensus-built transgender health objectives of training (THOOT), particularly in Adult Endocrinology and Metabolism Residency programs.MethodsWe conducted a two-round modified-Delphi process involving a nationally representative panel of experts, including Adult Endocrinology and Metabolism program directors, physician content experts, residents, and transgender community members, to identify THOOT for inclusion in Canadian Endocrinology and Metabolism Residency programs. Participants used a 5-point Likert scale to assess THOOT importance for curricular inclusion, with opportunities for written feedback. Data was collected through Qualtrics and analyzed after each round.FindingsIn the first Delphi round, panelists reviewed and rated 81 literature extracted THOOT, achieving consensus on all objectives. Following panelists' feedback, 5 THOOT were added, 9 removed, 34 consolidated into 12 objectives, and 47 were rephrased or retained. In the second Delphi round, panelists assessed 55 THOOT. Consensus was established for 8 THOOT. Program directors' post-Delphi feedback further consolidated objectives to arrive at 4 THOOT for curriculum inclusion.ConclusionsTo our knowledge, this is the first time a consensus-based approach has been used to establish THOOT for any subspecialty postgraduate medicine program across Canada or the United States. Our results lay the foundation towards health equity and social justice in transgender health medical education, offering a blueprint for future innovations.

Abstract Background Diabetic retinopathy is a leading cause of preventable blindness in Canada. Clinical guidelines recommend annual diabetic retinopathy screening for people living with diabetes to reduce the risk and progression of vision loss. However, many Canadians with diabetes do not attend screening. Screening rates are even lower in immigrants to Canada including people from China, Africa, and the Caribbean, and these groups are also at higher risk of developing diabetes complications. We aim to assess the feasibility, acceptability, and fidelity of a co-developed, linguistically and culturally tailored tele-retinopathy screening intervention for Mandarin-speaking immigrants from China and French-speaking immigrants from African-Caribbean countries living with diabetes in Ottawa, Canada, and identify how many from each population group attend screening during the pilot period. Methods We will work with our health system and patient partners to conduct a 6-month feasibility pilot of a tele-retinopathy screening intervention in a Community Health Centre in Ottawa. We anticipate recruiting 50–150 patients and 5–10 health care providers involved in delivering the intervention for the pilot. Acceptability will be assessed via a Theoretical Framework of Acceptability-informed survey with patients and health care providers. To assess feasibility, we will use a Theoretical Domains Framework-informed interview guide and to assess fidelity, and we will use a survey informed by the National Institutes of Health framework from the perspective of health care providers. We will also collect patient demographics (i.e., age, gender, ethnicity, health insurance status, and immigration information), screening outcomes (i.e., patients with retinopathy identified, patients requiring specialist care), patient costs, and other intervention-related variables such as preferred language. Survey data will be descriptively analyzed and qualitative data will undergo content analysis. Discussion This feasibility pilot study will capture how many people living with diabetes from each group attend the diabetic retinopathy screening, costs, and implementation processes for the tele-retinopathy screening intervention. The study will indicate the practicability and suitability of the intervention in increasing screening attendance in the target population groups. The study results will inform a patient-randomized trial, provide evidence to conduct an economic evaluation of the intervention, and optimize the community-based intervention.

Abstract Background Diabetic retinopathy is a sight-threatening ocular complication of diabetes. Screening is an effective way to reduce severe complications, but screening attendance rates are often low, particularly for newcomers and immigrants to Canada and people from cultural and linguistic minority groups. Building on previous work, in partnership with patient and health system stakeholders, we co-developed a linguistically and culturally tailored tele-retinopathy screening intervention for people living with diabetes who recently immigrated to Canada from either China or African-Caribbean countries. Methods Following an environmental scan of diabetes eye care pathways in Ottawa, we conducted co-development workshops using a nominal group technique to create and prioritize personas of individuals requiring screening and identify barriers to screening that each persona may face. Next, we used the Theoretical Domains Framework to categorize the barriers/enablers and then mapped these categories to potential evidence-informed behaviour change techniques. Finally with these techniques in mind, participants prioritized strategies and channels of delivery, developed intervention content, and clarified actions required by different actors to overcome anticipated intervention delivery barriers. Results We carried out iterative co-development workshops with Mandarin and French-speaking individuals living with diabetes (i.e., patients in the community) who immigrated to Canada from China and African-Caribbean countries (n = 13), patient partners (n = 7), and health system partners (n = 6) recruited from community health centres in Ottawa. Patients in the community co-development workshops were conducted in Mandarin or French. Together, we prioritized five barriers to attending diabetic retinopathy screening: language (TDF Domains: skills, social influences), retinopathy familiarity (knowledge, beliefs about consequences), physician barriers regarding communication for screening (social influences), lack of publicity about screening (knowledge, environmental context and resources), and fitting screening around other activities (environmental context and resources). The resulting intervention included the following behaviour change techniques to address prioritized local barriers: information about health consequence, providing instructions on how to attend screening, prompts/cues, adding objects to the environment, social support, and restructuring the social environment. Operationalized delivery channels incorporated language support, pre-booking screening and sending reminders, social support via social media and community champions, and providing using flyers and videos as delivery channels. Conclusion Working with intervention users and stakeholders, we co-developed a culturally and linguistically relevant tele-retinopathy intervention to address barriers to attending diabetic retinopathy screening and increase uptake among two under-served groups.

Endometrial cancer is the most common gynecologic cancer in the United States and it contributes to the second most gynecologic cancer-related deaths. With upfront surgery, the specific characteristics of both the patient and tumor allow for risk-tailored treatment algorithms including adjuvant radiotherapy and systemic therapy. In this narrative review, we discuss the current radiation treatment paradigm for endometrial cancer with an emphasis on various radiotherapy modalities, techniques, and dosing regimens. We then elaborate on how to tailor radiotherapy treatment courses in combination with other cancer-directed treatments, including chemotherapy and immunotherapy. In conclusion, this review summarizes ongoing research that aims to further individualize radiotherapy regimens for individuals in an attempt to improve patient outcomes.

Glioblastoma, the most common primary brain cancer in adults, is characterized by a poor prognosis and resistance to standard treatments. The advent of immunotherapy has revolutionized the treatment of several cancers in recent years but has failed to demonstrate benefit in patients with glioblastoma. Understanding the mechanisms by which glioblastoma exerts tumor-mediated immune suppression in both the tumor microenvironment and the systemic immune landscape is a critical step towards developing effective immunotherapeutic strategies. In this review, we discuss the current understanding of immune escape mechanisms in glioblastoma that compromise the efficacy of immunotherapies, with an emphasis on immune checkpoint inhibitors and chimeric antigen receptor T-cell therapy. In parallel, we review data from preclinical studies that have identified additional therapeutic targets that may enhance overall treatment efficacy in glioblastoma when administered alongside existing immunotherapies.

Keratinocytes are the predominant block-building cells in the epidermis. Emerging evidence has elucidated the roles of keratinocytes in a wide range of pathophysiological processes including cutaneous nociception, pruritus, and inflammation. Intraepidermal free nerve endings are entirely enwrapped within the gutters of keratinocyte cytoplasm and form en passant synaptic-like contacts with keratinocytes. Keratinocytes can detect thermal, mechanical, and chemical stimuli through transient receptor potential ion channels and other sensory receptors. The activated keratinocytes elicit calcium influx and release ATP, which binds to P2 receptors on free nerve endings and excites sensory neurons. This process is modulated by the endogenous opioid system and endothelin. Keratinocytes also express neurotransmitter receptors of adrenaline, acetylcholine, glutamate, and γ-aminobutyric acid, which are involved in regulating the activation and migration, of keratinocytes. Furthermore, keratinocytes serve as both sources and targets of neurotrophic factors, pro-inflammatory cytokines, and neuropeptides. The autocrine and/or paracrine mechanisms of these mediators create a bidirectional feedback loop that amplifies neuroinflammation and contributes to peripheral sensitization.

Introduction: East Toronto Health Partners (ETHP) is a network of organizations that serve residents of East Toronto, Ontario, Canada. ETHP is a newly formed integrated model of care in which hospital, primary care, community providers and patients/families work together to improve population health. We describe and evaluate the evolution of this emerging integrated care system as it responded to a global health crisis. Description: This paper begins by describing ETHP’s pandemic response mapping out over two years of data. To evaluate the response, semi-structured interviews were conducted with 30 decision makers, clinicians, staff, and volunteers who were part of the response. The interviews were thematically analyzed, and emergent themes mapped onto the nine pillars of integrated care. Discussion: The ETHP pandemic response evolved rapidly. Early siloed responses gave way to collaborative efforts and equity emerged as a central priority. New alliances formed, resources were shared, leaders emerged, and community members stepped forward to contribute. Interviewees identified positives as well as many opportunities for improvement post-pandemic. Conclusion: The pandemic was a catalyst for change in East Toronto that accelerated existing initiatives to achieve integrated care. The East Toronto experience may serve as a useful guide for other emerging integrated care systems.

Abstract Background Empathy levels decline through medical training. This has been associated with poor patient and physician outcomes, and strategies to combat this decline are increasingly recognized as critical aspects of medical education. The aim of this study was to qualitatively determine factors associated with empathy decline, and to assess the impact of a comics/graphic novel-based curriculum on enhancing empathy and a patient-centered approach to care in post-graduate medical learners. Methods Fourth and fifth year residents in the Adult and Pediatric Endocrinology and Metabolism Program at the University of Toronto were recruited from the 2017 cohort of the Empathy, Humanism & Comics course. Participants completed a 12-month curriculum, viewing a total of four animated graphic novels over six sessions. At the end of the course participants were interviewed either individually or in a focus group. A coding framework of emerging themes was developed based on consensus between the three authors using a qualitative descriptive approach and the constant-comparison method. Results Analysis of coded interview data revealed four themes. 1. The curriculum accurately reflected and addressed issues in real world medical practice; 2. The comics curriculum facilitated holistic development; 3. Participants appreciated the comics as an educational medium; 4. Participant feedback on the curriculum. The importance of empathy was noted, while participants acknowledged their own empathy decline and increased burnout. Stressors included increasing responsibility, long work hours, and competing work-life responsibilities. They felt the sessions developed resilience, an appreciation for the patient perspective, and communication skills. They appreciated the comics as a novel and engaging educational modality. Feedback on the effectiveness and relevancy of the curriculum was variable. Conclusions Residents appreciated sharing difficult experiences and seeking support. They acknowledged the curriculum as a commitment to wellness and felt it reduced burnout and improved empathy. The comics were viewed as an effective reminder of the patient perspective. Variable curriculum feedback highlights the challenge in designing a course for adult learners. Future investigations may include the development and incorporation of similar curricula in other post-graduate residency training programs.

Abstract Background Diabetes is a highly prevalent chronic disease that places a large burden on individuals and health care systems. Models predicting the risk (also called predictive models) of other conditions often compare people with and without diabetes, which is of little to no relevance for people already living with diabetes (called patients). This review aims to identify and synthesize findings from existing predictive models of physical and mental health diabetes-related conditions. Methods We will use the scoping review frameworks developed by the Joanna Briggs Institute and Levac and colleagues. We will perform a comprehensive search for studies from Ovid MEDLINE and Embase databases. Studies involving patients with prediabetes and all types of diabetes will be considered, regardless of age and gender. We will limit the search to studies published between 2000 and 2018. There will be no restriction of studies based on country or publication language. Abstracts, full-text screening, and data extraction will be done independently by two individuals. Data abstraction will be conducted using a standard methodology. We will undertake a narrative synthesis of findings while considering the quality of the selected models according to validated and well-recognized tools and reporting standards. Discussion Predictive models are increasingly being recommended for risk assessment in treatment decision-making and clinical guidelines. This scoping review will provide an overview of existing predictive models of diabetes complications and how to apply them. By presenting people at higher risk of specific complications, this overview may help to enhance shared decision-making and preventive strategies concerning diabetes complications. Our anticipated limitation is potentially missing models because we will not search grey literature.

Introduction Emergency medicine (EM) physicians serve at the frontline of disasters in our communities. The 2016 Model of Clinical Practice according to the American Board of EM identifies disaster management as an integral task of EM physicians. We described a low-cost and feasible tabletop exercise to implement such training for EM residents. Methods The exercise took place during 2 hours of resident didactic time. A lecture introduced the incident command system (ICS) and triage concepts, followed by a tabletop scenario with a map of a disaster scene or emergency department. Facilitators presented situational prompts of tasks for residents to address during the exercise. These exposed residents to challenges in disaster scenarios, such as surge and limited resources. The exercise concluded with a debrief and short lecture reviewing scenario-specific topics and challenges. Residents completed an online pre- and postexercise assessment, evaluating knowledge and perceptions of disaster scenario management. Results Eighteen residents participated in this exercise. The response rates to the pre- and postsurvey were 76% and 72% respectively. Using a Mann Whitney U test, no statistically significant difference was demonstrated on the medical knowledge component of the survey. There was, however, a statistically significant increase in perceived confidence of the residents' ability to manage disaster incidents. Discussion We developed a simple exercise that is an easily adaptable and practical option for introduction to disaster preparedness training. These concepts are difficult to teach and assess among learners, however it remains an important component of education for EM physicians-in-training.

Hyperhomocysteinemia (HHcy) is an independent risk factor for cardiovascular disease (CVD) which has been implicated in matochondrial (Mt) function impairment. In this study, we characterized Hcy metabolism in mouse tissues by using LC-ESI-MS/MS analysis, established tissue expression profiles for 84 nuclear-encoded Mt electron transport chain complex (nMt-ETC-Com) genes in 20 human and 19 mouse tissues by database mining, and modeled the effect of HHcy on Mt-ETC function. Hcy levels were high in mouse kidney/lung/spleen/liver (24–14 nmol/g tissue) but low in brain/heart (~5 nmol/g). S-adenosylhomocysteine (SAH) levels were high in the liver/kidney (59–33 nmol/g), moderate in lung/heart/brain (7–4 nmol/g) and low in spleen (1 nmol/g). S-adenosylmethionine (SAM) was comparable in all tissues (42–18 nmol/g). SAM/SAH ratio was as high as 25.6 in the spleen but much lower in the heart/lung/brain/kidney/liver (7–0.6). The nMt-ETC-Com genes were highly expressed in muscle/pituitary gland/heart/BM in humans and in lymph node/heart/pancreas/brain in mice. We identified 15 Hcy-suppressive nMt-ETC-Com genes whose mRNA levels were negatively correlated with tissue Hcy levels, including 11 complex-I, one complex-IV and two complex-V genes. Among the 11 Hcy-suppressive complex-I genes, 4 are complex-I core subunits. Based on the pattern of tissue expression of these genes, we classified tissues into three tiers (high/mid/low-Hcy responsive), and defined heart/eye/pancreas/brain/kidney/liver/testis/embryonic tissues as tier 1 (high-Hcy responsive) tissues in both human and mice. Furthermore, through extensive literature mining, we found that most of the Hcy-suppressive nMt-ETC-Com genes were suppressed in HHcy conditions and related with Mt complex assembly/activity impairment in human disease and experimental models. We hypothesize that HHcy inhibits Mt complex I gene expression leading to Mt dysfunction. Keywords: Database mining, Tissue expression profile, Homocysteine metabolism

The complexation of molecular clips containing fragments of diphenylglycoluril and benzocrown ethers with paraquat and its derivatives has been studied both in solution and in the solid state. In this paper we studied the influence of the crown ether ring size and the nature of the substituents at the nitrogen atoms of the paraquat derivatives on the composition and stability of these complexes.

ABSTRACT: Objective: To describe a case of diabetic ketoacidosis (DKA) associated with sodium-glucose cotransporter-2 inhibitor (SGLT2i) and dexamethasone use in a patient with type 2 diabetes.Methods: We present the case of an 87-year-old male with type 2 diabetes on canagliflozin who underwent resection of a meningioma and received postoperative dexamethasone. Eight days after discharge, he presented to the emergency department with generalized weakness, lethargy, and anorexia.Results: Laboratory investigations revealed hyperglycemia (blood glucose, 39 mmol/L), metabolic acidosis (venous pH, 7.26), an elevated anion gap (22 mmol/L), and positive serum ketones. He was diagnosed with DKA and required admission to the intensive care unit.Conclusion: This is the first report of possible SGLT2i-associated DKA that occurred during co-administration of glucocorticoids. Both SGLT2i and glucocorticoids decrease insulin release and increase glucagon secretion, which may thereby provide an overwhelming ketogenic stimulus. Accordingly, clinicians should exercise caution when co-administering glucocorticoids and SGLT2i until further data are available.Abbreviations: DKA diabetic ketoacidosis; SGLT2i sodium-glucose cotransporter-2 inhibitor

Circular RNAs (circRNAs) are non-coding RNAs that form covalently closed continuous loops, and act as gene regulators in physiological and disease conditions. To test our hypothesis that proatherogenic lipid lysophosphatidylcholine (LPC) induce a set of circRNAs in human aortic endothelial cell (HAEC) activation, we performed circRNA analysis by searching our RNA-Seq data from LPC-activated HAECs, and found: (1) LPC induces significant modulation of 77 newly characterized cirRNAs, among which 47 circRNAs (61%) are upregulated; (2) 34 (72%) out of 47 upregulated circRNAs are upregulated when the corresponding mRNAs are downregulated, suggesting that the majority of circRNAs are upregulated presumably via LPC-induced “abnormal splicing” when the canonical splicing for generation of corresponding mRNAs is suppressed; (3) Upregulation of 47 circRNAs is temporally associated with mRNAs-mediated LPC-upregulated cholesterol synthesis-SREBP2 pathway and LPC-downregulated TGF-β pathway; (4) Increase in upstream chromatin long-range interaction sites to circRNA related genes is associated with preferred circRNA generation over canonical splicing for mRNAs, suggesting that shifting chromatin long-range interaction sites from downstream to upstream may promote induction of a list of circRNAs in lysoPC-activated HAECs; (5) Six significantly changed circRNAs may have sponge functions for miRNAs; and (6) 74% significantly changed circRNAs contain open reading frames, suggesting that putative short proteins may interfere with the protein interaction-based signaling. Our findings have demonstrated for the first time that a new set of LPC-induced circRNAs may contribute to homeostasis in LPC-induced HAEC activation. These novel insights may lead to identifications of new therapeutic targets for treating metabolic cardiovascular diseases, inflammations, and cancers.

ABSTRACT: Objective: We describe a case of co-existing Graves disease and struma ovarii, which has seldom been reported.Methods: We present the clinical, biochemical, and imaging findings of one such case and review the relevant literature for the evaluation and treatment of co-existing Graves disease and struma ovarii.Results: A 33-year-old woman presented with a palpable right-sided pelvic mass, clinical and biochemical thyrotoxicosis, and elevated thyroid-stimulating hormone receptor antibody levels. On ultrasound, the thyroid was enlarged and hyperemic with a heterogeneous echotexture. Pelvic ultrasound showed a complex cystic-solid right adnexal lesion with calcifications (14 × 5.4 × 8.3 cm), favored to be an ovarian teratoma. Magnetic resonance imaging (MRI) of the pelvis showed bilateral adnexal lesions of mixed T1 and T2 signal intensity containing fat, soft tissue components, and calcification suspicious for teratomas. Whole-body uptake and scan showed homogenous thyroid uptake at 2 hours and 24 hours of 54% and 77%, respectively, and increased activity in the right adnexa. Following bilateral laparoscopic ovarian cystectomies, postoperative histology showed benign, bilateral cystic teratomas with histologic evidence of hyperfunctioning thyroid tissue bilaterally. Positive immunohistochemical staining of the teratomas for thyroid transcription factor 1 confirmed the presence of thyroid tissue. Postoperative whole-body scintigraphy did not show residual pelvic iodine uptake.Conclusion: Our patient had clinical, biochemical, and radiographic evidence of Graves disease with thyrotoxicosis while also having bilateral ovarian teratomas containing hyperfunctioning thyroid tissue. Although bilateral, the right-sided teratoma was likely the primary pelvic source of thyroid hormone secretion given that increased iodine uptake on whole-body scan was seen only in the right adnexa. In cases of co-existing Graves disease and struma ovarii, pre-operative MRI and whole-body scintigraphy with 123I is preferred for diagnosis. Keys to management include ensuring patients are euthyroid prior to surgery to avoid precipitating a thyroid storm, titrating antithyroid medications closely postoperatively, and completing repeat whole-body scintigraphy postoperatively to assess for residual thyroid tissue in the pelvis.Abbreviations: CT = computed tomography; SO = struma ovarii; SPECT = single-photon emission computed tomography; TSH = thyroid-stimulating hormone; TTF-1 = thyroid transcription factor 1